Immunology
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| Chronic granulomatous disease | Deficiency in NADPH oxidase production so that MO's can't make O2 metabolites to kill phagocytosed shit
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| Leukocyte adhesion deficiency (LAD) | Absence of CD18 (a b2 chain of integrin) so that leukocytes can no longer move around= omphalitis, chornic bacterial infxns, etc. Can be treated with bone marrow translplant
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| What's the natural broad-spec antibiotic on skin? | Defensin
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| Neutrophils | Early phagocytosis and killing of microbes
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| Macrophages | Efficient phagocytosis and killing of microbes, secretion of cytokines that stimluate inflammation (IL-12....which stimulates NK to make INF-y to stimulate the macrophage to kill!)
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| NK cells | Lysis of infeted cells, activation of macrophages (by INF-y)
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| Complement | Kills microbe, opsonization (BBQ sauce) of microbes, activation of leukocytes
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| CRP | opsonization of microbes, activation of complement
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| TNF, IL-1, chemokines | Inflammation
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| IFN-a and b | resistance to viral infxn
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| IFN-y | Macrophage activation
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| IL-12 | IFN-y production by NK cells and T cells
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| IL-15 | Proliferation of NK cells
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| IL-10, TGF-b | Control of inflammation
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| What Ab isotype is not bifunctional (only one)? | IgD
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| Abs are structurally made up of what? | 4 peptide chains: 2 identical light chains, 2 identical heavy chains
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| What cells have receptors for Ab constant regions (the FC receptors)? | Mononuclear cellsNeutrophilsNK cellsEosinophilsBasophilsMast cells
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| What is avidity? | It's like affiinity, but depends on the Antibody number of binding sites and its ablitly to engage MULTIPLE epitopes on the antigen
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| What is an allotype? | The protein of an allele that may be detectalbe as an antigen by another memeber of the same species
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| What is an epitope? | The part of an Ag that contacts the antigen-binding sites of an Ab or the T-cell receptor
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| What is an idiotype? | It's a single antigenic determinant to an antibody V region (variable)
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| What Igs are the following CD markers specific for (the Fc receptors)?CD16CD23CD32CD64 | CD16: IgGCD23: IgECD32: IgGCD64: IgG
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| What are the main cells/systems of the innate immune system? | PMNs, MOs, DCs, NKs, C'
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| What are the main cells of the adaptive immune system? | T-cells, B-cells, Antibodies
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| What are the genes of MHC I | HLA-A, B, C
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| What are the genes of MHC II? | HLA-DP, Q, R
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| What cells express MHC I? | Almost all nucleated cells (so that excludes RBCs)
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| What cells are MHC II expressed on? | APCs
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| What is special about MHC I production? | TAP protein is used to get the antigen into the RER
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| What are the special proteins used in the MHC II production? | Invariant chain and CLIP protein
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| What MHC class has 2 membrane spanning chains? | MHC II (2! Convinient)
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| What are the are some of the main jobs of B-cells? | - Make Ab: opsonization of bacteria, activate C' (IgM, IgG), neutralize viruses (IgG), sensitize mast cells (IgE)- Allerigies: IgE- Cytotoxic & Immune complex hypersensitivities: IgG-Hyperacute organ rejection: Ab mediated
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| What are the main jobs of T-cells? | - Help out B-cells: CD4+ Th cells help them to make Ab and INF-y (activates MOs)- CD8+ T-cells kill virus-infected cells directly (CTLs)- DTH: Delayed cell mediated hypersensitivity - Acute and chronic organ rejection
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| What are the 3 main APCs? | DC (professional), MO, B-cell
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| During the 1st signal of Th cell activation, what cell has the B7? The CD28? | B7: APCCD28: Th cell
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| What is the 2nd signal in CTL activation?(1st signal is Endogenous protein...self or virus...presented to MHC I & recognized by the TCR on the CTL cell...CD8+) | IL-2 from a Th cell activates CTL to kill the virus infected cell
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| What kinds of cytokines released from a Th cells will induce a B-cell to undergo class switching? To what class? | IL-4: to IgGIL-5: to IgEIL-6: to IgG****Requires 2nd signal: CD40 receptor (B-cell) binding to CD40L (Th cells)
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| Th1 cells regulate what kind of immune response? | Cell-mediated response
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| What cytokines does Th1 release? | IL-2IFN-y
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| IFN-y inhibits and promotes what Th cells? | Th1 are promotedTh2 are inhibited
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| Th2 cells mediate what kind of immune response? | Humoral response (b/c the y help B-cells make Ab (IgE>IgG)
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| What can inhibit Th2? | IFN-y (from the Th1 cells)
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| What cytokines are secreted by Th2? | IL-4, IL-5, IL-10
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| What are the functions of Th1? | Secretes IL-2, IFN-yActivates MOs and CD8+ cells (hence the cell-mediated immunity)
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| What can inhibit Th1? | IL-10 (from Th2)
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| How are CTL (Cytotoxic T cells) so killer-ish? | They release:perforin--punches holes into the target cells so that granules can be released into it...Granzyme---a protease, activates apoptosis in the target cells
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| What are the main fxns of antibodies? | They can be C.O.N.'s!Complement activation (activates C', which enhances opsonization even more, and lysis via Mac-attack!)Opsonization (making the pathogen tasty" to be phagocytosed)Neutralization (prevents bacterial adherence to our cells)"
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| What region of an Ab determines the isotype? The idiotype? | Isotype (IgM, IgG, IgD, etc.)= FcIdiotype (unique antigen binding pocket)=Fab
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| What creates Ab diversity? | 1. Random VDJ (heavy chain) or VJ (light chain) recombination of genes2. Random recombination of heavy chains with light chains3. Somatic hypermutation (after antigen stimulation)4. Random addition of nucleotides to DNA during recombination (see #1)
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| What Ig's are expressed on mature B lymphocyes (before isotype switching)? | IgM and IgD
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| What mediates isotype switching of IgM and IgD on mature B-lymphocytes? | Cytokines and CD40L (switches them into IgA, IgE, or IgG)
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| What are the main points of IgG? | Delayed (secondary) response to AgMost abundant in BLOODFixes complement (so does IgM)CROSSES PLACENTA (=passive immunity)Opsonizes bacteriaNeutralizes bacterial toxins and viruses
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| What are the main points of IgM? | Primary (immediate) response to AgFixes complementAntigen receptor on surface of mature B-cellsMonomer (on B cell) or pentamerPentamer is really effective at binding free antigens while humoral response evolves
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| What are the main points of IgD? | Suface of many mature B-cellsUnclear fxn
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| What are the main points of IgE? | Allergies=mast cells, worms=eosinophilsBinds to mast cells and basophils. Releases inflmamatory mediators (i.e. histamine) when it cross-links if exposed to an allergen.Mediates immunity to worms (by activating eosinophils)Lowest concentration in serum
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| What's the deal with T-indepentdent antigens (Thymus/T-cell independent)? | LACK PEPTIDE component (so they are likely LPS or some other sugar component)....so they CANNOT be presented by an MHC to a T-cell.Stimulates release of IgM Ab's ONLY; have NO immunologic memory
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| What's the deal with T-dependent (thymus/t-cell dependent) Ag's? | Have a PROTEIN/peptide component, so they present, via MHC, to T-cells.T-cells then help stimulate class switching and IMMUNOLOGIC MEMORY via direct contact of B-cells with Th2 cells (CD40:CD40L interaction) and subsequent release of IL-4, IL-5, IL-6
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| C' protects us primarely from what kind of bacteria? | Gram (-)!
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| What activates the classical C' pathway? The alternative? | Classical: IgG, IgM (GM makes classic cars)Alternative: molecules on the surface microbes (esp endotoxin)
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| What helps to prevent C' activation on self-cells (like RBCs, etc.) in addition to sialic acid? | DAF (decay-accelerating factor)C1-esterase inhibitor (C1INH)CR1: C' receptor 1; allows cleavage by Factor IMCP: cofactor of Factor I found on self" membranes"
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| What components of the C' system cuase anaphalaxis (anaphalotoxin)? | C3aC5a (especially)
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| What component of C' causes neutrophil chemotaxis? | C5a
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| What makes up the MAC attack complex? | C5b-9
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| What is caused by a C1 esterase inhibitor deficiency...C1INH (this usually prevents C' activation on self-cells)? | Hereditary angioneuroticedema (HANE)Attacks of swelling with no obvious cause
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| What is the primary C' inactivator? | Factor I (I=inhibitor)This prevents the formation of the C3 and C5 convertasesRequires cofactors: C4-bp, MCP, CR1
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| What primarely prevents C5 convertase from forming? | Factor H (also a target for Factor I), binds to C3b (unlike C4-bp, which binds to C4b), but prevent formation of the convertases!
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| What regulates the formation of MAC? | CD59 (blocks binding of C9 to C5bC678 complex) so blocking C5-9"!"
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| What is the main opsonin? | C3b (primarely b/c of it's abundance)C4b also does this (both bind to C' receptors: CR 1, CR2, CR3, CR4 on phagoytic cells, which are all receptors for fragments of complement C3)==makes pathogens tasty""
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| What would a C3 deficiency result in? | Overwhelming infxns, development of immune complex disease (esp with encapsulated bacteria) soon after birth; life-threatening. Factor H and Factor I deficiencies can mimic; causes C3 to be used up in serum!
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| What would a MAC deficiency (C5-9) look like? | Increase in Neisseria bacteremia (N. gonorrhoeae, N. meningitidis)Otherwise mostly healthy
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| What is the most common form of complement deficiency what results? | C2 deficiencyHigh degree of SLE (systemic lupus erythematosis)
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| What results with a DAF deficiency? | Paroxysmal nocturnal hemaglobinuria (PHN)Spontaneous episodes of RBC lysis (remember that DAF helps to prevent C' activation on self RBCs by preventing deposition of C3b)Tx: EPO to stimulate RBC production
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| What happens if there were to be a deficiency in the Lectin (Mannose binding lectin, MBL) pathway? | MBL deficiencies would be associated with increased yeast infxns or infxns with encapsulated bacteria
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| What C' pathway does properdin actin in? What does it do? | The Alternative pathwayActs to stabilize C3 and C5 convertase and by doing so increases it's half-life a lot!
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| What can some viruses do with C' (little assholes!)? | Hijack C' to ENHANCE INFECTIVITY. Epstein-Barr (uses CR2 as a receptor for attachement)Measles virus (uses MCP..cofactor of Factor I...as a receptor)West nile virus. C3b to coat the viral particle and enters cells using CR3 receptor)
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| The C1INH controls what C' pathways? | The Classical and the Lectin(they act essentially the same way, just activated differently)
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| Where are the receptors of C1q present? | ON phagocytes, mast cells, and platelets
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| What are the main fxns of Complement? | O.I.LOpsonizationInflammation (priming of adaptive immune response)Lysis
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| Is the alternative pathway Ab independent or dependent? | Independent. It binds to PAMPs to be activated.
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| What secretes the following cytokines: IL-1, IL-6, IL-8, IL-12, TNF-a? | MACROPHAGES!
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| What secretes the following cytokines?IL-2, IFN-y | Th1 cells
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| What secretes the following cytokines?IL-4, IL-6, IL-10 | Th2 cells
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| Hot T-Bone stEAk"" | IL-1: fever (hot)IL-2: stimulates T cellsIL-3: stimulates bone marrowIL-4: stimulates IgE productionIL-5: stimulates IgA production
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| Clean up on "I-L" (aisle) 8"" | IL-8: neutrophils are recruited by IL-8 to clear infections
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| What are the main fxns/ideas with IL-1? | Can always be thought of as acting the same and together with TNF-a- Induces Intergrins (I=1) to help with extravasation of leukocytes- Activated by TLRs (by LPS PRR)-Induces fever (pyrogen), acute phase proteins (inflammation), neutrophil and platelet pr
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| What are the main fxns/ideas with IL-8? | Major chemotactic factor for neutrophils
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| What are the main fxns/ideas with IL-12? | - Mediator of innate immunity (induces differentiation of T cells → Th1 cells)- Stimulates NK and Th1 cells to produce IFN-y (IFN-y then stimulates MΦ's to phagocytose stuff!)
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| How are IL-12, IFN-y, MOs and Th1 cells related? | MO's that have just phagocytosed a pathogen release IL-12.IL-12 stimulates a naiive T-cell to become a Th1 cell. Th1 cells then secrete IFN-y with more IL-12 stimulation.IFN-y then stimulates MO's to kill the microbes they've phagocytosed (releasing
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| What are the main fxns/ideas with TNF-a? | - Clinically muy importante!!- Mediates SEPTIC SHOCK- Acute inflammaory response to Gram (-) bacteria via TLRs-Aso activated by IFN-y (released by T-cells and NK cells) - Recruits 1st responders to the site (neutrophils!)- Extravasation of leukocytes
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| What are the systemic complications of septic shock with high levels of TNF-a??(**VIP**) | -Inhibits myocardial contractility and vascular smooth muscle tone-Decreases in HR, CO, BP- Thrombosis -Low blood glucose (due to under production by liver and overuse by muscle)
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| What's the main fxn of IL-3?What about GM-CSF? | Supports growth an differentiation of immature bone marrow progenitors (into mature hematopoeitic cells).GM-CSF (granulocyte macrophage colony-stimulating factor) works with IL-3 to mature bone marrow cells into DENDRITIC CELLS and MONOCYTES.Used to recov
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| What's the main fxn/idea with IL-2? | -Stimulates T cell growth (Th and CTL cells!)-Required for survival of Treg cells!- Clinical: IL-2 shedding into blood stream can tell us if a pt is rejecting a transplant
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| What's the main fxn/idea with IFN-γ? | -Works with IL-12- Activates MΦs and Th1 cells- Supresses Th2 cells- Promotes B-cell class switching to IgG-Promotes extravasation (like TNF)- Stimulates Ag processing on APCs (induce MHCs, etc.)-Stimulates MO's to kill what they've phagocytosed (via
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| What's the main fxn/idea with IL-4? | - Signature cytokine of Th2 subset-Stimulates differentiation to Th2 cells!- Inhibits Th1 differentiation-Mast cell/eosinophil mediated rxns: class switching to IgE = Allergies (mediated hypersensitivities)- Produced by naiive T-cell and mast cells
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| What's the main fxn/idea with IL-5? | - Promotes B-cell class switching to IgA- Stimulates growth and differentiation of eosinophils (deal with helmiths/allergies)-Secreted by Th cells & mast cells
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| What's the main fxn/idea with IL-10? | -Tones down the inflammatory response!-Inhibits innate immune response-Made by Th cells and Treg cells!- Limits production of IL-12 (thereby inhibits IFN-y)-Inhibits expression of MCH II
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| What's the main mechanism of interferons (γ, α, β)? |
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| What's the main job of IFNs? | -Interferes with viral infections: protects the neighbors= paracrine fxn- Innate immune response- Activated by viral nucleic acids and mononuclear phagocytes (CD40:CD40L activation---T-cell activating a leukocyte)-Increases particularly MHC I expression=
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| What kind of signalling is employed by Type I & II cytokine receptors? | Jak-STAT (to induce transcription factors related to inflammation)
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| What kind of receptor is used for IL-1 class cytokines? | TLR
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| How many cytokine receptor classes are there? | 5 (Type I, II, IL-1, TNF, GPCR)
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| What is the effect of low, moderate and high levels of TNF? | Low: local inflammationModerate: systemic effectsHigh: SEPTIC SHOCK
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| Chemokines primarely stimulate what? | Leukocyte movement and extravasationChemotactic cytokines: inflammatory (produced by leukocyes) or cell trafficking (produced by various tissues)
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| Extracellular (pyogenic/purulogenic) bacteria employ what cytokines? To promote what? Who is the main responder? | TNF, IL-1, and other chemokinesPromotes extravasationMain responder: Neutrophils (first responder)
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| Intracellular bacteria employ what cytokines? What do those promote? Who is the main responder? | IL-12, INF-yPromotes phagocytosis, stimulates adaptive responseMain: Macrophages
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| Viruses employ what cytokines? What those promote? Who is the main responder? | IFNs Type I (interferon), IL-12Inhibit viral replicationMain: NK cells
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| What's the fxn of IL-13? | Shared effects with IL-4- Mediator of a lot of allergic reactions!!!Unlike IL-4, it is NOT experessed in T-cells
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| What's the job of TGF-β? | - INHIBITS proliferation of lymphocytes and leukocytes!- Cleans up the mess left by inflammation!-Dampens immune response-Stimulates healing
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| What are the main mediators of hematopoesis (colony-stimulating factors)? | C-kit ligand (stem cell factor): makes bone marrow cell responsive, readyIL-7: expansion of immature B and T cells (lymphocytes)IL-3: expansion of immature bone marrow progenitorsGM-CSF: works with IL-3, promotes maturation of bone marrow cells into DC ce
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| What disease results in an IL-7 deficiency? | X-linked severe combined immunodeficiency (SCID):cannot mount an immune response b/c IL-7 is not stimulating the expansion of lymphocytes (T and B cells!!)
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| What cell surface markers are specific for T-cells aside from TCR)? | CD3 (associated w/TCR, needed for signal transduction)CD28 (binds with B7 on APC for 2nd signal)
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| What are specific surface markers on Th cells? | CD4CD40L (binds to CD40 on B-cells)
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| What are the cell surface markers specific for CTL (cyotoxic T-cells)? | CD8
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| What are the cell surface markers on B cells? | Ig (IgM or IgD)B7 (an APC!)CD19CD20CD21CD45HLA-DR (MHC II)CR2
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| What are the cell surface markers specific for Macrophages? | MHC II, B7, CD40, receptors for Fc, receptors for C3b
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| What are the cell surface markers specific for NK cells? | Receptors for MHC ICD56
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| What cells surface proteins are found on all cells except for mature RBCs (all nucleated cells)? | MHC I
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| Cyclosporin is a commonly used immunosupressant used particularly with transplants and select autoimmune disorders. How does it work? | It basically prevents the production of IL-2, effectively blocking the differentiation and activation of T-cells.
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| What region of an Ab defines its idiotype? | Hypervariable region, aka: complementary determinig region (CDR)
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| What region of an Ab defines its isotype? | The c (constant) region of the H chain
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| What's an allotype? | Subtle allelic differences in the isotypes of Igs: these involve the H chains
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| What is the 1st Ab produces in response to an Ag? | IgM (pentamer, allows for really efficient binding of Ag and efficient binding of C')
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| What's the first Ig expressed on B cells? | IgM
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| How are Fc's linked in IgA and IgM? | J-chain
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| What is the most abundant class of Ig in serum? | IgG
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| What are the subclasses of IgG? | IgG1-4All can cross placenta! IgG3---really effective at activating C'IgG1 & 3 are really effictive opsonizers IgG2 is restricted to carb Ags
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| What are the CD markers for IgG (believe it or not, this is clinically pretty important)? | CD16:NK cells, monocytes/macrophages, granulocytesCD32: B-cells, monocytes/macrophages, granulocytesCD64: monocytes/macrophages
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| What Ig crosses the placenta? | IgG
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| Is IgA part of the primary or secondary immune response? | Secondary!
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| What contributes to newborn immunity? | IgA secreted in colostrum
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| What cells do IgEs bind to? | Mast cells and basophils
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| What is IgE primarely involved in (reactions are strong with what)? | Asthma, hay fever, food allergiesHelmith infections
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| What is the epitope? | The specific part of the Ag that contacts the Ag-binding site of an Ab or TCR. It's the antigenic determinate!
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| What are haptens? | The are really small MW molecules that can bind to an Ab, but must be attached to a large carrier macromolecule to stimulate an immune response specific for that small MW molecule. Really important in vaccine production.
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| What are some factors that influence the immongenicicty of an Ag? | Molcular mass, foreignness, chemical composition, physical form, degradability (easily phagocytosed=more immunogenic), genetic factors (idiopathic network), age
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| What is the most immunogenic? Proteins, polysaccharides, nucleic acids, or lipids? | Proteins! They are listed in decreasing immunogenic order from thereon out!
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| Do B cells recognize linear epitopes (peptides)? | Ummn NO! They see in 3D---so the conformation/shape of an immunogen is super important. B-cells are the only cells that see immunogens in their SOLUBLE FORM!!!
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| What sequence of amino acids in proteins are recognized by T-cells (primary, secondary, tertiary, quartenary)? | Primary! They recognize the linear sequences, and DO NOT recognize polysaccharides or nucleic acid antigens.
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| Are free peptides recognized by T-cells? | HELL NO! They only see linear peptides that have been processed and are being presented by the MHC (HLA)!
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| How do B cells interact with antigens? How about T-cells? | B-cells: by complex of the Ig on it's membrane and the Ag.T-cells: using the TCR, MHC molecule and the Ag
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| What is the strength of interaction between an a univalent Ag (epitope) and a univalent Ab (idiotype)? What about multivalent Ag/Ab? | AffinityAvidity (IgG--functional, not intrinsic--and IgM!)
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| Drugs alone are poor stimulators of the immune system, but can cause an immune response by forming multivalent hapten-carrier complexes. What is a typical example of this? | Penicillin (and other b-lactam antibiotics)
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| What kind of antibodies are isolated in the making of drugs? | Monoclonal Abs: mAb or moAB
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| What are the imortant CD markers for Ig's? | IgG: CD16, CD32, CD64IgE: CD23 (convenient, 2+3=5, E is the 5th letter in the alphabet. I know I'm weird.)
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| Spleen filters antigen from? Lymph nodes? | BloodLymph
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| Which one of the C' pathways is the most efficient and rapid? | Classical pathway
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| C1q can mind to a single IgM molecule to activate the Classical C' pathway. How many IgG's are required to activate C1q? | At least 2!
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| What makes up C3 convertase in the Classical Pathway? C5? | C4b2bC4b2b3b
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| What is the main amplification step in the classical pathway? | The cleavage of C3 by C3 convertase
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| In the classical pathway, what complement component is responsible for determening self from non-self? | C3 (it deposits to non-self surfaces)
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| What kind of lysis occurs with the Mac-attack complex? | Osmotic lysis
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| What C' pathway will be employed if you've never been exposed to a pathogen? | Alternative (does not require an Ab) or Lectin (only if the PAMP is a mannose residue)It's a little slower and less effective though.
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| How does C3b or C3bi recognize whether a surface is self vs non-self? | Self surfaces have high levles of sialic acid, so they can't bind
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| What forms C3 convertase in the Alternative pathway? What about C5 convertase? | C3bBb(P) (cleaves even more C3!)C3bBb3b(P) note the P's: this is only if Properdin binds
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| In the lectin pathway, bound MBL/MASP is structurally very similar to what? | C1qMBL=mannose-binding lectinMASP=MBL-associated serine proteaseThis is also the complex that cleaves the C4 and C2 components, so the Lectin and Classical pathway are very similar!
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| Regulation of C' occurs primarely during? | Activation, amplification, and membrane attack. This is done either by binding with dissociation or via proteolytic digestion
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| There is an innate regulation system involved with the C' pathway....what is it? | The fact that C3b is degraded rapidly, which limits the formation of C5 convertase
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| Who makes Ig's? | B-cells
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| What is contained within the immunoglobulin superfamily? | Ig-a/Ig-b heterodimersIg'sTCRsMHC molecules
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| Describe clonal selection on simple terms. | The gene rearrangement that occurs in absence of an Ag.More complicated: It's the gene rearrangement of both heavy and light chians, and the random association of these during B-cell development. Independent of Ag!Ag's then simply select those clones whic
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| Does somatic hypermutation occur in TCRs? | NO!!
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| What are the mechanisms of creating Ab diversity? | 1. Multiple germ line genes (Combinatorial diversification)---mommy or daddy genes2. VJ or VDJ recombinations3. Junctional diversity: random addition of nucleotides during the D-J (light chains) or V to D-J (heavy chains) joining4. Somatic hypermutation:
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| How many genes are contained within the C region (constant) the lambda light chains? kappa? | Lambda: 4 (Chromasome 22)Kappa: 1 (Chromasome 2)Heavy chain on Chromasome 14
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| Because there is a huge variance in V, D, and J regions, you have to have DNA rearrangements and a clipping of parts you don't want to express (i.e introns). What flanks the VDJ regions to help make this happen? | RSS (recombination signal sequences)---correspond to one or two turns of the DNA.
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| What 2 proteins catalyze the recombination of VDJ regions using RSSs? | Rag-1 and Rag-2
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| What results if you have a mutation in the genes for Rag-1 or Rag-2 (which normally catalyze the rearragnement of VDJ/VJ using RSS)? | SCID: severe combines immunodeficiency disease
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| What enzyme helps create Junctional diversity (where nucleotides are radnomly added bwtwn VDJ/VJ)? | TdT (deoxyribonucleotidyl transferase)
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| What are P nucleotides? N? | P: nucleotides added during junctional diversity using TdT, that add asymmetrically in a templated mannerN: added in a non-templated manner
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| Where exactly is diversity added utilizing junctional diversity? | In the hypervarialbe region (idiotype)
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| In order for affinity maturation (as a result of somatic hypermutation where random point mutations in the V regions of Ig genes) requires what? | CD40:CD40L (T-dependent antigen)
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| What are the primary surface markers for stem cells, Pro-B, Pre-B, immature B, and mature B cells? | Stem: CD43Pro: CD43, 19, 10Pre: CD43, B220Immature: CD43, IgMMature: CD23, IgM, IgD
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| What are CAMs? | Cell adhesion molecules (integrins, selectins) that allow leukocytes to gain traction on another cell or ECM , which allows the cell to move through tissues
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| Where are E- and P-selectins expressed? L-selectin? | E- and P-: predomintantly on endothelium and platelets (associate with CD15)E binds primarely with leukocytesP primarily with platelets, endothelium, neutrophilsL-: on some leukocytesbinds primarely to HEV, endothelium
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| Chemokines fall into two families: alpha and beta. What structure do these have? Don't really get what the heck this means... | α: CXCβ: CC
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| What surface marker is specific for Treg cells? | CD25***CD25 is also the α-chain portion of IL-2!!! These are very much related!!
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| What surface markers are specific for B-lymphocytes? | CD19, CD21, MHC II
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| What is the main cell surface marker for NK cells? | CD16
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| What's the 3 step model of leukocyte adhesion? | 1. Thethering (CD15-Eselectin)2. Triggering (chemokines, CXC or CC)3. Adhesion (CR3/LFA-1, ICAM-1)
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| What is the function of CTLA-4? | To inhibit T-cell activation by blocking CD28 signalling to the TCR complex
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| What MHC class has an open end? Closed? | IIISo II= bigger=bigger peptide
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| During hematopoesis 2 cytokines in particular are extremely important. One is important in the porgression of the stem cell into immature progenitors and the other is necessary in commitment to lymphoid lineages (B and T). What are they? | IL-3 (made by T-cells), IL-7 (made by bone marrow stromal cells)
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| What is allelic exclusion? | Use of either mom's or dad's genes. Not both.
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| What sequence helps to ensure that recombination occurs between 1-2 DNA turns so you actually get a V to a J, etc? Who catalyzes this? | RSSRag-1, Rag-2
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| What enzymes helps to catalyze junctional diversity (addition of random nucleotides)? | TdT
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| The pre-B cell has what sort of arrangement of heavy and light chains? | a Igμ heavy chain (IgM) and surrogate light chains with Igα and Igβ.The heavy chain must work, if it does, you get to move on to the immature B cell. If not=apoptosis. Too bad.
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| Light chains do NOT have what sort of genes? | D (Diversity!)
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| In order for Immature B cells to move onto mature B cells, they have to be checked by the BCR (B-cell receptor). This checks via negative and positive selection. Describe. | Negative selection: if immature B cells react with self-Ags (MHCs), they're outta there!Positive selection: if they bind with low avidity, they are selected for and released into the periphery.
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| When immature B cells get checked before moving on to mature B cells, they undergo receptor editing (in addition to pos and neg selection). What is this? | Activation of Rag genes and editing of LIGHT CHAINS (usually κ-chains). It's easier to edit a light chain than have to totally start over!!!
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| Mature B cells exit the bone marrow and migrate to secondary lymph organs. How do they enter those tissues? What happens if they are not activated? | HEVApoptosis
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| What surface markers do resting mature B-cells express? | CD: 19, 21 (CR2), 23, 81HLA-DRCD40CD45sIg, Iga, Igb
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| What are the 2 B-cell subsets? | B-1: from fetal liver (CD5+)B-2: from bone marrow progenitorsB-2 is divided into follicular (re-circulating B-cells) and marginal (reside in spleen) B-cells
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| How are B-cells activated? | Antigens are recognized by a B-cell specific for that antigen. This binds and activates the naiive cell. Activation can happen in a T-dependent or independent fashion.
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| In order for B-cells to be activated after antigens recognized a specfic sequence, what must happen? | There must be cross-linking of 2 or more BCRs (Ig's). Can be done with CR2 (CD21) and IgM or C3d!
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| SCID resutls form mutations in what? What if it's x-linked? | Rag-1/2 (so recombination events won't happen)X-linked: mutations in IL-7 (cytokine receptors)***Lethal, bone marrow transplant. Neither lymphocyte pool matures into effector cells! Bubble kids""
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| What B-cell co-receptor comolex enhances the sensitivity of B-cell activation by low quantities of antigen? | CD19CR2 (CD21)
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| What form of immunity is the principal defense against EXTRACELLULAR pathogens? | Humoral immunity (a branch of adaptive immunity mediated by Ab's produced by B-cells)
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| How are naiive B-cells activated? | The sIg on their cells are bound by an antigen that recognizes the Ig as specific to it....binding activates it. It's like the Prince kissing Snowhite to wake her from her sleep. Can occur in a T-dependent or independent fashion!
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| What kind of follicle (in lymph nodes) contains a germinal center? What happens within the germinal center? | A secondary follicle. The germinal center is the site of B-cell profliferation and differentiation (so after it's been activated in a primary follicle.)
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| What kind of B-cells are spitting-out huge amounts of antibodies? | Plasma B-cells (Plasma cells)
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| Once a mature (but naiive) B-cell leaves the bone marrow, it works by internalizing offending antigens....which makes B-cells what?? | APCs!
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| After a naiive B-cells has internalized an antigen, loaded pieces of that antigens peptides onto an MHCII, and had it presented to a CD4+Th cells (which ACTIVATES the B-cell!)...where in the body would you find this particular cell? | In the germinal center of a secondary lymph node!
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| After a naiive B-cell has been activated (by a MHC II/CD4+ Th cell complex) in the germinal center of a LN, it may differentiate into what 2 types of cells? | Either MEMORY B-CELLS or PLASMA CELLS.If it becomes a plasma cell, it's going to become a plasmablast first, then a plasma cell and will begin to produce a crap-load of antibodies!The mechanism by which one or the other of these is the resultant cell is p
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| After a B-cell becomes a plasma cell, can it secrete high levels of antibodies? Can it switch antibody classes? Can it still act as an APC? Is it still displaying MHC-II? Can it take up more antigen? | Yes (makes LOTS of Abs!)NO! Can't class-switchNO! Can't act as an APC!NO! It no longer displays MHC-IINO! It can't take up more antigen b/c it no longer displays signficant quantities of Ig on the cell surface.
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| When naiive B-cells are activated, they must have 2 signals. Describe the steps to signal 1 in the 2 different ways this can be done. | First signal: Happens in one of two ways:1. Ag directly: Ag recognizes a sIg on the naiive B-cell. 2 or more BCRs must cross-link! Then the cell is prepared for signal #2 via signalling through Igα and Igβ cytoplasmic tails.2. Via Ag boun
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||||
| What percentage of mucosal IgA's are dimers? What about serum IgA's? | 100% (monomers can't be secreted)In the serum, it's about 80%
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||||
| What signal can be used for B-cell activation INSTEAD of cross-linking 2 sIgs (BCRs)? | The CR2/C3d signal (which actually makes the Ag 1000fold more immunogenic---i.e. more tasty!)
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||||
| What is a brief summary of the 2 signals in B-cell activation? | Signal 1: From the TCR/MHC II (Ig/antigen) interaction via B7 (on B-cell) with CD28 (on T-cell). Cytokines can then provide help to B cells. Signal 2: CD40 (B-cell) to CD40L (T-cell) interaction. This induces biochemical changes to the B-cell that ca
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| Cytokines releasd by the Th cell promotes 2 general functions. What are these? | 1. Induce H-chain class-switching (isotype)2. Augment B-cell differentiation/proliferation
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||||
| Cytokines are released by Th cells to induce H-chain class switching on mature naiive B-cells. What cytokines class switch to IgE? IgG? IgA? | **VIP***IgE: IL-4IgG: IFN-γ (done a lot!)IgA: TGF-β
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||||
| What sort of signalling triggers the release of cytokines form Th cells to fascilitate class switching of B-cells? | CD40:CD40L. This allows for increased accessiblity of the DNA at a specific C region (to switch the Ig isotype)!
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| In addition to CD40:CD40L and cytokine involvement in class-switching, what key enzyme is required (aided") to make this all happen??" | AID (activation-induced deaminase)---converts Cs to Us. Whatever.
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||||
| Describe briefly the process of affinity maturation? | In LN, Somatic mutation: B-cell are activated and migrate into germinal centers for proliferate. There they proliferate and there is hypermutation of Ig V genes (variable). In LN, Selection: B-cells then recognize antigen on follicular dendritic cell
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| What are surface markers for plasma cells? | CD19, 20, 27
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| What are memory B-cells responsible for? | Mounting the secondary immune response (the respond quickly to subsequent Ag exposure) and survive for a long time without additional Ag stimulation.
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||||
| Compared to a primary immune response, what is the response size of a secondary immune response? What about the antibody affinity? What's the difference in Ab isotype? | Much largerMuch greater affinity (affinity maturation)IgM-primary; IgG-secondary
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| Can T-independent antigens stimulate B-cells to become memory cells? | NOPE! You need Th cell help for 2nd signal. Only T-dependent antigens can result in affinity maturation, class-switching, and memory cell creation.
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| There are 2 B-cell subsets. Wat are they and how are they important? | 1. B1 cells (CD5+): make IgA in mucosa2. B2 cells: primarely make IgG,2 subsets:- Follicular B-cells (majority)---hang out in lymph-Marginal B-cells--hang out in the spleen
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| What kind of Ig is capable of antibody feedback (a mechanism of turning OFF to prevent further Ab production)? | IgG only!
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| There are 3 mechanisms by which B-cells that are generated with specficity for self-antigens are silenced (in order to prevent an autoimmune disease). What are they? | 1. Central deletion: elimation of those cells in the bone marrow)2. Anergy: functional silencing3. Receptor editing: reinitiating V gene rearrangement of the light chain (to not react to self)
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| IgE binds to Fc receptors (CD23) on what cells? What does this cause?? | Mast cells! =allergies due to degranualtion of histamine, etc.!
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||||
| What region on immune cell populations promote phagocytosis (opsonization) and deliver signals? | Fc'!!
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||||
| What is ADCC? What's the main cell type involved? | Antibody-dependent cytotoxicityThis happens when NK cells bind to Ab-coated cells (the Abs are of course bound tosurface antigens of a bad" cell) by Fc' receptors and destroy them!!"
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| Activation of the Classical C' pathway requires either binding of 1 IgM or 2 _____? | IgG
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||||
| What is the neonatal Fc receptor? | FcRn Fc=FcR=receptorn=neonate
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| What happens in Hyper-IgM Syndrome"?Where is the defect if it's x-linked? Autosomal recessive?" | This is a syndrome that results from many of the IgM Ab's reacting with blood elements, resulting in hemolytic anemia, thrombocytopenia, and neutropenia. :-(X-linked: defect in CD40LAutosomal recessive: mutation in AIDBoth of these act in class switching,
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| What happens if there is a deficiency in C2 of the C' pathway (the most commonly ID'd form of complement deficiency)? | High degree of SLE (systemic lupus erythematosis)- May result in immune complexes depositing in blood vessel walls & tissues and activate the alternative C' pathway=local inflammation-May promote breakdown of tolerance to self-antigens=autoimmunity
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| T-independent (TI) antigens activate B-cells w/o T-cell help. They are divided into 2 grous: TI-1 and TI-2. What do these do? | TI-1: act as polyclonal stimulatorsTI-2: are polymers that activate by cross-linking the B-cell receptor. **neither of these are capable of inducing B memory cells.
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| What is the primary cytokine needed for B-cell division and differentiation? What about for T-cells? | B-cell: IL-4T-cells: IL-2
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|
||||
| Do T-cells recognize antigens in their free or soluble form? | NO!! Remember, they hate free lovin' hippies"....quite sad. THey only recognize portions of protein antigens (peptides) associated with HLA. "
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| The 5' end of a regions of genes containing the HLA cluster of genes was clipped out. Loss of what HLA (MHC) will result? | Loss of Class II MHC. Class I MHC locus is closer to the 3' end.
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| MHC genes are located on what chromasome? | 6
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||||
| Can haplotypes of HLA (mom and dad) be expressed simulatenously? | Yes! More diversity! =co-dominate expression.
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|
||||
| HLA I consist of 2 chains. What are they? | α-chain (3 globular domains---1 & 2 make up the peptide binding cleft)β2-microglobulin (has no transmembrane region---associates covalently with the α3 domain)
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||||
| The peptide binding groove on an HLA has the greatest polymorphism, which is this important? | So that a different, specific range of peptides can bind in the groove.
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|
||||
| Can all 6 alleles (3 from mom, 3 from dad) be expressed on a cell at the same time? | Yes! Due to their slightly different shapes, they can present a different set of peptides...
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|
||||
| Where are MHC II primarely found? | On APCs (MΦ's, DCs, B-cells)
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|
||||
| T/F Does HLA II have 2 transmembrane regions? | True! one from α2, and one from β2.
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||||
| What region forms the peptide binding groove on MHC II? | α1 and β1.
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|
||||
| What class of MHC has a larger/open-ended conformation of the peptide binding groove? | MHC II
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||||
| Synthesis of MHC II requires 3 special proteins not seen in the production of MHC I? What's the special protein in MHC I? | II: Invariant chain, CLIP, HLA-DM (to remove the CLIP)I: TAP
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||||
| A minor HLA we know about is H-Y. What is this? | It's an HLA coded on the Y-chromasome. Significant b/c it's associated w/ acute rejection of male grafts in female recipients! Crazy.
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|
||||
| HLA restriction comes down to what in terms of CD4 and CD8? | CD4+ Th cells----> HLA IICD8+ CTL -----> HLA I RULE OF 8
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|
||||
| Dendritic cells are also called what? Where are they found? | Professional APCsT-cell rich areas in nodes & spleen!
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|
||||
| DC are capable of activating naiive CD4 cells, CD8 cells, neither or both? | Both!
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|
||||
| What kind of APCs are best at activating memory T-cells? | Macrophages
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|
||||
| What kind of APCs are most effective when Ag levels are low? | B-cells (due to their high affinity binding to Ag)
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|
||||
| B-cells may not be as effective at presenting Ag to naiive T-cells as DCs or MO's, but they are very effective at presenting to who? | Memory T-cells
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|
||||
| What class of HLA is most effective at dealing with intracellular pathogens and self? What about extracellular pathogens? | Intracellular & self: Class I (on all nucleated cells)Extracellular: Class II (on APCs)
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|
||||
| HLA-DM is part of what HLA class? What does it do? | HLA II: it removes the CLIP and exchanges for a peptide!****
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|
||||
| What does the TAP protein do in the HLA-I pathway? | It transports peptides (that have been chewed up by proteasomes) form the cytosol into the ER and loaded onto a class-I molecule.
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|
||||
| Autoimmune dz and susceptibility is largely linked to particluar HLA alleles. ONe in particular is commonly seen (ex: in ankylosing spondylitis)? Another one that's signficant is one associated with rheumatoid arthritis/rheumatic fever, what is that? | HLA-B27RA/RF: DR4
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|
||||
| What's the general structure of a T-cell receptor (TCR)? | A β-chain and an α-chain, both of which have a constant and a variable region.
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|
||||
| Do TCRs undergo class switching? Affinity maturation? | No and No!
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|
||||
| TCRs have hypervariable regions (3), little loops, that contact with the peptides presented by the MHC molecule. Which of these hypervariable loops is the most hypervariable? | CDR3 (complimentary determining region)
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|
||||
| MHC restriction of T-cells requires TCR recognition of both the peptide (antigen) AND ______? | The MHC molecule!
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|
||||
| In what organs does lymphopoesis occur? | Primary lymph organs (bone marrow & thymus)
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|
||||
| What does IL-7 stimulate? | Survival and proliferation of early lymphocyte precursors (both T and B)
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|
||||
| The IL-2 receptor γ chain (gamma common chain) is part of the IL-7 receptor (remember that IL-7 stimulates survival/proliferation of early lymph precursors, B and T). What would happen if there was a mutation in the gamma common chain? | X-linked SCID: severe combined immunodeficiency
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|
||||
| The TCR is made up of a β and an α chain and they are made in that respective order. What helps to create diversity? | Combinatorial diversity (number of possible V-(D)-J comibinations) & Junctional diversity (addition and removal of nucleotides---N and P---mediated by Rag1/2)....just like making Igs!
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|
||||
| What's a brief summary of negative and positive T-cell slection? | Positive selection: You don't see my MHC?? DIE!(selects for those cells whose receptor bind to self-MHC molecules)Negative selection: You love me too much?? DIE!!!(selects agains those cells who have too high of an affinity for self-MHC.)
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|
||||
| After T-cells have completely taken care of and eradicated an infectious agent, what happens to them? What about to T-memory cells? | They die (apoptosis)T-memory cells are retained
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|
||||
| What kind of cells are capable of activating naiive T-cells? What about memory T-cells? What about B-cells and macrophages? | Naiive T-cells: DCs (alone)Memory T-cells: MΦ's and B-cellsB-cells and MΦ's: CD4+ Th cells
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|
||||
| Through what do naiive T-cells enter LN's? | Via HEVs in the cortex
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|
||||
| Once T-cells have entered a LN via HEV and checked out what macophages and DCs had to present in terms of antigens and found nothing interesting, what happens to them? What if they do find something interesting (antigen)? | They leave the LN through lymphatics if nothing is found. If they do encounter something exciting, they stay, proliferate and differentiate into effector cells. This results in cytokine release, CD4+ and CD8+ cells.
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|
||||
| There are various accessory molecules that help the TCR of the T-cell and the MHC interact. Take the example of a CD4+ Th cell and a MHC II. What sorts of accessory molecules are involved? | For signal transduction: CD4, CD3, CD28 (on Th)/B7 (on APC)For antigen recognition: TCR binding with MHC II (and peptide) For adhesion: LFA-1 (on Th)/ICAM-1 (on APC)
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|
||||
| What would happen to T-cell function if you were to target CD3? | CD3 is essential for signal transduction by the TCR complex, so you would block this and therefore prevent activation!
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|
||||
| What does CTLA-4 do? | It replaces CD28 and binds to B7 in order to block/down-reg signal transduction and therefore T-cell activation.
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|
||||
| In an autoimmune dz such as DM Type I, it would be beneficial to knock-down the autoimmune fxn. Would blocking CD3 work? | Yes! Prevents TCR complex from activating the Tcells.
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|
||||
| Integrins increase the time that the APC and the T-cell get to spend together. What increases integrin affinity? | Ag recognition by the T-cell, releases cytokines that increase this affinity, which allows for an increased T-cell response.
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|
||||
| As soon as B7 binds to CD28 during T-cell activation, what cytokine is released/produced? | IL-2 (Remember that CTLA-4 can bind to B7 and therefore shut-down IL-2 production)
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|
||||
| Co-stimulatory molecules in T-cell activation can either be activated by activated APCs (due to microbes) OR _________? | Adjuvants (in vaccines!)
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|
||||
| Cross-presentation if often necessary for CD8+ T-cell activation. How does this work? | An infected cell is phagocytosed by a DC cell (the only one capable of cross-presentation----DC is a big lover). DC then shows off what he's got to both CD8+ AND CD4+ T-cells. CD4+ T-cells get excited and release cytokines that then make CD8+ T-cells WAY
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|
||||
| Are superantigens capable of T-cell activation in absence of co-receptors and co-stimulation? | You bet. These little punks are involved in toxic shock syndrome, food poisoning (Staphyloccocal junk), etc. They just jump to the head of the line and bind directly to the TCR and MHC resulting in activation.
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|
||||
| What is the systemic response to superantigen activation? | Fever, rash, edema, hypotension, shock, muliple organ failure (due to intravascular volume depletion), reversible depression of the immune responseTNF-α and IL-1 (remember, associated with septic shock!) contribute to ↑ vascular permeabili
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|
||||
| Activation of T-cell trigger a cascade of protein production" that includes.....?" | CD40LIL-2, 4, and IFN-yIL-2R
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|
||||
| T cells have several subsets, primarely CD8+ and CD4+. CD4+ cells make Th1, Th2, and Treg cells amongst some others. What do these do? | Th1: Produces IFN-y, promotes cellular activity, MΦ activation; recruits primarely monocytes.Th1: Produces IL-4,5,13; promotes humoral immunity; recruits primarely eosinophils.Treg: Supresses T-cell fxn
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|
||||
| Cytokines produced by Th1 cells (IFN-y) and Th2 cells (IL-4, 5, 13..but we'll ignore 13 for a sec) do what specifically? | IFN-y: activation of macrophagesIL-4: B-cell switching to IgEIL-5: activation of Eosinophils (E is the 5th letter in the alphabet!!
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|
||||
| CD4+ T-cells activate macrophages and B-lymphocytes to do what? | MΦ: Kill their phagocytosed microbes!B-cells: to produce Ab= neutralization and elimination of antigen
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|
||||
| Which Th cell subtype do you associate with allergies? | Th2 (releasing IL-4,5,13)
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|
||||
| Which Th cell subtype do you associate with chronic inflammation and autoimmunity? | Th1 (releasing IFN-y and TNF-α)
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|
||||
| IFN-y secreted by Th1 has all sorts of jobs, including activating macrophages, stimulates C' on B-cells for opsonization, and stimulates ______ and ______? | MHC Class II B7
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|
||||
| Because Th2 cytokines tend to inhibit Th1 cytokines, what might be clinically important with respect to IL-4 and IL-13? | They INHIBIT microbicidal activity of macrophages! But, IL-4 and IL-13 ARE capable of promoting the expulsion of parasites and increase mucus production (allergic mechanisms) to increase barrier immunity.
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|
||||
| L-selectin is expressed in the lymph node while E- and P-selectin are expressed in the peripheral tissue. Why would you want L-selectin to be downregulated after T-cell activation? | B/c you don't want it to roll back into the LN....you want it to leave into the periphery!
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|
||||
| What is the function of L-selectin? What about E- and P-selectin? | L: adhesion of naiive T-cells to HEV in lymph nodesE/P: weak adhesion of effector and memory T-cells to cytokine activated endothelium at peripheral site of infxn.
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|
||||
| In what endothelial tissue is L-selectin ligand, ICAM-1 adn CCL19 (21) located? What about E- or P-selectin, ICAM-1 or VCAM-1, and CXCL10 (and others)? | Lymph node (L-selectin/L ligand, ICAM-1/LFA-1, CCL19/CCR7)Peripheral tissue (E/P selectin to ligand, ICAM-1/LFA-1, VCAM-1/VLA-1, CXCL10/CXCR3 and others)
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|
||||
| What cytokines increase expression of E and P selectin and ICAM-1, VCAM-1 on peripheral endothelial cells? | TNF-α and IL-1 (same stuff that causes septic shock!)
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|
||||
| The delayed-type hypersensitivity reaction (DTH) is in response to Th1, Th2 or what? | Th1----by CD4+ cells and MΦ'sEx: PPD test for TB resulting in an area of induration and erythema about 24-48 hrs after insult...due to Memory T-cells that have homed to site of infxn if you've had previous exposure.
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|
||||
| What would happen if you had an INF-y receptor deficiency?****** | You'd have uncontrolled bacterial infxns (you could never tell macrophages to kill what they've ingested with ROS/NO). Bacteria such as MYCOBACTERIUM take up a comfortable residence in macrophages!!!!!
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|
||||
| IFN-y receptor deficiency results in what kind of bacterial take-over? | Mycobacterium (listeria, leishmania, salmonella, legionella!!) YUCK!A similar susceptibility can be seen with defects in IL-12 or IL-12R. (IL-12 stimulates Th1 to release IFN-y!!!)
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|
||||
| Leprosy comes in 2 polar forms, tuberculoid and lepromatous. Which one has the highest infectivity? | Lepromatous. You can't mount an immune repsonse b/c Th1 is totally shut down (shutting down INF-y). In tuberculoid Th1 still works, though Th2 is low. In Lepromatous, Th1 is non-existent, and Th2 is super high.
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|
||||
| Are co-stimulatory molecules required for killing the targeted cells uing CTLs? | Nope. They just get shit done. Once viral proteins have been displayed to a CTL by MHC I, things begin quickly: granzymes (activate caspases) and perforins (punch holes---necessary for granzyme delivery) and WHAM....DEATH!
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|
||||
| What is the function of FasL and Fas with respect to CTLs? | They help target a cell for death, theough they are not required.
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|
||||
| How do CD4+ Th cells partake in cell-mediated immunity? How about CD8+? | CD4: by activating macrophages (IFN-y secreted by Th1 cells) CD8: direct killing of infected cells!
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|
||||
| What are the following chemokines & integrins specific for? LFA1-ICAM1 and CXCR1/CXCR2-CXCL8?What about VLA4-VCAM1 and CCR2-CCL2? | The first group is specific for neutrophils (acts within hours)The second group is specific for MΦs (acts within days)
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|
||||
| What is the primary/first responder to an infection? | Neutrophils
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|
||||
| Are neutrophils long or short lived? | Short
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|
||||
| TLRs (Toll-Like Receptors) function to be stimulated by various PAMPs (bacteria, viruses, etc.) and then activate gene transcriptions of what sort of molecules? | Inflammatory cytokines (TNF, IL-1, IL-12)Chemokines (IL-8)Endothelial adhesion molecules (E/P selectins)Costimulatory molecules ( B7)Antiviral cytokines (IFNs)
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|
||||
| Gram (-) bacterial LPS acts as a PAMP to stimulate what kind of TLR? | TLR4(TLR 1, 2, 4, 5, 6 all respond to bacteria)(TLR 3, 7, 8, 9 all respond to viruses)
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|
||||
| Macrophages may respond to sites of inflammation after neutrophils (1-2 days vs. few hrs), however they _________. | Survive longer!
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|
||||
| Both Macrophages and Neutrophils have what sort of receptors for IgG and subsequent opsonization (which really bridge the gap between innate and aquired immunity? | FcR (Fc' receptors)
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|
||||
| What is the use in macrophages being able to produce ROS and iNOS? | When activated, these allow the phagocyosed microbes to be KILLED! Ha!
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|
||||
| Can cytokines bind to and activated TLRs? | Nope! They need cytokine receptors. TLRs only respond to PAMPs from microbes.
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|
||||
| What complement pathway protects us from pathogens in the absence of antibody? | Alternative pathway! It's slower and less efficient, but it's good that we have it. It basically identifies and binds to non-self membranes (self membranes have high levels of sialic acid which quickly inactivates bound C3b molecules, which prev
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|
||||
| In the alternative pathway, who binds first, Factor B or D? What does Factor D do? | B is first. Factor D cleaves Factor B into Ba and Bb (which associates with C3b to make C3bBb= C3 convertase)
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|
||||
| Properdin bound to either of the convertases (3 or 5) does what? | It stabilizes it in order to increase its half-life!
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|
||||
| What component of complement acts as the most chemotactic, most potent anaphalotoxin? | C5a
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|
||||
| What sort of ligands induce DCs (Professional APCs) to express B7? | TLR ligands....help to bridge between innate and adaptive immunity in this way (allows antigens to be presented to Tcells, etc.)
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|
||||
| What molecule removes the CLIP protein/Ii chain from an HLA II and replaces it with a peptide? | HLA-DM
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|
||||
| What is the progression of maturation of stem cells to Mature B cells? | Stem cells→ Pro-B→ Pre-B→ immature B→ Mature B
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|
||||
| At what stage in B-cell maturation are the Rag proteins expressed? | Between Pro and Pre-BBetween Pre and Immature-B
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|
||||
| During what stage in B-cell maturation is TdT expression increased? | Between Pro- and Pre-B
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|
||||
| If you had a deficiency in E- or P-selectins, what might you have a huge problem with in terms of leukocytes? | You would have a really hard time getting them to extravasate through the endothelium
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|
||||
| Do naiive B-cells express L or E/P selectin? | L selectin (in order to help bind on LN HEVs)
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|
||||
| What chemokine mediates follicle migration in lymph nodes? | CXCL13
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|
||||
| Can B cells bind to soluble antigen? Is involment of MHC molecules required? | Yes!Not required
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|
||||
| What is the chemical nature of antigens that bind to B-cells? | Protein, polysaccharide, lipids (in 3D conformation)
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|
||||
| What is the chemical nature of antigens that T-cells can bind to? | Linear peptides only
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|
||||
| What happens if C3d is attached to protein antigen? | The Ag becomes about 1000 fold more immunogenic!!!
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|
||||
| What is the immunological synapse? | This is a specialized junction between a T-lymphocyte and an APC. It involves a central cluster of T-cell receptors surrounded by a ring of adhesion molecules.
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|
||||
| Describe the Th:APC synapse in terms of integrins, costimulators, etc.) | CD4+ Cell APCLFA-1 ICAM-1CD3TCR
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|
||||
| Describe the B-cell:Th synapse in terms of integrins, costimulators, and signals. | B-cell ThCD40 CD40LICAM-1
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|
||||
| In cross-presentation of an APC to both CD4+ and CD8+ cells, what do th Th cells do for the CTL cells? | They help them to become more effective killers due to increased cytokine stimulation (esp. IL-2) and if OFTEN NECESSARY for CD8+ T cell ACTIVATION!!!
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|
||||
| Within the lymph node, activated B-cells change their chemokine receptor expression from CXCR5 to CCR7.....while activated T-cells alter their expression from CCR7 to CXC5 (the exact opposite). WHY??? | This is so that they move in opposite" directions in order to effectively "meet in the middle" (they live in different places)....this will encourage migration towards one another to meet at the T:B-cell interface. (Cortex=5; Paracortex=7)"
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|
||||
| What immunoglobulin is primarely expressed on B-cells (before class switching)? | IgM
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|
||||
| What Fc-linked polypeptides is disulfide-bonded to 2 of the 10 chains in an IgM? | J-piece (J-chain)
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|
||||
| The C1qrs complex in the Classical pathway cleaves what? | C4 into C4a and C4b (which showers" down and attaches to the membrane....and attracts C2....) "
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|
||||
| The following cytokines are produced by T-cells.....describe their principal action:IL-2IL-4IL-5IFN-yTGF-β | IL-2: T-cell proliferation/differentiation/survival; differentiation fo T reg cells.IL-4: B-cell class switching to IgEIL-5: Activation of eosinophils, class switch to IgAIFN-y: Activation of macrophages; class switch to IgGTGF-β: INHIBITION of T-cel
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|
||||
| CTLs eliminate infected cells displaying peptide in MHC I molecules. Do they need co-stimulatory molecules to kill the targeted cell? | Nope, they just kill.
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|
||||
| What are the mechanisms by which CTLs kill their targeted cells? | Granular proteins (granzymes, which activate caspases; perforins, which punch holes to deliver granzymes)FasL and Fas (stimulates the apoptotic pathway)
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|
||||
| Of of the 4 subclasses of IgG, what 2 bind with the highest affinity to Fc receptors on phagocytic cells to promote opsonization? | IgG1 and IgG3
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|
||||
| Describe how APCs, naiive CD4+ T-cells, IL-12, IFN-y, Th1 and macrophages are all connected? | APCs (MΦs or DCs) release IL-12 after ingestion of a yummi microbe (lunch @ noon--12)......IL-12 stimulates the expansion of naiive CD4+ T-cells to Th1 cells. Th1 cells then release IFN-y, which then tells the APCs that they can go ahead and kill
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|
||||
| About how many days after an infection to which T-cells responded will you see immunolgical memory? | about 14 days
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|
||||
| After DC recognition of an Ag, the DC moves to the lymph node and enters by what? | Afferent lymphatic vessel
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|
||||
| With the creation of memory lymphocytes, where do these guys take up residence? | In secondary lymphoid organs and in tissues (niches")"
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|
||||
| What does immunological tolerance mean? | Unresponsiveness to self (if this doesn't work=autoimmunity)
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|
||||
| What is anergy? | This is a functional unresponsiveness of a cell once it's been exposed to a self-antigen.
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|
||||
| What immunogloulin is the most efficient at binding complement? | IgM
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|
||||
| What sort of selection occurs in central tolerance? What are 3 possible outcomes? | Negative selection (of developing lymphocytes....effective removal of autoreactive immune cells)1. Apoptosis2. Receptor editing3. Developemnt of CD4+ Treg cells
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|
||||
| In peripheral tolerance, self-antigen" recocgnition of mature lymphocytes (having gone through central tolerance) resutls in what 3 possibilities?" | 1. Anergy2. Apoptosis3. Supression (which can actually be mediate by Treg cells)
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|
||||
| What is death by neglect" with respect to T-lymphocytes?" | This is simply the failure of possitive selection (i.e. the MHC and peptide were not recognized.)
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|
||||
| In the thymus, a thymocyte with low affinity for self-ag goes through negative selection sucessfully and becomes a T-cell. A thymocyte that has a strong affinity for self-antigen undergoes APOPTOSIS (neg selection)....but a thymocyte that has intermediate | It becomes a Treg cells by up-regulating Foxp3 (which upregulates CD25).
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|
||||
| What is the fxn of Treg cells? | 1. They can inhibit T-cell activation using these cytokines: IL-10, TGF-β2. They can inhibit T-cell effector functions
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|
||||
| What would result should you have loss of Foxp3? | Widespread autoimmunity! (You essentially get rid of Treg....so self-antigen recognition in the periphery would not be regulated at all).
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|
||||
| What would result should you delete CD25? | Same thing as if you were to delete Foxp3...widespread autoimmunity as you lose your Treg functions (b/c you never stimulate Foxp3)
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|
||||
| Why is peripheral tolerance necessary? | B/c there will ALWAYS be some Ag's expressed in the thymus that are reactive to self during T-cell development.
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|
||||
| What induces costimulatory signals? | Danger signals" such as inflammation or microbes. "
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|
||||
| What could break" anergy?" | If you get really strong cytokine signals from pathogens (elsewhere) may cause activation...not good=autoimmunity.
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|
||||
| How does a cell T-cell become anergic? | If an APC presenting self-Ag presents to a naiive T-cell, the lack of B7 presentation (normally stimulated by the innate immune response to TLR stimulus), prevents the 2nd signal from happening. So having received only the 1st signal results in an anergic
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|
||||
| How come children with mutations in Fas develop autoimmune diseases? | B/c the expression of Fas/FasL results in paracrine signalling for cell death....necessary in situations where you recognize self-antigens and the body's attempt to rid those self-interactions via Fas is broken. No bueno.
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|
||||
| Do tolerogenic self-Ags present with 2nd signals (costimulation, innate immunity)? Will there be any persistence of antigen? | No, deficiency of the 2nd signal usually results in T-cell anergy or apoptosis.Yes....long-lived, should the cell end in anergy.
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|
||||
| What are the chemical compositions of T-cell INDEPENDENT antigens? | self polysaccharides, lipids, nucleic acids
🗑
|
||||
| What are the 2 primary contributing factors to the development of autoimmunity? | 1. Susceptibility genes2. Environmental agents
🗑
|
||||
| Autoimmune pathology can be mediated by humoral OR cell-mediated immunity....T/F? | True! However, often you do need T-cell help as necessary for autoantibody formation.
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|
||||
| Are autoimmune diseases organ-specific or systemic? | Both!
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|
||||
| It appears that males have a higher likelyhood/incidence of developing autoimmune diseases....T/F? | False. Females do. Damn it.
🗑
|
||||
| The breakdown" of tolerance resulting in an autoimmune disease consists of what 3 main components?" | GenesInfections (?)Environmental factors
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|
||||
| Which MHC allele is primarely responsible for anylosing spondylitis? DM Type 1? | HLA-B27HLA-DQ8
🗑
|
||||
| The non-HLA gene, AIRE, is responsible for what? | Autoimmune regulator" that is necessary for thymic expression or self-proteins so that you can develop self-tolerance. "
🗑
|
||||
| What results if there is a loss of AIRE expression? | Failure of central tolerance (results in diabetes, adrenal, parathyroid)
🗑
|
||||
| What results if there is a loss of C4 expression? | Defective clearance of IMMUNE COMPLEXES and perhaps a failure of B-cell tolerance. SLE (lupus) can be resultant.
🗑
|
||||
| What results if there is a loss of CTLA-4 expression? | Failure of anergy in CD4+ T-cells. (Associated with numerous autoimmune diseases)
🗑
|
||||
| What is the effect of a CTLA-4 agonist? What about a CTLA-4 antagonist? | Agonist: T-cell fxn would be shut-down....used to Tx autoimmune diseases.Antagonist: T-cells would stay active. Can be used to increase T-cells and prolong them to increase immune responses (used to Tx CA, esp melanoma).
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|
||||
| What results if there is a loss of expression of the Fas/FasL? | Defective deletion of anergic self-reactive B-cells; reduced deletion of mature CD4+ T-cells. ie. you can't delete self-reactive T-cells. (Adrenals, splenomegaly, lymphadenopathy)
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|
||||
| What results if there was loss in Foxp3 expression? | Deficiency of T-reg cells (CD25+)===results in immune disregulation, polyendocrinopathy, enteropathy-----so WIDESPREAD AUTOIMMUNITY.
🗑
|
||||
| What results if there is a loss in IL-2/IL-2R expression? | Defective T-cell development/survial; defective fxn of Treg cells.
🗑
|
||||
| What results if there is a loss of PTPN22? | Loss in tyrosine phosphatase, which is involved in cell signalling. (RA, DMT1, autoimmune thyroid disease).
🗑
|
||||
| How are some autoimmune diseases potentially triggered? | 1. Induction of costimulators on APCs: If a microbe stimulates the activation of an APC and that APC (expressing self antigen) can now show it's B7 to a T-cell...causing it to become reactive....resulting in autoimmunity. 2. Molecular mimicry: a micr
🗑
|
||||
| For the following autoimmune diseases, state whether T-cell, B-cells or Abs are the pathologic component:SLEDiabetesMyathenia gravisMultiple sclerosis | **SLE: T-cells AND Ab**Diabetes: T-cellsMyasthenia gravis: Ab (against AChR)MS: T-cells (agains myelin sheath)
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|
||||
| Give an example wherein an Ab may be stimulatory and one in which it is blocking? | Stimulating: Graves' (stimulating the TSH receptor)Blocking: Myesthenia gravis or Hashimoto's
🗑
|
||||
| How do Rhogam injections work to protect the baby from erythroblastosis fetalis? | Rhogam has purified immunoglobulins in it that basically block the RBC with Rh+ antigens on it from being able to activate B-cells and form memory cells.
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|
||||
| Biologic therapy is increasingly being researched and used. What sorts of benefits would there be if you could block TNF-α (a pleiotropic cytokine that has huge roles in inflammation and host defense)? | If you can block TNF-a, you could block inflammatory processes in things like Rheumatoid arthritis, etc.
🗑
|
||||
| Out of the 4 hypersensitivity pathways, which ones are cell based and which ones are Ab based? | I-III: Ab basedIV: Cell-based (specific T-cells)
🗑
|
||||
| Type I hypersensitivity is also called what? | Immediate or Atopy (the clinical terminology for allergy")"
🗑
|
||||
| What Ab's are Type 1 Hypersensitivities mediated by? | IgE
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|
||||
| About how long is the 1/2 life of IgE? What if IgE is bound to an FcR on mast cells or basophils? | 2 days in serum10 days if bound!
🗑
|
||||
| What kind of cells have a really high affinity for Fc regions of IgE? | The FcR of MAST CELLS and BASOPHILS
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|
||||
| What cells in the human body contain histamine? | Mast cellsBasophils (that's it!!!!)
🗑
|
||||
| What kind of cells have low affinity receptors for the Fc region of IgE, used in Ag presentation? | B-cells
🗑
|
||||
| Is class switching of IgM to IgE on B-cells dependent or independent of Tcells? | DEPENDENT! T-cells must release cytokines IL-4 or IL-13 to promote class switching to IgE
🗑
|
||||
| What cytokines (and T-cells) promote class switching to IgE? Which ones inhibit it? | Promote (LOW dose allergens): Th2IL-4 (class switch!), 13, 5, 10Suppress (HIGH dose allergens): Th1IFN-y (MΦ), IL-12 (Th1)
🗑
|
||||
| What is the nature of allergens (Ags) that give rise to Type I (immediate) hypersensitivity? | Proteins, classified by source, route, nature of protein
🗑
|
||||
| Would an inhaled allergen be considered a high or low dose allergen? What about food? | LowHigh
🗑
|
||||
| What are the preformed mediators of Type I hypersensitivities? (i.e. what is released from mast cells following cross-linking of 2 or more IgE's...within 5 minutes?) | HistmineHeparinTryptaseCalled degranulation""
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|
||||
| What are some inflammatory proteins that are released immediately after the degranulation after IgE stimulus of a Type I Hypersensitivity rxn? | Arachadonic acidLeukotriene Prostaglandin
🗑
|
||||
| Describe what happens with a Type I Hypersensitivity in terms of primary and secondary exposure. | 1st exposure to allergen→ activation of Th2's which stimulates class switching on B cells to IgE and subsequent IgE production→ IgE's bind to surface of mast cells via FcR's→ 2nd exposure to allergen→ allergen causes immediate cross-li
🗑
|
||||
| What are the immediate and what are the late phase mediators of Type I hypersensitivities? | Immediate: histamine, heparin, tryptaseLate-phase: arachadonic acid, prostaglandins, leukotrienes
🗑
|
||||
| What is urticaria? | Hives
🗑
|
||||
| What is the wheal and flare reaction? | It's used diagnostically to determine allergies
🗑
|
||||
| During late phase reactions, occuring 4-6 hrs after the initial Type I reaction, the is infiltration of what sort of cells? | PMNs (neutrophils), eosinophils, macrophages, lymphocytes, basophils
🗑
|
||||
| What do mast cells produce that leads to increased expression of cell-adhasion molecules and vascular endothelial cells? | TNF-a and IL-1
🗑
|
||||
| What are some symptoms of Type I reactions? | Vascular leaking (histamines)Bronchoconstriction (PAF, PFD, LTC)Intestinal hypermotilityInflammation (TNF, PAF, PFD, LTC)Tissue damage (tryptase, eosinophil peroxidase)Killing of parasites and host cells (via degranulation after stimulation of eosinophils
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|
||||
| Type II Hypersensitivities are mediated by Ab's including 4 different mediator surfaces"; what are they? " | IgGIgMFcRC'
🗑
|
||||
| In Type II reactions, where is the damage"?" | It's localized to the specific cells OR tissues bearing the antigen.
🗑
|
||||
| In Type II rxns, if Abs are directed against cell surface Ags, is this usually pathogenic? What about if their are directed against internal Ags? | Surface: PATHOGENICInternal: not pathogenic
🗑
|
||||
| In Type II rxns, what determines the amount of damage that is done? | Amount of Ag on target cells and ability of those cells/tissues to handle the damage (i.e. RBC's are killed by one MAC, nucleated cells would not be affected much by one MAC)
🗑
|
||||
| In Type II rxns, frustrated phagocytosis" is usually followed by what?" | Extracellular enzyme release (b/c phagocytosis was unsuccessful.
🗑
|
||||
| Hemolytic disease of the newborn (HDNB) is what type of hypersensitivity reaction? | Type II
🗑
|
||||
| In the development of erythroblastosis, in order for the memory B-cells (with anti-Rh IgM) to attack fetal RBCs, what must first happen? | IgM must class switch to IgG in order to cross the placenta.
🗑
|
||||
| What Ig causes agglutination in blood? C' activation? Intravascular hemolysis? | All IgM (primarely)!!
🗑
|
||||
| If you are about to transfuse a patient and find out that there is a minor blood group incompatability, are you worried? | Not really. Minor blood group reactions are rare unless there are REPEATED transfusions.
🗑
|
||||
| What are the immediate reactions to transfusion reactions? | Fever, hypotension, nause/vomitting, back/chest pain.
🗑
|
||||
| What kind of hypersensitivity rxn is Autoimmune hemolytic anemia? | Type II
🗑
|
||||
| What are the 3 main causes of autoimmune hemolytic anemias? | All causing C'-induced lysis:SpontaneousDrugsABO incompatablity
🗑
|
||||
| What is the difference between warm and cold Abs? | Warm: different epitopes than transfusion rxns (ex. Rhesus)Cold: strangely high titer of IgM (often in old people during winter)
🗑
|
||||
| What are some typical drugs that tend to cause autoimmune hemolytic anemia? | PCN, quinine, sulfanamides
🗑
|
||||
| Goodpasteure's and Pemphigus are both autoimmune diseases that are associated with what kind of hypersensitivity class? What mediates their pathology? | Type IIIgG and C' mediated
🗑
|
||||
| In Goodpasture's Dz, Abs are made against what? What results?What about in Pemphigus? What results? | Abs to glomerular (or lung) basement membrane. Results in nephritis and proteinuria (leaking of neutrophils into urine). Abs to desmosome proteins. Results in blistering of the mucosa and epithelium.
🗑
|
||||
| Pemphigus shows a very strong association with which rare HLA haplotype? | HLA-DR4
🗑
|
||||
| Myasthenia gravis is what kind of autoimmune hypersensitivity class? What are Abs made against? | Type IIAbs to AChR! So IgG and C' mediate this and IgG binding actually partially occupies that ACh binding site== extreme muscle weakness
🗑
|
||||
| There are some therapeutic uses of ADCC, used to destroy specific sAb's that we don't want. What is the Anti-CD20 monoclonal drug used for? What about the Anti-CD52? | Anti-CD20: marker found on mature B-cells, this is used in B-cell non-Hodgkins lymphomasAnti-CD52:marker found on both B & T cells; used to Tx chronic B & T leukemias and for immunosupression in pt's undergoing stem cells transplants.
🗑
|
||||
| Type III hypersensitivity rxns result from what? | Immune complexes that deposit in tissue b/c they are not cleared by liver or spleen MO's.
🗑
|
||||
| What determines where immune complexes are deposited? | Their size and localization of Ag in tissue.
🗑
|
||||
| Type III sensitivities happen primarely due to what? | Persistent infectionAutoimmuneInhalation of Ag
🗑
|
||||
| Normally immune complexes are cleared/removed by what? | Macrophages in the liver and spleen.
🗑
|
||||
| When in an inflammed states, immune complexes can act on basophils and plateles to produce what? What does this cause? | Vasoactive amines (histamine, tryptamine)Causes vascular permeability with subsequent deposition of immune complexes= Type III rxns
🗑
|
||||
| Type IV hypersensitivity (a cellular mediated sensitivity) is also called what? | DTH (Delayed-type hypersensitivity)
🗑
|
||||
| If you have persistent Ag with sensitized T-cells being present, what can happen? | Granuloma formation
🗑
|
||||
| DTH sensitivities (mediated by Ag-specific CD4+ T cells) are characterized by? | Local inflammatory response about 24-72 hrs after exposure (think PPD test)
🗑
|
||||
| Granulomas, contact hypersensitivities, and tuberculin response are all a form of what? | Type IV hypersensitivity (DTH)
🗑
|
||||
| What type of DTH rxn are you most clinically concerned about? | Granulomatous (b/c there canbe hardening of tissues in lungs= severely compromised pulmonary fxn)
🗑
|
||||
| With contact sensitivity DTH, how long does the sensitization take (from epidermis, through Langerhans presentation to HLA II in LN's to effector/memory T-cell formation)? | 10-14 days (hapten driven)
🗑
|
||||
| You want to check a patient's ability to deal with cell-mediated immunity. What type of test will you perform? | Tuberculin skin test (tests for T-cell mediated responses to soluble Ag/organisms)
🗑
|
||||
| Granulomatous DTH results from persistence of what cell? Why? What is it most commonly associated with? | MΦ'sB/c they are somehow unable to destroy the pathogen (either b/c it can resist killing, or whatever other reason). CAN occur in absence of infxn, such as with a foreign body (silicosis, etc)Associated with chronic, persistent infections.
🗑
|
||||
| Leperosy results form what kind of hypersensitivity? | Type IV DTH Granulomatous
🗑
|
||||
| Atopy, anaphalaxis, and asthma are associated with what kind of hypersensitivity? | Type I
🗑
|
||||
| Autoimmune Dz's (autoimmune hemolytic anemia, thrombocytopenia, erythroblastosis fetalis, and Goodpasture's syndrome) are associated with what kind of hypersensitivity? | Type II
🗑
|
||||
| Serum sickness, Arthus Reactions, and SLE are resultant of what kind of hypersensitivity? | Type III
🗑
|
||||
| Contact dermatitis, tuberculin tests, multiple sclerosis, and chronic transplant rejections are all mediated by what kind of hypesensitivity reaction? | Type IV
🗑
|
||||
| Is IgE distinct or similar to other dimeric immunoglobulins? | Distinct, it has a unique hinge region
🗑
|
||||
| What Ig plays a significant role in helminth infection? | IgE
🗑
|
||||
| A transfusion rxn to RBCs are produced by Abs to blood group antigens. What type of rxn is this? | Type II
🗑
|
||||
| Type II hypersensitivity rxns may targe tissues and cuase damage by Abs produced against functional cell surface receptors through ____regions. | Fab
🗑
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| Serum sickness is induced with large injections of what? | Foreign antigen
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| Does the size and charge of an immune complex affect it's deposition? | Yes! Small, positively charged complexes have the highest propensity for deposition within vessels. Lrg ones are readily removed by the spleen and liver.
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| Granuloma formation is driven by Tcell activation of MΦs and is dependent on _____? | TNF. This can lead to formation of Giant Cells.
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| What 4 factors make the brain an immunologically privileged site"?What 3 factors may call this into question (defining the CNA as a "relatively" immunologically priviledged organ?" | 1. Existence of a blood-brain-barrier (BBB)2. Expression of pro-apoptotic molecules at the BBB3. No epxression of MHC complex antigens on nerve cells4. No occurence of professional APCs (dendritic cells) in CNS**************************1. Existence of lym
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| What disease results from autoimmune responses against central myelin? What about peripheral myelin? | Central: MS (multiple scelrosis)Peripheral: Guillan-Barre syndrome (GBS)
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| What immune factors regulate the destruction of the CNS in MS?What about the regeneration? | Destruction: Glutamate, NMDAR, Neurotoxins, ComplementRegeneration: Progenitor cells, oligodendroglial cells, neural cells, astroglial cells
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| How does the immune system and nervous system communicate with one another? | Via soluble factors and cell-to-cell contact (gap junctions, tunnelling nanotubules)
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| What sorts of cytokines are involved in the cytokine-hypothalamic-pituitary-adrenal (HPA) axis? What do they induce the release of? | IL-1, 2, 6, 11, 12TNF-α, IFN-γInduce release of glucocoricoid, which in turn control the production of cytokines by immune cells.
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| Describe the involvement of the HPA (hypothalamic-pituitary-adrenal axis) in stress reaction of the immune system. | Stress is perceived by the brain→ the hypothalamus releases CRH to the pituitary→ pituitary (which has an IL-1 receptor) releases ACTH on the adrenal gland AND β-endorphin to the immune system. Adrenal gland: releases glucocortico
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| A patient comes into you for a repeat allergy shot. Next thing you know (well, about 5 hrs later), she's has incredible edema around the site and you get worried about possible vascular occlusion or even necrosis. What is going on? | Type III reaction called Arthus Reaction. Common following allergy shots if there has been prior Ag exposure. Pt has Ab complexes with it and this complex deposits into vasculature of small blood vessels near site. Causes edema, etc.
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