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IMMUNOLOGY: CMOD-Week 2 > (07) T Cell Development > Flashcards

(07) T Cell Development Flashcards

1
Q

T Cell

- Describe its distribution at different points in time

A

Generated - bone marrow
Maturation - Thymus
Active in - 2˚ lymphoid tissue

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2
Q

What are 3 differences of T cells from B cells?

A
  1. Can only recognize peptides bound to MHC
  2. Do not secrete Antibodies
  3. Have the ability to kill
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3
Q

What is the T-cell receptor analogous to?

A

Fab region of Antibodies

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4
Q

Distinguish between alpha-beta and gamma-delta domains

A

Gamma-delta
- NOT a component of the acquired immune system

  • Primative - do not recognize peptide/MHC complexes (not MHC restricted)
  • Mucosal epithelium of Gut primarily
  • mature extrathymically
  • Significant role in recognition of LIPID antigens
  • Usually double negative
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5
Q

What is the signal transduction unit for T-cells?

  • where is it found?
  • Describe the components
A

CD3 - signal transduction unit expressed on ALL T Cells

  • alpha, beta, delta, gamma, epsilon units
  • zeta unit is mostly cytoplasmic
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6
Q

What is the functional difference between CD4 and CD8 receptors?
- what do we call cells with these?

A 
CD4
- recognizes and binds (weakly) to MHC class II
CD8
- recognizes and binds (weakly) to MHC class I
  • Cells are CD4+ or CD8+, NEVER BOTH
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7
Q

What are 6 different surface markers that are expressed by T Cells?

A
  1. CD 28
  2. Fas ligand
  3. Adhesion Molecules
  4. CTLA-4
  5. PD-1
  6. CD4 and CD8
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8
Q

What is CD28?

T-cell

A
  • Recognized B7 expressed by APCs after PRRs PAMPs
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9
Q

What is Fas Ligand?

T-cell

A

Homotrimeric protein that can bind 3 Fas receptors on a target cell and trigger programmed cell death

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10
Q

what is an Adhesion molecule?

T-cell

A

Allows T-cell to interact with APC, Vascular Endothelial Cells, and Potential target cells

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11
Q

What is CTLA-4?

T-cell

A

Acts as the breaks on T-cell differentiation and proliferation in contrast to CD28

CTLA-4, analogous to CD28, that binds B7 on APC

BUT does it 20x more effectively

*This is expressed when T-cells become activated

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12
Q

What is PD-1?

T-cell

A
  • Supressor of T-cell activation/proliferation that becomes active when it binds PD-L1 or PD-L2 ligands on APCs

**Important in suppressing T-cells that bind self antigens

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13
Q

Thymus

  • organization
  • cell populations within organizational layers
A

Cortex

  • Cortical epithelial cells
  • thymocytes (immature T cells)
  • Macrophages

Medulla

  • Dendritic Cells
  • Macrophages
  • Nearly mature Thymocytes
  • Hassall’s corpuscle

*between = corticomedullary junction

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14
Q

What are macrophages in the thymus called?

- what makes them distinct functionally and morpholically?

A

Tingible body macrophages

  • Phagocytose Self Reactive T-cell
  • Have unique appearance due to ultra high levels of chormatin
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15
Q

Differentiate in general terms between positive and negative selection

A

Positive Selection
- Things that bind are encouraged to keep living

Negative Selection
- things that bind are killed

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16
Q

Where do thymocytes enter the thymus and what happens when they get there?

A
  • Enter in medulla and subcapsular area

What happens:
- They undergo somatic recombination using RAG-1/2 and TdT

  • gamma/delta, and beta chains compete in rearrangement

2 possible outcomes:

  • if beta finishes 1st then alpha-beta peptide
  • if delta/gamma finishes 1st then delta/gamma peptide
17
Q

What does the beta chain do while the alpha chain is forming?
- what problems could arise here?

A
  • Binds pTalpha which prevents beta chain degradation

- if pTalpha is under/malexpressed then SCID would result because patient has no more functional T-cells

18
Q

Expression of what other surface marker(s) occurs simultaneous with TCR expression?

A

CD4 and CD8 resulting in cells that are CD4+ and CD8+

19
Q

Describe + selection

A
  • MHC I and MHC II are expressed on Thymic Epithelial Cells.
  • Thymocytes that binds these the tightest will survive
20
Q

T or F: positive selection strongly selects for self reactive cells

A

True, self reactive cells will in fact bind the tightest

21
Q

Before proceeding to the coritcomedullary junction, what must happen to thymocytes?

A
  • They need to adjust their CD4 and CD8 receptors to represent what they bind
  • MHC I binding –> CD8 up and CD4 down
  • MHC II binding –> CD4 up and CD8 down
22
Q

What happens if you lack AIRE?

A

Severe autoimmune disease

AIRE = Autoimmune Regulator
- transcription factor that causes expression of most body proteins in the thymus

23
Q

What happens to cells that bind strongly during negative selection?

A

Apoptosis

24
Q

During positive selection a thymocyte binds really hard to MHC I or II. What should happen to this cell in the medulla?

A

Medulla = positive selection

- this cell should be selected and will die

25
Q

Hassall’s corpuscles

- what happens here?

A
  1. Destruction of Self-reactive cells (its in the medulla)

2. Treg formation that converts some Self-reactive CD4+ T cells to Treg cells that actually Prevent autoimmune disease

26
Q

Draw analogy between parts that get somatically recombined in TCRs and Antibodies?

A
  • Alpha chain of TCRs is similar to that of the light chain of antibodies
  • Beta chain of TCRs is like the heavy chain of antibodies
27
Q

Chromosomes of alpha and beta chains?

A

14 and 6 respectively

28
Q

What happens to the alpha chain if beta chain rearrangement isn’t successful?

A
  • nothing because it was never made
29
Q

Why are you super fucked if you lose both RAG-1 and RAG-2 enzymes?

A

RAG is involve in BOTH B cell and T cell somatic rearrangement

  • without these your lymphocytes would float around bald
30
Q

Why is losing Terminal Deoxynucleotidyl Transferase (TdT) No Big Deal

A

You will have slightly less variance in your heavy chain and beta chains but it probably won’t be clinically significant

31
Q

Suppose you have T cell tumor. How could you find out what phase of the process is messed up?

A
  • Look at surface proteins

- You can do this because tumor cells generally express the same surface proteins as whatever cell that they came from

IMMUNOLOGY: CMOD-Week 2 (11 decks)

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