MHC recognition and immune tolerance Flashcards
Memory cells generated in primary responses provide long-lived immunity
-They have rearranged genes. Uptake of antigen by B-cells and T-cell help are very fast leading to rapid generation of plasma cells and antibody
Vaccination induces immunological memory
-Vaccines generate memory B-cells and memory T-cells
What is self?
-Immunological self is encoded in the MHC/HLA genes and is recognised by T-cells
-HLA and MHC are the same thing:
=HLA: Humans (Human leucocyte antigen)
=MHC: Mouse (Major histocompatibility complex)
What does the MHC do in pathogen recognition
- MHC proteins provide a conveyor belt to present peptides normally inside the cell to the immune system.
- MHC presents pathogen peptides to T-cells
- The conveyor belt allows the MHC to present virus peptides to T-cells. This allows the T-cell to see inside the cell to find the virus!
HLA/MHC genes make two main classes of MHC proteins: MHC class I and MHC class II
- MHC II = antigen-presenting cell
- MHC I = Most cells: except neurons
MHC/HLA varies greatly between individuals
-HLA/MHC genes provide your personal immune system. It defines ‘self’.
What does HLA define?
-HLA genes define a genetic locus that varies between individuals.
How does MHC link to T-cells?
-During rejection the T-cells
recognise cells as non-self. They
do not recognise antigens directly
What does the Antigen conveyor belt do with MHC proteins?
- The conveyor belt also loads SELF peptides onto MHC/HLA proteins
- The T-cell recognises MHC plus SELF peptide
What happens if the incorrect MHC or peptide is loaded?
- If the MHC or peptide are wrong, the T-cell is activated
- This occurs during infection and tissue rejection
The benefit of MHC
-MHC varies greatly between individuals.
-This provides populations with diversity in their
immune systems so they are not wiped out
by pathogens.
How do B and T-cells find the antigen?
- The lymphoid organs concentrate antigen and B and T-cells
- T-cell help to B cells is crucial for an immune response.
- The lymph nodes concentrate antigen and lymphocytes
Pathogen associated molecular patterns PAMPs are
recognised by Toll- like receptors and can trigger
phagocytosis by dendritic cells
-Dendritic cells make a lot of MHC class II that binds peptides
Dendritic cells migrate to the lymph nodes to find T-cells
- antigen presenting cells find antigens throughout the body.
- They take up antigen and present peptides on MHC class II
- They migrate to lymph nodes to find T-cells
T-cells and B-cells are concentrated in special areas of the lymph node
-Dendritic cells bring antigen to lymph node and enter T-cell area
Dendritic cells present antigens to T-cells. T-cells help B-cells make antibody
- Dendritic cells present antigen to helper T-cells
- T-cells give help to B-cells
- B-cells make antibody
- The antibody is secreted
Why do lymph nodes swell during infection?
- Memory B-cells divide in the germinal centre
- Plasma cells move to lymph and blood to deliver antibody
T-cells are educated in the thymus
- T-cell precursors within hematopoietic stem cells from bone marrow and liver have not rearranged genes.
- T-cells differentiate in the thymus
- T-cells leaving thymus have rearranged T- cell genes and recognise antigens but most do not recognise self
VDJ recombination occurs in the thymus before the T-cells get to the lymph nodes
-SELF reactive T-cells are removed in the thymus before they get to lymph nodes
What do thymic medulla do?
-Thymic medulla cells use MHC to educate T-cells by presenting self proteins (peptides) to immature T-cells
What is positive selection?
- If immature T-cells have weak binding for MHC self-peptide they survive.
- This is known as positive selection.
What is negative selection?
- If immature T-cells that have strong binding for MHC self-peptide they die.
- This is negative selection
What is central tolerance?
-Elimination of self reactive T-cells in the thymus is called
central tolerance
