MHC/HLA serotypes

1. Familial inheritance

a) Many alleles of class I and class II molecules are present at each locus on chromosome 6.

b) Haplotypes from both parents are inherited and expressed codominantly.

2. Disease associations

a) DR4 Rheumatoid arthritis

b) DR3, DR4 IDDM

c) DR3 Sjogren’s syndrome

d) B27 ankylosing spondylitis

3. Transplant compatibility

a) Matching the donor and recipient at the HLA locus improves graft acceptance

b) Both the donor and recipient are typed for HLA profiles using DNA sequence analysis of the HLA genes or more than 200 specific anti-HLA antisera

c) HLA antigens on allographs stimulate recipient CD4+ T cells which respond by secreting cytokines and by inducing adhesion molecules

(1) IL-2 activates CD8+ T cells to a state of cytotoxicity, thus releasing effector molecules such as perforins

(2) IFN-g activates monocytes/macrophages to expresses delayed type hypersensitivity, resulting in increased lysosomal activity, phagocytosis, respiratory burst and release of TNF-a

(3) Activated selectins, integrins, intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAM) promote leukocyte extravasion into the graft bed.

d) Acute rejection

(1) Within weeks

e) Chronic rejection

(1) Episodic bouts of rejection, occurring months to years after transplantation

f) Hyperacute rejection

(1) Within minutes—graft never takes because of pre-existing sensitivity

Category: Pathology Notes