T cell development and Effector Function

Question 1

how does is the T cell receptor different/similar to the B cell receptor

Answer 1

similarities: undergoes gene recombination using RAG 1 and RAG2, junctional diversity w/ Tdt, allelic exclusion, selected for via positive and negative selection
differences: completely membrane bound, no class switching or affinity maturation w/ activation

Question 2

What additional cell surface molecules are necessary for TCR activation?

Answer 2

CD28 - further activation and IL-2 production (binds to B7)
CD40L - binds to CD40R on APC, strengths adhesion and increase B7 production by APC
LFA-1 and VLA-4 - adhesion

Question 3

what composes the TCR?

Answer 3

beta and alpha chains - antigen recognition
CD8/CD4 - recognition of specific MHC
CD3 and sigma - signal transduction

Question 4

describe MHC restriction

Answer 4

T cells can only be activated when (1) recognize MHC, (2) recognize peptide presented

Question 5

positive vs. negative selection

Answer 5

positive selection - occurs first w/ the cortex and selects for DP T cells that recognize MHC (cotrex epithelial cells)

negative selection - occurs 2nd w/in the medulla and selects SP T cells that recognize MHC with low affinity (DC, macrophages, and medullary epithelial cells

Question 6

what receptor is necessary to ‘shut down’ T cell?

Answer 6

CTLA-4 - bind B7 as well but prohibits the production of IL-2 by T cell

Question 7

describe the functions of Th1, Th2, Th17 helper cells?

Answer 7

Th1 - (IFN-gamma) involved in intracellular pathogen immune response (classical macrophage activation)
- autoimmune/tissue damage w/ chronic infection

Th2 - (IL4. IL5, IL13) involved in extracellular pathogen immune response (alternative macrophage)
- allergic reactions

Th17 - (IL17, IL6) involved in extracellular bacteria, fungi, induces neutrophilic, monocytic inflammation; also involved in gut tolerance
- autoimmune/inflammatory disease

Question 8

what is the relationship between Th1 and Th2

Answer 8

it is the balance between the two helper cells and how they are implemented in the immune response against a pathogen that determines the outcome of the intracellular infection:
example: mycobacterium leprae: Th1 dominated response leads to controlled pathogens, Th2 dominated response leads to wide spread pathogen

Question 9

how does CD8+ cells mediated cell death of infected cells?

Answer 9

1. activation of infected cells Fas by FasL of T cell leading to induced apoptosis
2. release of granular proteins that contain granzymes (activated caspases) and perforin (for delivery into cell)