T-cell Physiology

Question 1

Define “cellular immune response”

Answer 1

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

Question 2

Structure of Thymus

Answer 2

• Primary Lymphoid organ
• Lympoepithelial organ.

Features:

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

Question 3

TCR structure (draw it)

Answer 3

• 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.

Question 4

A-Chain locus:

Answer 4

HAS NO DIVERSITY Segment.

Variable -> 70-80
Joining -> 61

Question 5

B-chain

Answer 5

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

Question 6

Co-receptors in T-cell activation

Answer 6

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

Question 7

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

Answer 7

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

Question 8

Activation of TCR

Answer 8

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.

Question 9

order of T-cell development

Answer 9

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.

Question 10

pro t-cell

Answer 10

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

Question 11

pre t-cell

Answer 11

-> pre-tcell receptor expressed.
    consists of (b-chain, zeta chain, Cd3).

• > proliferative expansion occurs.
• > initiation of TCR a-chain gene recombination.

Question 12

double positive

Answer 12

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

Question 13

Signal positive

Answer 13

cells migrate to secondary lymphoid organs.

Question 14

MHC- general

Answer 14

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

Question 15

Classes MHC

Answer 15

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)

Question 16

Difference in structures of MHC I and II

Answer 16

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

Question 17

Antigen presentation by MHC Class I

Answer 17

• 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.

Question 18

Antigen presentation by MHC Class II

Answer 18

-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.

Question 19

Possible routes of antigen entry

Answer 19

can enter:

• GI tract
• Resp system
• skin

Dendritic cells:

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

Question 20

general course of T-cell

Answer 20

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

Question 21

T-cell subtypes

Answer 21

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

–>C8+ cell (cytotoxic T-lymphocytes)

Question 22

CD8+ cell effector functions:

Answer 22

• 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

Question 23

Th 1 effector functions

Answer 23

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

Question 24

Responses of an activated macrophage

Answer 24

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

Question 25

Th 2 effector functions

Answer 25

1) production of neutralizing IgG antibodies 2) Production of IgE (causes mast cell degranulation) 3) Eosinphil activation 4) suppression of macrophage activation

Question 26

Th1 and Th2 inhbition on one antoher

Answer 26

Activated Th1 secretes: -> IFN-gamma (inhibit Th2 proliferation). Activated Th2 secretes: ->TGF-B ->IL-10 cytokines act to inhibit activation and growth of Th1