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Introduction to histopathology
Introduction to histopathology

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1.5 Hypersensitivity

Hypersensitivity is defined as an immune response, where the reaction is out of proportion to the damage caused by the antigen or pathogen and does more harm than good. Autoimmune diseases are by their very nature a type of hypersensitivity reaction; however, there are many instances where the immune reaction against an antigen or a pathogen is out of proportion to the damage that it causes. A simple example is hay fever or asthma induced by pollen, where the pollen itself is clearly harmless, but the inflammatory reactions, especially in the lung, can be life-threatening. In some infectious diseases, such as M. tuberculosis, a significant component of the pathology is the collateral damage caused to lung tissue by the ongoing immune reaction against the bacteria. Obviously the bacterial infection is itself potentially damaging, but the severity of the disease in different individuals is at least partly due to the variability in their immune responses. Diseases such as multiple sclerosis are even more complex. In this case, it is suspected that there is an autoimmune reaction, although the target antigen is unclear, and there is clearly a hypersensitive response taking place in the brain. The fact that this immune response is particularly damaging is partly related to the nature of the CNS, which is delicate and normally shielded from immune and inflammatory reactions.

Hypersensitivity reactions can be classified into four main types depending on the type of immune response that causes them. Although the causes of hypersensitivity are beyond the scope of this course, the histological appearance of the different types of hypersensitivity reactions is often distinctive and can aid in diagnosis. Referring to the examples given above, hay fever and allergic asthma are examples of type-1 hypersensitivity reactions, which develop rapidly following exposure to antigen. They are characterised by neutrophils and eosinophils in mucosal and submucosal tissues of the respiratory tract; basophils are also common in the bronchial wall in asthma. In contrast, tuberculosis is an example of a type-4 hypersensitivity reaction, which develops slowly, in association with chronic inflammation, and is characterised by macrophages and T-lymphocytes. The other types of hypersensitive reaction are due to antibodies in tissues. For example the autoantibodies seen in pemphigus (Figure 7) are an example of a type-2 reaction, whereas type-3 reactions are caused by the deposition of antigen-antibody complexes from the circulation in organs where filtration occurs, particularly the kidney.

Figure 7 Autoantibodies in pemphigus bind to components of the desmosome, a cellular structure that connects cells to their neighbours. The antibodies disrupt inter-cellular adhesion causing blistering of the skin. The section is stained with a fluorescent antibody which detects bound auto-antibodies (IgA) of the patient. (Courtesy of Dr R. Mirakian and Mr P. Collins)