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Immunology Jenny > 7. T cells and cell-mediated immune response > Flashcards

7. T cells and cell-mediated immune response Flashcards

1
Q

Primary lymphoid organs

A

Thymus and bone marrow

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2
Q

Direction of maturation in thymus

A

Cortex -> medulla

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3
Q

Two classes of TCR

A

1) αβ T cell

2) γδ T cell

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4
Q

Double negative lymphocytes

A
  • DN1-DN4
  • In cortex
  • No TCR, CD4 or CD8
  • Determine αβ or γδ cell line
  • Gene rearrangement of receptor chain
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5
Q

γδ T cell development

A
  • Cells with γδ TCR arise first in embryonic development
  • γδ leave thymus without any selection
  • Migrate to mucosal and cutaneous tissues: first line defence
  • Recognition of antigen not MHC-restricted!!
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6
Q

αβ T cell development

A
  • Generation of double positive (DP) T-lymphocytes (CD4+ CD8+)
  • Selected in thymus
  • > Recognition of self MHC molecules (useless if not)
  • > NOT recognition of self antigens (dangerous if it does)
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7
Q

Positive selection

A

Aim: recognize self MHC+peptide

  • Test by cortical thymic epithelial cell
  • Weak/no binding -> apoptosis
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8
Q

Negative selection (central tolerance)

A

Aim: differentiate self and foreign antigens.
Eliminate self-reactive T cells (bind tight to MHC+self peptide
- Test by dendritic cells
- Tight binding -> apoptosis
*Cannot eliminate T cells w/receptors specific for self peptides not expressed in thymus! These cells enter circulation.

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9
Q

Promiscous gene expression

A

1% of thymic medullary epithelial cells possess this

  • Express many different genes
  • T cells are selected for self antigens specific for different tissues - while in thymus!
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10
Q

AIRE

A

“Autoimmune regulator”: controls expression of self peptides by mTEC

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11
Q

Development of single positive T cell

A

Bind to MHC I (CD8+) or MHC II (CD4+) on thymic epithelial cell

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12
Q

Percentage of αβ T cells that survive selection to leave thymus as naive cells

A

Positive selection: 45 % survives

NEgative selection: 5 % survives

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13
Q

Where T cell and foreign antigen meet

A

Lymph node

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14
Q

How foreign antigen gets to lymph node

A

By immature dendritic cell via afferent lymphatics

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15
Q

T cell activation signals

A

Signal 1:
- Binding of peptide-MHC complex by TCR+co-receptor (CD4 or CD8)
Signal 2:
- Costimulation (APC: B7-CD28)

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16
Q

Activation of T cell by APC

A

1) MHC II-peptide binds TCR+CD4
2) Costimulation B7 binds CD28
3) Phosphorylation of CD3 ITAM motif
4) Signalling pathways->activate transcription factors
5) IL-2 mRNA transcribed
6) Autocrine activation by IL-2 -> T cell proliferation

17
Q

IL-2 (T cell)

A

Autocrine growth T-cell-growth-factor

18
Q

Immunological synapse leads to

A
  • Lymphocyte activation
  • Cytokine production
  • Proliferation
  • Differentiation
19
Q

Negative costimulation APC-T cell

A

B7 binds to CTLA 4

20
Q

Types of T-cells (by receptor)

A
  • Conventional αβ T cells
  • γδ T cell
  • Non-conventional αβ NK T cell
21
Q

Types of T-cells (by role)

A
  • T effector cells (cytotoxic, helper, regulatory)

- Memory T cells

22
Q

αβ T cells

A
  • Naive CD8+

- Naive CD4+ (->Treg or Th)

23
Q

T helper cell examples

A
  • Th1: IFNγ, TNFα, IL-2
  • Th2: IL-4, -5, -13
  • Th9: IL-9, -10
  • Th17: IL-17, -26, -22
  • Th22: IL-22
  • TFh: IL-21
24
Q

Treg cytokines

A

TGFβ and IL-10

25
Q

Cytotoxic T cell (CD8+)

A
  • TCR+CD8
  • Fas ligand (bind Fas of infected cell)
  • Granules with: perforin and granzymes (released into infected cell)
26
Q

CD4+ regulator cells

A
  • Treg (TGFβ and IL-10)
  • Tr1 (IL-10)
  • Th3 (TGFβ)
27
Q

CD4+ effector cells

A
  • Th1 (IFNγ -> NK cells and macrophages)
  • Th17 (IL-17 -> Inflammatory PMNs)
  • Th2 (IL-4 -> Eosinophils, basophils, B-cells)
28
Q

Th1 cells

A
  • IFNγ, TNFα, IL-2
  • Activates Tc cells, NK cells and macrophages
  • Th1 and Th2 cells can inhibit eachother
29
Q

Th2 cells

A
  • IL-4, -5, -13

- Activated B-cells and eosinophils, basophils

30
Q

If CD4+ cells have intermediate avidity in thymus

A

We get Treg cells

31
Q

If CD4+ cells have moderate self/MHC avidity in thymus

A

We get effector Th cells

32
Q

γδ T cells

A
  • Interact with non-protein antigens that are not processed or associated with MHC molecules
  • γδ TCR: pattern recognition -> activate γδ T cell -> can be either cytotoxic or helper
  • Immunosuppressive
  • Pleiotropic regulatory function
33
Q

NKT cell

A
  • Direct and indirect killing of virally infected and tumor cells
  • Indirect: Secrete IFNγ -> activate NK or CD8+ T cell
  • Direct: Has TRAIL and FasL on surface -> bind their receptors on tumor cell -> NKT cell release perforin and granzymes
  • Has receptors for IL-12 and CD1d (on DCs)

Immunology Jenny (16 decks)

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