Flashcards
Humoral Immunity
Cards in this deck (32)
- 1What is humoral immunity mediated by?Antibodies
- 2What does humoral immunity do?It is a part of the adaptive immune response that functions to neutralise and eliminate extracellular microbes and microbial toxins. It is the principal mechanism against microbes with capsules rich in polysaccharide, lipids and proteins.
- 3What are the two antibodies present on naive B cells?IgM and IgD
- 4What is heavy chain isotype switching?This is a process during B cell maturation where IgM antibodies differentiate into IgM, IgA, IgE and IgG antibodies.
- 5What is affinity maturation?Repeated exposure to protein antigen results in production of antibodies with increasing affinity.
- 6Which antigens are T-dependent and which antigens are T-independent?Responses to protein antigens are T-dependent. Responses to non-protein antigens such as polysaccharides and lipids are T-independent.
- 7What are follicular B cells?They make T-dependent, class-switched, high affinity responses to protein antigens. They produce long-lived plasma cells and reside/circulate in follicles of lymphoid organs.
- 8What are marginal-zone B cells?Marginal-zone B cells are located in the peripheral region of the splenic white pulp and respond to blood-borne polysaccharide antigens.
- 9What are B-1 cells?B-1 cells exist in mucosal tissues and the peritoneum and respond to non-protein antigens.
- 10What do marginal-zone B cells and B-1 cells have in common?They have antigen receptors of limited diversity, predominantly IgM responses, and they both lack features of T-depedent responses.
- 11What are the primary and secondary responses?The primary response is due to the immune system's first exposure to an antigen. The secondary response is due to it's second exposure.
- 12How much can you remember about antigen-induced signalling in the activation of naive B cells?
- 13Do innate immune signals play a role in B cell activation?Yes, for e.g. the complement system.
- 14What is the role of complement proteins in B cell activation?B cells recognise antigen and simultaneously recognise bound C3d via complement receptor 2 (CR2). This engagement of CR2 enhances activation.
Furthermore, some naive B cells have TLRs that can recognise PAMPs on microbes.
- 15What is the sequence of events in helper T cell-dependent antibody responses?1. CD4+ Th cells and B cells are independently activated by the same protein antigen in different regions of the lymph node and migrate towards each other.
2. Effector T cell and activated B cell interact outside the follicles: the B cell processes and presents the antigen to the T cell
3. the T cell expresses CD40L and secretes cytokines which act on the B cell to initiate proliferation and differentiation into plasma cells
4. some activated B cells migrate back into the follicle into a germinal centre
- the germinal centre required Tfh cells and antigen presentation by DCs
- it produces high-affinity antibodies and results in long-lived plasma and memory cells
- 16How do T cells and B cells migrate towards one another in T-dependent responses?T cells reduce their expression of CCR7, which recognises chemokines produced in T cell zones, and increases expression of chemokine receptor CXCR5, which promotes migration into B cell follicles.
B cells increase their expression of CCR7 and decrease CXCR5.
Antigen-activated B and T cells migrate towards one another and meet at the edges of lymphoid follicles or in inter-follicular areas. - 17What do Tfh cells do?Tfh cells assist in the production and function of germinal centres for the maturation of B cells. The generation of Tfh cells depends on the ICOS family of proteins, they can develop from uncommitted T cells or from Th1/Th2/Th17 subsets.
Most Tfh cells secrete IL-21, and depending on if they developed from another subset they will also secrete IFN-gamma, IL-4 and IL-17. - 18What induces heavy chain isotype (class) switching?Th cells stimulate progeny of IgM and IgD-expressing B cells to produce antibodies of different heavy chain isotypes. Cytokines produced by Th cells determine which heavy-chain isotype is produced by influencing which heavy-chain C-region participates in switch recombination.
BAFF is a B-cell activating cytokine involved in switching to IgA, especially in T-dependent responses. TGF-beta also plays this role.
The production of opsonising antibodies is stimulated by IFN-gamma, which is secreted by Th1 cells.
Switching to IgE is stimulated IL-4, the signature cytokine secreted by Th2 cells. - 19How does heavy chain isotype (class) switching occur at the molecular level?
- 20How are high-affinity B cells selected in germinal centres?Mutations generate B cells with different affinities. Follicular DCs display antigen by utilising Fc receptors to bind immune complexes and using C3 receptors to bind immune complexes with attached C3b and C3d. B cells also present antigen to Th cells in germinal centres.
As more antibody is produced, the amount of antigen decreases. Only B cells that express receptors with higher affinities can bind antigen and be selected to survive.
- 21What is somatic hyper-mutation?Affinity maturation is the result of somatic hyper-mutation (point mutations of the Ig V region, particularly in the antigen-binding hypervariable region). This can be a result of the enzyme AID, which replaces nucleotides with uracil in the DNA which then gets substituted during translation.
- 22How do we shut off antibody production?Secreted antibodies form immune complexes with residual antigen and shut off B cell activation by engaging an inhibitory Fc receptor on B cells.
- 23Where do secreted antibodies go?To the blood and in mucosal secretions.
- 24How much can you remember about the function of antibodies?
- 25What is FcRn and what does it do?The neonatal Fc receptor (FcRn) contributes to the long half-life of IgG molecules. It is expressed in the placenta, endothelium, phagocytes and a few other cells. In the placenta, the FcRn transports IgG from the mother's circulation to the fetus. In other cells, the FcRn protects IgG antibodies from intracellular catabolism (see image).
- 26What are the four mechanisms that antibodies use to neutralise microbes and toxins?1. antibodies at epithelial surfaces, e.g. GI and respiratory tracts, block entry of ingested and inhaled microbes, respectively.
2. Antibodies prevent binding of microbes to cells, thereby blocking the ability of microbes to infect host cells.
3. Antibodies inhibit the spread of microbes from an infected cell to an adjacent, uninfected cell.
4. Antibodies block binding of toxins to cells, thereby inhibiting pathological effects of toxins. - 27How does antibody-mediated opsonisation and phagocytosis work?.
- 28What are the human Fc receptors and what do they do?.
- 29What is antibody-dependent cellular cytotoxicity?Antibody-dependent cellular cytotoxicity occurs when the antibodies generate signals that cause NK cells to discharge granule proteins which kill opsonised cells. ADCC is also the mechanism by which therapeutic antibodies can eliminate tumour cells.
- 30How does IgE recruit eosinophils to kill helminths?Most helminths are too large to be phagocytosed, their thick integument makes them resistant to microbicidal substances produced by neutrophils and macrophages.
IgE antibodies activate mast cell and eosinophil-mediated reactions. They bind to worms and promote the attachment of eosinophils through high-affinity Fc receptor for IgE = Fc-epsilon-RI, which is expressed on eosinophils and mast cells.
The engagement of this receptor, together with IL-5 produced by Th2 cells reacting against helminths, leads to activation of the eosinophils, which release their granule contents, including proteins that kill worms.
IgE antibodies may also bind to and activate mast cells, which secrete cytokines, including chemokines, that attract more leukocytes that function to destroy helminths.
- 31How does IgA get through the epithelium?.
- 32How does a fetus acquire immunity?Maternal antibodies are actively transported across the placenta to the fetus, and across the gut epithelium of neonates, providing protection to the newborn from infections.
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- IMED2001 (Immunology: Adaptive Immunity) Flashcards on Humoral Immunity, created by Allira Payne on 05/05/2018.
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