Etiology and Nature of Antigens
The primary triggers for Type III hypersensitivity reactions are soluble proteins. Pathology develops when these protein structures enter the body in excess amounts, are encountered repeatedly, or are continuously produced within the body itself.
Depending on their origin, antigens are divided into two major groups:
- Exogenous (external) antigens. These enter the body from the environment. They include therapeutic foreign sera and plasma, as well as vaccine solutions. Additionally, sources may include insect bites, inhalation of protein-containing substances, and infections with various microorganisms or fungi.
- Endogenous (internal) antigens. These form directly within the patient's tissues. This occurs during prolonged infectious processes, parasitic infestations (e.g., trypanosomiasis or helminthiasis), tumor growth, and paraproteinemias.
Pathogenesis: From Antigen Encounter to Inflammation
The development of precipitin reactions follows a strict five-stage sequence.
1. Immunological Phase Begins with the recognition of a soluble protein by macrophages. This is followed by complex cellular cooperation: the macrophage presents information to a T cell, which activates a B cell. Activated B cells differentiate into plasma cells and actively synthesize specialized antibodies—IgM and IgG.
2. Formation of Immune Complexes (ICs) Upon re-exposure to the same antigen, molecules bind together. The main feature of the synthesized immunoglobulins is their high propensity to precipitate upon contact with the antigen. The resulting structures are called immune complexes.
3. Sensitization Phase (Fate of the Complexes) These precipitates circulate via the blood and lymph throughout the body and subsequently deposit (settle) in various tissues and organs, leading to systemic sensitization.
4. Pathochemical Phase Fixation of ICs and activation of clearance mechanisms lead to the release of allergy mediators into the blood and tissues, with the complement cascade heavily involved.
5. Pathophysiological Phase (Tissue Damage) Mediators and the deposited complexes exert destructive effects on target tissues, causing direct cellular and non-cellular structural damage. Vascular permeability and basement membrane permeability increase dramatically. Severe immune-mediated inflammation is triggered, activating the coagulation cascade and leading to microthrombosis.
Clinical Manifestations
Disorders developing via the Type III mechanism are termed immune complex diseases. Their clinical presentation depends on the precise site of immune complex deposition.
If complexes form in the systemic circulation or lymph and disseminate to various organs, a systemic (generalized) form occurs. A classic example is serum sickness.
Major pathologies based on immune complex mechanisms include:
- Serum sickness;
- Arthus reaction (local manifestation);
- Membranous glomerulonephritis;
- Allergic forms of vasculitis;
- Polyarteritis nodosa;
- Hypersensitivity pneumonitis (extrinsic allergic alveolitis);
- Allergic forms of cytopenias/pancytopenias.