Theme 7: CD4 Subsets Flashcards
What induces T cell differentiation?
Cytokines
What are the main functions of CD4+ T helper cells?
1) Viral clearance
2) Worm expulsion
3) Intracellular/extracellular pathogens
4) Tumor defense/progression
What are some examples of cytokine sources?
DCs (most potent), macrophages, tissue cells, eosinophils/basophils, other T cells
Describe the characteristics of Tregs
1) Induced by IL-2 and TGF-β
2) Master regulator = FoxP3
3) Releases IL-10 and TGF-β
4) Suppresses immune responses
5) May be involved in inhibiting antitumor response
Describe the characteristics of Tfh
1) Induced by IL-6 and IL-21
2) Master regulator = Bcl-6
3) Releases IL-4 and IL-21
4) Affinity maturation, antibody production
Describe the characteristics of TH1
1) Induced by IL-12, IFN-y, IL-18
2) Master regulator = T-Bet
3) Releases IFN-y and TNF
4) Targets macrophages, neutrophils, and epithelia
5) Combats intracellular pathogens, activates macrophages, induces lysis, antimicrobial production
6) May be involved in tissue inflammation (autoimmunity)
Describe the characteristics of TH2
1) Induced by IL-4
2) Master regulator = GATA3
3) Releases IL-4, IL-5, and IL-13
4) Targets eosinophils, basophils, mast cells, and epithelia
5) Combats extracellular pathogens (worms like helminths), histamine release, mucus production
6) May be involved in allergy
Describe the characteristics of TH17
1) Induced by IL-6, IL-23, TGF-β
2) Master regulator = RORyt
3) Releases IL-17A, IL-17F, IL-22
4) Combats extracellular pathogens at barrier sites
5) May be involved in autoimmunity and tissue inflammation
Describe the characteristics of TH9
1) Induced by IL-4 and TGF-β
2) Master regulator = PU.1
3) Releases IL-9
4) Combats extracellular pathogens
Describe the characteristics of TH22
1) Induced by IL-6 and TNFα
2) Master regulator = AHR
3) Releases IL-22
4) Combats extracellular pathogens in skin
Describe the process of TH1 induction and responses
1) IL-12 (IFN-y and IL-18) is released by DCs and induces T-bet
2) Interaction of TH1 with DCs induces licensing
3) Release of IFN-y, TNF
4) Increased phagocytosis, increased ROS, increased killing of intracellular pathogens by macrophages
5) Antiviral response in epithelial cells and apoptosis
Describe the process of DC licensing by CD4+ Th1
1) Involves TCR interactions with MHC-antigen
2) Involves CD28:B7 and CD40L:CD40 (cross presentation)
3) Involves CD27:CD70 interactions (survival, T-bet and NFkB activation)
Describe the process of TH2 induction and responses
1) IL-4 is released by basophils and induces GATA3
2) Releases IL-4,5,13
3) Histamine release in mast cells, eosinophils, basophils
4) B cell IgE production
5) Macrophage cytokine production to promote TH2 environment
6) Epithelia mucus secretion and peristalsis
What is the pattern observed regarding TH1 and TH2 responses and leishmania infection?
1) Type I response allows for expulsion of infection
2) Type II response prevents phagocytes from being able to kill the pathogen
3) Individuals with responses skewed in favour of type II are susceptible to leishmania
What is the pattern observed between autoimmunity and helminth infection?
1) Countries with pervasive helminths (worms) infection have higher TH2 responses and less incidence of autoimmunity
2) Countries with higher rates of autoimmune disease do not have helminths and are more skewed towards TH1 response