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Immune system > T-cell Physiology > Flashcards

T-cell Physiology Flashcards

1
Q

Define “cellular immune response”

A
  • generation of effector cell that has specificity for an antigen.
  • mediated by “T-Cells”
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2
Q

Structure of Thymus

A
  • Primary Lymphoid organ
  • Lympoepithelial organ.

Features:

  • > frequent cell divisions
  • > maturation
  • > selection
  • > apoptosis
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3
Q

TCR structure (draw it)

A
  • 2 chains (TCRa and TCR b).
  • constant + variable regions
  • clone specific.
  • each segment has own transmembrane part
  • 1 ANTIGEN BINDING SITE.

-no secreted form of TCR.

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4
Q

A-Chain locus:

A

HAS NO DIVERSITY Segment.

Variable -> 70-80
Joining -> 61

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5
Q

B-chain

A

Varibale -> 52
Diversity->
joining segment -> 6

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6
Q

Co-receptors in T-cell activation

A
  • CD3 (indicates B-chai and A-chain rearrangement).
  • Zeta chain
  • CD2
  • CD28
  • LFA-1 (integrins)
  • CD4+ = helper t-cell
  • CD8+ = cytotoxic T-cell
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7
Q

What type of signals can APC deliver to Naive T-cell

A

1) activation (TCR + CD4/CD8)
2) costimulation (CD28)
3) Differentiation (cytokines)

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8
Q

Activation of TCR

A
  1. CD4/8 binds to MHC2/1. conformational change.
  2. Lck (On their cytoplasmic tail) activated, phosphorylates ITams of CD3, Zeta.

3)ZAP-70 will phosphorylate various proteins which will cause signalling events.

ATLEAST 2 SIGNALS NEEDED TO ACTIVATE T-CELL.

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9
Q

order of T-cell development

A

Pro-T cell -> Pre T-cell ->Double positive –> signal positive -> naive mature cell.

*transition between double positive and signal positive moves from cortex of thymus to medulla.

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10
Q

pro t-cell

A
  • > No TCR expressed
  • > CD4-/CD8-
  • > Rag1 + Rag2 recombinase expressed, TCR B-chain rearrangement occurs.
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11
Q

pre t-cell

A 
-> pre-tcell receptor expressed.
    consists of (b-chain, zeta chain, Cd3).
  • > proliferative expansion occurs.
  • > initiation of TCR a-chain gene recombination.
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12
Q

double positive

A
  • CD4+ and CD8+ expression.
  • TCR (a+b chains).
  • Positive/Negative selection occurs.
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13
Q

Signal positive

A

cells migrate to secondary lymphoid organs.

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14
Q

MHC- general

A
  • T-cells need MHC to act on the antigen
  • polymorphisms (HLA-B -> 250 alleles)
  • co-dominant expression
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15
Q

Classes MHC

A

Class I: (HLA-A/B/C)
-found in all nucleated cells.

Class II (HLA-DR/DQ/DP)
-found on antigen presenting cells (dendritic cells, monocytes, macrophages, b-cells)
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16
Q

Difference in structures of MHC I and II

A

Class I:

  • A1, A2, A3, B2-microglobulin subunit.
  • 1 transmembrane part.

-A3 -> CD8

Class2:

  • B1, B2 subunit
  • A1, A2 subunit
  • 2 transmembrane parts.

-B2 is binding site of Cd4

17
Q

Antigen presentation by MHC Class I

A
  • cystolic proteins (from viruses + tumours) are degraded by proteosomes.
  • Small peptide fragments leave proteosome enter ER via “TAP complex”.
  • MHC I -peptide complex transported to cell surface and interacts with CD8+ T-cells.
18
Q

Antigen presentation by MHC Class II

A

-picks up pathogen from extracellular flud.

  1. endocytosis of extracellular pathogen (endosome)
  2. Acidifaction (by fusion of lysosome), activates proteosomes,.
    3) Vesicle fuses with vesicle containing MHC II molecule.

4) MHCII-peptide complex is exported to the cell surface itneracts with CD4+ T-cells.

19
Q

Possible routes of antigen entry

A

can enter:

  • GI tract
  • Resp system
  • skin

Dendritic cells:

in intestinal fluid -> go to lymph node
in blood -> spleen

20
Q

general course of T-cell

A

antigen recognition ->lymp activation -> clonal expansion -> differentiation -> effector function

21
Q

T-cell subtypes

A
  • ->CD4+ cell:
  • Th 1 cells
  • Th 2 cells

–>C8+ cell (cytotoxic T-lymphocytes)

22
Q

CD8+ cell effector functions:

A
  • activated by MHC 1 cells.
  • kill pathogen via:

1) lytic granules:

  • granzymes/perforins are endocytosed by target cells.
  • granzymes enter cytoplasm via perforin-dependent mechanism
  • activates apoptic pathways (activation of caspases)

2)Fas-Ligand - Fas mediated target cell apoptosis:

  • Fas-ligand on cytotoxin interacts with Fas (on target cell)
  • induces apoptosis
23
Q

Th 1 effector functions

A

1) macrophage activation
2) neutrophil activation
3) complement binding + opsonizing antibodies

24
Q

Responses of an activated macrophage

A

1) production of ROS, NO, lysosomal enzymes:
- >killing microbes in phagolysosomes

2) secretion of cytokines -> TNF, IL-1: leukocyte recruitment (inflammation)
IL-2: Th1 differention

3) increased expression of B7 costimulators, MHC molecules -> increase T-cell activation

25
Q

Th 2 effector functions

A

1) production of neutralizing IgG antibodies
2) Production of IgE (causes mast cell degranulation)

3) Eosinphil activation
4) suppression of macrophage activation

26
Q

Th1 and Th2 inhbition on one antoher

A

Activated Th1 secretes:
-> IFN-gamma (inhibit Th2 proliferation).

Activated Th2 secretes:
->TGF-B
->IL-10
cytokines act to inhibit activation and growth of Th1

Immune system (3 decks)

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