BMS3021 Lecture Notes - Lecture 10: Skin Grafting, Phagocytosis, Nod Mice
30 May 2018
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Week 4. MHC and its role in transplantation and
autoimmunity, Genetic manipulation of the immune
system and transgenics and, Gene targeting in
immunology
MHC AND ITS ROLE IN TRANSPLANTATION AND AUTOIMMUNITY
• Transplantation: Process of transferring cells/tissues, organs from one individual to another
o Autograft = one part of body to another (same person)
o Isograft = between genetically identical individuals
o Allograft = between different members of the same species
o Xenograft = between members of different species
• Graft rejection: Is an example of where immune response acts detrimentally to the host and
exhibits the classic features of an immune response that shows specificity and memory
• Two antigens important in graft rejection:
ABO blood group antigens
Histocompatibility antigens
o Essential for organ transplantation
o Easier to match because not as polymorphic
as MHC
o Stimulate strong rejection responses which
are encoded by MHC
o Present antigen peptides to T cells which
stimulates strong allograft rejection
reactions
find more resources at oneclass.com
find more resources at oneclass.com
• HLA = human leukocyte antigen (same as MHC)
o Inheritance is codominant expression (from each parent)
o Highly polymorphic
• MHC I = expressed on all nucleated cells = CD8 = cytotoxic T cells
o Kills virally infected cells, kills parasites, kills foreign cells and cancerous cells
o Peptides that bind MHC I are usually 8-10 aa long (short)
• MHC II = expressed on professional APC = CD4 = helper T cells
o Provides help for CD8 and B cells and can be regulatory T cells
o Peptides that bind MHC I are usually 13-17 aa long (long)
• MHC genes are highly polymorphic:
o Variability allows presentation of a wide variety of peptides
o Beneficial for initiation of specific protective host defences
but
o Challenging for matching transplant donor and recipient
o Populations can adapt to potentially lethal infection (eg. malaria)
o Diversity:
Profound effect on Ag presentation and T cell recognition
Greatly extends range of peptides that can be presented
Advantage at individual and population level
Disadvantage = difficulty in matching
find more resources at oneclass.com
find more resources at oneclass.com
• MHC restriction:
TCRs recognise complex of antigenic peptide plus MHC (recognition of peptide alone or MHC
alone is insufficient)
o MHC molecules are highly variable between individuals therefore T cells need to be
educated to reogise self MHC oleules durig deelopet (positie seletio is
responsible for self-MHC-restriction)
• Matching for both class I and II MHC alleles increases graft survival
-survival begins to drop with mismatch
o Graft rejection is the result of a T cell mediated anti-graft response
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Mhc and its role in transplantation and autoimmunity, genetic manipulation of the immune system and transgenics and, gene targeting in immunology. Mhc and its role in transplantation and autoimmunity: transplantation: process of transferring cells/tissues, organs from one individual to another, autograft = one part of body to another (same person) Abo blood group antigens: essential for organ transplantation, easier to match because not as polymorphic as mhc. Histocompatibility antigens: stimulate strong rejection responses which are encoded by mhc, present antigen peptides to t cells which stimulates strong allograft rejection reactions, hla = human leukocyte antigen (same as mhc) Profound effect on ag presentation and t cell recognition. Greatly extends range of peptides that can be presented. Disadvantage = difficulty in matching: mhc restriction: These peptides are derived from: are derived from proteins that are only present in the donor eg. h-y male antigens.
