Lecture 24: Cellular immunity and histocompatibility Flashcards
Describe the potential cells that can be formed from the immature thymocyte that has the CD4 and CD8 receptors:
Immature thymocyte (CD4 and CD8) can go on to form:
-> CD8+ Cytotoxic T cells (~20% in blood)
or
-> CD4 T helper cells (~80%)
What are the subtypes of the CD4+ T helper cells?
Treg
Th1
Th2
Th17
What do the different types of CD4+ T Helper cells do?
They characterise different immune responses depending on the pathogen
(this is extra detail but to make sense of things)
Where is the thymus located and what does it do?
The thymus is located at the top of the pericardium above the heart.
Primary lymphoid organ
Site of T cell maturation
Describe T cell maturation in the thymus:
Heamopoetic lymphoid precursors migrate from bone barrow to the thymus where they mature into T lymphocytes.
Only small percentage of T cells survive the thymus as mature t cells… Most die from ‘neglect’
The t cells that survive the thymus have been taught to recognise what?
Educated to recognise self MHC molecules expressed in thymic tissue.
Viruses replicate inside cells, so how doe the immune system detect and kill virus producing cells?
Regulated by a set of highly polymorphic genes that were first identified as controlling tissue transplantation
Major histocompatibility complex (MHC) (Class one vs class two)
These genes code for human leukocyte antigens (HLA) on the cell surface.
How do cytotoxic T cells kill cancerous cells or viral infected cell?
CD8+ T cells react to own cells when there is a change in MHC class one molecules i.e when they express neoantigens picked up from inside the cell (because its cancerous or infected and fucked)
This neoantigen could be viral or altered self antigen
Describe MHC restriction:
Histocompatibility genes control viral immunity.
CD8+ cells only kill viral infected cells from the same strain i.e cytotoxic T cells only recognise self cells and when they express virus. i.e you cant transplant CD8+ cells as they wont work in another body.
Viral immunity requires what when it comes to MHC restriction?
Viral immunity requires two antigens:
Self: Antigen(s) encoded by MHC
Non-self: Antigen(s) encoded by virus
Describe MHC restriction in molecular / receptor terms:
T cell: Has T cell receptor (TcR) bound to its membrane (like Ig molecule)
Target cell: Has HLA expressed (determined by MHC genes) and they sample the cell and present peptide antigens to the T cell.
TcR recognises the HLA and presented peptide simultaneously
Naming is confusing for the HLA and MHC, explain these:
MHC = Genetic locus regulating histocompatibility
HLA: Human leukocyte antigen, referring to the six different molecules expressed on human cells
Class one MHC: A,B,C
Class two MHC: DR, DP, DQ
KNOW ALL THESE
compare and contrast the function of CD4 and CD8:
CD4 and CD8 are accessory molecules to the T cell receptors. They physically associated and are essential for function.
CD4 = T helper cells, recgonise antigens in MHC calls 2.
CD8 = Cytotoxic T cells, recognise antigens in MHC class 1.
Describe the intracellular signalling processes of CD4 and CD8:
CD4 and CD8 have intracellular tyrosine kinases associated with their cytoplasmic tails that initiate T cell signalling through phosphorylation. They are crucial for that activation of your adaptive immune system
Describe T helper/CD4 activation:
[TcR+CD4]+[MHC class+Bacterial peptide] = activation
T helper cell activates, proliferates and produces cytokines that ‘help’ other cells