immunology of transplantation parts 1/2 W3 Flashcards
components of the innate immune system?
macrophages
neutrophils
complement and natural antibodies
components of the adaptive immune system?
dendritic cells (antigen presentation)
T cells (helper and cytotoxic T cells)
natural killer cells (cytotoxic)
B cells (antibody generation and memory)
what is the major histocompatibility complex in humans?
histocompatibility locus antigen (HLA)
HLA features?
molecules imprint individuality on cells and are pivotal in the generation of immune responses
very polymorphic - there are many different variations possible at each gene locus
categories of HLA molecules?
HLA class I and class II
class I HLA molecules? features?
HLA-A, HLA-B, HLA-C
expressed by most somatic cells of the body
used to present peptides from internally processed proteins
class II HLA molecules? features?
HLA-DP, HLA-DQ, HLA-DR
expressed by antigen presenting cells (DCs etc) that constantly sample their microenvironment
used to present antigenic peptides derived from digested material (including pathogens, abnormal or foreign cells)
peptide groove on HLA class I molecules?
small peptide derived from internally processed protein sits in peptide groove. this is what is looked at by passing immune cells.
what happens if class 1 HLA molecule is associated with virus-derived protein?
the cell is recognised as infected and will be killed by cytotoxic T cells
peptide groove on HLA class II molecules?
used by antigen presenting cells (DCs etc) to present antigenic peptides derived from digested and processed material
cell surface expression of peptide derived from pathogen or foreign cell will stimulate a T cell immune response.
what happens at a T cell synapse?
other molecules have to be engaged to create a signal strong enough to engage and ensure the T cell is activated.
ways a T cell can kill another cell expressing viral protein or abnormal cell?
use FasL (Fas ligand) which can induce cell death
can release tumour necrosis factor which can induce death
molecules perforin and gz B can punch a hole in the membrane, pass through and induce cell death.
t cell activation pathway?
dendritic cell finds abnormal cell, takes up material and present the antigen which initiates T cell responses. T cells are antigen specific, facilitated by production of IL-2 which is required for their proliferation. causes clonal expansion of T cells with unique specificity. circulate body, find target and exert effector functions. once infection is eradicated then these clones die, but memory T cells remain.
key principles of transplant immunology?
rejection of transplanted organs is directed at specific proteins called antigens
rejection is donor specific
rejection may be cell or antibody mediated
rejection exhibits memory - ie a 2nd similar transplant is rejected more rapidly (due to rapid generation of cytotoxic antibodies recognising transplant)
how is the best match for kidney transplants found?
all patients on transplant waiting list have their HLA tissue type on a central UK database
what is HLA profiling used for
used to allocate kidneys. less important for other organs eg liver as they are less immunogenic.
