IMMUNOLOGY

Bios 328a textbook-based study of immunologySpring 2003

http://www.lehigh.edu/~sk08/Courses/Bios328/mainpage.htm

MHC diversity arises from:

• Polygenicity

• Polymorphism

• Co-dominance

• Linkage disequilibrium

Polygenicity:

Polymorphism:

n [ISV] (1941) : possessing any of a group of nonallelic genes that collectively control the inheritance of a quantitative character or modify the expression of a quantitative character

n [ISV] (1839) : the quality or state of being able to assume different forms: as a : existence of a species in several forms

And by extension: existence of a gene in several forms

Co-dominance:

• Full expression in the heterozygous state

Linkage disequilibrium:

• When the observed frequencies of haplotypes in a population does not agree with haplotype frequencies predicted by multiplying together the frequency of individual genetic markers in each haplotype.

http://hal.weihenstephan.de/genglos/asp/genreq.asp?nr=519

MHC haplotypes are in disequilibrium:

Two explanations are offered:

1. There has not been enough “evolutionary” time to achieve equilibrium

2. Some allelic sequences in the haplotype are adaptive

(i.e., they are suited to displaying frequently occurring “foreign” peptides.)

Haplotype:

• Think “Polygenicity,” “polymorphism,” “co-dominance,” and “linkage disequilibrium”….

Haplotype:

• Think “Polygenicity,” “polymorphism,” “co-dominance,” and “linkage disequilibrium”….

Genetic organization in the mouse is similar…

continue to think about polygenicity, polymorphism, co-dominance, and linkage disequilibrium

And, the result is:

So…that’s the genetics…

what does the synthesis of the protein look like?

“Classical” and “non-classical” MHC’s

“Classical” are expressed continuously.

“Non-classical” are expressed in specific tissues and/or at specific times.

Linkage disequilibrium (again)

Some haplotypes correlate with increased incidence of disease.

Such association is measured by a “relative risk” factor (RR).

(Ag+/Ag-) disease RR = _____________________

(Ag+/Ag-) control

Question: to what does “Ag+” refer?)

MHC- III

• Complement• Tumor necrosis factor• Heat shock proteins• Hydroxylases• (generally) genes related to inflammation