Complement, Hypersensitivity & Autoimmunity

The complement system is about 30 blood proteins acting as the immune system's rapid demolition team. When antibodies tag an invader, complement activates in a chain reaction that punches holes in microbes, marks them for phagocytes and summons inflammatory cells. Hypersensitivity is the same weaponry firing too hard or at the wrong target, causing allergy and transfusion reactions, while autoimmunity is the immune system attacking the body's own tissues.

Complement deficiency brings repeated bacterial infections in children, hypersensitivity ranges from mild rash to fatal anaphylaxis in minutes, and autoimmunity underlies lupus and rheumatoid arthritis. One story connects a protective cascade, its misfiring, and its turning against self.

Key Concepts

• Three activation pathways: classical (antibody-bound C1), lectin (microbial sugars) and alternative (direct C3b deposition); all converge on making a C3 convertase.
• C3b opsonization: C3b coats microbes like handles that phagocytes grip for engulfing.
• Anaphylatoxins C3a/C5a: fragments that trigger mast cells, widen vessels and summon neutrophils.
• Membrane attack complex (C5b-9): C5b through C9 assemble a pore that lyses the target cell.
• Gell-Coombs types: I: IgE allergy/anaphylaxis; II: antibody vs own cells (hemolytic transfusion reaction); III: immune-complex deposition (serum sickness); IV: delayed T-cell (tuberculin test, contact dermatitis).
• Loss of self-tolerance: failed deletion of self-reactive lymphocytes lets autoantibodies attack joints, kidneys and glands, as in SLE.

How It Works

Complement is a cascade: each step activates many molecules of the next, amplifying hugely. C1 binds antibody-antigen complexes, activating C4 and C2 to form C3 convertase; the alternative pathway builds its own convertase on microbial surfaces. Both chop C3 into C3a and C3b; C3b coats microbes for phagocytosis and helps form C5 convertase, launching the membrane attack complex. Regulators like Factor H protect our own cells. In Type I hypersensitivity, IgE on mast cells meets allergen and releases histamine explosively, causing itching, wheezing or anaphylactic collapse within minutes. In autoimmunity, self-reactive B and T cells escape control and treat the body's own tissues as foreign.

Worked Example

A complement fixation test uses doubling serum dilutions 1:2 through 1:128. Fixation occurs up to 1:64 but not at 1:128. The antibody titre is the reciprocal of the highest positive dilution:

1. Highest positive dilution = 1:64
2. Titre = reciprocal of 1/64 = 64

A titre of 64 means antibodies were detectable after 64-fold dilution, indicating a strong response; falling titres on repeat testing show resolving disease.

Common Misconceptions

• "Allergies mean weak immunity." Allergy is overactive, misdirected immunity; allergic people often fight infections perfectly well.
• "Positive ANA means lupus." ANA appears in many conditions and some healthy people; diagnosis needs the full clinical picture.
• "Complement only kills bacteria." Opsonization and the inflammatory call of C3a/C5a are equally important jobs.

Real-World Applications

• Anaphylaxis: intramuscular adrenaline is the first, most important drug, reversing airway swelling and low blood pressure.
• Allergy diagnosis: skin prick and specific IgE tests identify triggers for avoidance and desensitization.
• Autoimmune workup: ANA, rheumatoid factor, anti-CCP, and low C3/C4 (active immune-complex disease) guide diagnosis and monitoring.
• Transfusion safety: grouping and cross-matching prevent Type II hemolytic reactions.

Complement is the immune chain reaction destroying invaders; hypersensitivity is that power misfiring in four classic patterns; autoimmunity is broken self-tolerance behind diseases like lupus. Measuring complement, identifying allergy triggers and interpreting autoantibodies in context turn this theory into daily diagnosis and treatment.