Alloimmune hemolytic reactions
Type II hypersensitivity is frequently underpinned by alloimmune hemolytic diseases. A classic example is transfusion reactions due to ABO incompatibility. The core of the process lies in the presence of pre-existing antibodies in an individual against those blood group antigens that are absent in their own body.
The pathogenesis develops rapidly: as soon as incompatible donor erythrocytes enter the recipient's bloodstream, they immediately bind to these antibodies. The result is massive lysis (destruction) of erythrocytes. Furthermore, erythrocyte membrane proteins together with antibodies form immune complexes, the deposition of which leads to additional tissue damage. Clinically, this may manifest, in particular, with the development of jaundice. A similar pathogenetic mechanism underlies alloimmune neonatal thrombocytopenia, where platelets become the target.
Rh incompatibility and hemolytic disease of the newborn
A special place is held by Rh-incompatible hemolytic anemia. The Rh system includes antigens C, D, E, c, d, e, but the antigen D acts as the strongest antibody inducer. It is encoded by the dominant gene D, whereas its recessive allele is the d gene.
Conflict arises due to incompatibility specifically involving these genes, most commonly during pregnancy when an Rh-negative mother (dd genotype) carries an Rh-positive fetus (DD or Dd genotypes).
- First pregnancy. Usually proceeds without severe immune disorders. However, fetal erythrocytes penetrate the maternal bloodstream, where the immune system recognizes the foreign D antigen and sensitization occurs. Primary anti-D IgM antibodies are produced. They are practically incapable of crossing the placental barrier, but they leave memory cells behind.
- Subsequent pregnancies (reimmunization). Upon repeated contact, the maternal organism begins actively synthesizing IgG class antibodies (especially the IgG3 subclass). These molecules easily cross the placenta into the fetal bloodstream, bind to its erythrocytes, and cause their total destruction. Hemolytic disease of the newborn (HDN) develops, which can lead to severe consequences up to intrauterine fetal death.
Prevention and the role of the ABO system
Specific prophylaxis is used to prevent the development of HDN. An Rh-negative mother is administered ready-made IgG anti-D antibody preparations. This method works effectively through the mechanism of FcR-dependent regulation: exogenous antibodies suppress the production of the mother's own antibodies.
An interesting feature concerns combined incompatibility: if the Rh incompatibility is accompanied by maternal-fetal ABO system incompatibility as well, the risk of sensitization to the Rh factor is paradoxically attenuated. This is because fetal erythrocytes (carrying A or B antigens) are rapidly destroyed by pre-existing maternal isohemagglutinins even before they can trigger a full-blown immune response to the D antigen.
Autoimmune cytotoxic pathology
In addition to alloimmune reactions, the second type of hypersensitivity includes autoimmune disorders:
- Autoimmune hemolytic anemias (AIHA). Classified according to the thermal optimum of antibody activity. In warm AIHA, antibodies attack Rh system antigens (except the D antigen). In cold AIHA, targets include I and P blood group antigens.
- Pathologies with antitissue antibodies. In Hashimoto's thyroiditis, specific antibodies cause damage to thyrocytes (thyroid cells), while in Goodpasture's syndrome, the cytotoxic attack is directed against the basement membrane of renal glomeruli.
- T-cell cytotoxicity. This mechanism accounts for tissue damage in type 1 diabetes mellitus and a number of other diseases.
Drug-induced sensitization
A distinct variant is the hemolytic manifestation of drug-induced sensitization. The development mechanism is as follows: a pharmacological drug molecule tightly binds to the blood cell membrane. The immune system begins to produce antibodies specific to this drug. Then these antibodies attack the formed cell-drug complex, leading to cell damage.
Clinical consequences depend on precisely which cells are affected:
- Hemolytic anemia can be induced by the intake of phenacetin and chlorpromazine.
- Immune agranulocytosis is provoked by aminophenazone and quinidine.
- Thrombocytopenic purpura can also be caused by taking a number of medications.
Briefly: answers to topical questions
What mechanisms of target cell destruction are implemented in type II hypersensitivity?
In type II hypersensitivity, immune cytolysis acts as the main effector mechanism. The following variants of target cell destruction are distinguished:
- Cellular contact cytolysis is the primary mechanism for executing the protective activity of cytotoxic T lymphocytes, natural killers, as well as macrophages and neutrophils.
- Complement-dependent cytolysis is antibody-mediated cell destruction involving the complement system.
- FcR-dependent cytolysis is antibody-mediated destruction carried out by phagocytes (predominantly macrophages) and natural killers.
Which diseases belong to autoimmune manifestations of type II hypersensitivity?
Autoimmune manifestations of type II hypersensitivity include autoimmune cytotoxic pathology caused by the action of antitissue antibodies. This group includes:
- Autoimmune hemolytic anemias — divided into warm (antibodies to Rh system antigens) and cold (antibodies to I and P blood group antigens).
- Hashimoto's thyroiditis — a pathology accompanied by damage to thyrocytes.
- Goodpasture's syndrome — a disease characterized by damage to the basement membrane of renal glomeruli.
Which components of the complement system participate in cell lysis during cytotoxic reactions?
Target cell lysis involves components of the terminal phase of complement activation, which form the membrane attack complex:
- C5b binds C6;
- the C5bC6 complex binds C7, and the hydrophobic regions of C7 facilitate the fixation of the complex on the membrane;
- C8 ensures membrane piercing and the formation of the primary pore;
- 12–20 molecules of C9 attach to the C5bC6C7C8 complex.
To easily remember the difference between antibodies in Rh incompatibility: IgM — "Massive" (initially produced, but do not cross the placental barrier). IgG — "Flexible" (small, produced during subsequent pregnancy, penetrate to the fetus and cause hemolysis).
What else to study on this topic
- Structure and genetics of Rh system antigens (C, c, E, e)
- Molecular mechanism of FcR-dependent regulation
- Thermal optima and pathogenesis of cold and warm AIHA
- Pathogenetic mechanisms of Goodpasture's syndrome and Hashimoto's thyroiditis
- Mechanisms of drug-cell immune complex formation
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