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