Characteristics of plasma cells
No surface Ig, no MHC class II, no growth, no SHM, no CSR, high rate of Ig secretion
-Pentameric or monomeric.
-Low affinity, high avidity. Size limits diffusion.
-Found mainly in blood.
-Good at activating complement, but not much else.
-High affinity, in blood and extracellular fluid.
-Transported out of blood by FcRB transporter, out of blood and across placenta into fetal circulation by FcRN
-Can bind and neutralize toxins directly and indirectly (complement, NK cell targeting).
-Dimeric or monomeric.
-High affinity, in secretions and mucosal surfaces (dimer), blood (monomer). Plasma cells secreting IgA found mainly in submucosal sites.
-Dimeric form transcytosed across epithelial cells to lumen by binding to poly-Ig receptor. pIg receptor cleaved on lumenal side, leaving secretory component bound to IgA. Secretory component can bind to mucin in mucosal lining.
-Good at neutralizing toxins directly.
-High affinity, diffuses to extravascular sites, sequestered in subepithelial and submucosal tissues
-Sensitizes mast cells; binds to FceRI.
Antibody types involved in direct neutralization
Tail end of constant region of IgA and IgM allow polymerization by hooking to J chain.
IgM activation of complement
Pentameric IgM binds multivalent ligands on microbe, transitioning to "staple" form exposing C1q binding sites which activate complement.
IgG activation of complement
Multivalent ligand binding of two properly spaced IgG antibodies can allow C1q binding and activation.
Clearance of immune complexes
-Antigen-antibody immune complexes recruit complement factors C3b, C4b, C2b, creating binding site for CR1 on RBCs.
-RBC-bound immune complexes brought to liver and spleen, where CR1 and FcR on phagocytes allow endocytosis and destruction.
Fc(gamma)R mediated endocytosis
-Fc(gamma)R are receptors for Fc region of IgG on neutrophils, macrophages.
-Multiple IgG bound to microbe crosslink FcgR on macrophages, neutrophils. CR on phagocyte helps by binding C3b on microbe, activating ITAM-Syk signaling.
-Microbe ingested, destroyed in phagolysosome.
1. IgG binds to viral antigens on surface of infected cells.
2. Fc(gamma)R on surface of NK cell allows them to bind to IgG.
3. Crosslinking of Fc receptors signals NK cells to destroy target cell.
Fc(epsilon)R on mast cells
-Fc(epsilon)R are high affinity, ensuring almost all IgE in body is bound to mast cells.
-Binding of multivalent antigen by antibodies crosslinks them, causing release of granule leading to allergic reaction/response to parasites.
ITIM and ITAM
-Cytoplasmic tail of many cell surface molecules allowing downstream signaling from CD3, Fc receptors, NK cell receptors, others.
-ITAM = activation, ITIM = inhibition
-Phosphorylation of two tyrosine residues allows formation of signaling complex to transduce signal.
Defect in AID means no CSR or SHM, no IgG, IgA or IgE.
Common variable immunodeficiency
Defective B cell maturation.