Type II hypersensitivity

General characteristics and essence of the reaction

The cytotoxic type is based on the production of antibodies (primarily IgG and IgM) against antigens located on the cell surface. These antigens can be either intrinsic membrane components (endogenous) or external agents, such as drugs that act as haptens and firmly bind to the cell wall.

When antibodies "recognize" the antigen, a cascade of effector mechanisms aimed at destroying the formed complex is triggered. As a result, destruction (cytolysis) of the target cell occurs.

In some cases, anti-receptor reactions (previously classified as type V) are also attributed to this type, since their essence likewise involves the interaction of antibodies with cellular structures, namely receptors.

Pathogenesis: how the cell dies

Destruction of the target cell can occur via one of three main pathways:

1. Complement-dependent cytolysis. The antibody binds to the antigen on the membrane, after which its Fc fragment activates the complement system via the classical pathway. During this process, anaphylatoxins (C3a, C5a) are generated and the membrane attack complex (MAC) is formed. The MAC literally punctures the cell membrane, causing cell death.
2. Phagocytosis (opsonization). The target cell becomes coated with antibody molecules and complement components (specifically C3b). Phagocytes easily recognize such a "prepared" (opsonized) cell, engulf and digest it.
3. Antibody-dependent cell-mediated cytotoxicity (ADCC). In this case, natural killer (NK) cells play the main role. They recognize the Fc fragments of antibodies already attached to the cell and release toxic enzymes (perforins and granzymes). As a result, lysis occurs without the involvement of the complement system.

Clinical manifestations

Depending on which specific tissues autoantibodies are produced against, various pathologies develop:

• Hematologic disorders. In autoimmune hemolytic anemia, antibodies attack the Rh antigen of erythrocytes, leading to their phagocytosis and complement-mediated destruction. In drug-induced cytopenias, drugs act as haptens, resulting in blood cell lysis (anemia, thrombocytopenia, granulocytopenia).
• Structural tissue damage. In pemphigus vulgaris, antibodies attack intercellular adhesion molecules, causing blister formation due to the loss of cell adhesion. In Goodpasture syndrome, the target becomes the basement membrane of the alveoli and renal glomeruli, causing hemoptysis and nephritis.
• Anti-receptor diseases. Antibodies may not destroy the cell, but rather disrupt its function. In myasthenia gravis, antibodies block acetylcholine receptors, causing muscle weakness. In Graves' disease (thyrotoxicosis), antibodies stimulate TSH receptors, forcing the thyroid gland to work in overdrive.

Diagnostic Principles

Laboratory diagnostics are based on confirming the presence of specific antibodies in the patient's tissues or blood.

Two main approaches are used:

• Searching for circulating anti-tissue antibodies in blood serum.
• Examining biopsy samples from affected areas using direct immunofluorescence (IF). This method allows visualization of accumulations (deposits) of complement components and antibodies directly in the tissues.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Detailed mechanism of membrane attack complex formation
• The role of anaphylatoxins C3a and C5a in the inflammatory response
• The mechanism of opsonization and the role of component C3b
• Pathogenesis of drug-induced cytopenias
• Technique of the immunofluorescence (IF) assay

Other topics in "Immunology"

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