Hypersensitivity

Clinic

• Also called hypersensitivity reaction or intolerance
• It refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity.
• It can be classified into four types.
  1. Type I: IgE mediated immediate reaction
  2. Type II: Antibody-mediated reaction (IgG or IgM antibodies)
  3. Type III: Immune complex-mediated reaction
  4. Type IV: Cytotoxic, cell-mediated, delayed hypersensitivity reaction

The first three types are considered immediate hypersensitivity reactions because they occur within 24 hours. The fourth type is considered a delayed hypersensitivity reaction because it usually occurs more than 12 hours after exposure to the allergen, with a maximal reaction time between 48 and 72 hours.

Gell and Coombs classification[edit]

The Gell and Coombs classification of hypersensitivity is the most widely used, and distinguishes four types of immune response which result in bystander tissue damage.

Immunologic aspects of hypersensitivity reactions

Type	Alternative names	Antibodies or Cell Mediators	Immunologic Reaction	Examples	Entities/ Miasms
I	Allergy Immediate Anaphylactic	Antibody IgE	Fast response which occurs in minutes Free antigens cross link the IgE on mast cells and basophils Testing can be done via skin test for specific IgE.	Atopy Anaphylaxis Asthma Churg–Strauss Syndrome	Eosinophilia Asthma Vasculitis MTB
II	Antibody-dependent	Antibody IgM Antibody IgG Complement MAC	IgM or IgG binds to antigen on a target cell, which is actually a host cell that is perceived by the immune system as foreign, leading to cellular destruction via the MAC. Testing includes both the direct and indirect Coombs test.	Autoimmune hemolytic anemia Rheumatic heart disease Thrombocytopenia Erythroblastosis fetalis Goodpasture's syndrome Graves' disease Myasthenia gravis Pemphigus vulgaris	Hemolytic Anemia Thrombocytemia Nephritis EBV
III	Immune complex	Antibody IgG Complement Neutrophils	IgG binds to soluble antigen, forming a circulating immune complex. This is often deposited in the vessel walls of the joints and kidney, initiating a local inflammatory reaction.	Serum sickness Rheumatoid arthritis Arthus reaction Post streptococcal glomerulonephritis Membranous nephropathy Reactive arthritis Lupus nephritis SLE Extrinsic allergic alveolitis (hypersensitivity pneumonitis)	Interstitial pneumonitis Nephritis Arthritis EBV
IV	Delayed, Cell-mediated immune memory response, Antibody-independent Cytotoxic	Cells T-cells	CTL's and T helper cells are activated by an antigen presenting cell. When the antigen is presented again in the future, the memory Th1 cells will activate macrophages and cause an inflammatory response that can lead to tissue damage.	Contact dermatitis, including Urushiol-induced contact dermatitis (poison ivy rash). Mantoux test Chronic transplant rejection MS Coeliac disease Hashimoto's thyroiditis Granuloma annulare

Type I hypersensitivity

• It occurs as a result of exposure to an antigen.
• The response to the antigen occurs in two stages: the sensitization and the effect stage.
• In the "sensitization" stage, the host experiences an asymptomatic contact with the antigen.
• Subsequently, in the "effect" period, the pre-sensitized host is re-introduced to the antigen, which then leads to a type I anaphylactic or atopic immune response.

• Types of antigens involved
  • Food: nuts, eggs, soy, wheat, shellfish, etc.
  • Animal source: bee, wasp, cats, insects, rats, etc.
  • Environmental factors: dust mites, latex, pollen, mold, etc.
  • Atopic diseases: allergic asthma, allergic rhinitis, conjunctivitis, dermatitis, etc.
  • Medication-induced reactions: antibiotics

Type II hypersensitivity

• Type II hypersensitivity reaction refers to an antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.^{[citation needed]}
• Damage can be accomplished via three different mechanisms:
  • Antibody binding to cell surface receptors and altering its activity
  • Activation of the complement pathway.
  • Antibody-dependent cellular cytotoxicity.

• The pathophysiology can be broadly classified into three types:
  1. Cell depletion or destruction without inflammation
  2. Inflammation mediated by complement or Fc receptor
  3. Cellular dysfunction by antibodies

Type III hypersensitivity

• In type III hypersensitivity reaction, an abnormal immune response is mediated by the formation of antigen-antibody aggregates called "immune complexes".
• They can precipitate in various tissues such as skin, joints, vessels, or glomeruli, and trigger the classical complement pathway.
• Complement activation leads to the recruitment of inflammatory cells (monocytes and neutrophils) that release lysosomal enzymes and free radicals at the site of immune complexes, causing tissue damage.
• The most common diseases involving a type III hypersensitivity reaction are
  • Serum sickness
  • Post-streptococcal glomerulonephritis
  • SLE
  • Farmers' lung (hypersensitivity pneumonitis)
  • RA
• The principal feature that separates type III reactions from other hypersensitivity reactions is that in type III reaction, the antigen-antibody complexes are pre-formed in the circulation before their deposition in tissues.

Type IV hypersensitivity

• Type IV hypersensitivity reactions are, to some extent, normal physiological events that help fight infections, and dysfunction in this system can predispose to multiple opportunistic infections.
• Adverse events can also occur due to these reactions when an undesirable interaction between the immune system and an allergen happens.