Question

A two month old baby does not have class I MHC molecules. How does this affect the baby's adaptive immune response? What pathogen is the baby likely most susceptible to?

Answer 1

MHC molecules:

All human cells have a series of molecules on their surfaces that are recognized by other individuals as foreign antigens. Major histocompatibility complex (MHC) molecules were discovered as products of genes that evoke rejection of transplanted organs and responsible for tissue compatibility between individuals.

The human MHC are commonly called the human leukocyte antigen (HLA) complex is the name of the loci of genes densely packed (clustered) on a small segment on chromosome 6 (6p21.3). They were named HLA because in humans MHC-encoded proteins were initially detected on leukocytes by the binding of antibodies.

Physiologic function of MHC molecules: To display peptide fragments of proteins for recognition by antigen-specifc T-cells.

The MHC molecules are products of MHC gene. The best known of these genes are the HLA class I and class II genes. Their products are important for immunologic specifcity and transplantation histocompatibility, and they play a major role in susceptibility to a number of autoimmune diseases.

Polymorphism of MHC gene:

– MHC gene is highly polymorphic. Polymorphism means that there are many alleles of each MHC gene resulting in extreme (high degree) variation in the MHC in human population (genetic diversity).

Each person inherits one set of these alleles that is different from the alleles in most other persons. Te possibility of two different individuals having the same combination of MHC molecules is very remote. Therefore grafts exchanged between individuals are recognized as foreign and attacked by the immune system. Polymorphism is an important barrier in organ transplantation.

– HLA haplotype: It is the combination of HLA alleles in each individual. Each individual inherits one set of HLA genes from each parent and thus typically expresses two different molecules for every locus.

Importance of MHC:

(1) In organ/tissue transplantation

(2) HLA is linked to many autoimmune diseases

Class I MHC Molecules

They are the products of MHC class I genes and are expressed on all nucleated cells and platelets (except erythrocytes and trophoblasts)They are encoded by three closely linked loci, designated HLA-A, HLA-B and HLA-C.

Highly polymorphic in the population and most highly polymorphic segment known within the human genome.

Functions: Products of MHC class I gene are integral participants in the immune response to intracellular infections, tumors and allografts.

Class I molecules interact with CD8+ T lymphocytes during antigen presentation and are involved in cytotoxic reactions. CD8+ T lymphocytes recognize antigens only in the context of self- class I molecules, they are referred to as class I MHC-restricted

Diseases related to MHC1 molecules :

1) Ankylosing spondylitis

2) Postgonococcal arthritis

3) Acute anterior uveitis

4) Behçet’s syndrome

5) 21-hydroxylase deficiency

6) Hereditary Hemochromatosis

In the absence of MHC I molecules, NK cells are activated and recognize the cell as aberrant, suggesting that it may be infected by viruses attempting to evade immune destruction.