Cellular Immunity and Histocompatibility Flashcards
What are the two things that the T lymphocytes express
CD4 and CD8 surface antigens
What is CD4
Helper T cell that respond by secreting cytokines
What do T lymphocytes encounter on thymic epithelium
MHC class 1 and MHC class 2
What happens if a T lymphocyte responds to MHC class ll
They become CD4 helper T cells
What happens if a T lymphocyte responds to MHC class l
They become CD8 cytotoxic T cells (CTL)
What is CD8
Cytotoxic - they kill all other infected cells
What percentage of blood T cells are each CD4 and CD8
CD4 - 80%
CD8 - 20%
What are the functional subsets of CD4 helper T cells
Treg, Th1, Th2, Th17
What does Treg do
Suppresses the immune response
What does Th1 do
Promotes cell-mediated immunity
What does Th2 do
Promotes antibody mediated immunity
What does Th17 do
promotes inflammation
What is the thymus and where is it located
The thymus is a primary lyphoid organ that is largest at birth and shrinks with age. It sits at the top of the percardium above the heart.
Haemapoietic lymphoid precursors
Migrate from the bone marrow to the thymus where they mature into T lymphocytes
What is a viral infection
Infects epithelial tissue and replicates inside cells.
What are viral infections regulated by
A set of highly polymorphic genes that were first identified as controlling tissue transplantation.
What is a T cell receptor (TcR)
It is an Ig molecule on the surface of all T lymphocytes
What does the TcR gene locus undergo
Rearrangement (just like B cells)
What does the TcR recognise, and why
Only one antigen - which are the proteins of the Major Histocompatibility Complex (MHC) because the T cells were ‘selected’ during thymic development for their ability to respond to self MHC molecules
Does the TcR undergo affinity maturation or not, and why?
It does not undergo affinity maturation because you dont want the affinity of TcR to increase to a self-antigen (MHC)
How do T cells recognise foreign antigens from both virus and bacteria
Only when there are presented by MHC molecules on the surface of cells. This is how they detect host cells that have become virally infected.
How do T cells pick up viral infections
They detect small fragments of virus picked up inside the cell and expressed in the binding groove of MHC molecules on the cell surface.
MHC restriction means that T cells can see what two antigens at the same time?
- Foreign peptide antigen (non-slef) imbedded in MHC
- MHC molecules (self)
Describe how and why TcR has affnity towards the combination of MHC
The antigen binding surface of the TcR (top molecule) binds to the top of MHC which represents the ‘peptide groove’ containing the foreign peptide antgien. Thus the TcR has affinity towards the combination of MHC.
Label (3) of MHC restriction
TCR, peptide non-self, MHC (HLA) self)
Where are HLA molecules expressed and where are they present
HLA molecules are expressed on most cells and present peptide antigens to T cells.
Are HLA molecules weakly or highly polymorphic
Highly polymorphic
What are HLA
Human kekocyte antigens - refers to the 6 different molecules expressed on human cells.
What are the two forms of MHC
Class I and Class II
What do Class I molecules do
Class I picks up antigens from inside the cell (intracellular) and presents them to CD8 cytotoxic T cells. Cd8 cells can then kill the presenting cell.
What is the function of Class 2 MHC molecules
They pick up digested antigens from the phagolysosome (extracellular pathogens) and present them to CD4 helper T cells.
What are CD4 and CD8
Accessory molecules on T cells that physically associate with the T cell receptor
What do CD4 and CD8 both have
Intracellular tyrosine kinases associated with their cytoplasmic tails that initiate T cell signalling through phosphorylation.
What are CD4 and CD8 crucial for
That activation of your adaptive immune response
CD4 and CD8 bind to what
CD4 - MHC Class II
CD8- MHC Class I
What does the CTL (CD8+ cytotoxic function) produce
Produces granzyme and perforins that punch holes in the target cell membrane and destroy cell viability.
What is the CD4+ helper function
Proliferate and produce cytokines that “help” other cells.
Peptide source for MHC class 1
Intracellular
Peptide source for MHC class 2
Extracellular
Peptide source for MHC class 1
Intracellular
MHC class 1 and 2 work on viruses or bacteria
Class 1 - viruses
Class 2 - bacteria
Restriction of polymorphism
Polymorphism is restricted to the protein domains that form the peptide groove
What are the two important consequences of MHC polymorphism
- Tissue transplantation is difficult except for identical twins
- MHC polymorphism are strongly linked to many autoimmune diseases.
What does it mean when MHC is polymorphic
It varies between individuals. T cells from the recipient recognises the donor MHC antigens as foreign.
What part of the MHC is polymorphic
The locus
How many polymorphic molecules are expressed on your cells
12 - 6 from mother and 6 from father.
