Lecture 24 Cellular immunity Flashcards
What are the two classes of T lymphocytes and where do they originate
Starts from immature thymocyte which expresses CD4+ and CD8+ –> CD8+ is cytotoxic (20%) and CD4+ (80%) is a helper cell which reduces cytokines.
What are the main types of cytokines?
Treg = dampens immune response
Th1 = Cellular response
Th 2 = Antibody type response
Th 17 = Inflammatory response
What is the thymus
Shrivels up as you age, most active just before birth -> entire T cell repertoire generated before birth.
Haematopoietic lymphoid precursors migrate from bone marrow to the thymus where they mature into T lymphocytes. Only a small percentage will survive as most die from neglect or are killed due to overreaction to MHC. T cells that have survived are educated to recognize self MHC molecules expressed in thymic tissue
What are human leukocyte antigens?
A polymorphic set of genes that control tissue transplant
Why is tissue transplantation not possible?
Because cytotoxic T cells react to cells when there is a change in MHC class I molecules.
What is a neoantigens?
A viral or altered self antigen
What was the experiment which identified the MHC gene locus which controlled tissue rejection?
A mice and B mice = AxB mice
AxB mice backcrossed with B mice around 20x, selecting for tissue rejection so that it is congenic with original B strain.
How did they find that genes that regulate tissue rejection control viral immunity
Infected congenic strains with the same virus, and injected T lymphocytes from A to the other strain. They found that cytotoxic T lymphocytes only killed infected cells from the same strain
What is the MHC restriction?
T lymphocytes can only kills cells that are encoded by MHC and the virus
What does a TcR look like?
Looks like a immunoglobulin, it has 6 loops. Has a antigen binding site which interacts with MHC
What are the different MHC types in humans?
Class I: A, B, C
Class II: DR, DP, DQ
These are co-dominant so everyone has 2 copies
MHC class I
2 alpha helices and a pleated sheet on the bottom forming the peptide groove. Polymorphism occurs in helices or floor. Peptide length restricted to around 8-10 amino acids
MHC class II
two alpha helices, carries all the polymorphism. Peptide is much longer because ends of the groove are open.
How do CD4+ cells work?
Cell recognize antigens from outside the cell and express MHC class II. Helper T cell proliferates and produces cytokines that help other cells
How does the CD8+ cell work?
Cell expresses MHC class I, and CD8+ kills the cell by producing granzymes and perforins
