T-cell immunity

What are the kinetics of T-cells?

• naiive T-cells → not seen their antigen and cannot induce immunity

• effector T-cells → have seen their antigen and can induce immunity

• memory T-cells → long lived, have seen their antigen and can respond faster upon re-infection

Dendritic Cells

• bridge between innate and adaptive immune system

• activate naive + cells to become cones of eflector T-cells

• reside in tissues where they take up pathogens upon encounter with their dendrites

• when they detect dnanger they go to the secondary lymphoid organs and activate T/B cells

• they use pattern recognition receptors to sense self and non-self

What are the 3 signals given to naive T cells to become effector cells?

Where are dendritic cells mature/immature?

How do dendritic cells migrate?

• they migrate via the lymphatics system and mature during maturation and in the lymph nodes they are highly structured

How do DCs enter the lymph nodes?

• via the afferant lymphatics: teh arrival of dendritic cells is chemokine mediated and they can no longer exit them

How do naive T-cells enter the lymph nodes?

• arrival of naive T-cell

• chemokine mediated

• adhesion molecules

• search for specific antigen

How do T-cells leave the lymph nodes?

• if antigens are not presented by MHC molecules then T-cells can leave via the efferent lymphatics

When are co-stimulatory molecules expressed and why does this matter?

Only expressed by mature DCs upon TLR stimulation during infection — ensures T cells are only activated during real threats, not harmless antigens

What happens when a naïve T cell receives signal 1 without signal 2?

Anergy — permanent state of unresponsiveness. No way of reactivating an anergic T cell. This is a peripheral tolerance mechanism.

What happens after B7-CD28 (signal 2 - costimulation) interaction in T cell activation?

T cell upregulates high-affinity IL-2 receptor → secretes IL-2 → IL-2 drives proliferation of antigen-specific T cells

What determines which Th subset a CD4 T cell differentiates into?

The cytokine cocktail (signal 3) secreted by DCs — combination determines subset identity and function

What does Th1 do and what cytokines does it need/produce?

• function: instruct macrophages to enhance elimination of phagocytosed pathogens

• interaction between macrophage and Th1: recognition of antigen by MHC II, expression of activating ligands CD40, secretion of cytokines (IFNgamma)

What does Th2 do and what does it target?

Driven by IL-4 → instructs B cells to produce IgE (granulocyte-activating antibodies) → mobilises granulocytes → eliminates parasites

What is the difference in signals for effectors and naive T cells?

• effector only signal 1 → antigen presentation

• naive t-cells → 1-3 signals

What do T follicular helper cells do?

Driven by IL-6 → guided toward B cell follicles by chemokines → interacts with naïve B cells → provides stimulatory signals (cytokines + activating ligands) → B cells undergo affinity maturation and isotype switching in germinal centres

What do regulatory T-cells do and how?

• inhibit other T-cells and DC functions

• mechanisms: depriving other T cells of cytokines (IL2 for proliferation), secretion of anti-inflammatory cytokines (TGFbeta & IL10), incudcing cytolysis, supressing DC function

What are killer T cells (CD8+ T-cells)?

• selective mass killers

• Focused Rilling through local release of cytotoxins in synapse with target cell.

How do CD8+ T-cells become cytotoxic T lymphocytes, which secrete cytotoxins?

By receiving signal 1, 2 (antigen presentation and co-stimulation)

What are cytotoxins?

How do cytotoxic lymphocytes kill multiple cells together?

• start by receiving signal 1

• cytotoxins found in lyic granules

• perforins perforate membrane of the target cell (make membrane pores)

• granzyme cut inside the cell and activate nucleases

• target cell nucleases degrade DNA

• apoptosis of target cells

• clerance by macrophages via phagocytosis.

CTLs can produce cytotoxic compounds and …

cytokines for signal

What makes CTLs so dangerous?

they can keep killing target cells until exhausion