Aspects of Immunology

 

A patient's guide to autoimmunity

   
In the immune response, there is an activation of various immune cells, which transmit messages to each other via chemicals called cytokines. The immune process, when directed against self, is called autoimmunity and is the fundamental cause of most inflammatory rheumatic diseases.

In this model, foreign matter known as antigens are identified by cells called antigen presenting cells, especially macrophages, which consume these particles (A), and process them, before displaying them on their surface (B), to immune cells called lymphocytes (C). In order for these lymphocytes to be activated, the antigens must be recognized as foreign, and are presented to the lymphocyte in association with a genetic surface marker. Therefore for the reaction to take place, both a gene marker and the foreign particle are required. Genetic markers are identified in several diseases. The B27 gene n chromosome 6 is associated with Ankylosing spondylitis, and the DR4 gene has associations with Rheumatoid arthritis. The lymphocyte then makes cytokines which activate more and more lymphocytes in a progressive cascade, to multiply and spread the message. The resulting response includes the development of antibodies to the original offending agent / antigen. 

Figure 1 - the immune response

To explain this in a simple way related to a joint....

The joints are lined by a thin tissue called the synovium. This tissue consists of millions of genetically determined molecules in certain sequences - determined by inheritance. For illustrative purposes, we can draw in the diagram of the joint, a sequence of molecules in the synovium as shown in (A). This genetic marker is an intrinsic part of the normal tissue of that individual. 
If the individual is exposed to an external agent - i.e. an infective organism (B), the body will identify it as foreign to itself and mount an immune response to remove or eradicate it (C). 
Many of these external agents (also called antigens), are in fact infective in origin. In certain diseases, these organisms are known (i.e. yersinia, or chlamydia organisms - which cause reactive arthritis, or streptococcal organisms - which cause rheumatic fever.). But in others such as rheumatoid arthritis, the actual starting agent is as yet unidentified.
In the process of mounting a response to the organism, the body makes a memory to it. This memory is a protective function in our normal defense against infection - giving us immunity in the event of a re-exposure to the same organism. 
However - in autoimmunity - by chance -  the organism / agent / antigen, has a sequence of molecules which resembles the molecular sequence in the joint lining itself (C). The body gets 'confused'. It sees the agent as resembling itself, and therefore mounts an attack against itself (D), as it sees its own tissue as foreign. Therefore since the agent and the body's own tissue look alike at a molecular level, the similarity is called molecular mimicry, and the resultant immune response is called autoimmunity.

Figure 2 - Molecular mimicry and autoimmunity

What follows is an ongoing attack on one's own tissue...in this case the joints, and the consequence is an arthritis.
   
Other links

 

HLA - the basics
Tumour necrosis factor
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