Causes of Altered Cell Antigenic Profiles
Normally, cytotoxic immune responses are directed against foreign agents (microbes, fungi, tumors, transplants). For the body's own tissues to become targets for antibodies, their antigenic structure must change. Contributing factors include:
- Chemicals: metals (gold, zinc, nickel, copper) and drugs (antibiotics, sulfonamides, antihypertensives).
- Hydrolytic enzymes: released from lysosomes during massive destruction of microorganisms or cells, accumulating in excess in the extracellular fluid.
- Reactive oxygen species (ROS): free radicals, as well as organic and inorganic peroxides.
Mechanisms of Target Cell Destruction
In Type II hypersensitivity, damage becomes generalized due to an excess of cytotropic mediators. There are two main pathways of cell death:
- Complement-dependent cytolysis. Complement factors assemble into membrane attack complexes. Their speed of action depends on composition: the complex of factors C5–8 acts slowly, the addition of C9 accelerates the process, and the combination of C3b and C5–9 yields the fastest effect. They punch pores 5 to 20 nm in diameter into the cell membrane. Na^+ and Ca^{2+} ions passively rush inward through these openings. Intracellular osmotic pressure rises sharply, the cell becomes overloaded with water (hyperhydration), its membrane overstretches, and an "osmotic explosion" occurs. The process is facilitated by opsonization of targets by immunoglobulins and complement components. Basement membranes can be destroyed similarly.
- Antibody-dependent cell-mediated cytotoxicity (ADCC). Effector cells (macrophages, granulocytes, NK cells, T killers, monocytes) are activated upon contact with IgG bound to the target cell. T killers release hydrolytic enzymes and generate reactive oxygen species. Neighboring normal tissues often suffer as well—the so-called bystander effect.
In addition to direct membrane perforation, cells are destroyed due to oxidative stress (free radicals, lipid peroxides). Phagocytosis is activated simultaneously, stimulated by complement factors (C3b, C3a, C5a, C4b2a3b complex) and lipid hydroperoxides.
Reactions Without a Sensitization Period (Idiosyncrasy)
Clinical practice features conditions that biochemically mimic allergy but occur without an immunological phase (without visible sensitization). Idiosyncrasy is an increased sensitivity to food or drugs, often inherited as a predisposition. Triggers include:
- Foods: chocolate, egg white, fish, milk, citrus fruits, berries.
- Drugs and chemicals (herbicides, pesticides).
Liver pathology (total insufficiency after viral hepatitis, malaria, or chronic exposure to hepatotropic poisons) plays a huge role in their development. The liver loses its ability to selectively inactivate biogenic amines (primarily histamine) and other vasoactive substances. Upon exposure to a trigger, their concentration in the blood rises rapidly.
Clinical Manifestations
The pathophysiological stage of true cytotoxic reactions underlies several severe syndromes:
- Drug-induced cytopenias: decrease in formed blood elements (erythropenia/anemia, leukopenia, thrombocytopenia).
- Hemolytic disease of the newborn.
- Agranulocytosis.
- Infectious-allergic organ damage: inflammatory processes such as nephritis, myocarditis, encephalitis, hepatitis, thyroiditis, and polyneuritis.
If the reaction proceeds via a non-immunological pathway (idiosyncrasy), clinical features include rashes, local pruritus, skin erythema, urticaria, diarrhea, angioedema, asthma attacks, and severe conditions resembling anaphylactic shock.