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Immunology > T cell differentiation/effector functions > Flashcards

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
Q

IL5(Th2)

A

Recruitment and survival of eosinophils, IgA production from B cells
- Eosinophil
- B cell

26
Q

IL3/IL9 (Th2)

A

Recruitment and survival of mast cells and basophils

  • basophil
  • mast cell
27
Q

Actions of IL4

A

B cell
- Isotype switching to Ige and IgG1

Macrophages
- inhibition of macrophage activation

Naive CD4+ T cell
- development and expansion of Th2 cells

28
Q

Leprosy, caused by

A

intracellular bacteria, Mycobacterium leprae

29
Q

Leprosy definition

A

a paradigm of T cell helper differentation

30
Q

The type of T helper response elicited determines the outcome of infection: two main presentatins of the disease:

Tuberculoid

A
  • Th1 type CD4+ T cell response
  • IFNgamma activates macrophages
  • Macrophages then destroy intracellular bacteria
31
Q

The type of T helper response elicited determines the outcome of infection: two main presentatins of the disease:

Lepromatous

A
  • Th2 type CD4+ T cell response
  • IL4 inhibits macrophage activation
  • Macrophage unable to kill intracellular bacteria
32
Q

Tuberculoid Leprosy

A
  • 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
Q

Lepromatous Leprosy

A
  • 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
Q

APC + Naive CD4+Tcell = Activated T cell

A

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
Q

Th17 Cells

A
  • 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
Q

Th17 appear early in infection

A

before Th1 and Th2

37
Q

TGFbeta by itself leads to..
‘
TGFbeta + IL6 leads to..

A

Treg cell

Th17 cell

38
Q

Th17 cell differentation

A

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
Q

Th17 produced cytokines

A

IL17 - activated endothelial cells (which then recruits neutrophils via IL6)

40
Q

Treg cells ( T regulatory cells)

A
  • 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
Q

T regualtory signature cytokines

A
  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
Q

Treg cells are very efficient at shutting down

A

autoimmine T cell responses

43
Q

Tumors and Tregs

A

T regulatory cells can have a negaitve effect.

Tumors secrete TGFbeta which induces Tregs at the tumor site to suppress anti-tumor respones.

44
Q

FOXP3 drives

A

functional properites of Tregulatory cells

45
Q

T follicular helper cell (Tfh)

A
  • 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
Q

TGFbeta signal on a T cell, leads to production of

A

Treg cells, which then produce TGFbeta and IL10

47
Q

IL6 signal on a T cell leads to production of

A

Tfh cell, which then produce IL21

48
Q

Main function of Tfh

A

Isoptype switching and affinity maturation in B cells

49
Q

TGFbeta and IL6 signal on a T cell leads to prudction of

A

Th17 cells, which then produces Th17

50
Q

IL12 signal on T cells produce

A

Th1 cells, which then produce IFNgamma

51
Q

IL4 signal on a T cell produce

A

Th2 cells, which then produce IL4

52
Q

Functional outcome of Th1

A

IFNgamma activates macrophages to kill intracellular bacteria

53
Q

Functional outcome of IL4

A

Activates B cells to produce IgE which then work with mast cells and eosinophils. Work well against multicellular parasites.

Type I hypersensitivity

54
Q

Funcitonal outcome Th17

A

inducing neutrophil recruitment and clearing of extracellular bacteria

55
Q

functional outcome of Tfh

A

isotype switching anf affinity maturations of B cells

56
Q

functional outcome of Treg

A

overall just suppressive and inhibit responses of T cells.

Immunology (18 decks)

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