Page 81 - Textbook of Pathology, 6th Edition

Out of various genes for histocompatibility, most of the 1. Organ transplantation. Historically, the major 65
transplantation antigens or MHC are located on a portion of importance of HLA system is in matching donor and recipient
chromosome 6 of all nucleated cells of the body and platelets. for tissue transplantation. The recipient’s immune system
These genes occupy four regions or loci—A, B, C and D, on can recognise the histocompatibility antigens on the donor
the short (p) arm of chromosome 6 and exhibit marked organ and accordingly accept it or reject it. Both humoral as
variation in allelic genes at each locus. Therefore, the product well as cell-mediated immune responses are involved in case
of HLA antigens is highly polymorphic. The letter w in some of genetically non-identical transplants. CHAPTER 4
of the genes (e.g. D w3 , C w4 , B w15 etc) refers to the numbers 2. Regulation of the immune system. Class I and II
allocated to them at international workshops. HLA system histocompatibility antigens play a role in regulating both
is part of immunoglobulin superfamily of CAMs. cellular and humoral immunity:
Depending upon the characteristics of MHC, they have
been divided into 3 classes (Fig. 4.2): Class I MHC antigens regulate the function of cytotoxic
T cells (CD8+ subpopulation) e.g. in virus infections.
Class I MHC antigens have loci as HLA-A, HLA-B and
HLA-C. CD8+ (i.e. T suppressor) lymphocytes carry Class II MHC antigens regulate the function of helper
receptors for class I MHC and these cells are used to identify T cells (CD4+ subpopulation).
class I antigen on them. 3. Association of diseases with HLA. An increasing
Class II MHC antigens have single locus as HLA-D. number of diseases have been found to have association with
These antigens have further 3 loci: DR, DQ and DP. Class II some specific histocompatibility antigens. These disorders
MHC is identified by B cells and CD4+ (i.e. T helper) cells. include the following:
Class III MHC antigens are some components of the i) Inflammatory disorders e.g. ankylosing spondylitis. Immunopathology Including Amyloidosis
complement system (C2 and C4) coded on HLA complex but ii) Autoimmune disorders e.g. rheumatoid arthritis, insulin-
are not associated with HLA expression and are not used in dependent diabetes mellitus.
antigen identification. iii) Inherited disorders of metabolism e.g. idiopathic
In view of high polymorphism of class I and class II genes, haemochromatosis.
they have a number of alleles on loci numbered serially like The exact mechanism of such associations between the
HLA-A 1, HLA-A 2, HLA-A 3 etc. disease and HLA type is not clearly understood.
MHC antigens present on the cell surface help the
macrophage in its function of bacterial antigen recognition TRANSPLANT REJECTION
i.e. they help to identify self from foreign, and accordingly
present the foreign antigen to T cells (CD4+ or CD8+) or to B According to the genetic relationship between donor and
cells. recipient, transplantation of tissues is classified into 4 groups:
1. Autografts are grafts in which the donor and recipient is
ROLE OF HLA COMPLEX. The HLA complex is significant the same individual.
in a number of ways:
2. Isografts are grafts between the donor and recipient of
the same genotype.
3. Allografts are those in which the donor is of the same
species but of a different genotype.
4. Xenografts are those in which the donor is of a different
species from that of the recipient.
All types of grafts have been performed in human beings
but xenografts have been found to be rejected invariably due
to genetic disparity. Presently, surgical skills exist for skin
grafts and for organ transplants such as kidney, heart, lungs,
liver, pancreas, cornea and bone marrow. But most
commonly practised are skin grafting, and kidney and bone
marrow transplantation. For any successful tissue transplant
without immunological rejection, matched major histocom-
patibility locus antigens (HLA) between the donor and
recipient are of paramount importance as discussed already.
The greater the genetic disparity between donor and recipient
in HLA system, the stronger and more rapid will be the
rejection reaction.
Besides the rejection reaction, a peculiar problem
occurring especially in bone marrow transplantation is graft-
versus-host (GVH) reaction. In humans, GVH reaction results
when immunocompetent cells are transplanted to an
immunodeficient recipient e.g. when severe combined immu-
Figure 4.3 HLA system and loci on chromosome 6. nodeficiency is treated by bone marrow transplantation. The