Immuno 13: T-cell differentiation and effector function

Naive, effector, memory

Three stages of T cells

L-selectin, VLA-4

Naive cells are high in ___, while effector cells are high in ___.

CD8+ T cells

Functionally less diverse but can interact with a wide range of target cells

CD4+ T cells

Functionally diverse but primarily interact with a limited range of target cells, especially other immune cells

naive, effector

Co-stimulatory signals (signal 2) are required for activating ___ T cells but not for activating ___ T cells.

Perforin, granzymes, granulysin

Proteins in granules of cytotoxic T cells

Perforin

Protein in granules of cytotoxic T cells

Aids in delivering contents of granules into the cytoplasm of target cell

Granzymes

Protein in granules of cytotoxic T cells

Serine proteases, which activate apoptosis once in the cytoplasm of the target cell

Granulysin

Protein in granules of cytotoxic T cells

Has antimicrobial actions and can induce apoptosis

Cytokine environment (signal 3)

Important factor determining T cell subset differentiation/polarization

Th1

Coordinates immune response to intracellular pathogens

Th2

Coordinates immune response to extracellular pathogens (helminths)

Hint: There are two worms inside of you

Th17

Produces IL-17 and recruits neutrophils → extracellular bacteria and fungi

Treg

Suppresses immune response and regulate other T cells

JAK/STAT

Cytokine receptor signaling

Therapeutic target for autoimmune disease

Th1

Differentiation: IL-12 —> T-bet

Major cytokine: IFN-gamma

Activate macrophages to enhance killing of phagocytosed microbes

Th2

Differentiation: IL-4 —> GATA-3

Major cytokines: IL-4, IL-5, IL-13

Defends against parasitic infections and allergic reactions

Th17

Differentiation: TDF-beta + IL-6 (+IL-23)

Major cytokines: IL-17A, IL-17F, IL-22

Major player in autoimmune diseases

Recruits and activates neutrophils

Defends against extracellular bacteria and fungi

T_FH

Differentiation: IL-6, IL-21, and other signals —> Bcl-6

Major cytokine: IL-21

Location: B-cell follicles and germinal centers

Activate and provide help to B cells

Promote B cell proliferation and differentiation

Essential for effective Ab-mediated immunity

T_reg

Differentiation: TGF-beta + IL-2 —> FoxP3

Major cytokines: IL-10, TGF-beta

Suppress immune responses

Suppress activation and function of T cells and other immune cells

Important for maintaining peripheral immune tolerance and preventing autoimmune diseases