Hypersensitivity Reactions: Immunology and Allergies

Hypersensitivity Reactions

• Hypersensitivity reactions are exaggerated responses to typically harmless antigens, resulting in injury, disease, or even death.
• These reactions are undesirable and can be damaging, uncomfortable, or occasionally fatal.

Types of Hypersensitivity Reactions

• Hypersensitivity reactions can be divided into four types based on the mechanisms involved and the time taken for the reaction: • Type I: Immediate, anaphylactic • Type II: Cytotoxic or cytolytic • Type III: Immune complex • Type IV: Cell-mediated, delayed

Antibody-Mediated Hypersensitivity

• Types I, II, and III are antibody-mediated hypersensitivity reactions
• These reactions involve the activation of B cells and the production of IgE antibodies

Cell-Mediated Hypersensitivity

• Type IV is a cell-mediated hypersensitivity reaction
• This reaction involves the activation of T cells and the production of cytokines

Causes of Tissue Injury in Hypersensitivity Reactions

• Release of vasoactive materials
• Phagocytosis or lysis of cells
• Activation of the complement system
• Release of cytokines and cytolytic enzymes

Type I Hypersensitivity (Anaphylaxis)

• Also known as immediate hypersensitivity
• The most common form of hypersensitivity reactions
• Mediated by IgE antibodies and produced by the immediate release of mediators by basophils and mast cells
• Exposure to allergens can be through ingestion, inhalation, injection, or direct contact

Th1 and Th2 Cells

• In normal immune responses, there is a balance between Th1 and Th2 cells
• In allergic individuals, the immune response is shifted towards Th2 cells, leading to the production of IgE antibodies

Mast Cells

• The principal effector cells of immediate hypersensitivity reactions
• Found throughout the body, particularly in areas around small blood vessels, lymphatics, nerves, and glandular tissue
• Have abundant cytoplasmic granules that store preformed inflammatory mediators

Basophils

• Similar to mast cells, but distinct in terms of appearance and function
• Present in peripheral blood, representing less than 1% of total white blood cells
• Have fewer, but larger granules than mast cells, and the concentrations of inflammatory substances in the granules differ from those of mast cells

Factors Predisposing to Type I Hypersensitivity

• Genetic factors, such as atopic allergies (hay fever, asthma, food allergy)
• Atopic individuals have an IL-4 gene that codes for high levels of IL-4

Primary Mediators

• Histamine: the most important vasoactive amine of human anaphylaxis, leading to burning, itching, and other symptoms
• Eosinophil chemotactic factor of anaphylaxis (ECF-A): attracts eosinophils, which are prominent in immediate allergic reactions
• Neutrophil chemotactic factor: attracts neutrophils to the site of allergic reaction
• Serotonin: causes capillary dilation, increased vascular permeability, and smooth muscle contraction
• Proteases: causes vasodilation and increased permeability

Secondary Mediators

• Leukotriene: slow-reacting substance of anaphylaxis (SRSA), leading to bronchoconstriction, hypotension, and vascular permeability
• Prostaglandins: causes bronchoconstriction, hypotension, and vascular permeability
• Platelet-activating factors (PAF): causes bronchoconstriction, hypotension, and vascular permeability

Clinical Manifestations of Type I Hypersensitivity Reaction

• Asthma
• Allergic conjunctivitis
• Rhinitis (hay fever)
• Atopic dermatitis (atopic eczema)
• Urticaria (hives)/angioedema

Systemic Anaphylaxis (Anaphylactic Shock)

• The most severe form of type I hypersensitivity, characterized by severe bronchoconstriction and hypotension (shock) that can be life-threatening
• Antigen enters the bloodstream, leading to widespread reaction and affecting almost the entire body
• Loss of fluid from blood vessels into tissues causes swelling and possibly shock

Anaphylactoid Reactions

• Result from systemic release of mediators from mast cells and basophils
• Mimic signs and symptoms of anaphylaxis
• Not IgE-mediated, but occur at the first contact with the inciting agent
• Inciting agents include drugs, iodinated media, vigorous exercise, contrast media, and others

Diagnosis of Type I Hypersensitivity Reaction

• Medical history
• Skin Prick Allergy Test: involves putting a drop of liquid containing a substance onto the forearm, and then gently pricking the skin with a needle
• Detection of total and specific IgE: using Paper Radioimmunosorbent Test (PRIST) and Radioallergosorbent test (RAST) or Enzyme-linked immunosorbent assay (ELISA)

Treatment of Type I Hypersensitivity Reaction

• Allergen avoidance
• Drugs: anti-histamines, mast cell and basophil stabilizing drugs, and general anti-inflammatory agents
• Immunotherapy: desensitization (hyposensitization) using allergy shots, which involves weekly injections of very small doses of the allergen for the first year, and then gradually decreasing to monthly injections.