HTHSCI 1DT3 Lecture Notes - Lecture 10: Interleukin 2, Regulatory T Cell, Dendritic Cell
23 Jun 2018
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Mechanisms of immune rejection – Andrew george
Broadly speaking, 5 year graft survival is approximately 85-90% for most transplants; which has hugely
increased over the last 30 years
Immunological rejection of grafts is the main abrrier to transplantation
Rejection can be acute, hyperacute or chronic
Hyperacute rejection
- Occurs due to pre-formed antibody
- Occurs within minutes of the bloody supply being created
- ABO antibodies / porcine carbohydrate antibodies in xenotransplantation
- Cross-matching is to prevent this type of rejection
Acute rejection
- Is T-cell mediated
- Occurs within days/weeks generally, but is defined as rejection occurring within a year of
transplantation
Chronic rejection
- Can be antibody or Tcell mediated i.e. is a more complex response
- An element of organ injur is implicated
- Occurs >1 year after transplantation
T cell alloreactivity
Characteristics:
1) specificity
2) memory on second transplant form the same donor
3) stronger than primary alloresponse against conventional antigens (allowing it to be seen in vitro,
where a mixed lymphocyte response can be demonstrated)
T cell alloreactivity is facilitated by MHC antigens
The strength of the response is due to:
- a high frequency of allospecific T cells
- high determinant density model: peptide-non-specific response involving multivalent
recognition (i.e. lots of weak - multiple MHCs/surface area of T cell - compound leading to
overall strong response)
- multiple determinant model: peptide-specific response, refers to the huge number (30 000)
different molecules of the body, all of which trigger T cell reactivity (i.e. the idea that there
are so many T cells)
both models are correct, their relative importance dependant on the circumstances of the
reaction
Minor histocompatibility antigens
- Induce a slower alloresponse
- Molecules presented to T cells by MHC that are antigenically distinct
- Classical H-Y antigen, which is male-specific, thus transplanttaions from males females can
cause immune response
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