Hypersensitivity Chapter Notes | Microbiology - NEET PG PDF Download

Type I Hypersensitivity Reaction

Mechanism

Type I hypersensitivity reactions occur in two phases: the sensitization phase and the effector phase.

Sensitization Phase

• During the initial exposure to an allergen, antigen-presenting cells (APCs) process the allergen.
• The allergenic peptide is presented to T-cells, activating T_H2 cells.
• T_H2 cells release IL-4, which stimulates B-cells to produce IgE antibodies.
• IgE coats mast cells, particularly at mucosal sites, preparing them for future encounters with the allergen.

Effector Phase

• Upon subsequent exposure to the same allergen, IgE bound to mast cells recognizes and binds the allergen.
• This binding triggers mast cells to release various mediators, which can be classified into:
  • Primary Mediators: These are preformed and released immediately upon activation.
  • Secondary Mediators: These are synthesized and released later.
• The released mediators have a range of pharmacological effects that contribute to the allergic response.

Mediators of Type I Hypersensitivity Reaction

Primary Mediators

• Histamine, Heparin, and Serotonin: These substances increase vascular permeability and cause smooth muscle contraction.
• Eosinophil Chemotactic Factor (ECF-A): This factor attracts eosinophils to the site of the allergic reaction.
• Neutrophil Chemotactic Factor (NCF-A): This factor attracts neutrophils to the site of the allergic reaction.
• Proteases: These enzymes cause bronchial mucus secretion and degrade the membranes of blood vessels.

Secondary Mediators

• Platelet-Activating Factor: This factor leads to platelet aggregation, degranulation, and contraction of pulmonary smooth muscles.
• Leukotrienes (Slow Reactive Substance of Anaphylaxis, SRS-A): These substances increase vascular permeability and cause contraction of pulmonary smooth muscles.
• Prostaglandins: These compounds cause vasodilation, contraction of pulmonary smooth muscles, and platelet aggregation.
• Bradykinin: This peptide increases vascular permeability and causes smooth muscle contraction.
• Cytokines (IL-1 and TNF-α): These cytokines can lead to systemic anaphylaxis and increase the expression of cell adhesion molecules (CAMs) on venular endothelial cells.

Common Allergens Associated with Type I Hypersensitivity Reaction   

Common Allergens

• Food Allergens: Nuts, eggs, peas, seafood, beans, and milk.
• Plant and Pollen Allergens: Rye grass, ragweed, and timothy grass.
• Protein Allergens: Foreign serum vaccines.
• Drug Allergens: Penicillin, sulfonamides, local anesthetics, and salicylates.
• Insect Bite Allergens: Venom from bees, wasps, ants, cockroaches, and dust mites.
• Other Allergens: Mold spores, animal hair, and dander.

Examples of Type I Hypersensitivity Reactions

• Experiments Demonstrating Type I Hypersensitivity: P-K reaction, Schultz Dale phenomenon, and Theobald Smith phenomenon.
• Systemic Anaphylaxis
• Localized Anaphylaxis (Atopy), including:
  • Allergic Rhinitis (Hay Fever)
  • Asthma
  • Food Allergies
  • Atopic Urticaria
  • Atopic Dermatitis (Allergic Eczema)
  • Drug Allergies
  • Wheal and Flare Reactions
• Parasitic Diseases/Tests:
  • Casoni Test (for Hydatid Disease)
  • Tropical Pulmonary Eosinophilia (TPE)
  • Loeffler’s Pneumonia (Ascaris)
  • Ground Itch (Hookworm)
  • Hydatid Fluid Leakage
  • Cercarial Dermatitis/Swimmer’s Itch (Schistosoma)

Detection of Type I Hypersensitivity

• Skin Prick Test
• Radioimmunosorbent Test (RIST): Measures total serum IgE levels.
• Radioallergosorbent Test (RAST): Quantifies allergen-specific serum IgE levels.

Treatment of Type I Hypersensitivity Reactions

• Avoidance of known allergens.
• Hyposensitization: Gradual exposure to increasing doses of allergens to reduce or eliminate the allergic response.
• Humanized Monoclonal anti-IgE: Treatment that binds and blocks IgE antibodies.
• Medications: Antihistamines, adrenaline, cortisone, theophylline, and cromolyn sodium are effective in suppressing Type I hypersensitivity responses.

Type II Hypersensitivity Reaction

In type II hypersensitivity reactions, the damage to the host is caused by antibodies, specifically IgG (or rarely IgM ), that bind to various types of antigens. These antigens can include:

• Host cell surface antigens: Such as red blood cell membrane antigens, including blood group and Rh antigens.
• Extracellular matrix antigens
• Exogenous antigens: These are antigens that are absorbed onto host cells, like a drug coating on a red blood cell membrane.

When the antibody binds to the antigen, it triggers type II reactions through the Fc region of the antibody via three main mechanisms:

Activation of the Complement System by Antibody (Fc)

This mechanism involves:

• Complement-dependent cytolysis: Caused by the formation of the membrane attack complex.
• Inflammation: Mediated by complement components C5a and C3a.
• Opsonization: Facilitated by complement components C3b and C4b.

This mechanism is observed in conditions such as:

• Transfusion reactions (e.g., ABO incompatibility)
• Erythroblastosis fetalis
• Autoimmune hemolytic anemia, agranulocytosis, or thrombocytopenia
• Drug-induced hemolytic anemia
• Pemphigus vulgaris
• Hyperacute graft rejection

Antibody (Fc Portion) Interacting with Fc Receptors on Target Cells

This mechanism includes:

• Antibody-dependent cellular cytotoxicity (ADCC): A process where immune cells kill target cells coated with antibodies.
• Opsonization: Marking pathogens for destruction by phagocytes.

Antibody Dependent Cellular Dysfunction or ADCD

This mechanism involves the dysfunction of target cells due to the binding of antibodies. Some examples include:

Autoantibody Mediated:

• Graves' disease: Activation of receptors by autoantibodies.
• Myasthenia gravis: Inhibition of receptors by autoantibodies.

Other examples of ADCD include:

• Goodpasture syndrome: Antibodies against type IV collagen in the kidney and lung.
• Pernicious anemia: Antibodies against intrinsic factor, leading to vitamin B12 deficiency.
• Rheumatic fever: Antibodies against streptococcal antigens that cross-react with heart tissues.
• Myocarditis in Chagas disease: Due to antibodies against Trypanosoma cruzi affecting heart tissue.

Type-III Hypersensitivity Reaction

Type-III hypersensitivity reactions occur when there is an excessive formation of immune complexes (antigen-antibody complexes). This triggers an inflammatory response by activating the complement system, which can lead to tissue damage.

Localized or Arthus Reaction

• In Skin: Following insect bites and during allergic desensitization.
• In Lungs: Farmer's Lung: Caused by exposure to Saccharopolyspora species. Bird-Fancier's Disease: Also known as bird fancier's lung, this condition is similar to farmer's lung but is triggered by exposure to bird droppings.

Generalized or Systemic Type III Reactions

• Examples: Serum sickness and other systemic conditions.

Diseases Linked to Generalized Type III Hypersensitivity Reactions:

• Connective Tissue Disorders: Autoantibodies form immune complexes with self-antigens.
  • SLE (Systemic Lupus Erythematosus): Characterized by anti-DNA antibodies.
  • Rheumatoid Arthritis: Involves antibodies against human immunoglobulin.
  • Polyarteritis Nodosa (PAN): A condition causing inflammation of blood vessels.
• Parasitic Diseases: Resulting from immune complex deposition.
  • Nephrotic Syndrome: Can arise from various causes, but malaria is not a direct factor.
  • Katayama Fever: Associated with schistosomiasis.
  • African Trypanosomiasis: Also known as sleeping sickness.
• Antibody-Dependent Cellular Dysfunction (ADCD): Examples include rheumatoid arthritis, where both type III and type IV hypersensitivity reactions occur.

Type-IV Hypersensitivity Reaction

Type-IV hypersensitivity reactions are unique in several aspects:

• They are delayed reactions, occurring 48–72 hours after exposure to an antigen.
• These reactions are cell-mediated, primarily involving specific cells known as TDTH cells.
• Tissue damage in Type-IV reactions is mainly caused by activated macrophages.

Mechanism of Type-IV Reactions

• Sensitization Phase (1–2 weeks after antigen exposure): Antigen-presenting cells (APCs) process the antigen and present its fragments to TH cells. TH cells then differentiate into T1 cells, which further develop into TDTH cells.
• Effector Phase: Upon re-encountering the antigen, TDTH cells release various cytokines, including:
  • Interferon gamma (IFN-γ)
  • Interleukin-2 (IL-2)
  • Monocyte chemotactic and activating factor (MCAF)
  • Tumor necrosis factor beta (TNF-β)
  • Migration inhibitory factor (MIF)
  • Interleukin-3 (IL-3)
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF)
• These cytokines play various roles that can be either protective or harmful to tissues.

Infections and Conditions Associated with Type IV Hypersensitivity

Intracellular Bacteria:

• Mycobacterium tuberculosis
• Listeria monocytogenes
• Brucella abortus

Intracellular Fungi:

• Pneumocystis jirovecii
• Candida albicans
• Histoplasma capsulatum
• Cryptococcus neoformans

Non-infectious Conditions:

• Type 1 Diabetes Mellitus
• Multiple Sclerosis
• Peripheral Neuropathies
• Hashimoto’s Thyroiditis
• Crohn’s Disease
• Chronic Transplant Rejection
• Graft-versus-Host Disease

Intracellular Viruses:

• Herpes Simplex Virus
• Variola Virus (Smallpox)
• Measles Virus

Skin Tests to Demonstrate Delayed-Type Hypersensitivity (DTH):

• Tuberculin Test (Mantoux Test)
• Lepromin Test
• Montenegro Test (Leishmaniasis)
• Frie Test (Lymphogranuloma Venereum)

Granuloma Formation Observed In:

• Tuberculosis
• Sarcoidosis
• Schistosomiasis
• Other Trematode Infections

Other Examples:

• Contact Dermatitis: Occurs due to exposure to contact antigens like nickel, poison ivy, poison oak, and picryl chloride.