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BLG 307 (38)
Clare Chua (38)
Lecture

alloresponses

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Department
Biology
Course
BLG 307
Professor
Clare Chua
Semester
Fall

Description
ALLORESPONSES/ TRANSPLANTATION IMMUNOLOGY Transplant rejection is an immune response - transplants WITHIN inbred strains succeed - transplants BETWEEN inbred strains fail second set rejection is faster, more intense (due to immunologic memory) second set from an unrelated part is akin to a first set (specificity) memory resides in lymphocytes (and can thus be transferred) Terminology: autologous – same person syngeneic – between genetically identical individuals (inbred strains) allogeneic – genetically different but same species xenogeneic – different species Genes responsible for transplant rejection are at HLA and encode MHC I and II Laws of transplant rejection 1. transplants within inbred strains succeed 2. transplants between inbred strains fail 3. from inbred parental (aa) to F1 (ab) will succeed; reverse won’t 4. from F2 and all subsequent generations to F1 will succeed 5. parental to F2 GENERALLY fail, but not always n % graft survival = (3/4) where n=number of histocompatability genes (approx. 30-50) ONE-WAY MLR = mixed lymphocyte reaction; in vitro correlate to tissue rejection mix blood samples from patient A and B (irradiate B  no mitosis) monitor T cell proliferation of patient A in response to B antigens primary response to ALLOANTIGENS is much more vigorous than primary responses to generic antigens (ie ovalbumin) CD4 cell involvement in alloresponse: they recognize foreign MHCII molecules IL-2 secretion: CD8+ activation γIFN: MHC expression increases, APC activity increases NK cells activated, macrophages activated IL4/5/6: activate B cells, stimulate antibody production  causes vascular damage in vivo CD8 cells recognize and target foreign alloresponsive cells based on MHCI evidence: - CD8 ardivation depends upon MHCI difference - if a 3 party cell has same MHCI as stimulator of alloresponse it will also be targeted for cytolysis - covering stimulator cell MHCI with antibodies protects them - transfecting MHCI genes to previously resistant target cells renders them susceptible to cytolysis **CD4 recognition of MHCII differences is more important than CD8/MHCI in vivo** MOLECULAR BASIS = alloparadox 1. magnitude of alloresponse is due to high number of responding cells (10%) as compared to antigen-specific responses (1/50,000) 2. T cell education is supposed to select for those TCR’s that recognize a
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