lecture 5- T cell differentiation/effector functions

Question 1

name the five CD4 T helper subsets

Answer 1

Th1
Th2
Th17
Treg
Tfollicular

Question 2

the three signal hypothesis for T cells is… and induces these two processes

Answer 2

MHC/peptide and costimulation induce activation
cytokines instruct T cell differentiation

Question 3

describe Th1 cells function

Answer 3

Th1 driven responses protect against intracellular pathogens and tumors, pro-inflammatory
- life cycle that allows them to live inside host cells (bacteria & viruses)
- support CD8 T cell response
- activate phagocytes that kill the pathogen via respiratory burst and dispose of cells that were killed as a result of infection, upregulates MHC
- recruit NK cells to kill infected cells
- signature cytokine produced: IFN-y
- induced by IL-12

Question 4

cytokine that induced Th1
signature cytokine produced by Th1

Answer 4

IL-12
IFN-y

Question 5

activation of IFN-y has these 4 effects

Answer 5

1- macrophage activation
2- isotype switching to opsonizing antibodies
3- development of Th1 effector cells
4- increased MHC expression

Question 6

describe Th2 cells function

Answer 6

• Th2 responses protect against multicellular parasites and mediate hypersensitivity responses
• only enhance certain types of antibody responses
• provide proliferative signals to B cells
• drive B cell isotype switching to IgG1 and IgE
• allergy- helps with hay fever
• strong enhancement of eosinophils and mast cells; inhibits macrophages
• signature cytokine = IL-4
• cytokine that induces = IL-4

Question 7

signature cytokine produced by Th2

Answer 7

IL-4

Question 8

cytokine that induces Th2

Answer 8

IL-4

Question 9

describe regulation of Th subsets- Th1 and Th2 with leprosy

Answer 9

leprosy- the type of T helper response elicited determines the outcome of infection:
- less severe = tuberculoid: Th1 response – IFN-y activates macrophages – macrophages destroy intracellular bacteria
- more severe = lepromatous: Th2 response – IL-4 inhibits macrophage activation – macrophage unable to kill

Question 10

name a few characteristics of tuberculoid and lepromatous leprosy

Answer 10

tuberculoid- has good granulomas- structure containing cells that are infected, walled off from rest of body to protect
- normal serum immunoglobulin levels
lepromatous- high infectivity, hypergammaglobulinemia

Question 11

how is cell driven to be Th1 or Th2?

Answer 11

well signal from IL-2, but mostly from IL-12 (Th1) or IL-4 (Th2)

Question 12

describe Th17 cells function

Answer 12

pro-inflammatory, protects against extracellular bacteria by recruiting neutrophils
- Th17 cells appear very early in infection- before Th1 and Th2
- associated with autoimmune disorders
- major cytokine produced = IL-17 – IL-17 activate endothelial cells which then recruit neutrophils through IL-6
- induced by TGF-beta and IL-6 TOGETHER
- IL-23 important for maintenance of Th17

Question 13

major cytokine produced by Th17

Answer 13

IL-17

Question 14

cytokine that induces Th17

Answer 14

TGF-beta AND IL-6

Question 15

if a naive T cell is exposed to cytokine TGF-beta alone, it will become ___

Answer 15

Treg

Question 16

describe Treg (regulatory T cells) function

Answer 16

Tregs act to suppress immune responses
- T cells expressing CD4 & CD25 (alpha chain of IL-2 receptor) were found to be highly enriched in suppressor activity
- has neg effect with tumors- suppress anti-tumor responses
- FoxP3 is the TF that regulates the Treg phenotype
- produced by TGF-beta alone
- signature cytokines are TGF-beta and IL-10

Question 17

signature cytokines of Tregs and their function

Answer 17

IL-10 : reduces production of IL-12 and TNF-alpha, reduces expression of MHC and costimulatory molecules

TGF-beta : blocks cytokine production, proliferation of T and B cells, and cytolytic activity

Question 18

describe Tfollicular cell function

Answer 18

• reside within B cell follicle to help with isotype switching and affinity maturation for high antibody production
• distinct lineage from Th1 or Th2, but can produce cytokines typical of either one
• IL-6 induces Tfollicular
• signature cytokine = IL-21