Lecture 7 Flashcards
What are the 5 types of t helper cells
Tfh, TH1, TH2, TH17, treg cells
What do treg cells do
dampen inflammatory responses and secrete cytokine IL-10
What does Th17 do
stimulate inflammation by secreting interleukin 17- helps trigger recruitment of neutrophils and macrophages
What does Th2 do
recruit eosinophils to combat parasitic infections and inhibit Th1 proliferation
What does Th1 do
assist in activation of cytotoxic t cells
What does Tfh do
drives B cell differentiation into antibody secreting plasma cells. They secrete different combinations of cytokines that trigger antibody isotype class switching
What do t helper cells do and their receptor
Augment/ help immune responses. Have CD4+ve
What do T cytotoxic cells do
They specifically kill infected host cells. CD8+VE
General structure of a t cell receptor
Made of two chains, an alpha chain and a beta chain. Structure is very similar to the FAB arm of an antibody.
Within each variable region, there are 3 hypervariable loops or complementary determining regions
What does expression of t cell receptors on the cell surface require
Requires the association with additional proteins (Cluster differentation/ CD3)
What do CD3 subunits contain
ITAMs in their cytoplasmic regions. When the whole complex bind to antigen, these motifs can be phosphorylated and we get down stream signalling.
What are T cell receptor genes like
They’re very similar to antibody genes. There are two gene loci
What’s the main difference between t cell receptor rearrangement compared to antibody rearrangement
Occurs in the thymus rather than the bone marrow
Stages of t cell receptor diversity
- Multiple copies of V region gene segments
- a x b chain combination (junctional diversity)
CDR1 and CDR2 are encoded in the germline by the V segments. CDR3 corresponds to the V chain or the VDJ join so its very diverse
What is B cell immunity important for
In defence against extracellular pathogens. They recognise free, “native” antigens that haven’t been processed
What is T cell immunity for
Important in extracellular bacteria but also important in defence against intracellular pathogens.
What do T cells require
Antigen presentation by cells expressing Major histocompatibility proteins
What does histocompatibility mean
Determines whether a given antigen is recognised as coming from the host or from another source
What are the two classes of MHC proteins
Class 1: expressed by all nucleated cells - non professional APCS. These present peptides derived from endogenous proteins to cytotoxic t cells.
Class 2: They’re expressed by certain leukocytes- professional APCs. They present peptides derived from exogenous proteins to helper t cells.
Structure of MHC1 proteins
They’re made up of an alpha chain and a beta chain - they stabilize the molecule on the membrane. These genes are polymorphic. They are heterodimer made of an alpha chain and a b2-microglobulin.
What’s the structure of MHC2 proteins
They’re made of two chains, the ones closest to the membrane are immunoglobulin like, the domains furthest away are the most polymorphic and bind to peptide. Alpha and beta subunits both contribute to the antigen binding cleft.
Whats the structure of the peptide binding groove
The bottom is made of beta pleated sheets and the alpha helical region comes up out of the surface to form the sides of the domain
Where do anchor residues bind
They bind to specificity pockets formed by polymorphic residues
What’s a proteosome
A multi-subunit complex that breaks down misfolded proteins. They’re present in all cells
Stages of antigen presentation of MHC1
- Antigen processing to peptides in the proteosome
- Peptide transport into endoplasmic reticulum (ER)
- Peptide binding by MHC class 1
- MHC class 1 presents peptide at cell surface
Why is cross presentation important
Allows antigen presentation to cytotoxic t cells without the dendritic cells themselves being infected
Important in cytotoxic t cell responses in many tumours
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