Core Concepts-L16-Effector Mechanism of T cells

explain CD4 T helper differentiation

• driven by signal 3 cytokines from APC

• JAK/STAT pathways activate master transcription factors

• Th-1- Tbet

• Th-2-GATA3

• Th18- ROR gamma t

• BcI6- Tfh

naive CD8- what do they require? what do they do?

1. signal 1-TCR-MHC I

2. costimulation-CD28 to CD80/86

3. cytokine polarisation

use perforin and granzymes or Fas-FasL pathways

how are T cell responses regulated?

• CTLA-4 and PD-1 are inhibitory receptors

• cytokines always modulate responses- IL-10, TGF beta

talk about the phases of cell mediated immunity

1. induction of response by antigen recognition in the lymphoid organs

2. T cells expansion and differention

3. differentiated effector T cells enter circulation

4. migration of effector T cells and other leukocytes to site of the infection

5. effector T cells encounter antigens in peripheral tissues

6. activation of effector T cells

how do T cells enter and exit?

• naive T cells are always circulating

• cross the high endothelial venues and need homing molecules

• CCR7(guides it to the lymph node) senses CCL21 and L selectin- allows rolling

• receive survival signals

• uses S1P gradient to leave via efferent lymph

how do effector T cells stay in lymph nodes etc?

• held in the lymph node to allow differentiation and clonal expansion

• down regulate CCR7(keeps it in the lymph node) and S1PR to bring them into circulation

• expression of adhesion molecules like E/P selectin to roll and bind loosely

• VLA-4 for firm adhesion

types of memory in T cell?

1. memory central- Tim- circulate through lymph nodes express CCR7 and L selectin

2. effector memory- patrol peripheral tissue

explain the CD8 function and the phases

1. viruses replicates in tissues, DC’s detect via TLR3/7 became activated. up regulation of CCR7 to bring it to lymph nodes

2. viral proteins are processed by proteasome and transported via TAP loaded onto MHC I

3. 3 signals- cytokine support by IL-2 proliferation from CD8 and Th1 cells enhances proliferation

differentiation and effector function of T cells

1. Th1- IL-12, IFN gamma- activate macrophages and help CD8

2. Th2- IL4- combat parasites and allergy responses

3. Th17- IL6- TGF beta and recruit neutrophils

Th1 effector functions and the steps

• cytokine secretion- IFN gamma to activate macrophages and enhance killing and supports CD8 T cell differentiation

• B cell hel- B cell present antigens on MHC II and secretes IFN- gamma and helps with class switching

1. trafficking to tissue- Th1 leaves efferent lymph to tissue

2. macrophages present MHC II and Th1 binds and costimulates with CD40(macro) and CD40L on Th1 and cytokines by Th1 amplify activation

3. IFN gamma from Th1 activates macrophages killing mechanisms like reactive oxygen/nitrogen, phagosome/lysosome fusion

how are parasites/helmith get treated?

1. pathogen is detected by DC, it is processed and up regulate CCR7 to migrate the the lymph nodes and present MHC II to CD4 naive T cells

2. polarising signals like iL-4 from DCs- activate STAT6 and triggers GATA3 TF to make Th2

3. proliferation by IL-2

1. B cells will recognise antigens and become activated and present to Th2 cells which helps with IgE and IgG antibodies

TH2 cells!!

how are extracellular bacteria and fungal infections dealt with?

Th17 cells

• activated by DC present antigen to MHC II

• polarising cytokines like TGF-beta, IL6,IL-23 to activate STAT3 to induce RORgammaT

• make IL-17 cytokines- induces antimicrobial peptides and chemokine like IL-8/IL-6 for neutrophil recruitment

what do Tfh cells do? what type of cells are they?

• isnide- B cell follicles in lymphoid organs

• help b cells during germinal centre and help with class switching

• make IL-21