I&I B5

Naïve T cells recirculate through…

blood and T cell areas of secondary lymphoid organs

1. Enter LNs through high endothelial venules (HEVs).

2. CD62L (L-selectin) on naïve T cells bind to PNAd (peripheral node addressin) on HEV.

3. Chemokine receptor CCR7 on naïve T cells binds chemokine CCL21 on HEV.

4. Integrin LFA-1 on T cells and ICAM-1 on HEV mediate firm arrest.

5. T cells browse APCs in LN for antigen

6. If they don’t encounter: S1PR1+S1P interaction→ Leave through efferent lymphatic vessels → rejoin the bloodstream at thoracic duct

7. If they encounter: lose the ability to exit LN→ proliferate → differentiate into effector cells

How do T cells migrate through spleen?

CCR7 : CCL19/21 controls T cell zone positioning BUT entry/exit is passive; arterioles filtering directly into PALS

How do T cells migrate through intestinal tissue?

α4β7 : MadCAM-1 binding mediates entry into Peyer’s patch in small intestine

leave by efferent lymphatics→ mesenteric lymph nodes→ lymphatic ducts

How can T cells be primed to enter mucosal tissue?

Priming in mucosal secondary lymphoid tissue will cause T cells to express receptors for entering mucosal tissues

What are the three signals necessary for T-cell activation?

• Ag specific TCR engagement

• costimulatory ligand engagement

• cytokines (autocrine and paracrine)

TRUE OR FALSE: Costimulatory ligand interactions can either promote or inhibit T cell activation and proliferation

TRUE

a) Purpose and b) general structure of the immunological synapse

a) allow T cells and APCs to effectively engage

b) central supramolecular activating complex: TCR/MHC-peptide complexes and coreceptors

Peripheral supramolecular activating complex: Adhesion molecules/bound ligands

a) what are the professional APCs and b) what feature do they have?

a) Dendritic cells, macrophages, and B cells

b) only cells with MHC class II (as well as MHC class I)

What kind of T cells can a) Dendritic cells, b) macrophages, and c) B cells activate?

a) naive; only APC to express sufficient costimulatory molecules for full activation

a+b+c) differentiated memory/effector T cells

T cell clonal anergy

absent or insufficient costimulatory signal from T cell:APC interaction means no microbial danger signal is generated, so the T cell becomes unresponsive forever. This helps provide peripheral tolerance

Cytotoxic CD8 cells induce cell death via…

apoptosis

During T cell activation, IL-2 is produced by … to act on … in a …crine manner, inducing…

During T cell activation, IL-2 is produced by T cells to act on T cells in an autocrine manner, inducing proliferation

Cytotoxic T cell (CTL) generation (3 steps)

1. priming naïve CD8+ T cell by APC with antigen-specific MHC class I/TCR complex and CD28/B7 co-stimulatory ligand interactions

2. signals from IL-2 (autocrine) and IFNγ (autocrine + paracrine) promote proliferation and differentiation

3. CTLs leave lymphoid organ to enter inflamed tissues and mediate effector functions

TRUE OR FALSE: All positive T cell interactions require costimulation

FALSE: For instance, CTL recognition of infected cells doesn’t

What are the two methods of CTL cell killing? Describe molecules

SECRETORY: perforin assembles into protein barrel pore on cell allowing for entry of granzyme which triggers apoptotic pathways

NON-SECRETORY: interaction of membrane-bound FasL of CTL with FAS on cell