Lecture 19 Flashcards
What are the two types of T lymphocytes and their relative conc in blood
CD8+ cytotoxic (20%) and CD4+ helper (80%)
What is the role of the Thymus in selection of T lymphocytes
haemopoietic lymphoid precursors from the bone marrow mature in the thymus and express both CD4+ and CD8+ surface antigens.
The T lymphocytes that survive to maturity are those that respond to self MHC molecules expressed in thymic epithelium.
What most of the T cells in the thymus die of and how many don’t enter the blood
die of neglect. 83% don’t enter the blood
What does the T cell respond to to become a CD4+ helper cell compared to a CD8+ cytotoxic cell
MHC class 1 = CD8+ MHC class 2 = CD4+
Describe the thymus
primary lymphoid organ largest at birth and shrinks with age. Sit on top of the pericardium.
What genes help T cells to detect and kill virus producing cells
Major Histocompatibility Complex (MHC) are highly polymorphic genes that code for Human Leukocyte Antigens (HLA) on the cell surface
What are the differences and similarities of T cell receptor compared to B cells
TcR locus undergoes rearrangement with two gene loci- Alpha and beta chain.
Unlike antibodies TcR only recognises 1 antigen- MHC protins. Unlike Ig it doesn’t undergo affinity maturation because affinity to self antigen doesn’t need to be increased
What does MHC Restriction mean
T cells only recognise foreign antigens from viruses or bacteria when they are presented by MHC molecules on the surface of cells.
How was MHC restriction figured out
The Tcells from two congenic strains of mice, were only able to kill infected cells from the same strain. AxB hybrid rejects strain B tissue after >20 back crosses as it has A genes for MHC while every other gene is B.
What are the two antigens required for Viral immunity as a result of MHC restriction
Self (antigens coded by MHC) and Nonself (antigen coded by virus)
What is molecular interaction initiates the T cell response
The antigen binding surface of TcR binds to the top of MHC which represents the peptide groove containing the foreign peptide. the TcRs affinity to the MHC peptide combo initates response.
What are the 6 different molecules expressed on human cells (HLAs) with class
MHC class 1 : ABC MHC class 2: DR, DP, DQ
Why must people who have transplants take immunosuppressive drugs like cyclosporine
Tissue varies from one person to another because MHC is polymorphic. The 3 class 1 and 3 class 2 molecules that are expressed from both maternal and paternal codominantly giving 12 combinations of polymorphic MHC molecules. hundreds of different variations at each MHC locus.
What antigens does Class 1 MHC pick up and how does it present this
Class 1 picks up peptide antigens from inside the cell (intracellular) and presents them to CD8 cytotoxic T cells which effectively kill the presenting cell.
What antigens does Class 2 MHC pick up and how does it present this
Class 2 pick up digeste antigens from the phagolysosome (extracellular pathogens) and present them to CD4 helper T cells.
What are CD4 and CD8 molecules
They are accessory co receptors that associate with the TcR .
What are intracellular pathogens vs extracellular
intra= virus, extra= bacteria
How do CD4 and CD8 become crucial to immune activation
They have intracellular tyrosine kinases associated with their cytoplasmic tails that initiate T cell signalling through phosphorylation.
What is the function of CD4+ helper T cell
T cells proliferate and produce cytokines that “help” other cells. (help B cells to mature)
What is the function of CD8+ killer T cell
Cytotoxic Tcells produce granzyme and perforins that punch holes in the target cell membrane and destroy cell viability.
Where is polymorphism of MHC restricted to
the protein domains that form the peptide grooves.
What is the reason behind polymorphism
natural selection for antigens in the specific environment.
What is the relationship between MHC polymorphism and disease
certain autoimmune diseases are associated with a higher relative risk of having specific types of polymorphisms in the MHC locus as it is the only very polymorphic part of the entire genome.
