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Chapter 10
ACTIVATION AND FUNCTION
OF T AND B CELLS
Activating T and B cells :Proliferation and differentiation T cells: activating B cells cytotoxic cells produce many cytokines B cells: produce antibodys
DC maturation
Key cell surface receptors for T-cell activation
Bind to MHC II T-cell signaling
Early event: activation of tyrosine kinases (Fyn, Lck)
T-cell activation via signaling events
DAG: PKC-mediated pathway > NF-kB IP3: Ca2+-mediated pathway > NF-AT Small G protein-mediated pathway > AP-1
Three Types of Inositol phospholipids
PI, PI(4)P, PI(4,5)P2
Phospholipase C-b
(PLC-b) Produces
DAG
(diacylglycerol) and
IP3 (inositol 1,4,5-
trisphosphate (IP3))
1. DAG: PKC-mediated pathway > NF-kB
2. IP3: Ca2+-mediated pathway > NF-AT
3. Ras Pathway (Small G protein-mediated pathway > AP-1
The regulation of Ras activity, a famous
downstream molecule of RTK responsible for
cancer development
The MAP-kinase regulated by Ras
T-cell proliferation by IL-2
FIGURE 10.4. Activated CD4+ T cell synthesizes and secretes IL-2 and synthesizes
the IL-2 receptor chain. The interaction of IL-2 and the high-affinity IL-2 receptor
results in proliferation of CD4+ T-cell clone.
T cell 종류와 기능
• CD4 Tcell:Th0, Th1,Th2, Th17 (based on the different cytokines they produce)
Not all activated CD4 Tcells synthesize the same cytokines.
CD4CD25 Tcell(Treg)
• CD8 Tcell
FIGURE 10.5. Major subsets of CD4+ T cells: TH1, TH2, TH17, and Treg.
FIGURE 10.6. Cytokines influence the differentiation into a particular subset of
CD4+ T cells. Cytokines synthesized by one subset of CD4+ T cells inhibit the
development of other subsets. Wavy lines indicate inhibition. Cytokines synthesized
by TH17 cells are not known to inhibit the function or development of other subsets.
Human TH17 cells develop in the presence of IL-21 and TGF- but mouse TH17 cells
develop in the presence of IL-6 and TGF-b.
Cell mediated immunity: CD8, macrophages …
B cell mediated immunity: Class-switching, allergy..
Virus, bacteria mediated
Allergens and paresites mediated
Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells[1], macrophages and human B-lymphoblastoid cells (NC-37) in response to antigenic
stimulation.
The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell
JAK-STAT signaling
APC function of B-cell
FIGURE 10.8. B cells present antigen to T helper cells. A B cell with the appropriate
antigen-specific receptor captures a protein antigen via interaction with membrane
Ig; the B cell processes the antigen and presents peptides associated with MHC
class II molecules to a helper CD4+ T cell with the appropriate receptor.
T-B cooperation
CD8 T cell activation
FIGURE 10.10. CD8+ T cells: Generation of effector cells and target cell killing. (A)
dendritic cells activate CD8+ T cells directly. (B) One pathway for CD4+ T cells to
activate CD8+ T cells. (C) Target cell killing by a CD8+ effector T cell.
Termination of the response
B-cell activation signaling
B-cell also has many co-receptors
Antibody feedback (inhibition of B-cell activation)
ITIM domain:immunoreceptor Tyrosine-based inhibitory motif
Simultaneous binding
Not all the antigen-activated cells die. Generate CD4 or CD8 memory T cells