Which T cells are depleted in HIV/AIDS?
CD4+ T cells
Define MHC restriction.
T cells recognise pathogens by recognising pathogenic peptide fragments on MHC molecules. They can not recognise whole antigen, only a combination of antigen peptide with MHC.
Describe the structure of MHC molecules.
MHC molecules are transmembrane proteins that contain a specific peptide binding groove to which the pathogenic peptide is held in for presentation to T cells.
MHC class I is expressed on all nucleated cells.
MHC class I consists of 3 alpha subunits and 1 Beta-2 microglobulin.
MHC class II is expressed on APCs such as Monocytes/Macrophages, Dendritic cells and B cells.
MHC class II consists of 2 alpha subunits and 2 beta subunits Disulphide bonds
Give an example of a human body cell that does not express MHC Class I.
Erythrocytes - Lack a nucleus
Where are the genes that encode both classes of MHC found?
On the short arm of chromosome 6.
How many polymorphic genes are involved in encoding an MHC class I molecule?
There are 3 HLA genes:
HLA-A, HLA-B and HLA-C
Describe the structure of the TCR.
Heterodimer of either alpha-beta or gamma-delta subtypes.
Consist of variable and constant domains
V-alpha, C-alpha, V-beta, C-beta
How many different genes make up the light chain of the TCR?
V, J and C
How many different genes make up the heavy chain of the TCR?
V, D, J and C
True or False: Interaction of peptide-MHC with TCR is sufficient to activate a naive T cell
False - 2 signals are required
TCR -> Peptide-MHC interaction only provides signal 1.
Signal 2 comes from co-stimulation by T cell CD28 and APC CD86 interaction.
What two events cause upregulation of co-stimulatory molecules like APC CD86 and T cell CD28?
Infection and Inflammation.
MHC class I presents peptide to what cell?
CD8+ T cell
MHC class II presents peptide to what cell?
CD4+ T cell
Describe the killing mechanisms of CD8+ cytotoxic T cells.
- CD8+ FasL binds to the infected cell's Fas receptor, which activates caspases and the apoptotic cascade.
- Release of TNF-alpha that binds to receptors on the infected cell to initiate apoptosis
- Release of Perforins which allow granzymes to invade the infect cell and induce apoptosis.
How are Th1 cells produced?
Exposure of naive T cells to IL-12
How are Th2 cells produced and under what circumstances are they present in high levels?
Exposure of naive T cells to IL-4
In allergy and asthma
How are Th17 cells produced?
Exposure of naive T cells to TGF-ß and IL-2
How are Treg cells produced and what key process are they involved in?
Exposure of naive T cells to TGF-ß and IL-10
Crucial in Immune Tolerance
How do Th1 cells help other immune cells?
Release of IL-2 and IFN-gamma to stimulate CD8+ T cells to proliferate, differentiate and become activated.
Release of IFN-gamma also activates Macrophages
How do Th2 cells help B cells?
Produce cytokines: IL-2, IL-4, IL-5 and IL-13
These cytokines stimulate class switching to IgG, affinity maturation, antibody production, proliferation and differentiation.
How do Th17 cells fight extracellular pathogens?
Release of IL-17 and Il-22 cytokines, which stimulate Epithelial cells and Fibroblasts to produce anti-microbial peptides, improe wound healing and upregulate chemotaxis to recruit neutrophils.
What is the function of Treg cells?
Production of anti-inflammatory cytokines - TGF-ß,IL-10 and through cell-cell contact, suppress activation of APCs, antibody and cytokine production, as well as control of the function of NK and CD8+ T cells.