Autoimmunity is normally avoided by thymic education; a breakdown in the processes involved leads to autoimmune disease
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While the immune system's activities are mostly beneficial, there are several situations in which they can have deleterious effects. These are best considered as aberrations of the quality, quantity or direction of the response (Table 36.3).
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Table 36-3.
Disorders of immune regulation. |
Body_ID: None |
Disorders of immune regulation |
Body_ID: T036003.50 |
Antigen source Level of response | Polyclonal response | Monoclonal response |
Body_ID: T036003.100 |
| Exogenous | Endogenous |
Body_ID: T036003.150 |
Decreased response | immunodeficiency primary and secondary | |
Body_ID: T036003.200 |
Increased response | tuberculosis, leprosy, immune complex disease | lymphoproliferative disease |
Body_ID: T036003.250 |
Inappropriate response | allergic disease - IgE | |
Body_ID: T036003.300 |
Increased and inappropriate response | allergic disease - EAA | autoimmune disease |
Body_ID: T036003.350 |
One particular aspect of these immunodysregulatory disorders, that of autoimmunity (self-reactivity), is avoided by the processes of thymic education. This is achieved via positive and negative selection and tolerance, which includes the processes of clonal deletion, clonal abortion and energy. These terms refer to the processes whereby self-reactive clones are eliminated or rendered impotent. These mechanisms can be seen as a multilayered fail-safe strategy.
Should these processes breakdown or be circumvented, the resulting state of self-reactivity and the resulting inflammatory damage constitute autoimmune disease. The form of disease is determined by the target antigen and the form of the immune response. At its simplest, reactions against ubiquitous antigens lead to what are termed nonorgan-specific autoimmune diseases, whereas reactions to unique components of individual tissues, organs or systems lead to organ-specific disease. The former are best exemplified by systemic lupus erythematosus (SLE), in which the apparent target antigens are components common to all nuclei. Damage is seen in several tissues, including the skin, joints, kidneys, and nervous system. The latter are exemplified by autoimmune thyroiditis, where the apparent target is thyroid peroxidase enzyme. The use of the word 'apparent' should be noted here, as on more detailed investigation it becomes clear that these particular antigen systems, while acting as markers or indicators of autoimmune disease, are not pathogenically responsible for the damage being inflicted. The methods used to detect such autoantibodies include indirect and direct immunofluorescence, particle agglutination, electroimmunodiffusion and enzyme immunoassay.
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These diseases, and the others mentioned in Table 36.3, are the focus of the discipline of clinical immunology and immunopathology. More information can be found by reading the books cited in the Further Reading list below.
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