Adaptive Immunity- T cells Flashcards
what is the purpose of MHC class1 and 2?
they are cell surface receptors specialised in presenting antigens - (only peptide antigens)
what recognizes MHC-peptide complexes?
they are rexognized by T cells -
T cell receptors (TCR) recognize these peptides, binds them, and becomes activated
what type of T cell does MHC class 2 activate?
What type of T cell does MHC class 1 activate?
MHC class 2= T helper cell
MHC class 1 = Cytotoxic T cell
does one T cell recognize many different peptides… or only one?
only one-
they are highly specialized, however there are 10^8 unique TCRs in the body
Once T cells recognize a MCH-peptide complex, what occurs?
once activated, clonal expansion occurs-
T cells must interact with other cells and generate memory T cells that live for more than 20 years
Where to T cells develop?
they develop in the Thymus (primary lymphoid tissue) into naive T cells
this is where TCR rearrangment occurs
selection process
differentiation into CD4/CD8 lineage
where are T cells activated?
they are activated whenever they come across a matching MHC class peptide complex -this occurs in Lymph nodes
clonal expansion then occurs - differentiation into effector cell
what is the T cell effector function?
happens in any tissue
direct killing of tumor or infected cell - it also recruits help
Where are T cells formed in the first 8 weeks gestation vs. at 15 weeks gestation?
8 weeks = in the thyroid gland and the bones
15 weeks - in the intestines?, spleen and lymph nodes
what are the three checkpoints for maturing T cells in the thymus?
- do you have a T Cell receptor?
- Cells at this point are also CD4 and CD8 positive
- CD4 and CD8 are co- receptors
- Can you recognise self MHC?
- •Positive selection also down-regulates either CD4 or CD8, depending on whether interaction occurred with MHC class I (CD8) or class II (CD4)
- • Results in single positive CD4 and CD8 T cell
- retains T cells that recognize self
- Do you recognise self antigen (negative selection)?
- Does the TCR bind to self-peptide too tightly – APOPTOSIS
- Does the TCR bind weakly/moderately - LIVES
- negative selection = eliminates T cells that recognise self peptide too tightly - protects against autoimmunity
how are there millions of T cell with different specificities if we only have about 30,000 genes in total ?
gene rearrangement - random and variable TCR molecules with unique specificities
what two signals are required to activate T cells?
Signal 1 = specific MHC-peptide complex molecule detected
- CD4 coreceptor interacts with residues on the side of the MHC
Signal 2= costimulatory receptors (B7 or CD80/CD86) on APCs are upregulated and interact with the CD28 (always present on T cells)
once these conditions are met, T cell activation occurs
What do activated T cells produce?
they produce the cytokine interleukin 2- IL2
IL2 is a T cell growth factor -
What effect does IL2 have on T cells ?
it proliferates and exapnds T cell clones
If you wnat to supress T cell activation or activity what do you target? What drug does this?
you supress IL2- this is what Tacrolimus does - it pevents IL2 expression as an immunosuppressive drug -
What are the T cell effector functions?
CD8= cytotoxic T cells - only recognize MHC Class 1 , directly kill virally infected or tumor cells
CD4 T helper cells - only recognize MHC class 2 - help active B cells and macrophages via cytokine production and interaction
How do cytotoxic T cells kill?
they bind to the MHC class 1 molecule with a processed antigen
they are packed full of vesicles with toxic enzymes for killing
once the cytotoxic T cell is activated perforin (perforates cells) and granzymes (proteolytic enzymes) are released that destroy structural cytoskeleton proteinas and degrade DNA
what are the two key functions of T helper cells?
- interact with B cells to activate them - produce antibodies
- production of cytokines to drive the immune repsonse - cytokines will activate T and B cells and macrophages to clear infection, cytokines produced depend on infection agent
What are the different subsets of T helper cells?
TH1
TH2 and
TH17
What differentiates the TH1, TH2 and TH17 subsets of T helper cells?
they all produce different cytokines based on the type of infection present
TH1= IFNgamma- IgG production for intracellular microbes- associated with chronic infections
TH2= IL4,5,13- IgE production for heminth parasites - associated with allergies
TH17= IL17A, IL17F, IL22 - neutrophilic monocytic inflamation associated with autoimmune diseases
What is DiGeorge Syndrome?
a deletion on the chromosome 22 leads to severe neuromuscular defects and hypothyroidism - no T cells
this has severe developmental and cardiac defects as well as immune disfuntion
What is SCID?
severe combined immunodeficiency
- majority due to mutations in the receptor for IL2- common gamma chain - T cells can’t proliferate in response to IL2 -
- normal B cell numbers however
- also a part of other cytokine receptors so severe defects
