IMMUNOLOGY



In 1882, the Russian biologist Elie Metchnikoff discovered the process of phagocytosis ('cellular eating'), when he observed that a rose thorn inserted into a sea urchin larvae was surrounded by immune cells from the host. He concluded that the immune cells were attempting to eliminate the foreign body and that this process may also be used by immune cells in our bodies to eliminate infecting microorganisms. Metchnikoff was awarded the Nobel prize in 1908 for his discovery and is considered to be the father of the field of immunology.

Research efforts rapidly focused on the mammalian immune system, with numerous scientists trying to uncover the cellular and molecular basis of immunity. It was soon realised that the cells and molecules within circulating fluids, such as blood, carried out immune reactions against pathogens. Indeed, immune reactions performed by blood cells (the fraction known as white blood cells) was referred to as cellular immunity, while those that were performed by soluble proteins in blood were termed humoral immune reactions. There was a close interaction between these two types of immune reactions.

Our current understanding of mammalian immunity indicates that there are two 'arms' of immunity: innate and adaptive. Although the molecular mechanisms underlying these systems are independent and unrelated, there is a close functional interaction between them. The main difference between innate and adaptive immune systems lies in what happens to genes whose proteins function in these systems. Genes that function in innate immune responses are inherited 'intact' from parental DNA. Hence, the innate immune system genes within the vertebrate embryo (referred to as germline genes) remain unchanged during the development of the embryo into an adult. The genes of the adaptive immune system, on the other hand, are inherited in a fragmented and non-functional manner and undergo significant changes during the development of the individual.

The genes of the adaptive immune system are closely related to one another and belong to a large gene family known as the immunoglobulin (Ig) superfamily. Ig loci (regions of the genome containing Ig sequences) in vertebrate embryos are not intact genes. They are organised as gene segments. There are several distinct segments (C=constant, V=variable, D=diversity, J=joining) and each segment is composed of several distinct, but slightly different exons. In a group of blood cells that will eventually become a type of white blood cells known as lymphocytes, the gene segments are 'joined' together to create functional genes. To do this, a single V exon is joined to a single D exon and a single J exon. The V-D-J exons are then joined to a C exon, to create a functional Ig gene (V-D-J-C). This process of randomly joining exons from different segments to form a functional gene produces a large number of possible Ig genes. This is the reason why adaptive immune system proteins are considered to be very diverse (note: there are additional diversification mechanisms within the adaptive immune system). In other words, the Ig genes within a vertebrate is produced only during development and the stochastic process of exon combination produces a large repertoire of Ig proteins (antibodies, T-cell receptors).


sham.nair@mq.edu.au
shamnair@gmail.com

Sham Nair 2014