2.7 Flashcards
Activation of B Lymphocytes and Production of Antibodies
outcome (4)
ab secretion
isotype switching
affinity maturation
memory b cell
t-dependent
isotype switched, high affinity ab; memory b cells, long lived plasma cells
t-independent
mainly IgM, low affinity ab; short lived plasma cells
reponse: primary lag after immunization: peak response: ab isotype: ab affinity:
5-10 days
smaller
IgM>IgG
lower average affinity, more variable
reponse: secondary lay after immunization: peak response: ab isotype: ab affinity:
1-3 days
larger
relative increase in IgG and under certain situations, in IgA or IgE (heavy chain isotype switching)
higher average affinity (affinity maturation)
Receptor clustering needed:
– or more receptors bound
to antigens
2
Figure 7-4. Antigen receptor-mediated signal transduction in B lymphocytes (5)
cross linking of membrane Ig by antigen tyrosine phosphorylation events biochemical intermediates active enzymes TF (myc, NFAT, NF beta, AP-1)
Figure 7-5. Role of innate immune signals
in B cell activation.
(A) complement receptor (CR2) binding by
— bound to microbe.
(B) (B) Toll-like receptor (TLR) binding by
—
3Cd
PAMP
c3a:
inflammation
c3b
opsonization and phagocytosis
c5a
inflammation
c6-9
lysis of microbe
antigen binding to and cross linking of membrane Ig changes in activated B cells functional consequences (5)
increased survival, proliferation interaction with helper t cells responsiveness to cytokines migration from follicle to t cell zone ab secretion
Figure 7-8. Antigen presentation by B lymphocytes to helper T cells (4)
b cell recognition of naive protein antigen
receptor mediated endocytosis of antigen
antigen processing and presenation
t cell recognition of antigen
Activated T cells that recognize antigen presented on B cells use — ligand
and cytokines to activate the B cell
CD40
activated helper t cell expressed CD40L, secretes cytokines
b cells are activated by CD40 engagment, cytokines
b cell proliferation and differentiation
Figure 7-10. The germinal center reaction (4)
activation of b cells and migration into germinal center
b cell proliferation
somatic mutation and affinity maturation; isotype switching
exit of high affinity ab secreting cells and memory b cells
IgM
principal effector functions
complement activation
IgG subclasses
principal effector functions
Fc receptor dependent phagocyte responses, complement activation, neonatal immunity (placental transfer)
IgE
principal effector functions
immunity against helminths
mast cell degranulation (immendiate hypersensitivity)
IgA
principal effector functions
mucosal immunity (transport of IgA through epithelia)
“Switch recombination”
Previously formed VDJ exon recombines
to become adjacent to a different
constant region gene (than µ; IgM)
S =
switch regions
AID =
activation-induced deaminase;
alters nucleotides so they can be cleaved
by other enzymes, allowing S regions to
be brought together
Figure 7-12. Mechanism of immunoglobulin heavy-chain isotype switching (4)
INDUCTION OF AID
recombination of Su with Sgamma, deletion of intervening C genes
transcription; rna splicing
translation