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๐Ÿ›ก๏ธImmunobiology

Types of Hypersensitivity Reactions

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Why This Matters

Hypersensitivity reactions represent the immune system's "friendly fire"โ€”when protective mechanisms cause harm instead of healing. You're being tested on your ability to distinguish which immune components drive each reaction type, how timing reveals mechanism, and why certain diseases cluster under specific hypersensitivity categories. These four types aren't arbitrary classifications; they reflect fundamentally different pathways involving distinct antibody classes, cell types, and effector mechanisms.

Don't just memorize that Type I involves IgE or that Type IV is T cell-mediated. Know why IgE-mast cell interactions produce immediate symptoms while T cell responses take 24-48 hours. Understand how the location of antigen (cell-bound vs. soluble vs. intracellular) determines which hypersensitivity pathway dominates. When an exam question describes a clinical scenario, you should be able to work backward from timing, symptoms, and mechanism to identify the reaction typeโ€”that's the conceptual skill being assessed.


Antibody-Mediated Immediate Reactions

These reactions depend on preformed antibodies and occur rapidly because the immune system has already been primed. The speed of response correlates directly with whether effector molecules are ready and waiting.

Type I (Immediate) Hypersensitivity

  • IgE antibodies bound to mast cellsโ€”prior sensitization means these cells are already "armed" and waiting for re-exposure to the allergen
  • Mast cell degranulation releases histamine, leukotrienes, and prostaglandins within minutes, causing vasodilation, bronchoconstriction, and increased vascular permeability
  • Clinical spectrum ranges from localized reactions (hay fever, hives) to life-threatening anaphylaxisโ€”same mechanism, different severity based on allergen dose and distribution

Antibody-Mediated Cytotoxic Reactions

When antibodies target antigens fixed to cell surfaces, the immune system destroys those cells as if they were pathogens. The key distinction from Type I is that the antigen is cell-bound, not soluble.

Type II (Antibody-Dependent) Hypersensitivity

  • IgG or IgM antibodies bind surface antigens on host cells, marking them for destruction through complement activation, opsonization, or antibody-dependent cellular cytotoxicity (ADCC)
  • Transfusion reactions occur when recipient antibodies attack donor red blood cells; autoimmune hemolytic anemia involves antibodies against one's own erythrocytes
  • Coombs testing (direct and indirect) detects antibodies bound to red blood cellsโ€”a high-yield diagnostic distinction for exam questions

Compare: Type I vs. Type IIโ€”both use antibodies as primary mediators, but Type I involves IgE triggering mast cells (soluble allergens), while Type II uses IgG/IgM to destroy cells bearing surface antigens. If an FRQ describes hemolysis or cytopenia, think Type II.


Immune Complex-Mediated Reactions

When antigen-antibody complexes form in circulation and deposit in tissues, they trigger inflammation at sites far from the original antigen encounter. Deposition location determines which organs suffer damage.

Type III (Immune Complex) Hypersensitivity

  • Circulating immune complexes of IgG and soluble antigens deposit in blood vessel walls, joints, and kidney glomeruli, activating complement and recruiting neutrophils
  • Systemic lupus erythematosus (SLE) exemplifies widespread complex deposition; serum sickness shows the classic timeline of symptoms appearing days after antigen exposure
  • Arthus reaction demonstrates localized Type III pathologyโ€”useful for understanding how complex size and clearance capacity determine disease pattern

Compare: Type II vs. Type IIIโ€”both involve IgG antibodies, but Type II targets cell-surface antigens (destruction at the cell), while Type III involves soluble antigens forming complexes that deposit elsewhere (destruction at deposition sites). The antigen's location is your key differentiator.


Cell-Mediated Delayed Reactions

Type IV stands apart because it involves no antibodiesโ€”T cells are the sole mediators. The 24-48 hour delay reflects the time required for T cell activation, proliferation, and migration to the antigen site.

Type IV (Delayed-Type) Hypersensitivity

  • CD4+CD4^+ T helper cells (primarily TH1T_H1) recognize antigen presented by macrophages and release cytokines like IFN-ฮณ, amplifying the inflammatory response
  • Contact dermatitis (poison ivy, nickel allergy) and the tuberculin skin test (PPD) are classic examplesโ€”both require prior sensitization and show peak reactions at 48-72 hours
  • Granuloma formation occurs in chronic Type IV responses when macrophages cannot eliminate the antigen, seen in tuberculosis and sarcoidosis

Compare: Type I vs. Type IVโ€”both can cause skin reactions, but Type I produces immediate wheals (minutes, IgE-mediated), while Type IV causes indurated erythema (days, T cell-mediated). Timing alone can distinguish them on an exam.


Quick Reference Table

ConceptBest Examples
IgE-mediated, immediateAnaphylaxis, allergic asthma, hay fever
IgG/IgM targeting cell surfacesTransfusion reactions, autoimmune hemolytic anemia, Goodpasture syndrome
Immune complex depositionSLE, serum sickness, Arthus reaction
T cell-mediated, delayedContact dermatitis, tuberculin test, granulomatous diseases
Complement involvementType II (cell lysis), Type III (inflammation at deposition sites)
Mast cell involvementType I only
Requires prior sensitizationAll four types, but clinically emphasized in Type I and Type IV

Self-Check Questions

  1. A patient develops widespread urticaria and bronchospasm within 5 minutes of a penicillin injection. Which hypersensitivity type is this, and what antibody class is responsible?

  2. Compare and contrast Type II and Type III hypersensitivity: both involve IgG, so what determines whether a reaction is classified as one versus the other?

  3. A tuberculin skin test is read at 48 hours. Why would reading it at 4 hours give a false-negative result, and which immune cells are responsible for the positive reaction?

  4. Which two hypersensitivity types would you consider if a patient presents with hemolytic anemia? How would you distinguish between them diagnostically?

  5. An FRQ asks you to explain why anaphylaxis occurs within minutes while contact dermatitis takes days to develop. What mechanistic differences account for this timing distinction?