IAI - T cells, effector functions and the MHC Flashcards
Peptides are displayed by cells in what context?
Peptides are displayed by cells in the context of highly polymorphic MHC molecules.
What structural property do both MHC I and MHC II share?
A peptide binding groove at the top
describe the structure of an MHC1 molecule
MHC class I is a single chain molecule but on the cell surface it associates non covalently with another molecule known as beta-2 microglobulin.
how is MHC1 molecule expressed?
expressed endogenously on all nucleated cells in the body.
describe the structure of MHC11 molecules
an alpha-beta heterodimer
how is MHC11 expressed?
- expressed on specialised antigen presenting cells:
- monocytes
- macrophages
- dendritic cells
- b lymphocytes
What is the functional role of MHC I?
- cell becomes infected
- host breaks down sample of all proteins being produced using proteasome
- proteasome takes peptides and transports them to ER
- loaded onto newly synthesised MHC1 molecules
- These molecules are then loaded to the cells surface displaying the peptides to the immune system
What is the functional role of MHC11
- A dendritic cell is taking up a bacterial antigen by endocytosis.
- The endocytic vesicles will contain proteolytic enzymes that will then degrade this protein.
- At the same time MHC II molecules are being synthesised and assembled in the endoplasmic reticulum
- These MHC class II molecules will migrate to late endosomes where they will fuse with the vesicles containing the degraded antigen.
- It’s in these vesicles that peptides are loaded into the MHC class II molecules.
- These peptide filled MHC class II molecules are then transported to the cell surface to be displayed by the rest of the immune system.
Where are the genes encoding for MHC class I and II found?
short arm of chromosome 6
(this is the most polymorphic region of the whole genome)
the short arm of chromosome 6 where the genes encoding for MHC 1 and 11 are found, is also called?
human leukocyte antigen or HLA.
HLA class 1 has 3 distinct genes leading to 3 HLA proteins:
HLA-A
HLA-B
HLA-C
HLA class 2 has 3 distinct genes leading to 3 HLA proteins:
HLA-DR
HLA-DQ
HLA-DP
describe the structure of a t-cell receptor
- membrane-bound heterodimer
- two chains joined by disulphide bonds
- two chains encoded by different genes
- two subtypes alpha-beta and gamma-delta
consist of variable and constant domains
Where is the greatest variability in T-cell receptors?
- In the receptor binding groove.
- These parts of the T-cell receptor reach down and make contact with the peptide MHC molecule.
what class does CD8 bind to?
CD8 binds with MHC CLASS 1
what class does CD4 bind to?
CD4 binds with MHC CLASS 2
What does the activation of t cells require
two signals
signal 1 = activation of T cell
signal 2 = co-stimulation when CD86 on APC surface binds to CD28 on T cell surface
What is a naive T-cell?
A T cell that has never encountered the peptide MHC molecule that can activate it.
What do Th1 cells secrete and what do Th 1 cells do
secrete interferon gamma (IFN-γ) and IL-2
- allows CD8 T cells to proliferate, it also allows them to differentiate and start to express the cytolytic cytokines ** perforins and granzymes.
- aid macrophage function via the secretion of interferon gamma.
what cytokines do Th2 cells produce?
IL4 and IL13
whats the function of Th2?
provides help for B cells
whats the function of Th17
helps fight extracellular pathogens
what cytokines do Th17 cells produce?
IL-17
IL-21
IL-22
Whats the 5 functions of Treg cells?
- suppress stimulatory activity of APC
- suppress proliferation of responder cells
- suppress cytokine production of responder cells
- suppress antibody production from B cells
- suppress functions of NK + NKT cells
do keats quiz on t-cells, effector functions, and the MHC
https://keats.kcl.ac.uk/mod/lesson/view.php?id=7651854
How do the sources of peptides loaded into MHC class I and II differ?
- Generally MHC class I molecules will present peptides derived from proteins currently being synthesised in that cell.
- MHC class II (generally expressed on specialised antigen presenting cells) will present peptides derived from antigens that they’ve pulled in from outside.
What is the difference between what MHC I and MHC II molecules display?
MHC II display exogenous antigens
MHC I displays endogenous antigens
What happens once T-cells finish their rearrangement of their T-cell receptor?
Unlike B cells in which immunoglobulin genes can then undergo affinity maturation, once the T-cells finish rearrangement of their T-cell receptor, it’s not able to change that configuration at all.
What does the tripartite interaction between the T-cell receptor with the combination of the peptide and MHC determine?
determines whether a particular T-cell will respond to a particular peptide presented by a particular MHC molecule.
T cells and B cells only recognise peptides presented by molecules encoded by genes of the major histocompatibility complex (MHC)
true or false, and why
FALSE - key word here is ‘only’
B cells can recognise a variety of antigens including proteins and carbohydrates with no need for antigen presentation.
T cell require MHC to recognise peptides
what number is CD on the T-cell, compared to the APC
t-cell (either CD4 or CD8) has CD28
APC has CD80 OR CD86
Which one is a co-stimulatory molecule, CD28 or CD86
CD28 is a costimulatory molecule on T cells.
how do CD8 T-cells kill target cells?
by release of granzyme and perforin into the target cells.
Perforins create holes in the target cell’s membrane, allowing granzymes to enter the target cell.
