Effector mechanisms of cell-mediated immunity

Question 1

What are the subsets of CD4⁺ T cells?

Answer 1

• T_H1
• T_H2
• T_H17

Question 2

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

Answer 2

• Stimulation by an antigen presenting cell
• Costimulation
• Cytokines

Question 3

What is the main costimulatory receptor of T cells?

Answer 3

CD28, which binds to B7 on APCs

Question 4

What are inhibitory receptors of T cells?

Answer 4

• CTLA-4
• PD-1

Question 5

How do CTLA-4 and PD-1 function?

Answer 5

• 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

Question 6

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

Answer 6

IL-2

Question 7

What is the function of IL-2?

Answer 7

Increased proliferation of activated T cells

Question 8

How do activated T cells evade cell death?

Answer 8

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

Question 9

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

Answer 9

Increased survival of activated T cells by evasion of apoptosis

Question 10

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

Answer 10

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

Question 11

What types of T cells migrate to sites of infection?

Answer 11

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

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

How are macrophages activated by T_H1 cells?

Answer 14

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

Question 15

What type of macrophage activation is stimulated by T_H1 cells?

Answer 15

Classical (M1) activation

Question 16

What are the main effector functions of T_H1 cells?

Answer 16

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

Question 17

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

Answer 17

• 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 T_H1 cells
• Increased expression of B7 and MHC molecules leads to more costimulation and activation of T cells, respectively

Question 18

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

Answer 18

• Classical (M1) activation of macrophages
• Class-switching of B cells to IgG
• Inhibition of class-switching to IgE
• Increased differentiation into T_H1 cells
• Decreased differentiation into T_H2 and T_H17 cells

Question 19

What are the main effector functions of T_H2 cells?

Answer 19

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

Question 20

What is the signature cytokine of T_H1 cells?

Answer 20

IFN-γ

Question 21

What is the signature cytokine of T_H2 cells?

Answer 21

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

Question 22

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

Answer 22

• Class-switching to IgE
• Increased differentiation into T_H2 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

Question 23

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

Answer 23

• 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

Question 24

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

Answer 24

• Antigen-presenting cells
• NK cells
• Basophils
• Mast cells

Question 25

What is the signature cytokine of T_H17 cells?

Answer 25

IL-17

Question 26

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

Answer 26

• 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

Question 27

How are CD8⁺ cells activated to their effector cells?

Answer 27

• Similarly to the process in CD4⁺ cells
• CD4⁺ T cells (mostly T_H1) also participate, either by
  
  • producing cytokines driving CTL differentiation
  • driving differentiation by CD40:CD40L interactions (with the CD40L supplied by CD4⁺ cells)

Question 28

What are the effector functions of cytotoxic T cells?

Answer 28

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

Question 29

How is the activity of CTLs regulated?

Answer 29

• Integrins
• Immune synapses

Question 30

What are the biomarkers of regulatory T cells?

Answer 30

• CD4
• FOXP3
• CD25

Question 31

What are the inhibitory cytokines produced by T_reg cells?

Answer 31

• IL-10
• TGF-β
• IL-35