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Step1 11.14.12
Immunology I
| Question | Answer |
|---|---|
| What is the structure of the lymph node? | secondary lymphiod organ with many afferents and 1 or more efferents. encapsulated with trabeculae. |
| What are the major functions of the LN? | non specific filtration by macrophages, storage and activation of B and T cells. Ab production |
| What happens in the LN follicle? | site of B cell localization and proliferation. in outer cortex |
| What is the difference between primary and secondary follicles in the LN? | primary are dense and dormant. secondary have pale centra germinal centers and are active |
| What is contained in the medulla of a LN? | medullary cords (closely packed lymphocytes and plasma cells). medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages |
| What is the morphology and function of the paracortex of the LN? | houses T cells. region of cortex b/w follicles adn medulla. contains high endothelial venules thru which T and B cells enter the blood. |
| What happens to the paracortex in an extreme cellular immune response and in what condition might it not be well developed? | enlarges in an extreme cellular immune response ( viral), not well developed in DiGeorge syndrome |
| What is the LN drainage for the upper limb and lateral breast? | axillary |
| What is the LN drainage for the stomach? | celiac LN |
| What is the LN drainage for the duodenum and jejunum? | superior mesenteric LN |
| What is the LN drainage for the sigmoid colon? | colic-->inferior mesenteric LN |
| What is the LN drainage for the rectum lower portion above the pectinate line? | internal iliac LN |
| What is the LN drainage for the anal canal below the pectinate line? | superficial inguinal LN |
| What is the LN drainage for the testes? | superficial and deep plexi-->para aortic LN |
| What is the LN drainage for the scrotum? | superifical inguinal LN |
| What is the LN drainage for the superficial thigh? | superficial inguinal LN |
| What is the LN drainage for the lateral side of the dorsum of the foot? | popliteal |
| What does the right lymphatic duct drain? | right arm and right half of head |
| What does the thoracic duct drain? | everything but right arm and right half of head |
| What is the structure of the sinusoids of the spleen? | long vascular channels in red pulp with fenestrated barrel hoop BM. marcophages found nearby |
| Where are T cells found in the spleen? | in periarterial lymphatic sheath and white pulp |
| Where are B cells found in the spleen? | follicles within white pulp of the spleen |
| What is the role of macrophages in the spleen? | remove encapsulated bacteria |
| What is the mechanism of splenic dysfunction and what types of organisms does it make a person vulnerable to? | splenic DysFx: decr IgM-->decr complement activation-->decr C3b opsonization--->incr suceptibility to encapsulated organisms |
| What is a mnemonic for the specific orgnaisms that asplenics are vulnerable to? | S SHiN: salmonella, S. pneumonidae, H. influenza, N. meningitidis. All encapsulated |
| What 3 features are seen post splenectomy? | Howell-Jolly Bodies (nuclear rements), Target cells, thrombocytosis |
| Where are APC's found in the spleen? | in the marginal zone |
| What is the major function of the thymus and what is its embryological origin? | site of T cell differentiation and maturation. from epithelium of 3rd branchial puches |
| What is the structure of the thymus? | encapsulated. Cortex dense with immature T cells, medulla pale with mature T cells and epithelial reticular cells and contains Hassall's corpuscles |
| Where do positive (MHC restriction) and negative (nonreactive to self) selection occur in the thymus? | corticomedullary junction |
| Where do B cells mature? | bone marrow |
| What are the major characterisitcs of innate immunity? | receptors are germline encoded. fast and non specific response with no memory |
| What cells are invovled in the innate immune response? | neutrophils, macrophages, dendritic cells, NK cells, complement |
| What are the general characterisics of the adaptive immune response? | receptors which recognize pathogens undergo VDJ recombination. response is slow on first exposure but memory is fast and robust |
| What cells are invovled in the adaptive immune response? | T cells, B cells, circulating Ab |
| What is MHC and where is it encoded? | encoded by HLA. presents Ag fragments to T cells and binds TCR |
| What does MHC I bind? | TCR and CD8 |
| What does MHC II bind? | TCR and CD4 |
| What are the 3 phenotypes of MHC I? | A, B, C |
| Where is MHC I expressed and what types of peptides does it present mediating immunity to what? | expressed on almost all nucleated cells. NOT on RBC. Ag loader by RER of intracellular peptides mediating viral immunity |
| With what is MHC paired with when transported to the surface? | Beta 2 microglobulin. improves transport |
| What are the 3 phenotypes of MHC II? | DR, DP,DQ |
| What cells express MHC II and how many tranmembrane domains does it have? | expressed only on APCs. 2 TM domains vs MCH I's 1 |
| How is the peptide loaded onto MHC II? | loaded following relase of invariant chain in acidified endosome. binds CD4 and TCR |
| What disease is associted with HLA A3 ? | hemochromatosis |
| What disease is associted with HLA B27? | PAIR: psoriasis, ankylosing spondylitis, inflammatory bowel, Reiter's syndrome |
| What disease is associted with HLA B8? | Grave's disease |
| What disease is associted with HLA DR2? | MS, hay fever, SLE, Goodpasture's |
| What disease is associted with HLA DR 3? | DM Type I |
| What disease is associted with HLA DR4? | RA, DM type I |
| What disease is associted with HLA DR5? | pernicious anemia-->B12 deficiency. Hashimoto's thyroiditis |
| What disease is associted with HLA DR7? | Steroid responsive nephrotic syndrome |
| What part of immune system are NK cells a part of and what do they kill and how? | only lymphocyte that is part of innate. uses perforin an granzymes to induce apotosis or virally infected cells and tumor cells |
| What 3 things might increase NK activity? | IL-12, IFN-Beta, IFN-alpha |
| When an how is an NK cell induced to kill? | when exposed to non specific activation on target cell or absence of MHC I on target cell surface |
| What immune cell makes Ab? | B cells |
| What Ab does a B cell use to opsonize bacteria and neutralize viruses? | IgG |
| What Ab does a B cell use to activate complement? | IgM, IgG |
| What Ab does a B cell use to sensitize mast cells? | IgE |
| What cells mediate Type I hepersensitivity and how? | B cells (allergies) IgE |
| What cells mediate cytotoxic (II) and immune complex (III) hypersensitiyvity and how? | B cells with IgG |
| What cells mediate hyperacute organ rejection? | B cells |
| What is the role of Cd4 T cells? | help B cells make Ab and produce IFN gamma, activating macrophages |
| What is the role of CD8 T cells? | kill virus infected cells directly |
| What cell type mediates delayed cell mediated hypersensitivity (IV)? | T cells |
| What cells are responsible for acute and chronic organ rejection? | T cells |
| What is positive T cell selection, and where does it occur? | thymic cortex. T cells expressing TCRs capable of binding self MHC survive |
| What is negative T cell selection and where does it occur? | Corticomedullary junction. T cells expressing TCRs with high affinity for self Ag will undergo apoptosis |
| What is the process of CD expresion for T cells? | double positive after + selection (cortex), single + after negative selection (medulla) |
| What causes a CD4 cell to become a Th1? What does the Th1 express? | IL-12 makes CD4+ intoTH1. TH1 express IL-2, IFN gamma to activate Macrophages and CD8 T cells |
| What causes a CD4 cells to become a TH2 and what does a TH2 produce? | IL-4 makes CD4 into TH2. TH2 make IL-4, IL-5 and help B cells make Ab (switch IgG to IgE |
| What 3 cells are APCs? | Macrophage, dendritic cell, B cell |
| What is the process of TH activation? What is signal 1 and signal 2? | 1.foreign thing phagocytosed by APC 2. presented on MHCII and recognized by Th TCR (signal 1) 3. costimulatory signal of B7 on APC interacitng with CD28 on T cell(signal 2) 4. activated Th produce cyotkines |
| How are cytotoxic T cells activated? What is signal 1 and 2? | 1. endogenously synth (self or viral) peptides presented on MHC I and recognized by TCR on Tc (signal 1) 2. IL-2 from Th activates Tc to kill virus infected cells (signal 2) |
| How are B cells activated/class switch? What is signal 1 and 2? | 1. helper T cell activated 2. foreign Ag presented on MHCII and recognized by Th 3. Il-4, 5, 6 made by Th2 (signal 1) 4. CD40 on Bcell binds CD40 L on Th2 (signal 2) 5. costimulation of B7 aand Cd28 |
| What response does Th-1 mediate, what do they release and what do they activate? | mediates cell mediated response. secretes Il-2 IFN-gamma. activates macrophage and CD* T cell |
| What inhibits Th1? WHat makes it? | IL-10 made by TH2s |
| What response do TH2s mediate, what do they secrete, and what cells do they activate? | regulates humoral response, secretes IL-4,5,10, helps b cells make Ab/class switch IgE>IgG |
| What inhibits Th2's and what makes it? | IFN-gamma from TH1's |
| How do TH1s and macrophages stimulate one another? | lymphocytes make IFN-gamma which activates macrphages to release IL-1, TNF-alpha |
| What on TH's binds MHC on macrophages? | CD4 |
| What types of cells to Cytotoxic T's kill? | virus infected, neoplastic, donor graft cells |
| What binds MHC on a virus infected cell from Tc? | CD8 |
| How do Tc's kill? What is the mech of the molecules used? | release granules with perforin:helps deliver granules to target, granzyme:serine protease which activates apoptosis in target cell, granulysin: antimicrobial which induces apoptosis |
| What is the role of regulatory T cells and what do they expres? | help maintain immune tolerance by surpressin DE4 and CD8s. express CD3, CD4, CD25(low affinity for IL-2) |
| What types of cells to Cytotoxic T's kill? | virus infected, neoplastic, donor graft cells |
| What part of the Ab recognizes Ag? | variable part of L and H chains |
| What binds MHC on a virus infected cell from Tc? | CD8 |
| How do Tc's kill? What is the mech of the molecules used? | release granules with perforin:helps deliver granules to target, granzyme:serine protease which activates apoptosis in target cell, granulysin: antimicrobial which induces apoptosis |
| What is the role of regulatory T cells and what do they expres? | help maintain immune tolerance by surpressin DE4 and CD8s. express CD3, CD4, CD25(low affinity for IL-2) |
| What do regulatory T cells produce? | antiinflammatory cytokines like IL-10 and TGF-Beta |
| What part of the Ab recognizes Ag? | variable part of L and H chains |
| What do regulatory T cells produce? | antiinflammatory cytokines like IL-10 and TGF-Beta |
| What part of Ab fixes complement? | Fc portion of IgM and IgG |
| What part of the Ab recognizes Ag? | variable part of L and H chains |
| Which fractions do heavy vs. light chain contributew to? | Heavy: Fc and Fab Light: only Fab |
| What is Ab complement activation? | Ab activates complement enhancing opsonization and lysis |
| What is the fab fragment? | antigen binding fragment, determines idiotype. only 1 Ag per B cell |
| What part of Ab fixes complement? | Fc portion of IgM and IgG |
| What is the Fc region of the Ab? | constant region, has carboxy terminal. Binds complement at CH2(M and G), carbohydrate side chains, determines the isotype |
| Which fractions do heavy vs. light chain contributew to? | Heavy: Fc and Fab Light: only Fab |
| Which Ig are expressed on the B cell surface and what are the options for class switching? | IgM, IgD on surfaces. Can then secrete IgA or E or G |
| Which part of Ab determines the isotype? | fc |
| What is the fab fragment? | antigen binding fragment, determines idiotype. only 1 Ag per B cell |
| What is Ab opsonization? | Ab promotes phagocytosis |
| What is the Fc region of the Ab? | constant region, has carboxy terminal. Binds complement at CH2(M and G), carbohydrate side chains, determines the isotype |
| What is Ab neutralization? | Ab prevents bacterial adherence |
| Which part of Ab determines the isotype? | fc |
| What is Ab complement activation? | Ab activates complement enhancing opsonization and lysis |
| What is Ab opsonization? | Ab promotes phagocytosis |
| What are the 4 mechanisms by which antibody diversity is acheived? | 1. random VJ (light chain) or VDJ (heavy) recombination 2. random combo of heavy with light chains 3. somatic hypermutation following Ag 4. addition of nucleotides during recombination by terminal deoxynucleotidyl transferase |
| What is Ab neutralization? | Ab prevents bacterial adherence |
| Which Ab is found in tears, saliva, mucus and breast milk (colostrum)? | IgA |
| Which Ig are expressed on the B cell surface and what are the options for class switching? | IgM, IgD on surfaces. Can then secrete IgA or E or G |
| How does IgA acquire its secretory component? | from epithelial cells before it is secreted |
| What is the major Ab in the secondary (delayed) response and is the most abundant in blood? | IgG |
| What is Ab complement activation? | Ab activates complement enhancing opsonization and lysis |
| What Ab is responsible for crossing the placenta and giving the infant passive immunity? | IgG |
| What are the 4 mechanisms by which antibody diversity is acheived? | 1. random VJ (light chain) or VDJ (heavy) recombination 2. random combo of heavy with light chains 3. somatic hypermutation following Ag 4. addition of nucleotides during recombination by terminal deoxynucleotidyl transferase |
| What are the antimicrobial actions of IgG? | opsonizes bacteria, neutralizes toxins and viruses. fixes complement |
| Which Ig are expressed on the B cell surface and what are the options for class switching? | IgM, IgD on surfaces. Can then secrete IgA or E or G |
| What is the mechanism of IgA? How does its structure based on its role? | prevents attacthement of bacteria and viruses to mucous membranes. monomer in circulation and dimer when secreted. crosses epithelial cell by transcytosis |
| What is the major Ab in the secondary (delayed) response and is the most abundant in blood? | IgG |
| What Ig mediates the allergic response and how? | IgE. binds mast cells and basophils. cross links when exposed to allergen mediating Type I hypersensitivity thru release of histamine |
| Which Ab is found in tears, saliva, mucus and breast milk (colostrum)? | IgA |
| Which Ig mediates immunity to worms and has the lowest serum concentration? | IgE |
| How does IgA acquire its secretory component? | from epithelial cells before it is secreted |
| What are thymus independent Ag and how is the immune response limited? | Ag lack a peptide component so cant be presented on MHc. ex LPS of G- bacteria or polysaccaride capsule. Therefore immune response is only IgM and can't form memory |
| What Ab is important in the primamry response (immediate) to an Ag? | IgM |
| What is the mechanism of IgA? How does its structure based on its role? | prevents attacthement of bacteria and viruses to mucous membranes. monomer in circulation and dimer when secreted. crosses epithelial cell by transcytosis |
| What are the major antibacterial roles of IgM? | fixes complement. Ag receptor on B cells, monomer or pentamer on B cells.pentamer allows it to bind Ag while the humoral response evolves |
| Which Ab is found in tears, saliva, mucus and breast milk (colostrum)? | IgA |
| Where is IgD found, what is its function? | unclear function. found on B cell surface and in serum |
| How does IgA acquire its secretory component? | from epithelial cells before it is secreted |
| What Ig mediates the allergic response and how? | IgE. binds mast cells and basophils. cross links when exposed to allergen mediating Type I hypersensitivity thru release of histamine |
| What Ab is important in the primamry response (immediate) to an Ag? | IgM |
| Which Ig mediates immunity to worms and has the lowest serum concentration? | IgE |
| What are the major antibacterial roles of IgM? | fixes complement. Ag receptor on B cells, monomer or pentamer on B cells.pentamer allows it to bind Ag while the humoral response evolves |
| What are thymus independent Ag and how is the immune response limited? | Ag lack a peptide component so cant be presented on MHc. ex LPS of G- bacteria or polysaccaride capsule. Therefore immune response is only IgM and can't form memory |
| Where is IgD found, what is its function? | unclear function. found on B cell surface and in serum |
| What are thymus dependent Ag? Which IL's might be released? | Ag contain a protein allow for class switching via b and Th cells. and can cause release of Il-4,5,6 |
| What Ig mediates the allergic response and how? | IgE. binds mast cells and basophils. cross links when exposed to allergen mediating Type I hypersensitivity thru release of histamine |
| What does the MAC complex of the complement pathway primarily defend against? | G- bacteria |
| Which Ig mediates immunity to worms and has the lowest serum concentration? | IgE |
| What mediates the classic complement pathway? | IgM, or IgG |
| What are the 2 primary opsonins in bacterial defencse? | C3b and IgG. C3b also helps clear immune complexes |
| What mediates the alternative complement activation pathway? | microbe surface molecules |
| What is the function of C1,2,3,4 in the complement pathway | viral neutralization |
| What does the MAC complex of the complement pathway primarily defend against? | G- bacteria |
| What is the function of C3b in the complement pathway? | opsonization |
| What is the function of C3a, C5a in the complement pathway? | anaphylaxis. C5a also does neutrophil chemotaxis |
| What is the role of C5b-C9 in the complement pathway? | cytolysis by MAC |
| What are the 2 primary opsonins in bacterial defencse? | C3b and IgG. C3b also helps clear immune complexes |
| What mediates the classic complement pathway? | IgM, or IgG |
| What mediates the alternative complement activation pathway? | microbe surface molecules |
| What is the function of C1,2,3,4 in the complement pathway | viral neutralization |
| What is the function of C3b in the complement pathway? | opsonization |
| What is the function of C3a, C5a in the complement pathway? | anaphylaxis. C5a also does neutrophil chemotaxis |
| What is the role of C5b-C9 in the complement pathway? | cytolysis by MAC |
| What are the 2 primary opsonins in bacterial defencse? | C3b and IgG. C3b also helps clear immune complexes |
| What 2 molecules help to inhibit complement activation? | DAF, C1 esterase help prevent complement activation on self cells |
| What is the process of the alternative complement pathway to C3b? What initiates it? | initiated by microbial surfaces. C3--C3b-->C3bBb convertase makes C3a and C3b |
| What is the Lectin complement pathway to C3b? What initiates it? | mannose on microbial surface. MBL--->C1 like Comlex via MASP1.2-->formation of C4a and C4b-->combines with C4b2a which converts C3 to C3a and C3 b |
| What is the classical complement pathway to C3b? What intiates it? | initiated by AgAb complexes. C1-->cleaves C2 into C2b and C2a which combines with C4b to make C4b2a convertase which splits C3 into C3a and C3b |
| What happens in all the complement pathways once the common pathway is reached via C3b? | form C3bBb3b convertase and C4b2a3b convertase which both cleave C5 to C5a and b. C5b activates c6-C9 in the MAC resulting in lysis |
| What is seen in a C1 esterase inhibitor deficiency? What m edicine is CONTRAindicated | hereditary angioedema. ACE inhbitors contraindicated |
| What happens in a C3 defieincy? | severe, recurrent, pyogenic sinus and RTI. incr suceptibilty to Type III hypersensitivity reactions |
| What happens in a C5-C8 deficiency? | recurrent Neisseria bacteremia |
| What happens in a DAF (GPI anchored enzyme) defieciency? | complement mediated lysis of RBCs and paroxsmal nocturnal hemoglobinuria (PNH) |
| What are the actions of IL-1? | endogenous pyogen. causes fever, acute inflammation. activates endothelium to express adhesion molecules, chemokine secretion to recruit leukocytes |
| What are the actions of IL-6? | endogenous pyrogen. secreted by TH. causes fever and stimulates production of acute phase proteins |
| What are the actions of IL-8? | major chemotactiv factor for neutrophils |
| What are the actions of IL-12? | induces differentiation of Th1's activates NK cells. Also secreted by B cells |
| What are the actions of TNF-alpha? | mediates septic shock. activates endothelium, causes leukocyte recruitment and vascular leak? |
| What interleukins are made by macrophages? | IL-1,6,8,12, TNF-alpha |
| What is a mnominc for the actions of the IL-1-5? | Hot T-Bone stEAk: Il-1: hot IL-2: stim T cells Il3: stimulates bone marrow Il4:stimulates IgE production Il5:stimulates IgA production |
| Which IL is made by all T cells? | Il-3 |
| What are the actions of IL-3 | supports gorwth and differentiation of bone marrow stem cells. acts like GM-CSF |
| What 2 IL are made by TH1 cells? | IL-2, Interferon gamma |
| What are the actions of IL-2? | stimulates growth of helper and cytotoxic T cells |
| What are the actions of Interferon gamma? | activates macrophages and Th1 cells. surpresses Th2 cells. antiviral and antitumor properties |
| What 3 IL are made by TH2's cells? | IL-4, 5, 10 |
| What are the actions of IL-4? | induces differentiation into TH2. promotes B cell growth. enhances class switching to IgE and IgG |
| What are the actions of IL-5? | promotes differentiation of B cells. enhances class switching to IgA. stimulates growth and differentiation of eosinophils |
| What are the actions of Il-10? What else makes it? | modulates the inflammatory response. inhibits actions of activated T's and TH1. activates Th2. also secreted by Tregs |
| What other molecule shares a similar role as IL-10? | TGF-Beta |
| What are the general roles of interferons (alpha, beta, gamma)? | place an unifnfected cell in an antiviral state. Activate NK's to kill virus infected cells.induce production of ribonuclease which degrades viral mRNA selectively |
| What are the specific actions of IFN-alpha and beta? | inhibits viral protein synthesis |
| What are the specific actions of IFN-gamma? | incr MHC I and II expression and Ag presentation |
| What cell surface proteins are found in a TH? | TCR, CD3, CD28, CD4 |
| What is the role of CD28? | binds B7 on APc |
| What is the role of CD3? | associated with TCR for signal transduction |
| What surface proteins does a cytotoxic T have? | TCR, CD3, CD28, CD8 |
| What surface proteins are found on B cells? | Ig, cD19,20,21,40. MHC II, B7 |
| What is significant about CD21 on B cells? | receptor for EBV |
| What surface proteins are found on macrophhages? | CD14, CD40, MHCII, B7, Fc and C3b receptors |
| What are the surface proteins and their function in NK cells? | CD16( binds Fc of IgG), CD56 (unique marker for NK) |
| What is a notable cell that lacks MHC I? | RBC |
| What is T cell anergy? | self reactive T cells become non reactive without a costimulatory molecule |
| What bacteria have superantigens and how do they work? | S. pyogenes, S aureus. cross link Beta of TCR to MHCII on APC. results in uncoordinated IFN-gamma release by TH1s causing release of IL1,6 and TNF alpha from macrophages |
| What bacteria have endotoxins/LPS and how do they work? | G- bacteria, directly stimulate macrophages by binding CD14. TH cells arent invovled |
| How does salmonella vary its Ag? | 2 flaggelar variants |
| What happens when Borellia alters its Ag? | relapsing fever |
| How does neisseria gonorrhoeae alter its Ag? | different pilus protein |
| How does a virus changes its Ag, esp influenza? | drift: minor. shift: major (RNA reassortment) |
| How does a trypanosome vary its ag? | programmed rearrangement |
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