Cornerstones of immunology

There are several cornerstones in our specialty, including immune systems deficits (discussed in other sections), anaphylaxis, allergy and atopy, transplantation and autoimmunity.

Bellanti has identified different hypersensibility reactions as follows¹, notwithstanding the implied immune response (type I, II, III, IV of Gell and Coombs):

• Allergy, when the allergen is a molecule not related to the human species, such as pollen, animal dander, a cosmetic product, or a medication.
• Transplant rejection, when the antigen derives from human tissue, such as a kidney, a liver, a heart or a lung.
• Autoimmunity, when the antigen is found in the same individual.

Anaphylaxis, allergy and atopy.

The word anaphylaxis, was used by Richet and Portier in 1902, to describe the reaction, often lethal, of dogs after a second injection of extracts from Actinaria tentacles: in contradistinction from "prophylaxis", obtained following true vaccination - hence the term "anaphylaxis".

The term allergy was introduced by Von Pirquet in 1906, and signifies a modified immune reaction, as in the case of "hay fever". Little by little, allergy has begun to encompass reactions other than those caused by "reagins", identified in 1966 as being antibodies of the class IgE (a type I reaction as described by Gell and Coombs ²): allergy now encompasses certain reactions mediated by other types of antibodies, such as agglutinins (belonging to reactions of type II), and precipitins (the cause of type III reactions). Certain reactions of type IV, mediated by lymphocytes and not antibodies, may also be considered "allergies" (example: contact dermatitis to poison ivy).

The concept of atopy was introduced in 1923 by Coca and Cooke ³ to designate allergies of a familial or hereditary nature. Historically, atopy was considered hereditary, limited to humans, a qualitatively abnormal response, and characterized clinically by allergic rhinitis, asthma, and atopic dermatitis (eczema), with positive allergy skin tests. The notion of atopy has however more recently been used interchangeably with the term allergy.

However, atopy only represents IgE mediated allergic reactions responsible for rhinitis, asthma, and is often associated with a form of eczema known as "atopic"⁴. Other types of IgE mediated allergic reactions, such as anaphylaxis to penicillin, are not considered atopic.

More recently, Novak and Bieber ⁵have attempted to define two types of atopy: classic or allergic atopy, as defined above, and non-atopic allergy, in order to encompass cases of rhinitis, asthma, and eczema not associated with IgE sensitization.

Transplants

With the progress of medicine and surgery, solid organ transplantation is now a well-defined, therapeutic alternative. Transplanted organs come from other humans, and the individual that receives an organ from another individual develops an immune response against the organ, and a tendance therefore to reject it.

Blood transfusion is an old example of transplantation of foreign cells, and if not enough attention is paid to ensuring that the surface antigens of the transplanted blood cells are identical to those of the recipient, the recipient will react to the transfused cells: this is known as a transfusion reaction.

In the case of solid organ transplantation, such as a kidney, a liver, a lung, or a heart, the quantity of surface antigens found on the organs' cells is substantially larger and diverse compared to the antigens found on red blood cells such that it is practically impossible to have perfect homology, except in the case of 2 identical twins. There is therefore an immune mechanism in place to reject the newly transplanted organ, which must be controlled with adequate medication.

A particular case of transplantation is that of bone marrow transplantation: bone marrow contains lymphocyte cells of the donor, and these are the cells that eventually shape the immune response of the recipient. Now, these cells recognize the antigens of the recipient, and develop an immune response against the recipient antigens. In effect it is then the cells of the donor which reject the cells of the recipient: one expects a rejection of the recipient by the transplanted cells. Here also, with appropriate medication, we try once again to control this particular type of rejection.

Autoimmunity

Finally, certain diseases are the result of abnormal activity of an individuals' lymphocytes, directed against self-antigens. This is known as autoimmunity.

The immune response can be specific to an organ, such as in the case of thyroid autoimmunity, or in certain cases of diabetes (type I diabetes, formerly known as juvenile, requiring treatment with insulin).

In other cases, the immune response is more generalized, and is responsible for a more systemic disease, such as in the case of lupus or scleroderma.

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André Caron, MD FRCPC
(translation: Andrew Moore, MD FRCPC)