View source for Hypersensitivity

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  DiseasesDB     = 28827 |
  ICD10          = {{ICD10|T|78|4|t|66}} |
  ICD9           = {{ICD9|995.3}} |
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  OMIM           = |
  MedlinePlus    = |
  eMedicineSubj  = |
  eMedicineTopic = |
  MeshID         = D006967 |
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{{SI}}

{{CMG}}

==Overview==
'''Hypersensitivity''' refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. The four-group classification was expounded by [[Philip George Houthem Gell|P. H. G. Gell]] and [[Robin Coombs]] in 1963.<ref>Gell PGH, Coombs RRA, eds. Clinical Aspects of Immunology. 1st ed. Oxford, England: Blackwell; 1963.</ref>

==Comparison table==
{|Class="wikitable"
|+ Comparison of hypersensitivity types
|-
! Type !! Alternative names <ref name=Immunology195Unless> Unless else specified in boxes, then ref is: Lippincott's Illustrated Reviews: Immunology. Paperback: 384 pages. Publisher: Lippincott Williams & Wilkins; (July 1, 2007). Language: English. ISBN-10: 0781795435. ISBN-13: 978-0781795432. Page 195 </ref> !! Often mentioned disorders<ref name=Immunology195Unless/> !! Mediators<ref name=Immunology195Unless/>
|-
! 1
| [[Allergy]] || 
*[[Atopy]]
*[[Anaphylaxis]]
*[[Asthma]]
|| 
*[[Immunoglobulin E|IgE]]
|-
! 2
| Cytotoxic, antibody-dependent || 
*[[erythroblastosis fetalis]]
*[[Goodpasture's syndrome]]
*[[autoimmune hemolytic anemia]]
|| 
*[[Immunoglobulin M|IgM]] or [[Immunoglobulin G|IgG]]
*([[Complement system|Complement]])
|-
! 3
| Immune complex disease || 
*[[Serum sickness]]
*[[Arthus reaction]]
*[[Systemic lupus erythematosus|SLE]]
||
*[[Immunoglobulin G|IgG]]
*([[Complement system|Complement]])
|-
! 4
| cell-mediated || 
*[[contact dermatitis]]
*[[tuberculosis]]
*[[Chronic transplant rejection]]
||
*[[Cell-mediated immunity|Cell-mediated]]
|}

==Type 1 - immediate (or atopic, or anaphylactic) ==
{{main|Allergy}}

Type 1 hypersensitivity is an allergic reaction provoked by reexposure to a specific type of [[antigen]] referred to as an allergen.<ref>{{eMedicine|med|1101}}</ref>  Exposure may be by [[ingestion]], [[inhalation]], [[injection (medicine)|injection]], or direct contact. The difference between a normal immune response and a type I hypersensitive response is that plasma cells secrete [[IgE]]. This class of antibodies binds to Fc receptors on the surface of tissue mast cells and blood basophils. Mast cells and basophils coated by IgE are "sensitized." Later exposure to the same allergen, cross-links the bound IgE on sensitized cells resulting in [[degranulation]] and the secretion of pharmacologically active mediators such as mastcell
, [[leukotriene]], and [[prostaglandin]] that act on the surrounding tissues. The principal effects of these products are [[vasodilation]] and smooth-muscle contraction.

The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from [[Anaphylaxis|anaphylactic shock]]. Treatment usually involves [[epinephrine]], [[antihistamines]], and [[corticosteroid]]s. If the entire body gets involved, then anaphylaxis can take place; an acute, systemic reaction that can prove fatal. 

Some examples:
*Allergic [[asthma]]
*Allergic [[conjunctivitis]]
*[[Allergic rhinitis]] ("hay fever")
*Anaphylaxis
*[[Angioedema]]
*[[Asparaginase Erwinia Chrysanthemi]]
*[[Urticaria]] (hives)
*[[Eosinophilia]]
*[[Penicillin]]
*[[Cephalosporin]]
*[[Lincomycin Hydrochloride]]

==Type 2 - antibody-dependent  ==<!-- This section is linked from [[Lupus erythematosus]] -->

In type 2 hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (absorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognised by [[macrophage]]s or [[dendritic cell]]s which act as antigen presenting cells, this causes a [[B cell]] response where antibodies are produced against the foreign antigen.

An example here is the reaction to penicillin where the drug can bind to red blood cells causing them to be recognised as different, B cell proliferation will take place and antibodies to the drug are produced.  [[IgG]] and [[IgM]] antibodies bind to these antigens to form complexes that activate the [[classical complement pathway|classical pathway]] of [[complement system|complement]] activation for eliminating cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and [[Complement membrane attack complex|membrane attack complex]]es cause cell [[lysis]] and death. The reaction takes hours to a day.

Another form of type 2 hypersensitivity is called [[antibody-dependent cell-mediated cytotoxicity]] (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer (NK) cells and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, [[CD16]] (FcγRIII)), which in turn kill these tagged cells. 

Some examples:
*Autoimmune hemolytic [[anemia]]
*[[Goodpasture's syndrome]]
*[[Pemphigus]]
*[[Pernicious anemia]] (if autoimmune)
*[[Thrombocytopenia|Immune thrombocytopenia]]
*[[Blood transfusion|Transfusion]] reactions
*[[Hashimoto's thyroiditis]]
*[[Graves disease]] (see type V below)
*[[Myasthenia gravis]] (see type V below)
*[[Rheumatic fever]]
*[[Hemolytic disease of the newborn]] (erythroblastosis fetalis)
*[[Acute transplant rejection]]

==Type 3 - immune complex ==

Type 3 hypersensitivity occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking. Large immune complexes that cannot be cleared are deposited in vessel walls and induce an inflammatory response. The reaction can take hours, days, or even weeks to develop.

Some clinical examples:
*[[Rheumatoid arthritis]]
*Immune complex [[glomerulonephritis]]
*[[Serum sickness]]
*Subacute bacterial [[endocarditis]]
*Symptoms of [[malaria]]
*[[Systemic lupus erythematosus]]
*[[Arthus reaction]]
*[[Farmer's lung]] (Arthus-type reaction)
*[[Polyarteritis nodosa]]

==Type 4 - cell-mediated (delayed-type hypersensitivity, DTH) ==
{{seealso|Cell mediated immunity}}

Type 4 hypersensitivity is often called delayed type as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response.

CD8+ [[cytotoxic T cell]]s and CD4+ [[helper T cell]]s recognise antigen in a complex with either type 1 or 2 [[major histocompatibility complex]]. The antigen-presenting cells in this case are macrophages which secrete [[IL-12]], which stimulates the proliferation of further CD4+ T cells. CD4+ T cells secrete [[IL-2]] and [[interferon]] gamma, further inducing the release of other Type 1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact while activated macrophages produce [[hydrolytic enzyme|hydrolytic]] [[enzyme]]s and, on presentation with certain intracellular pathogens, transform into multinucleated [[giant cell]]s.

Some clinical examples:
*[[Contact dermatitis]] ([[Toxicodendron radicans|poison ivy]] rash, for example)
*[[Atopic dermatitis]] (eczema)
*[[Temporal arteritis]]
*Symptoms of [[leprosy]]
*Symptoms of [[tuberculosis]]
*[[Mantoux test]]
*[[Coeliac disease]]
*[[Chronic transplant rejection]]

==Type 5 - stimulatory ==

This is an additional type that is sometimes (often in Britain) used as a distinction from Type 2.<ref>Rajan TV. The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. ''Trends Immunol''. 2003 Jul;24(7):376-9. PMID 12860528</ref>

Instead of binding to cell surface components, the antibodies recognize and bind to the cell surface [[receptor (biochemistry)|receptors]], which either prevents the intended [[ligand]] binding with the receptor or mimics the effects of the ligand, thus impairing cell signalling.

Some clinical examples:
*[[Graves disease]]
*[[Myasthenia gravis]]

(There is also a type 6 hypersensitivity reaction in which natural killer cells lyse cells that have been coated in antibody and this reaction is thought to be implicated with certain autoimmune diseases, tumour rejection & parasite rejection).


==Causes==
===Causes by Organ System===
{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" |'''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
|-
|bgcolor="LightSteelBlue"| '''Chemical/Poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Amoxicillin]], [[Aprotinin]], [[Bicalutamide]], [[Cytarabine]], [[Desmopressin]], [[Goserelin]], [[Meropenem]], [[Paclitaxel]], [[Phenobarbital]], [[Sorafenib]], [[Sulfasalazine]], [[Penicillin G potassium]], [[Pertuzumab]],[[Vedolizumab]]
|- 
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
|-
|}

===Causes in Alphabetical Order===
{{col-begin|width=80%}}
{{col-break|width=33%}}
* [[Amoxicillin]]
*[[Cytarabine]]
*[[Desmopressin]]
*[[Paclitaxel]]
*[[Phenobarbital]]
*[[Sorafenib]]

{{col-break|width=33%}}


{{col-break|width=33%}}

{{col-end}}

== See also ==

* [[Allergy]]

==References==
<references/>

==External links==
* {{GPnotebook|-529858552}}
* {{FPnotebook|ENT46}}

{{Consequences of external causes}}

[[Category:Immune system]]
[[Category:Immune system disorders]]
[[Category:Allergology]]
[[Category:Immunology]]

[[de:Überempfindlichkeitsreaktion]]
[[no:Hypersensitivitet]]
[[pl:Nadwrażliwość]]
[[vec:Clasificaxion de Gell e Coombs]]

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