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T cell receptors are always found where
Membrane bound
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What are the two major differences between BCR's and TCR's
- BCR's can be specific for proteins, lipids, carbohydrates, and phospholipids and recognize them without MHC
- TCR's recognize only peptides and must use MHC
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Where do T cells mature
Thymus
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Tumor and allograft rejection is mediate mainly by
T cells
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What are some of the Thymic peptides
- Thymosin alpha
- Thymosin beta
- Thymulin
- Thymopoietin
- Thymic humoral factor
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What is the role of Thymic peptides
They influence the phenotypic maturation of progenitor cells from the bone marrow and modulation of functions of mature T cells
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T cell progenitors enter the thymus where
At the junction between the cortex and medulla
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In what direction do the T cells migrate in the thymus as they develop
- Subcapsular zone
- Cortex
- Medulla
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T cell receptor gene rearrangements do not occur until
The cells enter the thymus
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When do the T cells begin expressing the CD2 adhesion molecule
Within one week of being in the Thymus
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The alpha chain of the T cell receptor has what gene segments
V and J
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The ß chain of the T cell receptor has what gene segments
V, D, and J
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Thymocytes with ß chain will associate with
Pre-T alpha chain and the CD3 molecule
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In what ways are TCR's tested
- 1. Ensure the TCR can interact with self MHC (positive selection)
- 2. Ensure that TCR is not specific for self-MHC or self antigen (negative selection)
- "not too hot or cold, but just right"
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In order for T cell destruction as a result of too strong of binding to a self antigen, the self antigen must be present where
In the thymus
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Which are longer lived, B cells or T cells, and for potentially how long
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What are the two forms of TCR's
- alpha beta (common)
- gamma delta (uncommon)
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What TCR operate without MHC
gamma delta
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What is a Treg
- regulatory T cell
- Tregs suppress the response of self reactive CD4 T cells
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A progenitor T cell that becomes committed to T cell linage expresses what
CD2
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Rearrangement of TCR involves what genes
RAG and TdT
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Rearrangement of TCR only happens
During development
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Expression of how many TCR can happen at one time
One
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Tregs are characterized by their expression of
CD25 and use of FoxP3
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A deficiency of FoxP3 would have what effect
- Fatal autoimmune disorder
- Found mostly in males due to its being encoded in the X chromosome
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What is the function of CD3, and what cells is it found on
- Helps transduce signal when antigen-MHC complex binds TCR
- Found on all T cells
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What is the role of CD4 on T cells
- Expressed on Helper T cells
- Attaches to Class II MHC
- Promotes adhesion to APC and to B cells
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What is the role of CD8
- Expressed on Cytotoxic T cells
- Attaches to Class I MHC
- Promotes adhesion to affected cell
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What is the role of CD28, and what cells can it be found on
- Provides co-stimulatory signal to T cells
- Found on many Helper and Cytotoxic T cells
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What does CD28 bind to
CD80/86 (B7)
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What is the role of LFA-1, and what cells express it
Promotes cell to cell adhesion and is found on most WBC's including T cells
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What is the ligand on the target cell that LFA-1 binds to
ICAM-1
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What beyond binding of the ligand and MHC must happen for the T-cell to activate
There must also be a co-stimulatory signal involving CD80/86 on the APC and CD28 in the T-cell to connect triggering activation
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What triggers the expression of CD80 on the APC
- TLR's or other receptors of innate immunity
- They are only expressed on the APC during infection
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What happens to a naive T cell when it attaches to a APC that does not express B7 (CD80/86) along with the MHC+ligand
The cell becomes non-responsive to the antigen and cannot become subsequently activated
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When are CD80/86 (B7) no longer necessary
After the T cell becomes activated it no longer needs the co-stimulatory signal
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Activated T cells under go clonal expansion and differentiation driven by what
Cytokine IL-2 (autocrine secretion from the T cell)
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When do the T cells acquire the proteins needed for their effector functions
Following IL-2 release, during differentiation
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What do CD4 T cells change into from Th0, and what initiates it
- Th1, Th2, or Th17
- Initiated by cytokines released by APC's and NK's
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During T cell differentiation, what cytokine exposure makes makes a Th1
IL-12 and IFN-gamma
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During T cell differentiation, what cytokine exposure makes a Th2
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During T cell differentiation, what cytokine exposure makes a Treg, and what does it secrete
- TGF-ß
- Secrete TGF-ß and IL-10
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During T cell differentiation, what cytokine exposure makes makes a Th17
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What are the effector molecules secreted by CD8 T cells
- Perforin
- Granzymes (activate apoptosis)
- Granulysin (antimicrobial action + induce apoptosis)
- Fas ligand
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Th1 cells secrete
IL-2 and IFN-gamma
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Helper T 1 cells target
Extracellular bacteria
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T helper 2 cells target
Helminth parasites
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T helper 17 cells target
Extracellular bacteria
-
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How does the expression of FasL and CD40L compare in Th1 and Th2 respectively
- Th1 expresses more FasL
- Th2 expresses more CD40L
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Th1 responses often lead to what type of killing
Macrophage activation for pathogen killing
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Th2 responses largely influence what differentiation
B cell differentiation resulting in a large antibody production (especially IgE for Helminths)
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What does the Th17 play an important role in
- Adaptive immune responses to extracellular bacteria and fungi
- It is characterized by the release on IL-17
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IL-17 initiates what
Inflammatory response by neutrophils
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What effect does CD8 have on cells containing infection
It causes them to undergo apoptosis
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What is the HIV receptor
CD4+ expressed on T cells
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What is the ratio of CD4 and CD8 expression
CD4 is 2x as prevalent
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What cell surface receptors are found on Treg cells
CD4 and CD25
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