MHC & INFECTIOUSDISEASES

By MAZIN S.SALMAN

.MHC (Major histocompatibility

complex).The immune system is

regulated bymolecules coded by some

genes.These are genes of the

histocompatibility systemwhich code

For Human leukocyte antigens.

(HLA.)

HLA : located in the short armof chromosome 6.( part of

MHC.)MHC: divided into 3 classes.

MHC class 1 : code the moleculesHLA-A, HLA-B, HLA-C.

(present in almost all somatic cells)MHC class11 : code the molecules

HLA-DR, HLA-DQ, HLA-DP.(expressed in APC , B- cells, activated

T-cells, macrophages, dendritic cells,Thymic epith.cells).

Each individual have: *2 antigens in each locus.

*one half inherited from each parent.

Expression of MHC alleles isCodominant.

(one haplotype inherited from each parent ).

HLA: the most polymorphicgenetic system in man.

*numerous alleles. *various possible combinations.

*Polymorphism contribute to: -the genetic diversity of the

species. -differences in susceptibility to

diseases.(among genetically distinct groups).

*this make it difficult for large-scale epidemics to occur.

MHC polymorphism &polygeny.

Polymorphism of MHC loci ensure thediversity in MHC gene expressionin the population as a whole.Polygeny (the presence of several differentrelated genes with similar functions) , ensuresthat each individual produces a numberof different MHC molecules.

The antigenic universe.Scientists estimate that the antigenic universecontain between - epitopes.(antigens.)This mean that there are at least - epitope –specific T-celland B-cell.(specific mean that there is a cell, T orB for each of the - epitopes.)

T-cells only recognize microbialpeptides in association withMHC.(restricted)

*MHC control :-resistance to infections.

-susceptibility to infections.Stimulation require 2 signals.

*Antigen peptide. *Co-stimulatory signal.

(2 key system).

*HLA-DRB1*7 and HLA-DQA1*0101:are associated with greater

susceptibilityto develop pulmonary T.B.

*HLA-DQA1*0301 &HLA-DQA1*0501:are associated with protection

against T.B.

Conclusion *HLA may act alone (or with other

genes )in conferring susceptibility to , or

protectionagainst , infectious diseases.

*Knowledge about genetic mechanisms

contribute to our understanding of the

pathogenesis of infectious diseases. *The mechanism of immune

responses toinfections that are influenced by HLA

may be the key to future vaccines.

* Future vaccines aim to use peptidesof the organisms that mimic the HLAantigens