Immunopathology: Hypersensitivity, Autoimmunity, Rejection

Immunopathology is disease caused by the immune system itself — when it overreacts, attacks the body's own tissues, or rejects transplanted organs. The three big groups are hypersensitivity (allergic overreactions, types I–IV), autoimmunity (the immune system mistakes self for foreign), and transplant rejection.

This matters because immune friendly fire causes enormous suffering: asthma and anaphylaxis, rheumatoid arthritis and type 1 diabetes, and the loss of transplanted kidneys. Modern medicine's fastest-growing drugs — biologics blocking specific immune molecules — all come from these mechanisms, making this chapter the key to immunotherapy.

Key Concepts

• Type I (immediate, IgE): allergen cross-links IgE on mast cells; histamine releases within minutes. Anaphylaxis, allergic asthma, hay fever. Epinephrine is life-saving in anaphylaxis.
• Type II (cytotoxic): IgG/IgM attack cell-surface antigens — autoimmune hemolytic anemia, myasthenia gravis, Goodpasture syndrome.
• Type III (immune-complex): antigen–antibody complexes deposit in tissues — systemic lupus erythematosus, post-streptococcal glomerulonephritis.
• Type IV (delayed, T-cell): takes 48–72 hours — tuberculin skin test, contact dermatitis, tuberculosis granulomas.
• Autoimmunity: loss of self-tolerance via molecular mimicry (streptococcal proteins resembling heart tissue), HLA-linked genetic risk, and failed regulatory T cells. Organ-specific (type 1 diabetes, Hashimoto thyroiditis) or systemic (lupus, rheumatoid arthritis).
• Transplant rejection: hyperacute (minutes–hours, preformed antibodies — prevented by cross-matching), acute (days–months, T-cell mediated), chronic (months–years, vessel scarring). HLA matching reduces risk.

How It Works

1. Sensitization: first exposure teaches the immune system — IgE is made (type I), memory T cells form (type IV), or self-tolerance breaks (autoimmunity).
2. Re-exposure: mast cells degranulate in minutes (type I); antibodies coat target cells (type II); complexes lodge in tissues (type III); T cells arrive over days (type IV).
3. Damage: histamine causes swelling and bronchospasm; complement punches holes in cells; cytotoxic T cells kill graft cells.
4. Chronicity: in autoimmunity the "antigen" is the patient's own tissue, so cycles of flare and remission repeat unless immunosuppression breaks them. Transplant patients take lifelong tacrolimus-based therapy.

Worked Example

A child eats a peanut and within 10 minutes develops hives, wheezing and blood pressure 70/40 mmHg. Step 1: timing — 10 minutes means an immediate type I reaction. Step 2: mechanism — peanut proteins cross-link IgE on mast cells; histamine dilates vessels (pressure falls) and constricts airways (wheezing). Step 3: two organ systems involved plus shock-level pressure confirms anaphylaxis. Step 4: intramuscular epinephrine 0.01 mg/kg — a 20 kg child receives 0.2 mg — constricting vessels and opening airways. Step 5: strict avoidance plus an auto-injector thereafter. Timing plus mechanism plus dose: type I hypersensitivity in practice.

Common Misconceptions

• "All allergies are the same." Type I (minutes, IgE, epinephrine) and type IV (days, T cells, steroids) differ in timing, cells and treatment.
• "Autoimmune diseases are cured with antibiotics." No microbe drives them; treatment is immunosuppression or immune modulation.
• "A transplant is accepted once surgery succeeds." Rejection risk is lifelong — acute rejection can strike months later, chronic rejection over years.

Real-World Applications

• Emergency medicine: epinephrine auto-injectors for anaphylaxis; patch testing identifies type IV contact allergens.
• Rheumatology: ANA screens for lupus, anti-CCP confirms rheumatoid arthritis; TNF blockers target the exact driving molecules.
• Transplants: HLA typing, cross-matching and tacrolimus-based immunosuppression push one-year kidney graft survival above 90 percent.
• Desensitization: allergy shots gradually retrain type I responses; type IV knowledge guides TB skin-test interpretation.

Hypersensitivity types I–IV are four distinct ways immunity damages tissue; autoimmunity is immunity turned against the self; transplant rejection is immunity working correctly against a foreign organ. Classify the mechanism first — timing, antibody or cell, tissue hit — and the diagnosis, emergency drug and long-term plan all follow.