T Cell Subsets and Function Flashcards
Describe T cell development
- stars in bone marrow
- thymocytes migrate to thymus
- TCR genes rearrange
- differentiates into CD4 or CD8
- undergo positive and negative selection to remove autoreactive T cells - migrate to periphery
Describe T cell Activation
- naive Th and Tc activated in secondary lymphoid tissues by DC
- cross-presentation critical
- proliferate upon activation
- aided by IL-2 production
- activated T cells express higher affinity IL-2 receptor
Describe IL-2 driving T cell proliferation
- clonal expansion of T cell with correct TCR
- cytokine can act on cell producing it - autocrine
- cell lineages differentiate into effector or memory cells
Where are activated T cells held?
lymph nodes
Describe CD8 T cells
- adhesion molecules change
- after activation: leave secondary lymphoid tissue and re-enters circulation
- alter homing receptors to target inflamed endothelium
- search for infected host cells by checking MHC class I presentation
- killing of host cells via apoptosis
- after proliferation, differentiation occurs
Describe CD8+ killing of host cells via apoptosis induction
- release of molecules such as perforin, granzymes, granulysin
- or Fas-FasL receptor interaction
What are the different forms of CD8+ differentations?
- helper T cells
- cytokine production dependent on signal III
What are the different forms of Th cells?
- Th1
- Th2
- Th17
- Treg
- TFH
Describe Th1 cells
- differentiation promoted by Signal 3 containing IL-12, IFN-ү
- transcription factors activated are STAT1, Tbet
- function is to secrete IFN-ү, IL-12, TNF-α
Describe what Th1 secretions lead to
- activation of macrophages (CD40-CD40L interactions)
- class switching to IgG (opsonizing Abs)
- increased MHC class I and II expression
- promotes NK cell activity
Describe the target of Th1 secretions
- activating macrophages to migrate
- killing infected macrophages
- increased MHC class I
- critical for intracellular infections such as viral diseases
Describe Th2 cells
- differentiation promoted by Signal 3 containing IL-4
- transcription factors activated are STAT6 and Gata3
- secretes IL-4, 5 and 13
- correct responses can be critical
Describe what Th2 secretion leads to
- B cell proliferation and antibody production
- antibody class switching to IgE (IL-4)
- mucus production
Describe the target of Th2 secretions
- IgE class switching
- increased antibody production
- activated mast cell and Eosinophils
Describe Th17 cells
- differentiation promoted by Signal 3 containing IL-23, IL-6, TGF-β
- transcription factor achieved is RORүT
- secretes IL-17, IL-21, IL-22
Describe what Th17 secretions lead to
- neutrophil recruitment - activation of fibroblasts and epithelial cells to secrete chemokines
- important at mucosa and epithelia
Describe the target of Th17 secretions
- pro-inflammatory response
- important in response to pathogens such as extracellular bacteria, fungi
- related to hypersensitivities such as Rheumatoid Arthritis
Describe Treg cells
- differentiation promoted by Signal 3 containing IL-10 and/or TGF-β
- transcription factors achieved is FoxP3 - some subsets only
- secretes IL-10 and/or TGF-β
What downregulation do Treg cells lead to?
- Th1 cytokine production
- MHC class II expression
- co-stimulatory molecules
Describe the target of Treg cell secretions
- regulatory immunosuppressive activities
- dampening immune response
- important in response to many infections, failure in hypersensitivities (autoimmunity)
What is an example of Treg suppression helping resolve a disease?
- Schistomaisis
- chronic infection, ~100eggs/day lodged in liver per worm pair
- without Treg suppression - inflammation caused by Th1 and Th2 leads to increased pathology
Describe TFH cells
- follicular helper T cells
- produced by IL-6
- transcription factor Bcl-6
- most niche subset
- leads to T cell dependent antibody production
Describe the function of TFH cells
- CXCR5 on surface - keeps them in B cell follicle
- ICOS on surface - key in B cell help
- IL-21 proliferation and differentiation B cells
What are the 3 types of cytokine production dependent on Signal 3 recieved?
- cytokines produced by innate immune responses
- cytokines produced by APC
- bystander cytokines
