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26 Cards in this Set

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4 things that happen in the Thymus:
1. Progenitor Tcells proliferate (before having any surface markers)

2. DNA gene rearrangement

3. T cell selection

4. Differentiation of mature T cells into distinct subpopulations
Steps in Differentiation of a Progenitor T cell:
1. Progenitor undergoes 1st DNA rearrangement -> 2 types of doub neg cells (a/b TCR, y/d TCR (minor)).
2. Gene rrngmt -> Doub POS cells.
3. Double selection (pos and neg)
4. diff into SINGLE POS, CD3+, MATURE T cells.
What are the two things that happen in Thymic selection?
-Positive selection
-negative selection
What is positive selection?

Where does it happen?
Selection of only the T cells that bind self-MHC.

Occurs in the Thymus cortex.
What is negative selection?

Selection of only the T cells that bind self-molecules appropriately - if too tight, they undergo apoptosis.

Occurs in medulla
How do Doub pos T cells differentiate into Single pos -> CD4+ versus CD8+?
-Instruction model

Those cells that interact with MHC1 become CD8;

Those cells that interact with MHC2 become CD4.
What is triggered by the initial formation of the trimolecular complex (TCR+Ag/MHC, and coreceptors binding)?
what are the components of the signal cascade?
-Tyrosine Kinase
-Ca2+ calcium ions
-Small g proteins
What is the consequnce of the signal transduction cascade?
induces the transcription/translation of activation factors like cytokines, cell-adhesion molecules, etc.
How many signals does Tcell activation require?
What are they?

1. Antigen binding (signal transduction)
2. Co-stimulatory signal (B7/CD28)
What three gene products does Signal 1 turn on, in what order?
1. Transcription factors

2. Cytokine/cytokine receptors

3. Adhesion molecules

In That Order
What REALLY activates the transduction signal cascade, on CD3?
ITAMs -> CD4 binds to MHC and makes Tyrosine kinases bind and phosphorylate ITAM motifs on CD3. triggers signaling cascade that activates the tcell
What is the Co-stimulatory signal?

What does it immediately cause?
A non-antigen-specific binding of CD28 on Tcells with B7 on APCs.

Immediately Tcell turns on CTLA-4; competes with its own CD28 to prevent over-activation.
What does the co-stim signal do to the APC themselves?
Upregulates B7 to enhance activation of more tcells
Tcells bind APC, but no co-stimulatory signal is available; what happens?
The tcell will go into Anergy - nonresponsiveness, no cytokines produced, no proliferation.
Tcell binds APC, and receives co-stim signal; what happens?
Tcell will proliferate into clones.
What type of mature T cells are produced from the maturation and selection in the thymus?

Where do they go?
mature Naieve tcells.

Go to peripheral lymphoid tissue to search for their antigens.
What happens when a mature naieve Thelper cell encounters its antigen?
-Activation makes it produce IL-2 and IL2-receptor.

-Proliferation and differentiation into Th1 and Th2 subsets.
what are the 2 subpopulations of Thelper cells, and what's the main difference?
Th1 subpopulations -> activate Tc cells and macrophages.

Th2 subpopulation -> activates Humoral Bcells.

Difference: which cytokines they secrete.
What are the PROFESSIONAL Ag-presenting cells?
Dendritic cells
What's the difference between PROFESSIONAL (dendritic) APC versus Macrophages or Bcells?
Dendritic have constitutive B7, MHC2, and activate every kind of Tcell.

Macrophages only have induced B7, MHC2, and do not activate naieve Tcells.

Bcells have induced b7 and have to be activated to activate naive Tcells.
What 2 factors can trigger Apoptosis?
-Tcr stimulation (without costim signal)

-Glucocorticoid treatments
What receptor/ligand interaction triggers Apoptosis?
Fas and Fas ligand
What do superantigens do?
Crosslink TcR and MHC nonspecifically and tightly, causing overactivation of Cytokine production.
What are consequences of Superantigen?
Toxic shock
Tcell population wipe-out
Where are yd Tcells mainly, what is the function?
in epithelial cells of skin.

remove dad cells and protect the skin from pathogens.