Tolerance, Autoimmunity and autoimmune disease

Question 1

Define antigen

Answer 1

Any substance capable of producing an immune response. (Normally biological substance, not just an inflammatory response.)

Question 2

Define immunological tolerance

Answer 2

unresponsiveness of immune system to an antigen. (not just self antigens, also fetal, gut flora and plant pollens.)

Question 3

Define autoimmunity What is it due to? What does it lead to?

Answer 3

An immune response to self antigens. Due to a failure of immunological tolerance. Due to a combination of genetic and environmental factors. Leads to immune mediated damage of specific tissues.

Question 4

How can autoimmunity occur?

Answer 4

• Immune system responds to “infinite” number of threats
• It is preprogrammed to response to all threats by genetic recombination of B and T lymphocytes
• This produces an infinite variety of receptors on differentiated T and B cells (only single R type expressed per cell.)
• Therefore an infinite number of antigens can be response to by specific T and B cells by cell cytotoxicity and antibody production.
• If a specific T or B cell is stimulated by a specific antigen it will replicate massively to provide a specific response –> clonal selection
• However:
  
  • This means we also have preprogrammed T and B cells that recognise our own self antigens –> needs to be controlled via Immunological tolerance

Question 5

Is the innate or adaptive immune system involved in autoimmunity?

Answer 5

• Innate immunity not primarily involved in autoimmunity and it is not intelligent enough to recognise self antigens (however it may be involved after the adaptive response, complement has been shown to be used up system lupus erythematosus).
• Adaptive response –> B cells receptors (BCRs) and T cell receptors (TCRs) have “infinite” variation via genetic recombination and therefore can recognise self antigen as well as foreign antigen.

Question 6

What happens during clonal selection?

Answer 6

• T and B lymphocytes with the best fit for an antigen will multiply –> evolve —> repeat
• Some of the selected cells may have receptors for self antigen –> needs to be controlled via immunological tolerance

Question 7

How does immunological tolerance work?

Answer 7

1. Central tolerance: By clonal deletion

• develops in the thymus and bone marrow as lymphocytes mature
• main role –> prevent immune response to SELF ANTIGEN
• most active in the fetus and declines after birth
• immature lymphocytes that recognise self antigens are destroyed after they have expressed receptors for self antigens, after exposure to self antigens –> clonal deletion.

2. Peripheral tolerance: By clonal deletion and anergy (inactivation)

• peripheral tolerance refers to mechanisms acting on mature lymphocytes after they have left primary lymphoid organ, develops in peripheral lymphoid tissues
• Not all genes are expressed in the thymus therefore developing T cells cannot be exposed to all self antigens.
• additional mechanisms needs for tolerising self reactive mature T and B lymphocytes
• prevents immune response to fetus, gut flora, plant pollens etc.
• Active throughout life

3. Clonal suppression

• mature lymphocytes that recognise self or benign antigens are suppressed by Regulatory T cells
• T Regs are specific for the antigen, able to inactivate the lypmphocyte with the same antigen.