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immunology
exam 4
| Question | Answer |
|---|---|
| cytokines | regulate intensity and duration of innate and adaptive immune response. receptor mediated. recognize foreign pathogens |
| monokines | those proteins from monocytes |
| lymphokines | those proteins from lymphocytes |
| interleukin | between leukocytes |
| interferons | interfere with viral replication |
| chemokines | chemotactic cytokines that attract specific cells to their location |
| colony stimulating factors | stimulate colony formation in bone marrow, stimulate stem cell differentiation |
| antigen receptor to trigger cytokine release | TCR |
| PAMPs receptor to trigger cytokine release | TLR |
| AB receptor to trigger cytokine release | FcR |
| IL-12 | produced by APCs in response to bacteria/viruses. Activate NK cells to be more efficient killers. induce IFNg production. stim diff of Th1 cells |
| Type I interferons have what activity | antiviral. make other cells resistant to viral infection. Alpha and beta. innate immunity. |
| Type II interferons | innate and adaptive. antiviral. activates macrophages, neutrophils, NK cells. promote Th1 dev. Promote B cell to produce IgG. upregulate MHC expression on APCs. gamma. |
| cytokines are produced primarily by | T lymphocytes. |
| what do cytokines regulate | lymphocyte activation, growth and differentiation |
| IL-2 | lymphocyte prolif |
| IL-4 | stim Th2, B cell diff (IgE) |
| IL-13 | B cell diff (IgE) |
| IL-10 | inhibit Th1 |
| TGFbeta | Treg cytokine, B cell diff (IgA) |
| IFN gamma | B cell diff (IgG). activate macrophages, neutrophils, and NK cells. |
| TNF | activate endothelial cells, neutrophils |
| IL-5 | Eosinophil activate and generation |
| erythropoietin | stim prod and diff of RBC |
| Thrompoietin and IL-11 | stim platelet prod |
| IL-3 | Stim bond marrow prod of WBC |
| IL-5 eosinophil | stim eosinophil diff during parasite infection/ allergic response. antagonists used in eosinophilia and asthma |
| GM-CSG | stim diff of neutrophil and monocyte |
| G-CSF | Stim diff of neutrophil |
| M-CSF | Stim diff of monocytes |
| cytokine regulation | 1. receptor antagonists 2. release of soluble receptors to soak up or neutralize cytokine 3. cytokines of opposite effect to counter act the response 4. a deceptor receptor |
| what makes a good antigen | large, complex, foreign. proteins! |
| ability of an antigen to elicit immune response depends on | route of administration. amount of antigen administered. genetic makeup of the immunized animal. |
| factors influencing antigenicity of a molecule | 1. size 2. stability 3. complexity 4. foreigness |
| what must happen in order for an antigen to elicit an immune response | a molecule must be degradable w/in APCs |
| glycoproteins immune response | AB are directed sp against the polysaccharide moiety of the molecule |
| lipid and Nucleic acids antigens | poor antigens b/c they are readily degradable. NA linked to a carrier protein |
| epitopes | large molecule with specific regions against which immune responses are directed. |
| haptens | the small molecules that can function as epitopes only when bound to other large molecules |
| what APCs can trigger a primary immune response the first time presented to a pathogen | DCs. activate naive T cells |
| Major functions of DCs | serve as sentinel cells. process exogenous antigens. reg adaptive immunity. |
| follicular DCs | do not migrate, located in lymphoid follicles, lack MHC II molecules on their surface, carry many complement and Fc receptors. retain antigen for many wks. Do not process antigens. |
| first signal of antigen presenting | T cell antigen receptors bind antigen fragments attached to MHC molecules |
| second signal of antigen presenting | Co stim molecules like CD40 and CD80/86 |
| third signal of antigen presenting | provided by cytokine secreted by DCs in response to microbial stimulus |
| why are macrophages not good APCs in resting stage | they do not express adequate levels of MHCII and/or co-stim molecules |
| how do macrophages become good APCs when activated by cytokines | expression of MHC II and co-stim molecules are up-reg. function as APCs |
| why are naive B cells not good antigen presenters | they do not express B7 needed for T cell activation. express low levels of MHC II molecules. |
| MHC class I | endogenous, innate immune. binding peptides are anchored at both ends and fit completely within binding groove |
| MHC class II | exogenous, adaptive immune. binding peptides extend outside the binding groove |
| what controls antigen presentation and therefore determine an animals susceptibility | MHC. antigen fragment triggers immune rxn |
| MHC class I distribution | most nucleated cells |
| MHC class I function | present antigen to cytotoxic T cells. |
| MHC class I result | T cell mediated toxicity |
| MHC class II distribution | B cells, macrophages, and DCs |
| MHC class II function | Present antigen to T helper cells |
| MHC class II result | T cell mediated help |
| MHC class Ia is adaptive or innate | adaptive |
| MHC class Ib, Ic, Id is adaptive or innate | innate |
| structure of MHC class Ia molecule antigen binding site is formed by what units | a1, a2 domains. Heavy a chain is polymorphic to increase variety. |
| steps of endogenous pathway of MHC I | 1. ubiquitin binds to cytoplasmic protein and targets proteasome 2.proteasome degrades protein in peptides 3.TAP bind cytosolic pep from proteasome. transported to lumen of ER 4. Peptides trimmed to ERAP 5. Bind MHC I in ER 6. move to golgi. suface. |
| structure of MHC class II molecule antigen binding site is formed by what units | a1 and B1 chains. polymorphic |
| steps of exogenous pathway of MHCII | 1. APC internalize antigen 2.lysosomal enzymes digest antigen into peptides 3.MHC syn in RER 4.a and B chains form binding groove 5.Invariant chain inserted as transport to golgi 6.form endosome/phagolysosome 7.digest invariant chain, leave CLIP |
| what removes CLIP from MHC II | removed by DM, antigen pep binds to MHC II groove |
| MHC restriction | only antigen fragments that can bind in the groove of MHC can trigger an immune response |
| why are MHC heterozygotes adventageous | they can respond to a greater range of antigens. optimal number is 6 |
| BoLA-Aw7 resistance to what | bovine leukosis. bovine leukemia virus |
| BoLA-A*16 resistance to what | mastitis |
| BoLA DR resistance to what | Dermatophilus sp |
| ELA-A9 susceptibility to what | equine recurrent uveitis |
| ELA-A3, ELA-A15, ELA,Dw13 and dev of what | sarcoid tumors |
| B cells general job | responsible for AB production |
| T cells general job | reg adaptive immunity. cell mediated immune reponses |
| NK cells general job | innate immunity |
| B cell distribution | lymph node cortex. splenic follicles |
| B cell antigen receptors | BCR immunoglobulin |
| B cell surface antigen | immunoglobulin |
| B cell antigen recognize | Free foreign proteins |
| B cell progeny cells | Plasma cells, memory cells |
| B cell secreted products | Immunoglobulins |
| T cell distribution | lymph node paracortex. splenic periarteriolar sheath |
| T cell antigen receptor | TCR- protein heterodimer associated with CD3, CD4, or CD8 |
| T cell important surface antigens | CD2, CD3, CD4, CD8 |
| T cell antigen recognized | processed foreign proteins in MHC |
| T cell progeny cells | effector T-cells, memory T cells |
| T cell secreted products | cytokines |
| CD4 is marker for | T helper cells. MHC II |
| CD8 is marker for | cytotoxic T cell. MHC I |
| what marker is always present on T cells | CD3 |
| T helper cells recognize what | antigen on MHC II |
| T helper cells differentiate into what | TH1, TH2, TH17, Treg. depends on signals from APC and env |
| Th 1 cells secrete | IFNgamma. activate macrophages, neutrophils, NK, CTLs. B cells to make opsonizing and complement fixing AB |
| Th2 cells secrete | IL-4,5,10,13 |
| Th2 cells activate | mast cells, eosinophils. B cells to make IgE |
| Th2 cells provide defense against | some parasites and some mucosal pathogens. |
| Th17 cells secrete | IL-17A, IL-17F, IL-22 |
| Th17 cells attract and activate | neutrophils and monocyte. leading to acute inflammation. |
| Th17 cells are important when responding to what | EC bacteria and fungi |
| Treg cells secrete | TFGB |
| Treg cells suppress | T cells response by secreting suppressive cytokines |
| Treg cells help prevent what | reactions to self peptides |
| cytotoxic T lyphocytes or CTLs or CD8 T cells recognize what | antigen on MHC 1 |
| what happens once CDB T cells encounter antigen | clonally expand, diff and dev killing machinery in cytoplasm |
| CD8 T cells are important in responding to what | protection from intracellular microbes that cause the syn of foreign proteins in cytoplasm (viruses) |
| first step of T cell activation | binding of antigen on MHC to APC |
| second step of T cell activation | need co stimulation. 1. stim of CD154 to CD40 2.stim of CD28 and CD80/86 |
| T cell deactivation step | stim of CD152 and stim of CD80/86 |
| what cell expresses CD80 | DCs |
| what cell expresses CD86 | B cells |
| superantigens | directly link binding region of TCR and MGH. binding is very strong therefore response is strong. dont need co stim |
| generation of Th substypes is regulated by what | stimuli that naive CD4T cells receive when they encounter microbial antigens |
| What is the most important signal for differentiation of naive CD4 T cells into distinct subtypes is what | cytokines produced by APCs that are determined by the type of infection |
| Major function of Th1 cells that produce IL2 | Activate T cells, B cells, NK cells, macrophages |
| Major function of Th1 cells that produce IFN-gamma | Inhibit Th2 cells, stimulate Th1 cells, activate NK cells, activate macrophages |
| Major function of Th2 cells that produce IL-4 | stimulate B cell growth and differentiation. activate mast cells |
| Major function of Th2 cells that produce IL-13 | stimulate B cell growth. suppresses macrophage function |
| Major function of Th2 cells that produce IL-5 | stimulate B cell growth. mobilizes and activates eosinophils |
| Major function of Th2 cells that produce IL-9 | T cell growth factor |
| Major function of Th2 cells that produce IL-10 | Inhibit Th1 cell function. suppresses macrophage function. |
| Lymphocytes | cells of our immune system that produce receptors specific for diverse antigen |
| Lymphocytes are distinguished by | surface proteins |
| B lymphocytes | subclass of lymphocytes capable of producing antibodies. |
| B lymphocytes express what | membrane forms of antibodies that serve as antigen receptors and initiate B cell activation |
| B lymphocytes are activated by what | binding of antigen to antibodies. |
| Activation of B lymphocytes lead to what | secretion of soluble forms of membrane bound antibodies |
| interactions needed to form an early pro-B cell | binding of VLA-4 integrin to VCAM-1 and SCF ligand to KIT |
| Pro B cells expressing IL-7 causes what | stimulates survival and proliferation of pro-B cells. activation of RAG. becomes Pre-B cell |
| DNA rearrangement of Pre-B cells is due to the activation of what | RAG1/2 genes |
| What is the first immunoglobulin expressed first on pre-B cells | mu. VDJ spliced to Cu exon, Transcript forms heavy chain |
| heavy chain locus contains coding sequences called what | VDJC |
| V chain locus | variable |
| D chain locus | diversity |
| J chain locus | jointing |
| C chain locus | constant |
| light chain locus contains coding sequences called what | VJC |
| in B lymphocyte maturation what is the first check point | assembly of pre-B receptor leading to survival signal. |
| Pre-B cell receptor expression causes what | 1.cell survival 2.turns off recombination on second chromosome 3.turns on recombination at Ig Kappa light chain locus |
| when is lambda locus turned on | only when kappa light chain locus fails to express functional protein |
| lymphocytes that successfully express surface IgM are referred to as | immature B cells |
| last step of complete formation of IgM recepetor | final light chain product associates with Ig mu chain to form complete IgM receptor |
| what features must a mature B cell have | 1. must have rearranged Ig heavy and light chain 2.must produce function of Ig protein (IgD, IgM) 3.immunoglobulins associate with Ig alpha and Ig beta chains to form functional B cell receptor |
| B cell receptor is composed of what | 1. Membrane bound IgM or IgD 2. associate trans membrane Ig alpha and Ig beta proteins |
| First step of B receptor activation | antigen binding to EC variable domain (CDR region in V domain) |
| where does the First step of B receptor activation occur | lymphoid tissue |
| T cell dependent antigens | must contain a protein component |
| T independent antigens | mutlivalet. ex bacterial polysaccharides or repeating determinatns on the surface of viruses. |
| diversity of B lymphocytes that recognize T cell dependent antigens | have the most diversity. produce majority of AB with highest affinity |
| diversity of B lymphocytes that recognize T cell independent antigens | have reduced diversity. produce low levels of IgM only. reduced antigen affinity |
| B lymphocytes that recognize T cell dependent antigens are found where | lymphoid organs |
| B lymphocytes that recognize T cell independent antigens are found where | mucosal tissues, peritoneum, spleen |
| T dependent B cell activation starts with what | antigen recognition, binding, cross linking by two or more B cell receptors |
| what happens once T dependent B cells are activated | 1. ITAMs of Ig alpha and Ig beta become phosphorylated(active) 2. recruit and activate sky tyrosine kinase 3.activate transcription factors that lead to prolif and diff |
| in general in T dependent B cell activation the initial signal leads to what | activation, proliferation, and migration |
| in general in T dependent B cell activation the receptor activation leads to what | Ig antigen complex is internalized and protein is processed via endosome/lysosome. peptide expressed on MHCII. Migration into paracortical region |
| directed migration of B and T cells toward each other is due to what | changes in chemokine receptors. CCR7 (Tcells) and CXCR5 (Bcells) |
| In T dependent B cell activation primary signal leads to what initial antibody production | IgM only. low levels with low affinity |
| In T dependent B cell activation secondary signal leads to what initial antibody production | 1.mature B cells differentiate into plasma cell or memory cell. 2. isotype switching 3.affinity maturation |
| after full activation, subsets of B lymphocytes differentiate into | 1.memory cells 2.plasma cells |
| isotype switching is prompted by what | activation of CD40 co stimulation and cytokines |
| what happens during isotype switching | intervening DNA segments are cleaved creating new VDJ C coding sequences |
| isotype switching uses what enzyme | AID |
| what determines which heavy chain isotype is involved of switch recombination` of B cells is produced | cytokines produced by CD4 T cells |
| production of IFN gamma leads to production of what antibody production | IgG, major opsonin. |
| production of IL-4 leads to production of what antibody production | IgE |
| Principal effector functions of IgM | complement activation |
| Principal effector functions of IgG | Fc receptor dependent phagocyte responses. complement activation neonatal immunity |
| Principal effector functions of IgE | immunity against helminths. Mast cell degranulation (immediate hypersenitivity) |
| Principal effector functions of IgA | Mucosal immunity (transport of IgA through epithelia) |
| T independent B cells | react to lipids, polysaccharides, toxins. molecules with repeating subunits. molecules that can't bind to MHC molecules (aren't seen by T cells). |
| Primary signal of T independent B cells | BCR activation by antigen recognition of repeating subunits. |
| Secondary signal of T independent B cells | engagement of Toll like receptor, complement receptor |
| T independent B cells induce what | low amounts of IgM, little class switching. |
| the vast majority of activated B cells differentiate into what | short lived plasma cells. |
| engagement of Fc receptor on B cells | forms antigen antibody complex. |
| special types of Fc receptor expressed on B cells | 1. FcyRIIB binds Fc portion of complexes 2. binding sends inhibitory signals via ITIM to terminate B cell response |
| immunoglobulins | component of B cell receptor that confers the antigenic specificity of the B cell. |
| Basic structure of immunoglobulins | consists of 2 identical heavy chains and 2 identical light chains linked by disulfide bonds |
| immunoglobulins can be fragmented by enzymatic digestion into what 2 components | Fc region (carboxyl end of heavy chains) Fab region (amino and of heavy and entire light chain) |
| what region determines the class of the immunoglobulin | constant region |
| antibody structure and function is determined by what | heavy chain sequence. the constant region |
| IgG is found where | in serum, lymph, CSF, colostrum, placental transfer |
| IgG has how many binding sites | 2 |
| In IgG the hinge region and proximate residues in CH2 domain is responsible for what | effector function. provide binding site for complement. bind to Fc receptor on effector cells |
| what is the most abundant IgG subclass in humans | IgG1 |
| what is the first Ig made after exposure to antigen | IgM, important for complement activation |
| IgM is found where | serum and lymph |
| IgA is found where | saliva, mucus, sweat, tears, milk |
| Secretory IgA is produced where | by plasma cells in the lamina propria |
| What does secretory IgA do | binds to polymeric Ig receptor on basolateral surface, taken up via endocytosis, transported to luminal surface |
| what Ig is reponsible for hypersensitivity | IgE. found bound to Fc receptors on mast cells and basophils. prim |
| FceRI | a high affinity receptor for the Fc portion of IgE. |
| FceRI is found where | found on mast cells, basophils, macrophages, platelets. |
| cross-linking of adjacent IgE attached to FceRI causes what | degranulation and allergic response |
| IgD is found where | on the surface of B cells. functions as an antigen receptor. co-expressed on IgM |
| IgY is found where | birds, reptiles, lungfish, egg yolk |
| IgM has how many binding sites | 10 |
| IgA has how many binding sites | 4 |
| Fc region contains binding sites for | complement, phagocytes, NK cells |
| Antibody Fc region function | 1. feedback inhibition of antibody production 2. prolongs antibody half-life |
| antigen binding results in what biological properties | 1.neutralizing of toxins 2. immobilization of organisms 3.aggultination and precipitation 4.opsonization 5.initiation of complement |
| what Ig neutralizes toxins | IgG |
| what Ig immobilizes organisms | IgG by binding flagella and cilia |
| what Ig is responsible for aggultination and precipitation | IgM, IgG. makes soluble substances insoluble and easily phagocytosed |
| first step of Ig heavy recombination | activation of recombinase genes |
| 2nd step of Ig heavy recombination | binding of recombinase proteins to D-J segments |
| 3rd step of Ig heavy recombination | binding of recombinase proteins to V-DJ segments |
| 4th step of Ig heavy recombination | processing of RNA transcript. results in VDJ-Cu joining and final mRNA transcript |
| 5th step of Ig heavy recombination | translation of a functional Ig heavy polypeptide. silences other alleles. activates light chain rearrangement |
| combinatorial diversity | Ig locus arranged in many segments only one of each type used in final polypeptide |
| combinatorial diversity occurs via | somatic recombination. happens for both heavy and light chains |
| allelic exclusion | only one copy of each allele is expressed at both havy and light chain loci |
| junctional diversity | mutations generated at splice junction |
| somatic hypermutation | due to actions of AID enzyme |
| isotype switching | due to cytokines stimulation from T cells |
| what mechanisms are only seen in T cell dependent B cell response | somatic hypermutation and isotype switching |
| apoptosis | programmed cell death. controlled dismantling of intracellular components while avoiding inflammation and damage to surrounding cells |
| morphological hallmarks of apoptosis | DNA fragmentation and membrane blebbing |
| major pathways of apoptosis | intrinsic or mitochondrial extrinsic or death receptor pathway |
| initiator caspases | 2,8,9,10,14. activated by multimolecular death complexes |
| effector caspases | 3,6,7. break down cellular structures |
| inflammatory caspases | 1,4,5,11. activated by multimolecular inflammations |
| perforin | pore-forming protein and the granzymes are serine proteases |
| CD95 or Fas | transmembrane 'death receptor'. |
| engagement of Fas on target cell by FasL or CD95L expressed by an armed CTL results in | death of the target cell by apoptosis |
| what regulates T cell survival | CD95L-CD95. |
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