T Lymphocyte Development and Activation

Question 1

what gives rise to the common lymphoid precursor?

Answer 1

pluripotent hematopoietic stem cells

Question 2

into what do the common lymphoid precursors differentiate into? where?

Answer 2

Pro-T cells with phenotype TCR-CD3-CD4-CD8-
outer cortex of thymus

Question 3

what do Pro-T cells become?

Answer 3

Pre-T cells, with CD3 and TCR beta chain
no CD4 or CD8, so double negative T cells

Question 4

what are double positive T cells?

Answer 4

when they are expressing both CD4 and CD8 (after Pre-T)

Question 5

after double positive T cells, what do they become?

Answer 5

single positive T cells with either CD4 or CD8

Question 6

why are positive and negative selection important?

Answer 6

to ensure that T cells are MHC restricted and self-tolerant

Question 7

what is positive selection?

Answer 7

double positive T cells encounter self-peptides on thymic epithelial cells
those that bind/recognize survive to become CD4+ or CD8+
some could have potential for autoimmune diseases- eliminated at next step

Question 8

what is negative selection?

Answer 8

T lymphocytes whose TCRs bind strongly to self peptide/MHC complexes in thymus are eliminated
presented by thymic APCs (dendritic cells and macrophages)

Question 9

what are the three signals for T cell activation?

Answer 9

1. recognition of specific peptide bound to MHC I or MHC II molecule on an APC by the T cell receptor
2. interaction with costimulatory molecule
3. cytokines present in local environment

Question 10

what is the T cell receptor complex composed of?

Answer 10

the TCR and associated CD3 delta, epsilon, gamma, and zeta and the CD4 or CD8 co-receptors

Question 11

what do the CD4 and CD8 chains do?

Answer 11

amplify the signal through the TCR complex up to 10,000 fold

Question 12

what is the immunologic synapse?

Answer 12

the TCR complex, adhesion molecules, and co-stimulatory molecules
association between T cell and APC

Question 13

what does the CD3 molecule do?

Answer 13

cascade of intracellular signals that leads to gene transcription and T cell proliferation upon TCR recognition

Question 14

what co-stimulatory molecule provides the second signal for naive T cell activation?

Answer 14

CD28

Question 15

what happens if the T cell receives the first signal through the TCR, but not the second signal?

Answer 15

undergoes apoptosis or become anergic

Question 16

what produces the cytokines for the third signal for naive T cell activation?

Answer 16

dendritic cells, or other cells in secondary lymphoid tissue environment

Question 17

what do mitogens do?

Answer 17

stimulate a vast number of lymphocytes in antigen non-specific manner

Question 18

what co-stimulatory molecules do we need to know and what do they do?

Answer 18

CD28 and B7 bind to each other

Question 19

what does cancer treatment of ipilimumab do?

Answer 19

blocks CTLA-4 negative signals
reactivates tumor fighting

Question 20

what are superantigens?

Answer 20

molecules that activate all T cells expressing a particular V-beta chain, regardless of the V-alpha chain of a TCR
cause massive cytokine production and massive system toxicity

Question 21

what do CTLA-4 and PD-1 do?

Answer 21

negative signals to T cells