Bioms: T Cells

Front 1

T cell development

Back 1

1. Generation of DP T cells in thymus
2. Selection of TCR that bind self MHC (positive selection)
3. Elimination of self-reactive T cells in thymus (negative selection)
4. recirculation of naive mature cells
5. activation of t cells by foreign antigen in SLT
6. differentiation to effector and memory T cells in SLT

Front 2

T cell receptors

Back 2

1. heterodimers
2. made of alpha-beta or gamma-delta chains

Front 3

gamma delta T cell receptors

Back 3

1. DON'T express CD4, only 30% express CD8
2. DON'T bind to peptide presented on MHC I or MHC II
3. Can bind non-processed Ag
4. Two types: fetal developedand post-partum developed

Front 4

gamma delta T cells (fetal developed)

Back 4

1. invariant
2. tissue specific tend to express the same Vgamma and Vdetla chains in particular tissues
3. no N-nucleotide diversification
4. equivalent to B1 cell?

Front 5

gamma delta T cells (post-partum developed)

Back 5

1. variable
2. continuously develop in thymus (like alpha beta T cells)
3. great TCR diversity (N-nucleotide additions)
4. constitute 5% of T cells in adults
5. mostly migrate to SLT

Front 6

B chai locus organized like Ig heavy chain loci?

Back 6

VDJ

Front 7

alpha chain locus organized like Ig heavy chain loci?

Back 7

VJ

Front 8

What is the implication for somatic recombination?

Back 8

beta, gamma, and delta chain genes start to rearrange at the same time

Front 9

T cell gene rearrangement

Back 9

1. double negative T cells start to rearrange their Beta, Gamma, and Delta loci
2. gamma and delta chains rearrange; gamma-delta receptor assembles; signals through gamma-delta TCR stop further rearrangemetns and commit cell to gamma-delta lineage; gamma delta T cells mature and leave thymus to peripheral tissues
OR
3. beta chain gene rearranges; pre-TCR assembles; signals through pre-TCR stop rearrangement; induce proliferation and expression of CD4 and CD8; pre-t cell resumes rearrangement of alpha, gamma, and delta genes

Front 10

2 beta constant gene loci

Back 10

1. allow for second rearrangement on the same chromosome
2. 2 chromosomes mean 4 possible attempts for beta cahin

Front 11

pre-TCR

Back 11

1. the first checkpoint in UV TCR development
2. if V chain can pair with surrogate U chain, pre-T cell receptor is expressed on surface
3. if V chain can't bind the pTU, cell dies by apoptosis

Front 12

what cell gives rise to alpha-beta and gamma-delta T cells

Back 12

common double-negative T cell progenitor (CD34)

Front 13

What happens if U arrangement succeed?

Back 13

The cell commits to expressing a UV TCR

Front 14

What eliminates the linked delta chain locus?

Back 14

rearrangement of an alpha chain gene

Front 15

antigen presentation T lymphocytes

Back 15

1. once receptor is generated development of UV T lymphocytes in the thymus involved antigen presentation
2. APCs present antigen fragments (peptides) on MHC I and II

Front 16

antigen presenting cells

Back 16

1. Epithelial cells
2 Dendritic cells
3. macrophage

Front 17

T cell education part 1

Back 17

1. T cells must recognize antigens presented by self class I and II allelic variants (aka MHC restriction)
2. cells with receptors that bind self MHC plus Ag are positively selected in thymus
3. cells lacking said receptors die
4. huge diversity of TCRs possible and only small portion will bind to self MHC
5, 98% of T cells die in thymus

Front 18

T cell education part 2

Back 18

1. T cells must not respond to self antigens
2. T cells with receptors that can bind self MHC plus self Ag (or just self MHC) are negatively selected in thymus
3. they are deleted by apoptosis
4. Cells emerging from thymus are described as 'self tolerant'

Front 19

1st checkpoint (T cells)

Back 19

V chain binds pTU''

Front 20

2nd checkpoint

Back 20

U chain binds V chain

Front 21

Thymocyte development in thymus

Back 21

1. lymphoctye precursor enter medulla and move towards cortex
2. screened by positive and negative selection deeper in thymic cortex
3. cortico-medullary junction contains mature, single-positive cells
4. they leave thymus and enter the bloodstream

Front 22

3rd checkpoint

Back 22

positive selection in thymic cortex

Front 23

4th checkpoint

Back 23

negative selection (throughout cortex and especially at cortico-medullary junction)

Front 24

what determines CD4 or CD8 expression?

Back 24

positive selecton

Front 25

positive selection: interacting with MHC class I

Back 25

CD8 recruited, CD4 synthesis halted

Front 26

positive selection: interacting with MHC class II

Back 26

CD4 recruited, CD8 synthesis halted

Front 27

positive selection: other responses

Back 27

1. degrade RAG genes
2. proliferate
3. express genes for helper T or cytotoxic T functions

Front 28

How are proteins of the body expressed in the thymus?

Back 28

Tissue specific proteins are expressed by some thymic epithelial cells using transcription factor AIRE

Front 29

Fate of naiive mature, T lymphocites

Back 29

1. recirculation and surveillance
2. migration to SLT
3. activation & development to effector cells

Front 30

effector cells

Back 30

T helper cells
cytotoxic T cells
memory T cells

Front 31

bone marrow transplantation: what type of transplant must occur for working adaptive immune response?

Back 31

Transplant patient must receive bone marrow sharing some HLA class I and II allotypes

Front 32

Where does T cell activation and differentiation take place?

Back 32

1. secondary lymphoid tissue (SLT)
2. SLT is connected by lymphatic and blood networks (immunce cells travel through both networks)

Front 33

where do lymphatic and blood circulatory networks region?

Back 33

left subclavian vein

Front 34

dendritic cells

Back 34

deliver Ag and pathogens from sites of injury to draining lymph nodes where T cells are activated and differentiate

Front 35

lymph nodes

Back 35

have functional areas defined by T and B cell rich zones

Front 36

T cell extravaste

Back 36

through HEV and recirculate through the blood an peripheral lymphoid tissues every 12 to 24 hours

Front 37

High endothelial venules (HEV)

Back 37

1. sticky for naiive T cells
2. help T cells enter lymph node cortex from blood

Front 38

Entering the HEV

Back 38

"Roll, Stop, Drop"
1. Circulating T cell enters the high endothelial venule in the lymph node
2. Binding of L-selectin to glyCAM-1 and CD34 allows rolling interaction
3. LFA-1 activated by chemokines bound to extracellular matrix
4. Activated LFA-1 binds tightly to ICAM-1
5. Diapedesis - lymphocyte leaves blood and enters lymph node

Front 39

Chemokine roll in HEV

Back 39

1. lead cells like a trail of bread crumbs:
2. CCL10, CCL21 secreted by stromal and dendritic cells
3. recruit T cell sinto lymph node
4. T cells express CCR7
5. binding activates LFA-1