Natural antibodies

Characteristics and origin

Natural antibodies are specific protein molecules belonging to the IgM isotype. In the body, they are produced by a special population of lymphocytes—B1 cells. An important distinguishing feature of these immunoglobulins (as well as other natural antibodies, including autoantibodies) is their ability to be synthesized without a classical active immune response.

In the scientific community, there is currently no proof that the production of these molecules is triggered in response to contact with cross-reacting antigens of bacterial origin. Their formation completely lacks key mechanisms characteristic of adaptive immunity:

• Isotype switching does not occur.
• Somatic hypermutation is absent.
• There is no increase in affinity (binding strength) for a specific antigen.

Interaction with erythrocytes and functions

The main function of natural antibodies lies in their ability to cause agglutination—the process of clumping erythrocytes on whose surface corresponding antigens are expressed. Blood-group natural antibodies are called isoagglutinins. For convenience, they are usually designated by Greek letters corresponding to the Latin names of the antigens. For example, the $\alpha$ (alpha) isoagglutinin is an anti-A antibody.

In clinical practice, the agglutination reaction is the baseline method for determining blood groups. In addition, with the participation of the complement system, isoagglutinins initiate direct lysis (destruction) of antigen-positive erythrocytes.

Pathogenesis of incompatible blood transfusion

Transfusion of blood incompatible by donor antigens and recipient antibodies triggers severe pathological reactions. The presence of antibodies against donor antigens in the recipient leads to massive lysis of the transfused erythrocytes.

As a result, circulating immune complexes are formed, consisting of antibodies and membrane fragments of destroyed erythrocytes. These complexes deposit on tissue structures carrying Fc receptors (FcR). First and foremost, the glomerular basement membranes of the kidneys undergo massive damage, leading to severe systemic consequences and the development of transfusion shock.

It is important to note that the donor's own antibodies present in the transfused blood (against the recipient's antigens) generally do not cause pathology. Due to the small volume of administered blood compared to the recipient's total circulating blood volume (CBV), their agglutinating capacity is neutralized by dilution.

Modern blood transfusion practice: Historical rules that allowed the use of "universal donors" (group I) and "universal recipients" (group IV) are now abolished. Blood transfusion is permitted only with complete compatibility between donor and recipient regarding ABO system antigens.

Immunological tolerance and chimerism

The study of the body's reaction to foreign antigens is closely related to the concept of immunological tolerance—a state of unresponsiveness of the immune system.

In 1945, researcher J. Owen (J. Owen) first described the phenomenon of stable chimerism—the coexistence of cells with completely different genotypes within a single organism. The objects of his observation were twin calves' erythrocytes. In the embryonic period, these animals experienced natural fusion (anastomosis) of umbilical cord vessels, which led to cell exchange. This observation laid the foundation for finding ways to induce unresponsiveness to foreign antigens.

Later, in 1953, scientists R. Billingham, L. Brent, and P. Medawar (R. Billingham, L. Brent, P. Medawar) published the results of successful experiments on the artificial induction of immunological tolerance during embryonic development.

Class and exam questions

What else to study on this topic

• Mechanisms of autoantibody production by B1 lymphocytes
• Structural and functional features of IgM isotype antibodies
• The role of the complement system in erythrocyte lysis
• Mechanism of immune complex deposition on Fc receptors of renal glomerular membranes
• Medawar's experiments on the induction of tolerance in the embryonic period

Other topics in the section "Immunity in defense and damage of the organism. Pathology of immunity"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.