II. Definitions

  1. Hypersensitivity
    1. Immune System sensitization after repeated allergan exposure
  2. Allergen
    1. Exogenous Antigens (typically Proteins) that trigger an immune response
  3. Gell and Coombs Classification of Hypersensitivity Reaction
    1. Categories of Hypersensitivity Response

III. Types: 1 - Immediate Hypersensitivity Reaction (IgE Mediated)

  1. Immediate allergan immune response after repeated exposure (esp. in Atopic Patients)
  2. Most common form of Hypersensitivity Reaction
  3. Mediated by IgE Antibody to specific Antigens
    1. Sensitization
      1. B-Cells are are exposed to Antigen (e.g. pollen)
      2. T-Helper Cells (TH2) bind to B-Cells
      3. B-Cells class switch to produce IgE Antibody against Antigen (instead of IgG and IgM)
      4. B-Cells produce the IgE against the specific Antigen
      5. IgE binds blood Basophils and tissue Mast Cells at the high affinity Fc receptor (FceRI)
      6. Mast Cells are now sensitized, awaiting allergan reexposure
    2. Mast Cells and Basophils are then stimulated with repeat exposure
      1. Release secretory granules including histamine (as well as Leukotrienes, Prostaglandins)
      2. Although there are four histamine receptors (H1, H2, H3, H4), H1 predominates in Type I Reaction
  4. Reaction Phases
    1. Early Phase (within minutes of exposure, <1 hour)
      1. Histamine-induced vasodilation, edema, congestion
    2. Late Phase (2 to 24 hours after exposure)
      1. Inflammatory cell infiltration (Eosinophils, Neutrophils, T-Cells)
  5. Examples
    1. Anaphylaxis (e.g. Penicillin)
    2. Urticaria
    3. Angioedema
    4. Anaphylactoid Reaction (e.g. Anaphylactoid Reaction to Radiocontrast)
    5. Atopic Allergy (e.g. Allergic Rhinitis, Allergic Asthma)
    6. Food Allergy
    7. Bee sting Allergy
    8. Allergic Occupational Asthma

IV. Types: 2 - Cytotoxic Antibody Reaction (non-IgE Antibody Mediated Reaction)

  1. Mediated by IgG and IgM (on cell surface or extracellular complex) to specific Antigens
  2. Antibody-Antigen Complex destruction by one of three mechanisms
    1. Opsonization and Phagocytosis
      1. Antibody-bound Antigen (Opsonin) is destroyed by cells (PMNs, Macrophages) engulfing complex (Phagocytosis)
    2. Antibody-dependent cellular cytotoxicity (ADCC)
      1. Antibodies bind infected cells with surface Antigen, targeted for Natural Killer Cell-mediated destruction
    3. Complement Activation
      1. IgG binds Antigen and activates complement
      2. Antibody-Antigen complexes by lysis or phagocytocsis
  3. Examples
    1. Transfusion Reaction (ABO Incompatibility)
    2. Delayed transplant Graft Rejection
    3. Rhesus Incompatibility (Rh Incompatibility)
    4. Mycoplasma pneumoniae related cold Agglutinins
    5. Autoimmune Hemolytic Anemia
      1. Autoantibodies to Red Blood Cell membrane Proteins
    6. Immune Thrombocytopenic Purpura
      1. Autoantibodies to Platelet surface Proteins
    7. Hashimoto's Thyroiditis
      1. Autoantibodies to Thyroid peroxidase
    8. Pernicious Anemia
      1. Autoantibodies to gastric Intrinsic Factor (required for Vitamin B12 absorption)
    9. Grave's Disease
      1. Autoantibodies to TSH Receptors
    10. Pemphigus
      1. Autoantibodies to epidermal Proteins
    11. Myasthenia Gravis
      1. Autoantibodies to acetylcholine receptors on Neurons
    12. Goodpasture's Syndrome
      1. Autoantibodies to renal glomeruli and pulmonary alveoli
    13. Type II Diabetes Mellitus
      1. Autoantibodies to Insulin receptors
    14. Rheumatic Fever
      1. Autoantibodies to myocardial Antigens

V. Types: 3 - Immune Complex Reaction (Antigen-Antibody Complex Deposition)

  1. Antigen-Antibody immune complexes deposit in tissue
    1. Contrast to typical immune complex processing
      1. Most immune complexes typically activate the complement system
      2. These complexes are then typically destroyed by phagocytic cells (PMNs, Macrophages)
    2. However, small complexes may be missed by Phagocytosis
      1. These complexes may instead precipitate, deposit in tissue with inflammation
    3. Other injury mechanisms triggered by immune complexes
      1. Unbridled Complement Activation
      2. Lysosomal enzyme secretion damages normal tissue
  2. Small immune complex deposition results in inflammatory reaction within 1-3 weeks of exposure
    1. Blood vessel walls resulting in Vasculitis
    2. Renal glomerular basement membrane resulting in nephritis
    3. Joint synovial membranes resulting in Arthritis
  3. Examples
    1. Serum Sickness (prototypical Immune Complex Reaction)
    2. Systemic Lupus Erythematosus
    3. Erythema Nodosum
    4. Post-Streptococcal Glomerulonephritis
    5. Arthus Reaction (e.g. Farmer's Lung)
    6. Rheumatoid Arthritis
    7. Elephantiasis (Wuchereria bancrofti reaction)
    8. Jarisch-Herxheimer Reaction
    9. Polyarteritis Nodosa
      1. Typically due to Viral HepatitisAntigen (esp. HepBsAg) and Antibody Complex

VI. Types: 4 - Delayed-Type Hypersensitivity (T Cell-Mediated)

  1. Reaction within 2-7 days after exposure
  2. Mediated by Effector T Lymphocytes (CD4+ and CD8+), activated in response to specific Antigens
    1. Triggering initial Antigens are often infectious (Mycobacteria, protozoa, and fungi)
    2. Antigen bound to Major Histocompatibility Complex (MHC) on Antigen Presenting Cells
    3. Activated T Lymphocytes release Cytokines (e.g. Interferon-gamma) and CD8+ cells may destroy Antigen directly
    4. Cytokines trigger Phagocytosis and inflammation
  3. Examples
    1. Allergic Contact Dermatitis (e.g. Nickel allergy, Poison Ivy)
    2. Non-Granulomatous Disease
      1. Type I Diabetes Mellitus
        1. Autoimmune cell-mediated destruction of Insulin-Secreting pancreatic beta cells
      2. Autoimmune Viral Myocarditis
      3. Autoimmune Peripheral Neuropathy
      4. Hashimoto Thyroiditis
      5. Multiple Sclerosis
      6. Rheumatoid Arthritis
    3. Granulomatous Disease
      1. Leprosy
      2. Tuberculosis
      3. Schistosomiasis
      4. Sarcoidosis
      5. Crohn disease
      6. Ulcerative Colitis
      7. Temporal Arteritis
    4. Mantoux Test (PPD)
      1. Immune Allergic Contact Dermatitis after prior Mycobacterium tuberculosis exposure
    5. Medications
      1. Allopurinol
      2. Lamotrigine
  4. References
    1. Vaillant (2021) Delayed Hypersensitivity Reaction, StatPearls, accessed 7/13/2021
      1. https://www.ncbi.nlm.nih.gov/books/NBK519023/

VII. Types: Other allergy mediated reactions

  1. Stimulatory Hypersensitivity
    1. Humoral Antibody activates receptor sites
    2. Example: Thyrotoxicosis (TSH autoantibodies)
  2. Fas/Fas Ligand-induced apoptosis
    1. Example: Stevens Johnson Syndrome
  3. T-Cell Activation
    1. Example: Sulfonamide induced Morbilliform rash

VIII. References

  1. Goldberg (2014) Clinical Physiology, MedMaster, Miami, FL
  2. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL
  3. Roitt (1988) Essential Immunology, Blackwell,p. 193-214
  4. Riedl (2003) Am Fam Physician 68:1781-90 [PubMed]

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Related Studies

Ontology: Hypersensitivity (C0020517)

Definition (ICF) Functions of the body's response of increased sensitization to foreign substances, such as in sensitivities to different antigens.
Definition (ICF-CY) Functions of the body's response of increased sensitization to foreign substances, such as in sensitivities to different antigens.
Definition (GO) An inflammatory response to an exogenous environmental antigen or an endogenous antigen initiated by the adaptive immune system. [GOC:jal, ISBN:0781735149]
Definition (MEDLINEPLUS)

An allergy is a reaction by your immune system to something that does not bother most other people. People who have allergies often are sensitive to more than one thing. Substances that often cause reactions are

Normally, your immune system fights germs. It is your body's defense system. In most allergic reactions, however, it is responding to a false alarm. Genes and the environment probably both play a role.

Allergies can cause a variety of symptoms such as a runny nose, sneezing, itching, rashes, swelling, or asthma. Allergies can range from minor to severe. Anaphylaxis is a severe reaction that can be life-threatening. Doctors use skin and blood tests to diagnose allergies. Treatments include medicines, allergy shots, and avoiding the substances that cause the reactions.

NIH: National Institute of Allergy and Infectious Diseases

Definition (SCTSPA) Reacciones alérgicas conocidas a una(s) sustancia(s) en particular
Definition (SNOMEDCT_US) Known to have allergic reactions to particular substance(s)
Definition (SNOMEDCT_US) A pathological process initiated by exposure to a defined stimulus at a dose tolerated by normal persons. It may be the manifestation of a disposition to hypersensitivity.
Definition (SCTSPA) Proceso patológico iniciado por la exposición a un estímulo definido, en una dosis que toleran las personas normales. Puede ser la manifestación de una disposición a la hipersensibilidad.
Definition (NCI) An immune response that occurs following exposure to an innocuous antigen, but that does not require the presence of preformed antibodies to the antigen.
Definition (NCI_FDA) Hypersensitivity; a local or general reaction of an organism following contact with a specific allergen to which it has been previously exposed and to which it has become sensitized.
Definition (NCI_NCI-GLOSS) An exaggerated response by the immune system to a drug or other substance.
Definition (MSH) Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.
Definition (CSP) state of previously immunized body in which tissue damage results from the immune response to a further dose of antigen.
Definition (HL7V3.0) <p>Hypersensitivity to an agent caused by an immunologic response to an initial exposure</p>
Concepts Pathologic Function (T046)
MSH D006967
ICD10 T78.4 , T78.40
SnomedCT 421961002, 106190000, 274211000, 418168000, 418925002, 157758001, 212998004, 127072000, 157754004, 257550005, 269284003, 269432007, 421668005, 91232002, 212999007, 282092005, 21957007, 418634005
LNC LP7756-2, LP31625-4, LP20697-6, MTHU020822, LA17771-9
English Allergic reaction, Allergy, Hypersensitivities, Allergy, unspecified, Hypersensitivity reaction, Allergy (disorder), Hypersensitivity reaction (disorder), HYSN, Allergic disorder, Allergic reaction NOS, Allergy disorder, hypersensitivity, hypersensitivity (symptom), allergic reaction, allergic reaction (diagnosis), Allergic reaction (NOS), Reaction allergic (NOS), Allergy NOS, Hypersensitivity NOS, Hypersensitivity reaction (NOS), Reaction hypersensitivity (NOS), Hypersensitivity symptom, Hypersensitivity reactions, Allergic reactions, Hypersensitivity [Disease/Finding], ALLERGY, Allergy., allergy, allergy disorders, hypersensitivity reactions, allergic disorder, allergic disorders, hypersensitivity symptoms, hypersensitivity symptom, allergies, allergic reactions, hypersensitivities, hypersensitivity reaction, Allergic disorders, Allergic state (disorder), Allergic reaction NOS (disorder), Disorder due to allergic reaction, Disorder due to allergic reaction (disorder), (Allergy, unspecified) or (hypersensitivity NOS), Allergic disorder (disorder), Allergy, unspecified (disorder), Allergic reaction (disorder), Immune hypersensitivity disorder (disorder), Disorder due to immune hypersensitivity reaction, (Allergy, unspecified) or (hypersensitivity NOS) (disorder), Immune hypersensitivity reaction (disorder), Immune hypersensitivity disorder, Hypersensitivity (finding), Allergic state, Hypersensitivity (qualifier value), Atopic AND/OR hypersensitivity state, Hypersensitivity, Allergies, Hypersensitivity Reaction, ALLERGIC REACTION, HYPERSENSITIVITY, Allergy/allergic reaction nos, hypersensitivity; reaction, allergic; reaction, reaction; allergic, reaction; hypersensitivity, Allergic reaction, NOS, Allergic state, NOS, Allergy, NOS, Hypersensitivity reaction, NOS, Allergic Disorders, Allergic reaction to substance, Allergic reaction to substance (disorder)
French HYPERSENSIBILITE, ALLERGIE, Réaction d'hypersensibilité, Réaction allergique, Allergie SAI, Hypersensibilité SAI, Réaction allergique SAI, Réaction d'hypersensibilité SAI, HYSN, Symptôme d'hypersensibilité, REACTION ALLERGIQUE, Allergie, Hypersensibilité
Portuguese HIPERSENSIBILIDADE, ALERGIA, Sintoma de hipersensibilidade, Reacção alérgica NE, Reacção alérgica, Hipersensibilidade NE, Alergia NE, Reacção de hipersensibilidade, Reacção de hipersensibilidade NE, REACCAO ALERGICA, Reação Alérgica, Alergia, Hipersensibilidade
Spanish HIPERSENSIBILIDAD, ALERGIA, reacción alérgica a una sustancia (trastorno), reacción alérgica a una sustancia, reacción de hipersensibilidad (trastorno), reacción de hipersensibilidad, Reacción alérgica, Reacción de hipersensibilidad (NEOM), Alergia NEOM, Hipersensibilidad NEOM, Síntoma de hipersensibilidad, Reacción alérgica NEOM, Reación de hipersensibilidad, Reacción de hipersensibilidad, Reacción alérgica (NEOM), alergia (trastorno), REACCION ALERGICA, trastorno de hpersensibilidad inmunológica (trastorno), trastorno de hpersensibilidad inmunológica, hipersensibilidad (hallazgo), trastorno alérgico, reacción alérgica, trastorno alérgico (trastorno), hipersensibilidad (calificador), hipersensibilidad, trastorno por reacción alérgica, reacción alérgica, SAI (trastorno), reacción alérgica, SAI, Allergic reaction NOS, estado atópico Y/O de hipersensibilidad, reacción por hipersensibilidad inmunológica, trastorno debido a reacción alérgica, trastorno de hipersensibilidad inmunológica (trastorno), trastorno de hipersensibilidad inmunológica, trastorno causado por reacción alérgica (trastorno), reacción por hipersensibilidad inmunológica (trastorno), alergia, no especificada, estado alérgico (trastorno), alergia, trastorno causado por reacción alérgica, trastorno por reacción inmunológica por hipersensibilidad, reacción alérgica (trastorno), alergia, no especificada (trastorno), trastorno inmunológico por hipersensibilidad, reacción de hipersensibilidad inmunológica (trastorno), estado alérgico, Reacción Alérgica, Alergia, Hipersensibilidad
German ALLERGIE, allergische Reaktion NNB, Uebersensibilitaetsreaktion, HYSN, Reaktion, allergisch (NNB), Ueberempfindlichkeit NNB, Uebersensibilitaetsreaktion (NNB), allergische Reaktion, allergische Reaktion (NNB), Uebersensibilitaetssymptom, Allergie NNB, ALLERGISCHE REAKTION, Allergie, nicht naeher bezeichnet, HYPERSENSIBILITAET, Ueberempfindlichkeit, Allergie, Hypersensitivität, Überempfindlichkeit
Dutch allergische reactie NAO, reactie allergisch (NAO), overgevoeligheidsreactie, allergische reactie (NAO), overgevoeligheid NAO, overgevoeligheidsreactie (NAO), allergie, reactie overgevoeligheid (NAO), hypersensitiviteitssymptoom, HYSN, allergie NAO, allergische reactie, Allergie/allergische reactie nao, allergisch; reactie, overgevoeligheid; reactie, reactie; allergisch, reactie; overgevoeligheid, Allergie, niet gespecificeerd, overgevoeligheid, Allergie, Overgevoeligheid
Italian Sintomo di ipersensibilità, Reazione da ipersensibilità (non specificata), Allergia, Allergia NAS, Reazione da ipersensibilità, Reazione di ipersensibilità (NAS), Reazione allergica, Reazione allergica (NAS), Reazione allergica NAS, Ipersensibilità NAS, Allergia (Specifica), Ipersensibilità
Japanese アレルギー反応, 過敏症状, 過敏症反応(NOS), 過敏症NOS, アレルギー反応(NOS), アレルギー反応NOS, アレルギーNOS, 過敏症反応, アレルギーNOS, カビンショウハンノウNOS, アレルギーハンノウNOS, カビンショウジョウ, カビンショウハンノウ, カビンショウNOS, カビンショウ, アレルギーハンノウ, アレルギー, アレルギー, 過敏症
Swedish Överkänslighet
Finnish Yliherkkyys
Czech Reakce přecitlivělosti, Alergická reakce, Alergie, Přecitlivělost NOS, HYSN, Alergie NOS, Reakce přecitlivělosti (NOS), Přecitlivělost, Alergická reakce NOS, Hypersensitivní syndrom, Alergická reakce (NOS), Hypersensitivní reakce (NOS), alergie, hypersenzitivita, přecitlivělost
Korean 상세불명의 알레르기
Polish Uczulenie, Reakcja alergiczna, Nadwrażliwość, Odczyn alergiczny, Alergia
Hungarian allergiás reakció, allergia k.m.n., Hypersensitivitási tünet, allergiás reakció (k.m.n.), HSYN, Allergiás reakció (k.m.n.), Túlérzékenységi reakció (k.m.n.), Hypersensitivitas k.m.n., Hypersensitivitas, Allergia, Hypersensitiv reakció (k.m.n.), allergiás reakció k.m.n., Hypersensitiv reakció
Norwegian Hypersensitivitet, Overfølsomhet, Allergi

Ontology: Type 1 hypersensitivity response (C0429892)

Concepts Pathologic Function (T046)
SnomedCT 12263007
English Type 1 hypersensitiv response, Hypersensitivity reaction mediated by reagenic antibody, Gell and Coombs reaction type I, IgE homocytotropic antibody reaction, Type I reaction, Hypersensitivity reaction type I, Type 1 hypersensitivity response, Type 1 hypersensitivity response (disorder)
Spanish reacción de Gell y Coombs tipo I, reacción de anticuerpo IgE homocitotrópico, reacción de anticuerpo homocitotrópico IgE, reacción de hipersensibilidad mediada por anticuerpo reagínico (trastorno), reacción de hipersensibilidad mediada por anticuerpo reagínico, reacción de hipersensibilidad tipo I, reacción tipo I, respuesta de hipersensibilidad tipo 1 (trastorno), respuesta de hipersensibilidad tipo 1

Ontology: Type 4 hypersensitivity response (C0429896)

Concepts Laboratory or Test Result (T034)
SnomedCT 142173005, 165001008
English Type 4 hypersensitiv response, Type 4 hypersensitivity response (observable entity), Type 4 hypersensitivity response, Type 4 hypersensitivity response (finding)
Spanish respuesta de hipersensibilidad tipo 4 (hallazgo), respuesta de hipersensibilidad tipo 4

Ontology: Type III immune complex mediated reaction (C1096071)

Concepts Disease or Syndrome (T047)
Italian Reazione mediata da immunocomplessi di tipo III
English Type III immune complex mediated reaction
Japanese 3型免疫複合体型反応, 3ガタメンエキフクゴウタイガタハンノウ
Czech Reakce III. typu zprostředkovaná imunokomplexy
Hungarian III. típusú immunkomplex mediált reakció
Portuguese Reação de tipo III mediada por imunocomplexos
Spanish Hipersensibilidad de tipo III mediada por inmunocomplejo
Dutch immuuncomplexgemedieerde reactie type III
French Réaction à immuns complexes de type 3
German Immunkomplexreaktion Typ III

Ontology: Type II hypersensitivity (C1096189)

Concepts Disease or Syndrome (T047)
Italian Ipersensibilità di tipo II, Ipersensibilità tipo II
Dutch hypersensitiviteit type II, hypergevoeligheid type II
German Allergie vom zytotoxischen Typ II, Allergie vom zytotoxischen Typ
Japanese 2型過敏症, 2ガタカビンショウ
Czech Přecitlivělost II. typu
English ii type hypersensitivity, hypersensitivity type ii, type ii hypersensitivity, Hypersensitivity type II, Type II hypersensitivity
Hungarian II. típusú hypersensitivitas, II. típusú túlérzékenység
Portuguese Hipersensibilidade tipo II
Spanish Hipersensibilidad tipo II
French Hypersensibilité de type II

Ontology: Immune hypersensitivity reaction (C3662866)

Concepts Pathologic Function (T046)
SnomedCT 418925002
English Immune hypersensitivity reaction