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T cell differentiation/effector functions Flashcards

1
Q

CD4 T cell can become what types of CD4 cells

A
  • TH2
  • Treg
  • TH17
  • TH1
  • Tfh (T follicular heper cells)
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2
Q

Cytokines made by TH2

A

IL4, IL13, IL5

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3
Q

Cytokines produced by Treg

A

IL10
TGF-beta

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4
Q

Cytokines produced by TH17

A

IL17

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5
Q

Cytokines produced by TH1

A

IFNy

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6
Q

TH2 cells become

A

Eosinophils
Basophils
Mast cells
Macrophages

Barrier immunity

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7
Q

Treg cells become

A

Dendritic cells

Inhibition of other effector T cell types

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8
Q

Th17 cells become

A

Neutrophils

acute inflammation

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9
Q

TH1 cells become

A

Activated macrophages, NK cells and CD8 T Cells

Systemic immunity

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10
Q

Three signal hypothesis

A
  1. MHC peptide
  2. Costumulation (B7-1, B7-2)
  3. Cytokines (IL12)
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11
Q

Signals 1 and 2 induce:
Signals 3 instructs:

A

T cell activation

T cell differentiation

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12
Q

Cytokines and T cell differentiation

A

usually only one or two of these would be the dominant cytokine produced

(IL6, IL12, TGFbeta, IL4)

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13
Q

Th1 functions

A
  • Protects against intracellular pathogens and tumors
  • Support CD8 T cell response (via IL2)
  • Activate phagocytes ( macrophages) that will kill the pathogen via respiratory burst and dispose of cells that were killed as a result of infection
  • Recruit NK cells to kill infected cells (often virus infection induces downregulation of MHC class I)
  • Signature cytokine product: IFN-gamma
  • Major cytokine that it induces: IL-12
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14
Q

IFN-gamma works against

A
  • inhibits TH2 responses
  • induces macrophage activation. Increases MHC class I and II
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15
Q

Individuals lacking IFN-gamma

A

susceptible to mycobacteria, and some viruses

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16
Q

IFN-gamma functions

A

Macrophages
- activation, increased microbicidial activity

B- cells
- Isotype switching to opsonizing antibodies

Naive CD4+ T cells
- Development of TH1 effector cells

Antigen presenting cells (APC)
- Increased MHC expression, antigen presentation

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17
Q

IL12 induces

A

IFN-gamma

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18
Q

CD4+ Effector T cell (TH1 cell) + Macrophage

A

TH1 secretes IFNgamma into macrophage while it is bound to macrophage through CD40L-CD40 interaction

Response:
- increased production of ROI and NO in macrophage
- Increased killing of phagocytosed microbed
- Increased expression of costimulators (B7 molecules)
- Secretion of Cytokines (TNF, IL1, IL12)
- Increased expression of MHC molecules

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19
Q

Which of the following would at Th1 response be the best?

A

Intracellular bacteria = Th1

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20
Q

Th2 Functions

A
  • Provide protection against multicellular parasites and mediate hypersensitivity responses
  • Provide proliferative signals to B cells
  • Drive B cell isotype switching to IgG1 and IgE
  • Often associated with allergy (due to IgE production and recruitment of mast cells)
  • Signature cytokine product: IL-4
  • Major cytokine that it induces: IL-4
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21
Q

IL4 (TH2)

A
  • ## Works against TH1
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22
Q

Th1 and Th2 responses are

A

antagonistic to eachother

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23
Q

Th2 produces

A
  • IL4/IL13
  • IL5
  • IL3/IL9
24
Q

IL4/IL13 (Th2)

A

Alternative activaiton of macrophages IgE production from B cells, activation of epithelial cells and smooth muscle cells

  • Macrophage
  • B cell
  • Epithelium
  • Smooth Muscle cell
25
IL5(Th2)
Recruitment and survival of eosinophils, IgA production from B cells - Eosinophil - B cell
26
IL3/IL9 (Th2)
Recruitment and survival of mast cells and basophils - basophil - mast cell
27
Actions of IL4
B cell - Isotype switching to Ige and IgG1 Macrophages - inhibition of macrophage activation Naive CD4+ T cell - development and expansion of Th2 cells
28
Leprosy, caused by
intracellular bacteria, Mycobacterium leprae
29
Leprosy definition
a paradigm of T cell helper differentation
30
The **type** of T helper response elicited determines the outcome of infection: two main presentatins of the disease: **Tuberculoid**
- **Th1** type CD4+ T cell response - IFNgamma activates macrophages - Macrophages then destroy intracellular bacteria
31
The **type** of T helper response elicited determines the outcome of infection: two main presentatins of the disease: **Lepromatous**
- **Th2** type CD4+ T cell response - IL4 inhibits macrophage activation - Macrophage unable to kill intracellular bacteria
32
Tuberculoid Leprosy
- Organisms present at low to undetectable levels - Low infectivity - Granulomas (structure containing infected cells) and local inflammation + peripheral nerve damage - Normal serum immunoglobin levels - Normal T cell responsiveness. Specific response to *M. Leprae antigens* Mild, under control
33
Lepromatous Leprosy
- Organisms show florid growth in macrophages - high infectivity - Disseminated infection. Bone, cartilage, and diffuse nerve damage - Hypergammaglobinemia - Low or absent T cell responsiveness. No response to *M. Leprae* antigens. Severe, poorly controlled
34
APC + Naive CD4+Tcell = Activated T cell
Activated T cell 1. IL12 - Activated macrophages, dendritic cells - Leads to **Th1 cells** 2. IL 4 - From other cellular sources - Leads to **Th2 cell**
35
Th17 Cells
- Recently discovered CD4 subset that is proinflammatory - Mainly protects against **extracellular bacteria** by recuirting neutrophils - Often associated with **autoimmine disorders** - major cytokine product **(IL17)** - Major cytokines that induce: **TGFbeta and IL6** **Acts on other cells that produce IL6 and chemokines that recruit Neutrophils**.
36
Th17 appear early in infection
before Th1 and Th2
37
TGFbeta by itself leads to.. ' TGFbeta + IL6 leads to..
Treg cell Th17 cell
38
Th17 cell differentation
To become a Th17 cell a naive CD4Tcell must be exposed to **TGFbeta and IL6**. If the naive cell is exposed to TGFbeta alone, it will become a Treg cell
39
Th17 produced cytokines
IL17 - activated endothelial cells (which then **recruits neutrophils** via IL6)
40
Treg cells ( T regulatory cells)
- Tregs, acts to **suppress** immune responses - T cells express **CD4 and CD25** (alpha chain of IL2), were found to be highly enriched in suppressor activity (could prevent autoimmune disease) - **FOX23** is the transcription factor that regulates the Treg phenotype.
41
T regualtory signature cytokines
1. **IL10** - Reduces production of IL12 and TNFalpha, reduces expression of MHC and costimulatory molecules 2. **TGFbeta** - blocks cytokine production, proliferation of T and B cells, and cytolytic activity **Both are very suppressive cytokines** - shut down immune responses
42
Treg cells are very efficient at shutting down
autoimmine T cell responses
43
Tumors and Tregs
T regulatory cells can have a negaitve effect. Tumors secrete TGFbeta which induces Tregs at the tumor site to suppress anti-tumor respones.
44
FOXP3 drives
functional properites of Tregulatory cells
45
T follicular helper cell (Tfh)
- reside within lymphoid follicles ( B cell zone) - Provide help to B cells for class swtictching., and high affinity antibody production - Distinct lineage from Th1 or Th2, but can produce cytokines typical of either one Signature cytokine: **IL21**
46
TGFbeta signal on a T cell, leads to production of
Treg cells, which then **produce TGFbeta and IL10**
47
IL6 signal on a T cell leads to production of
Tfh cell, which then **produce IL21**
48
Main function of Tfh
Isoptype switching and affinity maturation in B cells
49
TGFbeta and IL6 signal on a T cell leads to prudction of
Th17 cells, which then **produces Th17**
50
IL12 signal on T cells produce
Th1 cells, which then **produce IFNgamma**
51
IL4 signal on a T cell produce
Th2 cells, which then **produce IL4**
52
Functional outcome of Th1
IFNgamma activates macrophages to kill intracellular bacteria
53
Functional outcome of IL4
Activates B cells to produce IgE which then work with mast cells and eosinophils. Work well against multicellular parasites. Type I hypersensitivity
54
Funcitonal outcome Th17
inducing neutrophil recruitment and clearing of extracellular bacteria
55
functional outcome of Tfh
isotype switching anf affinity maturations of B cells
56
functional outcome of Treg
overall just suppressive and inhibit responses of T cells.

Immunology (18 decks)

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