Hypersensitivity Reactions

Hypersensitivity Overview

• Hypersensitivity reactions (HSR) occur when the normal immune system reacts excessively to an antigen, potentially causing damage or fatality.
• The Gell & Coombs classification categorizes hypersensitivity reactions into four types (I-IV).
• Type I (allergy/anaphylaxis/atopic): Characterized by an immediate reaction triggered by an allergen; antibody IgE binds to mast cells and basophils, leading to degranulation and the release of inflammatory mediators.
• Type II (antibody-dependent): Antibody (IgG or IgM) directly targeting cells or tissues with specific antigens; this leads to cell destruction through complement activation or antibody-dependent cell-mediated cytotoxicity (ADCC).
• Type III (immune complex-mediated): Formation and deposition of soluble antigen-antibody complexes in tissues, activating complement and initiating inflammation. This can lead to widespread tissue damage.
• Type IV (delayed-type): Cell-mediated immune response, typically instigated by T-cells, that involves the activation of macrophages and other immune cells, resulting in inflammation and tissue damage; takes 24-72 hours for a reaction to manifest.

Hypersensitivity Type I Reactions

• Immunological mechanisms underlying Type I hypersensitivity reactions are focused on IgE-mediated allergic responses.
• These reactions encompass a case study centered on allergic asthma.

Hypersensitivity Type II Reactions

• The immunological mechanisms and pathophysiology of this type of hypersensitivity reaction were characterized and their reactions displayed in a case study, Hemolytic Disease of the Newborn.

Hypersensitivity Type III Reactions

• The immunological mechanisms and pathophysiology of this type of hypersensitivity reaction are characterized by the formation of soluble immune complexes in the circulation, that can activate complement and lead to various localized or systemic manifestations.

Hypersensitivity Type IV Reactions

• The immunological mechanisms and pathophysiology that underlie Type IV reactions are characterized by a delayed response.
• A case study in this area is the tuberculin reaction(the Mantoux Test).

Types I-IV Summary

• A summary table displays the key characteristics of each hypersensitivity type including the immune reactant, antigen, effector mechanism, and examples.
• A graphical overview of Type I-IV reactions shows the relationships between the categories.

Common Sources of Allergens

• Inhaled, injected, and ingested materials are potential sources of allergens.
• Pollen, dander, mold, insect venoms, foods, and drugs are illustrative examples of allergens.

Allergic Reactions/Anaphylaxis

• Symptoms and signs: Puffy face, lips, tongue, hives, urticaria, stridor (difficult breathing), wheezing, hypotension, and collapse.
• Treatment: Epinephrine (adrenaline) administered intramuscularly (IM) should be considered as the first line of treatment for respiratory distress or anaphylactic shock.

Immune Complex Diseases

• Serum sickness
• Heterologous proteins
• Secondary reactions involving non-proteins
• Infection-associated immune complexes
• Complement deficiencies
• Systemic lupus erythematosus (SLE)

Localized Immune Complex Reactions

• Localized immune complex reactions, known as Arthus reactions, are characterized by the deposition of antigen-antibody complexes in tissues, triggering inflammation in localized areas such as with farmer's lung.

Type IV (Delayed Hypersensitivity) Reactions

• A case study displays how delayed hypersensitivity reactions manifest in localized reactions.
• A detailed overview of the mechanisms, including primary and secondary immune responses( sensitization and elicitation phases) is provided.

Clinical Variants of DTH Reactions

• This section details the variations in DTH reactions including tuberculin-type hypersensitivity, contact hypersensitivity and granulomatous hypersensitivity.