Flashcards in MHC and Transplantation Deck (32):
What are MHC proteins?
Expressed at the cell surface and function to present ‘self’ and ‘nonself’ antigens for inspection by T cell antigen receptors.
What is the medical relevance of MHC?
Histocompatibility - major role in graft survival.
What is the chromosomal location of the MHC?
What antigens are encoded by the class I region?
Encodes HLA-A, B, C (‘classical’) antigens.
What antigens are encoded by the class II region?
Encodes HLA-DR, DQ, DP antigens.
What antigens are encoded by the class III region?
Encodes HSP70, TNF, C4A, C4B, C2, BF, CYP21
Where are class I antigens primarily expressed?
Found on all nucleated cells.
Where are class II antigens primarily expressed?
On B lymphocytes, dendritic cells and macrophages (professional antigen presenting cells) but expression can be induced on T lymphocytes and other cells.
What is the structure of HLA antigens?
What type of inheritance does MHC show?
Mendelian inheritance (1:4, 1:2, 1;4)
En-bloc from each parental chromosome (HLA-A,B,Cw, DR, DQ,DP). Each individual inherits two antigens at a given locus.
What type of expression does MHC show?
Codominant - all inherited antigens are displayed on the cell surface.
How is HLA polymorphism created?
Large number of allelic variants at each locus
Allelic variation maintained at population level due to survival advantage
What is the significance of HLA polymorphism?
Significant in terms of capacity of individual to mount an immune response in response to an antigenic challenge.
What is sensitisation?
Any event which elicits an HLA directed immune response:
- Blood transfusion
What is the main function of MHC?
Bind to peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.
What kind of T cells does MHC class I present to?
Killer T cells (CD8)
What kind of antigen is presented by MHC class I?
Those that from intracellular pathogens, such as viruses and some bacteria, including bacterial L forms, bacterial genus Mycoplasma, and bacterial genus Rickettsia.
What kind of immunity is MHC class I involved in?
What kind of T cells does MHC class II present to?
Helper T cells (CD4)
What kind of antigen in presented by MHC class II?
Those from extracellular proteins, i.e. bacteria, parasites, fungi etc...
What kind of immunity is MHC class II involved in?
What is an autograft?
Grafts from one part of the body to another (eg, skin grafts). Undergo no rejection.
What is an isograft?
Grafts between genetically identical individuals (eg, monozygotic twins). Undergo no rejection.
What is an allograft?
Grafts between members of the same species that differ genetically.
What determines the likelihood of rejection in allografting?
The degree of histocompatibility.
What is a xenograft?
Grafts between different species?
What other factors influences the degree of graft rejection?
- Type of the transplant. Some sites, such as the eye and the brain, are immunologically privileged (ie, they have minimal or no immune system cells and can tolerate even mismatched grafts).
- Skin grafts are not initially vascularized and so do not manifest rejection until the blood supply develops.
- The heart, kidneys, and liver are highly vascular organs and lead to a vigorous cell mediated response in the host.
What is hyperacute rejection?
The transplanted tissue is rejected within minutes to hours because vascularization is rapidly destroyed. Hyperacute rejection is humorally mediated and occurs because the recipient has preexisting antibodies against the graft, which can be induced by prior blood transfusions, multiple pregnancies, prior transplantation, or xenografts against which humans already have antibodies.
What is acute rejection?
Manifests commonly in the first 6 months after transplantation.
What is chronic rejection?
Develops months to years after acute rejection episodes have subsided. Chronic rejections are both antibody- and cell-mediated.
What is the name given to antibodies that cause the agglutination of foreign erythrocyte?