12 - B cell Mediated Immunity Flashcards
What do forms do antibodies exist in
- Membrane-bound antibodies on the surface of B lymphocytes function as antigen receptors
- Secreted antibodies neutralise toxins, prevent the entry and spread of pathogens, and eliminate microbes.
3 hypervariable regions
- Three hypervariable regions of a Variable light domain and the three hypervariable regions of a Variable heavy domain are brought together to create an antigen-binding surface
- Also called complementarity-determining regions (CDRs): CDR1, CDR2, CDR3 (most extensive contact is with CDR#)
Dissociation constant (Kd)
Represents affinity of antibody
Main antibody functions
- Neutralisation of microbes and toxins
- Opsonisation and phagocytosis of microbes
- ADCC
- Phagocytosis of microbes opsonised with complement fragments
- Inflammation (through complement activation)
- Lysis of microves (through complement activation)
Antibody responses in lymphoid tissues
- Develop under direction of Tfh cells
- Antigen is retained for long periods in these complexes as iccosomes
What do activated B cells that undergo rounds of mutation and selection for higher affinity mutants in the germinal centre result in
High- affinity antibody-secreting plasma cells and high-affinity memory B cells
Half-life of IgE
- Very short (~2 days)
- Although cell-bound IgE associated with the high-affinity IgE receptor on mast cells has a very long half-life
Half life of IgA
~ 3 days
Half life of IgM
~ 4 days
Half life of IgG
21-28 days
B cell proliferation and differentiation outcomes
- Antibody secretion
- Isotope switching
- Affinity maturation
- Memory B cell
Distributions and functions of immunoglobulin classes
- Antibodies of different classes operate in distinct places and have distinct effector functions.
- Transport proteins that bind to the Fc regions of antibodies carry particular isotypes across epithelial barriers.
- Antibodies can block adherence of bacteria to host cells
- Antibody:antigen complexes activate the classical pathway of complement by binding to C1q.
- Complement receptors are important in the removal of immune complexes from the circulation.
High-affinity IgG and IgA
- Can neutralise bacterial toxins.
- Can inhibit the infectivity of viruses.
Structure of IgM and IgA
- Can form multimers, in association with an additional polypeptide chain, the J chain
- IgA is dimeric and IgM is pentameric
IgG function
- Opsonisation of antigens for phagocytosis by macrophages and neutrophils
- Activation of classical pathway
- ADCC
- Transfer of antibody across placenta and gut
IgM function
Activation of classical pathway and antigen receptor of naive B lymphocytes
IgA function
Mucosal immunity
IgE function
Mast cell degranulation (immediate hypersensitivity reactions)
IgD function
Antigen receptor of naive B lymphocytes
Secretary dimeric IgA
Binds to the layer of mucous overlaying the gut epithelium and acts as an antigen-specific barrier to pathogens and toxins in the gut lumen
Poly Ig receptor
Facilitates transport of dimeric IgA from the lamina proprietor, across the mucosal epithelium and into the lumen
What is the dominance of IgA production by intestinal plasma cells due to
Due to selective induction of IgA isotype switching in B cells in GALT and mesenteric lymph nodes
How do antibodies neutralise microbes and microbial toxins
- Blocks binding of microbe and infection of cell
- Blocks infection of adjacent cell
- Blocks binding of toxin to cellular receptor
What is classical complement pathway initiated by
Binding of the complement protein C1 to IgG or IgM molecules that have bound antigen
Which IgG antibodies are more efficient activators of complement
IgG3 and IgG1
Form of antibodies that can initiate classical pathway activation
Only antibodies bound to antigens, not free circulating antibodies
Do free Ig cross link Fc receptors
NOOOOOOOOOO
Opsonisation
- Bacterium is coated with complement and IgG antibody
- When C3b binds to CR1 and antibody binds to Fc receptor, bacteria are phagocytosed
- Phagosome is formed
- Lysosomes fuse with these vesicles, delivering enzymes that degrade the bacteria
Neonatal Fc recetor
- Involved in the transport of IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine in neonates
- Does this by recycling IgG to cell surface rather than destroying by lysosomes
How are neonatal mammals protected from infection at birth
- Maternally produced antibodies transported across placenta (IgG)
- Antibodies in ingested breast milk (IgA and IgG)
Mast cell activation
Activated by cross-linking of FcεRI molecules, which occurs by binding of multivalent antigens to the IgE molecules that are attached to the Fc receptors
Antibody Dependent Cellular Cytotoxicity (ADCC)
Natural killer (NK) cells and other leukocytes bind to antibody-coated cells by Fc receptors and destroy these cells
NK cells and ADCC
- NK cells use their Fc receptor, FcγRIIIA, to bind to antibody-coated cells.
- FcγRIIIA (CD16) is a low-affinity receptor that binds clustered IgG molecules displayed on cell surfaces but does not bind circulating monomeric IgG.
- Therefore, ADCC occurs only when the target cell is coated with antibody molecules
Immune complex removal
Immune complexes bind to CR1 on RBC, which transports them to the liver and spleen, where they are removed by macrophages expressing receptors for both Fc and bound C’
Antibody isotope in primary vs secondary response
- Primary: IgM > IgG
- Secondary: IgG predominates, and IgA or IgE depending on type of infection
