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Microbiology and immunology > Effector mechanisms of cell-mediated immunity > Flashcards

Effector mechanisms of cell-mediated immunity Flashcards

1
Q

What are the subsets of CD4+ T cells?

A
  • TH1
  • TH2
  • TH17
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2
Q

How are naive CD4+ T cells activated to differentiate into their effector subsets?

A
  • Stimulation by an antigen presenting cell
  • Costimulation
  • Cytokines
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3
Q

What is the main costimulatory receptor of T cells?

A

CD28, which binds to B7 on APCs

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4
Q

What are inhibitory receptors of T cells?

A
  • CTLA-4
  • PD-1
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5
Q

How do CTLA-4 and PD-1 function?

A
  • They bind B7, producing effects opposite to those of the stimulatory receptor (CD28)
  • By binding B7, they also decrease the amount of ligand available for stimulation of CD28
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6
Q

What is the cytokine that stimulates proliferation of activated T cells?

A

IL-2

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7
Q

What is the function of IL-2?

A

Increased proliferation of activated T cells

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8
Q

How do activated T cells evade cell death?

A

Increased production of the antiapoptotic proteins Bcl-XL and Bcl-2

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9
Q

What is the function of Bcl-XL and Bcl-2?

A

Increased survival of activated T cells by evasion of apoptosis

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10
Q

How do T cells migrate from secondary lymphoid organs to the affected regions?

A

Similarly to neutrophils in acute inflammation (selectins, integrins, CD31, following a chemokine gradient)

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11
Q

What types of T cells migrate to sites of infection?

A

Effector and memory CD4+ T cells (but not naive T cells)

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12
Q

What happens if effector T cells migrate to a site of infection where there are antigens that they are not specific for?

A

They either die by apoptosis or return via lymphatics to secondary lymphoid organs

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13
Q

Some activated CD4+ T cells do not leave the secondary lymphoid organs. What happens to them instead?

A

They become follicular helper T cells which activate B cells to produce high-affinity antibodies of different isotypes

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14
Q

How are macrophages activated by TH1 cells?

A
  • CD40:CD40L interactions, with CD40L contributed by the T cell
  • IFN-γ binds to its receptor on macrophages
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15
Q

What type of macrophage activation is stimulated by TH1 cells?

A

Classical (M1) activation

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16
Q

What are the main effector functions of TH1 cells?

A
  • Classical (M1) activation of macrophages
  • Isotype switching to IgG, leading to increased opsonization and complement binding
17
Q

What are the results of classically (M1) activated macrophages in cell-mediated immunity?

A
  • Increased ROS, NO, and lysosomal enzymes lead to more intracellular killing
  • Secretion of TNF and IL-1 leads to further inflammation
  • Secretion of IL-2 leads to further differentiation into TH1 cells
  • Increased expression of B7 and MHC molecules leads to more costimulation and activation of T cells, respectively
18
Q

What are the functions of IFN-γ?
| (in cell-mediated immunity)

A
  • Classical (M1) activation of macrophages
  • Class-switching of B cells to IgG
  • Inhibition of class-switching to IgE
  • Increased differentiation into TH1 cells
  • Decreased differentiation into TH2 and TH17 cells
19
Q

What are the main effector functions of TH2 cells?

A
  • Class-switching to IgE
  • Activation of eosinophils
  • Promoting helminth clearance
20
Q

What is the signature cytokine of TH1 cells?

A

IFN-γ

21
Q

What is the signature cytokine of TH2 cells?

A

IL-4
(IL-13 and IL-5 are also produced)

22
Q

What are the functions of IL-4?
| (in cell-mediated immunity)

A
  • Class-switching to IgE
  • Increased differentiation into TH2 cells
  • Alternative (M2) activation of macrophages
  • Increased peristalsis in the GI tract
  • Recruitment of leukocytes, mainly eosinophils, by promoting expression of adhesion molecules on endothelia and secretion of chemokines
23
Q

What are the functions of IL-13?
| (in cell-mediated immunity)

A
  • Alternative (M2) activation of macrophages
  • Increased peristalsis in the GI tract
  • Increased mucus secretion in airway and gut epithelial cells
  • Recruitment of leukocytes, mainly eosinophils, by promoting expression of adhesion molecules on endothelia and secretion of chemokines
24
Q

What is the source of cytokines needed for differentiation of CD4+ T cells into the different subsets?

A
  • Antigen-presenting cells
  • NK cells
  • Basophils
  • Mast cells
25
Q

What is the signature cytokine of TH17 cells?

A

IL-17

26
Q

What are the functions of IL-17?
| (in cell-mediated immunity)

A
  • Induction of neutrophil-rich inflammation by stimulating the production of other cytokines/chemokines, as well as by increasing production of G-CSF
  • Stimulating production of antimicrobial peptides
27
Q

How are CD8+ cells activated to their effector cells?

A
  • Similarly to the process in CD4+ cells
  • CD4+ T cells (mostly TH1) also participate, either by
    • producing cytokines driving CTL differentiation
    • driving differentiation by CD40:CD40L interactions (with the CD40L supplied by CD4+ cells)
28
Q

What are the effector functions of cytotoxic T cells?

A
  • Direct cell killing by perforin–granzyme mediation, leading to release of intracellular caspases
  • Providing FasL for activation of apoptosis by Fas–FasL
29
Q

How is the activity of CTLs regulated?

A
  • Integrins
  • Immune synapses
30
Q

What are the biomarkers of regulatory T cells?

A
  • CD4
  • FOXP3
  • CD25
31
Q

What are the inhibitory cytokines produced by Treg cells?

A
  • IL-10
  • TGF-β
  • IL-35

Microbiology and immunology (33 decks)

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