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34 Cards in this Set
- Front
- Back
Mature naïve B cells express surface Ig___
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IgM and IgD
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What cell-cell interaction is crucial for optimal Ab production?
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B:T Cell
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What is class switching? When does it occur?
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Occurs following B cell activation so that IgG, IgA and IgE may be produced
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Why is there a size difference between naïve B cells and plasma cells?
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Plasma cells are 2.5 times larger to produce tons of Ab
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Describe the three steps required to generate a humoral immune response.
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1. Hematopoiesis
2. Activation and Differentiation (process by which naïve B cells are act’d by foreign Ag and selectively expanded) 3. Antigen Elimination (process by which foreign antigen and pathogen that produced it is removed from body |
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Describe the cells required and produced by hematopoiesis.
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MHSC in BM (self-renewing) gives rise to:
Lymphoid Progenitor Cell: gives rise to B cells, T cells, NKC’s Myeloid Progenitor Cell: RBC’s, granulocytes, platelets (via megakaryocytes), macs, DC’s |
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Via what process and in what cell type does heavy chain arrangement occur?
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VDJ Rearrangement in Pre-B cells (Pre-B is between Progenitor-B and Immature B)
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Via what process and in what cell type does light chain arrangement occur?
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Rearrangement of lambda or kappa mRNA in immature B cell (between pre-B and mature B)
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Briefly describe what happens in VDJ rearrangement. What does this allow for?
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D is joined to J
V is joined to DJ Transcription! Generation of millions of Ab’s from relatively small amount of DNA |
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Where does foreign antigen-independent lymphocyte development occur? Describe the major events of this stage.
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Primary Lymphoid Organs (BM, Thymus)
BM: Ab gene rearrangement, pos/neg selection Thymus: migration of ProT from BM to thymic cortex TCR gene rearrangement pos/neg selection |
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Where does foreign antigen-dependent lymphocyte development occur? Describe the major events of this stage.
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Peripheral Lymphoid Organs: Spleen, LN's, MALT, LV's
LN, Spleen: Ag exposure: lymphoid follicles-->germinal Centers MALT: MORE PLASMA CELLS THAN IN ANY OTHER TISSUE COMBINED |
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Describe the path of immune cells from the BM.
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BM-->Blood-->Spleen, MALT, LN's-->Blood
BM-->Thymus-->Blood-->LN's, Spleen, MALT-->Blood Back and forth means surveillance! Lymphocytes are never in one place for very long |
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Thymus-Dependent Antigens vs Thymus-Independent Antigens
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Thymus-Dependent Ag’s :
Require B:T cell interaction for Ab production (most Ag’s fall in this category) Undergo Isotype Switching Undergo Affinity Maturation Have secondary response via memory B cells T-dependent = PROTEINS Thymus-independent Ag’s can induce Ab responses in absence of T cells; function as mitogens (agent stimulating mitosis), activating cells vis TLR’s regardless of Ig specificity (LPS), may cross-link membrane Ig (e.g. flagellin) T-independent = NON-PROTEINS Thymus independent antigens do NOT involve isotype stwitching, affinity maturation, or memory (demonstrates importance of T cells in humoral immunity) |
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Primary vs Secondary Immune Responses:
Lag after immunization Peak response (antibody number) Antibody isotype Antibody affinity |
Primary:
5-10 day lag time Smaller peak response (antibody number) IgM>IgG Lower avg Ag affinity, more variable Secondary: 1-3 day lag time Larger peak response (antibody number) Relative increase in IgG, IgA or IgE depending on situation (class switching) Higher average affinity (affinity maturation) |
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Describe the molecular events that follow a microbe binding a B cell surface immunoglobulin.
What changes does the B cell undergo in response to antigen binding? |
**Ig’s cross link on B cell
**ITAMs on cytoplasmic side get Pi’d Downstream signaling leads to actvn of transcriptional factors (NFAT, NF-kappaB, AP-1) Upon Ag binding, B cells: **Enter cell cycle (mitosis) to allow for clonal expansion **Increase expression of B7 costimulators (helps activate Th cells) Increase expression of cytokine receptors (now able to respond to cytokines produced by Th cells) **Migrate out of lymphoid follicles and into parafollicular cortex AKA T Cell zone (to interact with Th cells; B cells serve as APC’s) Secrete low levels of IgM (early phase of humoral immune response) |
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Describe the molecular events that follow microbe associated with C3d binding a B cell surface immunoglobulin.
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C3d is a breakdown product of complement factor C3(b)
Microbe will bind surface Ig (dimerization etc) C3d will bind CR2 (B cell co-recepgtor) Signals from Ig and CR2 complex both lead to B cell activation |
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Describe the molecular events that proceed B cell recognition of native protein antigens and result in T cell recognition of the antigen and B cell proliferation.
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B cell recognition leads to receptor mediated endocytosis of antigen
Undergoes Ag processing and presentation via MHC II Th Cell binds to MHC II AND B7 (via CD28 RECEPTOR) Activated Th cell expresses CD40L and releases cytokines B cells activated by CD40 engagement AND cytokines B cells proliferate and differentiate |
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What is isotype switching and what is required for it to occur?
Describe the process by which isotype switching occurs. Does this affect antigen specificity? |
Isotype switching is process through which CONSTANT regions of H CHAIN GENES are rearranged and lead to variety of act’d B cells expressing a new Ig isotype (IgG, IgA, IgE); DOES NOT AFFECT V REGIONS (variable regions); this is NOT VDJ REARRANGEMENT
Th cell cytokines required for isotype switching (result of isotype switching depends on cytokine to which it’s exposed) (some isotype switched act’d B cells enter recirculating pool and seek Ag in tissue, can produce Ab there) Isotype switching is the result of splicing out constant regions that proceed CDJ region DOES NOT AFFECT ANTIGEN SPECIFICITY OF ANTIBODY |
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What is affinity maturation and how does it occur? Purpose?
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Affitinity maturation is the result of somatic hypermutation which generates point mutations at a high rate in V regions of H and L genes of act’d cells
(Mutation occurs in “hypervariable’ regions: CDR1,2,3; CDR = complementarity determining region) A few of these mutant B cells have higher affinity for Ag and are selected for add’l proliferation (most undergo apoptosis bc of lower affinity) Result is avg affinity of Ab’s increases and thus affinity is said to “mature” |
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How is B cell regulation achieved?
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An antibody that is NOT secreted by the B cell to be regulated binds Ig AND Fc receptor
Results in inhibition of B cell response (“There’s enough Ab in blood; hold off production) |
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Agglutination vs Neutralization vs Opsonization
What do these all require? |
Agglutination:
Bacteria or viruses clumped together and immobilized Neutralization: Prevent pathogen (or toxin) from binding Opsonization: Coating of Ags or target cells with Abs and complement proteins to enhance phagocytosis ALL REQUIRE AB's |
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Antibody-Dependent Cell-Mediated Cytotoxicity vs Complement-Dependent Lysis
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ADCC: Ab's bind to offending/infected cells and direct non-specific cells to it via Fc portion of bound Ab's
Complement-dependent lysis: acts against cells or enveloped viruses via assembly of Membrane Attack Complex |
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Which Ig isotypes are involved in ADCC?
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ADCC: IgG, IgE
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Which Ig isotypes are involved in agglutination?
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IgM (first responder and involved in classical pw of complement)
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Which Ig isotype exists as a dimer? As a pentamer?
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Dimer: IgA (held by J chain)
Pentamer; IgM (lots of Ag binding sites) |
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How are intestinal pathogens neutralized in the gut?
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Multiple IgA's binds pathogen which prevents entry into epithelium
(Note: mucosal epithelial cells express polyIg receptor to allow transport of IgA through epithelium; must be proteolytically cleaved before exit) |
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Briefly describe the events of opsonization beginning with IgG.
Is there another molecule that can trigger this? How? |
IgG antibody binds microbe
Opsonized microbe binds phagocytic Fc receptor Fc receptor signal activates phagocyte Microbe is phagocytosed C3b can also activate opsonization! It does so by binding CR1 receptor on phagocyte |
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Describe the steps of antibody dependent cell-mediated cytotoxicity beginning with IgG and IgE.
Discuss receptor affinity. |
IgG binds surface antigen and coats cell
IgG coated cell binds LOW AFFINITY Fc receptor on NKC NKC kills IgE binds surface Ag on parasite IgE binds HIGH AFFINITY Fc receptor on eosinphil and results in degranulation |
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Describe the three complement activating pathways. Which complement proteins are important for each?
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Alternative:
C3b binds surface of microbe and serves as opsonin Also requires Factors B, D, Properdin Classical: IgG antibody binds microbe C1 binds Fc portion of IgG Also requires C2, C4 Lectin Pathway: Lectin binds Mannose on microbe Requires C2, C4 |
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What do all complement pathways result in?
In what order do the proteins involved assemble? |
Formation of Membrane Attack Complex
(C4 convertase: C5-->C5b, C6-C5b-C7-C8) Cell Lysis C5,6,7,8,9 |
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What are the three functions of complement?
How is the complement system regulated? |
Three fns:
1) Opsonization and phagocytosis (by a macrophage via C3b-CR1 interaction) 2) Complement-mediated cytolysis (by MAC complex via C3b) 3) Stimulation of inflammatory response (C3a, 4a, 5a recruit and activate leukocytes) REgulation by: 1) Decay-Accerlerating Factor (DAF): interferes with formation of C3 convertase by displacing Bb from C3b (blocks ALTERNATIVE AND CLASSICAL) 2) Membrane Cofactor Protein (MCP) destroys any C3b formed (Factor I mediated cleavage of C3B) 3) C1 Inhibitor (C1-INH) prevents assembly of C1 complex (blocks CLASSICAL) |
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What are three ways microbes evade humoral immunity? Provide examples of microbes.
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1) Antigenic Variation (viruses: HIV, flu)
2) Inhibition of complement activation (bacteria) 3) Resistance to phagocytosis (pneumococcus) |
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Would an immune response to capsular polysaccharides require T cells?
How does this relate to H. influenzae B vaccines and children? What's the solution? What antibodies are involved? |
No T cells required
Vaccine antigens = polysacchs and won't result in memory Children mount poor T-independent Ab responses Solution: Conjugate bacterial polysacchs to protein carrier to improve immunogenicity THUS makes it a T-dependent response and resulting in HIGH levels of IgG T cell independent vaccines would produce little IgG |
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What is passive immunization? When is its use indicated?
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Transfer of preformed ab's to recipient, conveying instant immunity
Transient protection, no memory induced (naturally occurs with maternal Ab's across placenta--IgG--and through colostrum--sIgA) Indications for Use: Immunodeficiency affecting Ab production Immunoprophylaxis in at-risk populations Rapid immunity needed (travel, recent exposure) |