L14- CD4+ T helper cells Flashcards
What are effector functions of CD4+ T helper cells?
Proliferation
Cytokines
B cell help
APC activation
How does T cell activation occur?
Signal 1- Recognition of MHCII molecule on APC/Bcell by the TCR provides a signal which initiates activation of T cells.
Signal 2- Interaction of co-stimulatory molecules on surface of B and T cells.
What types of T cells do naieve CD4+ T cells differentiate into?
Th1- Coordinate inflammatory immune responses to intracellular pathogens (bacteria, viruses)
Th2- Help B cells make antibodies required for immune responses to extracellular pathogens
Both promote the generation of more leukocytes
What cytokines do Th1 cells produce?
IL2
IFN gamma
TNF beta
GMCSF
IL3
What cytokines do Th2 cells produce?
IL4
IL5
IL13
GMCSF
IL3
What does IL2 do?
Proliferation of activated T cells, enhancement of NK and T cell activity
What does IFN gamma do?
Macrophage activation
Elevation of MHCI and MHCII expression
Enhances NK and CD8+ activity
Class switching to IgG2a
What does TNF alpha/beta do?
Macrophage activation
Killing of transformed cells
What does IL4 do?
B cell proliferation
Class switching to IgE
Suppresses Th0 to Th1 differentiation
What does IL5 do?
B cell proliferation
Class switching to IgA
What does IL13 do?
B cell proliferation
Class switching to IgE
What does IL3 do?
Haematopoiesis
What does GM-CSF do?
Haematopoiesis
Differentiation of monocytes to macrophages
What are the transcription factors controlling Th1 differentiation?
IFN gamma
IL12
——> Stat1+4 and T-bet
What are the transcription factors controlling Th2 differentiation?
IL4
——-> gata3, cMaf (master regulator), Stat6
What is the Th1 differentiation pathway?
Type 1 pathogens (bacteria,virus) Macrophage, Dendritic cells IL12 released NK cell stimulated IFN gamma released Conversion of STAT-1 to Tbet Increased IL12 Conversion of STAT-4 to IFN gamma Increased IL-19Ralpha causes Th1 cell to be produced
What is the Th2 differentiation pathway?
Type 2 pathogens (helminthes) Macrophages, Dendritic cells STAT-6 converted to GATA Increased cMaf causes increased IL-4 Th2 cells produced
What is the relationship between T-bet and Gata-3?
They both inhibit eachother
What is Th17?
A proinflammatory CD4+ T cell
What are the cytokines produced by Th17 and what do they do?
TNF-alpha= Inflammatory response, macrophage and fibroblast activation
IL-17A/F= Induces IL-6, TNF-alpha, chemokines
IL-22= innate immune responses against bacterial pathogens
IL-21= promotes B-cell and antibody responses, regulates activation and differentation of T cells, APC’s, NK cells
GM-CSF, CXCL8= Haematopoiesis, macrophage differentiation, neutrophil recruitment
What does IL-17 do?
Produced by Th17, CD8+,NK and innate lymphoid cells
Receptor ubiquitously expressed in tissue so effects are wide ranging
IL17A=
• Pathogenic role in autoimmune/inflammatory disorders
• Specialised and essential function in host defence against extracellular bacteria and some fungi (esp mucosal surfaces)
What is the non pathogenic Th17 differentiation pathway?
Naieve T cell
TGFbeta and IL6
Th17 produced (non pathogenic)
(can be induced by intra/extracellular pathogen)
What is the pathogenic Th17 differentiation pathway?
Naieve T cell TGFbeta and IL6 IL-23 RORgammaT T.F. produced which produces TGFbeta3 IL6 and IL1 produce pathogenic Th17
What do follicular helper T cells do?
Form cognate interactions with naive B cells through linked recognition of antigen and traffic to B cell follicles where they promote the germinal centre response.
Cause isotype switching and affinity maturation
What is the Tfh differentiation pathway?
TCR binds to dendritic cell
Releases IL-6
Causes STAT6 activation which activates BCL-6 transcriptional repressor
Signalling by IL-21
