Causes of altered cellular antigenic profile
Normally, cytotoxic immune reactions are aimed at destroying foreign agents (microbes, fungi, tumors, transplants). For the body's own tissues to become targets for antibodies, their antigenic structure must change. This is promoted by:
- Chemicals: metals (gold, zinc, nickel, copper) and medications (antibiotics, sulfonamides, antihypertensives).
- Hydrolytic enzymes: released from lysosomes during massive destruction of microorganisms or cells, accumulating in excess in the intercellular fluid.
- Reactive oxygen species (ROS): free radicals, as well as peroxides of organic and inorganic substances.
Mechanisms of target cell destruction
In Type II allergy, damage becomes generalized due to an excess of cytotropic mediators. Two main pathways of cell death are distinguished:
- Complement-dependent cytolysis. Complement system factors assemble into membrane attack complexes. Their rate of action depends on the composition: the complex of factors C5–8 acts slowly, the addition of C9 accelerates the process, and the combination of C3b, 5–9 yields the fastest possible effect. They punch pores ranging from 5 to 20 nm in diameter into the cell membrane. Through these openings, Na^+ and Ca^{2+} ions passively rush inward. Intracellular osmotic pressure rises sharply, the cell becomes overloaded with water (hyperhydration), its membrane is overstretched, and an "osmotic explosion" occurs. The process is facilitated by the opsonization of targets by immunoglobulins and complement components. Basement membranes can be destroyed in a similar manner.
- Antibody-dependent cellular cytolysis. Effector cells (macrophages, granulocytes, NK cells, T-killers, monocytes) are activated upon contact with IgG deposited on the target cell. T-killers release hydrolytic enzymes and generate reactive oxygen species. At the same time, neighboring normal tissues often suffer—the so-called bystander effect.
In addition to direct membrane perforation, cells are destroyed due to oxidative stress (free radicals, lipid peroxides). Concurrently, phagocytosis is activated: it is stimulated by complement factors (C3b, C3a, C5a, the C4b2a3b complex) and lipid hydroperoxides.
Reactions without a sensitization period (Idiosyncrasy)
In clinical practice, conditions occur that biochemically mimic allergy but proceed without an immunological stage (without visible sensitization). Idiosyncrasy is hypersensitivity to food or medications, which is often inherited as a predisposition. The triggers are:
- Food products: chocolate, egg white, fish, milk, citrus fruits, berries.
- Medicines and chemicals (herbicides, pesticides).
Liver pathology plays a huge role in their development (total failure following viral hepatitis, malaria, or chronic exposure to hepatotropic poisons). 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 a number of severe syndromes:
- Drug-induced cytopenias: a decrease in the count of formed blood elements (erythropenia/anemia, leukopenia, thrombocytopenia).
- Hemolytic disease of the newborn.
- Agranulocytosis.
- Infectious-allergic organ lesions: inflammatory processes such as nephritis, myocarditis, encephalitis, hepatitis, thyroiditis, and polyneuritis.
If the reaction proceeds via a non-immunological pathway (idiosyncrasy), the clinical presentation includes rashes, local skin itching, skin redness, urticaria, diarrhea, angioedema, asthma attacks, and severe conditions resembling anaphylactic shock.
Briefly: answers to topical questions
What components make up the membrane attack complex of the complement system?
The membrane attack complex of the complement system includes components C5b, C6, C7, C8, and C9: C5b initiates complex assembly by sequentially binding to C6 and C7, then C8 joins, and polymerization of C9 occurs. Ultimately, the C5b,6,7,8,9 complex is formed, creating a transmembrane pore.
Sources also indicate variants of complement-dependent membrane damage in order of increasing efficacy:
- C5, C6, C7, C8 — relatively slow membrane damage.
- C5, C6, C7, C8, C9 — faster damage.
- C3b, C5, C6, C7, C8, C9 — even more efficient lysis.
Which receptors on the surface of effector cells do IgG molecules bind to during antibody-dependent cytolysis?
During antibody-dependent cellular cytolysis, IgG molecules bind to Fc fragment receptors of antibodies on the surface of effector cells. The main recognition receptor is:
- FcγRIII (CD16) — a receptor expressed on the membranes of natural killer (NK) cells, phagocytes, and macrophages.
Specific regions in the C2 and C3 domains of IgG1 and IgG3 subclasses exhibit the highest affinity for this receptor. Recognition of antibodies fixed on the target by the FcγRIII receptor triggers an activation signal and facilitates the recognition of the target cell for its subsequent destruction.
To remember the mechanism of complement-dependent cytolysis, imagine a submarine (the cell) that has been breached (5–20 nm pores). Water and ions rapidly flood the compartments, pressure rises, and the submarine bursts from within ("osmotic explosion").
Class and exam questions
What is the main difference between type II allergy and a normal immune response?
Normally, cytotoxic reactions destroy foreign cells (bacteria, grafts). In type II allergy, antibodies attack the body's own cells, and the damage is massive and generalized in nature.
Which antibodies participate in cytotoxic-type reactions?
Immunoglobulins of classes IgG (subclasses 1, 2, and 3) and IgM play the primary role. They bind to antigens on the surface of target cells.
Why can liver pathologies cause allergy-like symptoms?
In liver failure, the inactivation of biogenic amines, primarily histamine, is impaired. Upon ingestion of certain foods or medications, the concentration of vasoactive substances in the blood rises sharply without prior sensitization.
What else to study on this topic
- Complement factors and their rate of action (C5–8, C5–9, C3b)
- The role of reactive oxygen species and lipid peroxidation in membrane damage
- Mechanisms of phagocytosis activation (role of C3b, C3a, C5a)
- Bystander effect: why healthy tissues perish during cellular cytolysis
Master the entire topic in the "Pathophysiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Type II allergic reactions" and another 4,913 pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 135 video lessons on the subject
Other topics from "Chapter 16. IMMUNOPATHOLOGICAL CONDITIONS"
Free video lessons: pathophysiologyShort lessons with lecture notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.