Hypersensitivity refers to excessive, 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. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction.

TYPE I HYPERSENSITIVITY Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticariaand eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis). The reaction may cause a range of symptoms from minor inconvenience to death. The reaction usually takes 15 - 30 minutes from the time of exposure to the antigen, although sometimes it may have a delayed onset (10 - 12 hours). Immediate hypersensitivity is mediated by IgE. The primary cellular component in this hypersensitivity is the mast cell or basophil. The reaction is amplified and/or modified by platelets, neutrophils and eosinophils. A biopsy of the reaction site demonstrates mainly mast cells and eosinophils. The mechanism of reaction involves preferential production of IgE, in response to certain antigens (often called allergens). The precise mechanism as to why some individuals are more prone to type-I hypersensitivity is not clear. However, it has been shown that such individuals preferentially produce more of TH2 cells that secrete IL-4, IL-5 and IL-13 which in turn favor IgE class switch. IgE has very high affinity for its receptor (Fcε; CD23) on mast cells and basophils. A subsequent exposure to the same allergen cross links the cell-bound IgE and triggers the release of various pharmacologically active substances (figure 1). Cross-linking of IgE Fc-receptor is important in mast cell triggering. Mast cell degranulation is preceded by increased Ca++ influx, which is a crucial process; ionophores which increase cytoplasmic Ca++also promote degranulation, whereas, agents which deplete cytoplasmic Ca++ suppress degranulation. The agents released from mast cells and their effects are listed in Table 1. Mast cells may be triggered by other stimuli such as exercise, emotional stress, chemicals (e.g., photographic developing medium, calcium ionophores, codeine, etc.),anaphylotoxins (e.g., C4a, C3a, C5a, etc.). These reactions, mediated by agents without IgE-allergen interaction, are not hypersensitivity reactions, although they produce the same symptoms.

Table 1. Pharmacologic Mediators of Immediate Hypersensitivity MEDIATOR Preformed mediators in granules histamine tryptase kininogenase ECF-A (tetrapeptides) bronchoconstriction, mucus secretion, vasodilatation, vascular permeability proteolysis kinins and vasodilatation, vascular permeability, edema attract eosinophil and neutrophils

Newly formed mediators leukotriene B4 leukotriene C4, D4 prostaglandins D2 PAF basophil attractant same as histamine but 1000x more potent edema and pain platelet aggregation and heparin release: microthrombi

The reaction is amplified by PAF (platelet activation factor) which causes platelet aggregation and release of histamine, heparin and vasoactive amines. Eosinophil chemotactic factor of anaphylaxis (ECF-A) and neutrophil chemotactic factors attract eosinophils and neutrophils, respectively, which release various hydrolytic enzymes that cause necrosis. Eosinophils may also control the local reaction by releasing arylsulphatase, histaminase, phospholipase-D and prostaglandin-E, although this role of eosinophils is now in question.

measurement of total IgE and specific IgE antibodies against the suspected allergens. particularly broncho-pulmonary ones. and are used therapeutically (Table 2). Conversely. Symptomatic treatment is achieved with anti-histamines which block histamine receptors.g. carbacol) WORSENING OF SYMPTOMS IMPROVEMENT OF SYMPTOMS elevation of cyclic-AMP stimulation of β-adrenergic receptor (epinephrine. myelomas. Thus. Substances which alter cAMP and cGMP levels significantly alter the allergic symptoms.Relationship between allergic symptoms and cyclic-nucleotides Lowering of cyclic-AMP stimulation of α-adrenergic receptor (nor-epinephrin. etc.Cyclic nucleotides appear to play a significant role in the modulation of immediate hypersensitivity reaction. 1A). probably.. agents which decrease cAMP or stimulate cGMP aggravate these allergic conditions. Late onset allergic symptoms. isoproterenol) blocking of α-adrenergic receptor (phenoxybenzamine) inhibition of phosphodiesterase (theophylline) binding of histamine-2 or PGE to their receptors Diagnostic tests for immediate hypersensitivity include skin (prick and intradermal) tests (fig. Total IgE and specific IgE antibodies are measured by a modification of enzyme immunoassay (ELISA). phenyl-epinephrin) or blocking of β-adrenergic receptor (propanolol) elevation of cyclic-GMP stimulation of γ-cholinergic receptor (acetyl choline. substances that increase intracellular cAMP seem to relieve allergic symptoms. There appears to be a genetic predisposition for atopic diseases and there is evidence for HLA (A2) association. Increased IgE levels are indicative of an atopic condition. Chromolyn sodium inhibits mast cell degranulation. Table 2 . although their exact function is ill understood. by inhibiting Ca++ influx. although IgE may be elevated in some non-atopic diseases (e. particularly bronchoconstriction which is mediated . helminthic infection.).

The reaction may be general (e. Accolate) or inhibitors of thecyclooxygenase pathway (Zileutoin). Treatment involves anti-inflammatory and immunosuppressive agents. The use of IgG antibodies against the Fc portions of IgE that binds to mast cells has been approved for treatment of certain allergies. Immunofluorescent stain of lungs (e. Albuterol). Type II cytotoxicity mechanism TYPE III HYPERSENSITIVITY Type III hypersensitivity is also known as immune complex hypersensitivity. TYPE II HYPERSENSITIVITY Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues. although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II close-up view of intradermal hypersensitivity. such as that seen in Goodpasture's nephritis (renal and lung basement membrane) (figure 3A) and pemphigus (skin intercellular protein. to some extent. Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement (Figure 2).. The antigens are Figure 1A normally endogenous.g.g. as it can block mast cell sensitization.g. Figure 2. particularly to insect venoms and. are treated with leukotriene receptor blockers (Singulair. The reaction time is skin test with multiple positive minutes to hours. desmosome) (figure 3B). Phagocytes and K cells may also play a role. rheumatoid arthritis) or other organs. pollens.g. Drug-induced hemolytic anemia. Hyposensitization (immunotherapy or desensitization) is another treatment modality which is successful in a number of allergies.. although short term. Arthus reaction)..by leukotrienes.. This reaction may be immunoglobulin G (IgG) the pathogenic mechanism of diseases caused by many microorganisms. The mechanism is not clear. granulocytopenia and thrombocytopenia are such examples. aspergillosis). allergen responses © Bristol Biomedical Image Archive. Used with permission The lesion contains antibody. lupus nephritis). relief from bronchoconstriction is provided by bronchodilators (inhalants) such as isoproterenol derivatives (Terbutaline. Suppressor T cells that specifically inhibit IgE antibodies may play a role.g.. complement and neutrophils. serum sickness) or Figure 3A may involve individual organs including skin (e.g. Diagnostic tests include detection of circulating antibody against the tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence. Thophylline elevates cAMP by inhibiting cAMP-phosphodiesterase and inhibits intracellular Ca++ release is also used to relieve bronchopulmonary symptoms. Symptomatic. The staining pattern is normally smooth and linear. showing linear pattern in . kidneys (e. polyarteritis). joints (e. blood vessels (e. systemic lupus erythematosus. but there is a correlation between appearance of IgG (blocking) antibodies and relief from symptoms..

SLE). The antigen is soluble and not attached to the organ involved. The lesion is characterized by induration and erythema. or endogenous (non-organ specific autoimmunity: e. Used with permission The reaction may take 3 . etc. The classical example of this hypersensitivity is tuberculin (Montoux) reaction (figure 5) which peaks 48 hours after the injection of antigen (PPD or old tuberculin). Treatment includes anti-inflammatory agents. 4a and 5a). viral or parasitic infections).10 hours after exposure to the antigen (as in Arthus reaction).. macrophages Antigen and site epidermal ( organic chemicals. followed by macrophages. The affinity of antibody and size of immune complexes are important in production of disease and determining the tissue involved. The lesion contains primarily neutrophils and deposits of immune complexes and complement. Used with permission Figure 3B Pemphigus vulgaris immunofluorescence © Bristol Biomedical Image Archive. Polyethylene glycol-mediated turbidity (nephelometry) binding of C1q and Raji cell test are utilized to detect immune complexes. although IgM may also be involved. edema of epidermis lymphocytes. Mechanism of damage in immune complex hypersensitivity Table 3 . The presence of immune complexes in serum and depletion in the level of complement are also diagnostic. Diagnosis involves examination of tissue biopsies for deposits of immunoglobulin and complement by immunofluorescence microscopy. Primary components are soluble immune complexes and complement (C3a. They are mostly of the IgG class. It is mediated by soluble immune complexes.) intradermal (tuberculin.) contact Figure 5 Mantoux intradermal tuberculin skin test for tuberculin 48-72 hr . The damage is caused by platelets and neutrophils (Figure 4). Macrophages infiltrating in later stages may be involved in the healing process.g. TYPE IV HYPERSENSITIVITY Type IV hypersensitivity is also known as cell mediated or delayed type hypersensitivity. The antigen may be exogenous (chronic bacterial. etc. lepromin. monocytes.Goodpasture's syndrome © Bristol Biomedical Image Archive. poison ivy. The immunofluorescent staining in type III hypersensitivity is granular (as opposed to linear in type II such as seen in Goodpasture's syndrome). systemic lupus erythematosus. Figure 4. heavy metals.Delayed hypersensitivity reactions Type Reaction time 48-72 hr Clinical appearance eczema local induration Histology lymphocytes.

Diagnostic tests in vivo include delayed cutaneous reaction (e. Major lymphokines involved in delayed hypersensitivity reaction include monocyte chemotactic factor. interferongamma. Another form of delayed hypersensitivity is contact dermatitis (poison ivy (figure 6). Cytotoxic T cells (Tc) cause direct damage whereas helper T (TH1) cells secrete cytokines which activate cytotoxic T cells and recruit and activate monocytes and macrophages. Type IV hypersensitivity can be classified into three categories depending on the time of onset and clinical and histological presentation (Table 3). etc. In vitro tests for delayed hypersensitivity include mitogenic response. toxoplasmosis. lympho-cytotoxicity and IL-2 production.) Type IV hypersensitivity is involved in the pathogenesis of many autoimmune and infectious diseases (tuberculosis. IgM soluble type-IV (delayed type) None tissues & organs . which cause the bulk of the damage (figure 4). The delayed hypersensitivity lesions mainly contain monocytes and a few T cells. leishmaniasis. etc. Poison Ivy CDC Figure 6 Table 5 . interleukin-2. Montoux test (figure 5)) and patch test (for contact dermatitis). heavy metals. TNF alpha/beta. IgM cell surface type-III (immune complex) IgG. blastomycosis. histoplasmosis. epitheloid and giant cells.tuberculosis granuloma 21-28 days hardening macrophages. fibrosis persistent antigen or foreign body presence (tuberculosis. leprosy. etc. leprosy.g.) and granulomas due to infections and foreign antigens.) in which the lesions are more papular. etc. Corticosteroids and other immunosuppressive agents are used in treatment. chemicals.Comparison of Different Types of hypersensitivity characteristics antibody antigen type-I (anaphylactic) IgE exogenous type-II (cytotoxic) IgG. Mechanisms of damage in delayed hypersensitivity include T lymphocytes and monocytes and/or macrophages.

Examples of different types of hypersensitivity and overlap among them.edu/ghaffar/hyper00. Diagnostic test for hypersensitivity diseases and treatments. Goodpasture's nephritis You have learned: Distinctions between different types of hypersensitivity. necrosis complement and neutrophils antibody SLE. Mechanisms of immune-mediated damages. granuloma examples allergic asthma. http://pathmicro. farmer's lung disease 48-72 hours erythema and induration monocytes and lymphocytes T-cells tuberculin test.htm .response time appearance histology transferred with 15-30 minutes weal & flare basophils and eosinophil antibody minutes-hours lysis and necrosis antibody and complement antibody erythroblastosis 3-8 hours erythema and edema. hay fever fetalis.sc. poison ivy.med.

Hypersensitivity reactions require a pre-sensitized (immune) state of the host. uncomfortable. including allergies and autoimmunity.Hypersensitivity From Wikipedia. Gell and Robin Coombs in 1963.[1] Contents [hide]  1 Coombs and Gell classification o   1.1 Type V 2 References 3 External links [edit]Coombs and Gell classification . H. This article is about the medical condition.4 ICD-9 995. or occasionally fatal. These reactions may be damaging. The four-group classification was expounded by P. Hypersensitivity Classification and external resources ICD-10 T78. G. see Hypersensitive.3 DiseasesDB 28827 MeSH D006967 Hypersensitivity (also called hypersensitivity reaction) refers to undesirable reactions produced by the normal immune system. For the music album. the free encyclopedia Not to be confused with Sensory processing disorder#Hyposensitivities and hypersensitivities.

receptor mediated (see below)  . antibody-independent    V Autoimmune disease. cell-mediated immune memory response.Comparison of hypersensitivity types Type Alternative names  Often mentioned disorders Mediators Atopy Anaphylaxis Asthma Autoimmune hemolytic anemia Thrombocytopenia Erythroblastosis fetalis Goodpasture's syndrome Membranous nephropathy Graves' disease *see type V explanation below Myasthenia Gravis *see type V explanation below Serum sickness Arthus reaction Rheumatoid arthritis Post streptococcal glomerulonephritis lupus Nephritis Systemic lupus erythematosus(SLE) Extrinsic allergic alveolitis(Hypersensitivity pneumonitis) Contact dermatitis Mantoux test Chronic transplant rejection Multiple sclerosis [4] Graves' disease  IgM or IgG  T-cells   IgG (Complement)   IgM or IgG (Complement)  IgE and IgG4 I Allergy (immediate)      II Cytotoxic. antibody-dependent        III Immune complex disease      IV Delayed-type hypersensitivity[2] [3](DTH).

Some clinical examples:   Graves' disease Myasthenia gravis The use of Type 5 is rare. thus impairing cell signaling. the antibodies recognise and bind to the cell surface receptors. [edit]Type Myasthenia Gravis  (Complement) V This is an additional type that is sometimes (often in the UK) used as a distinction from Type 2.wikipedia. though sometimes they are specifically segregated into their own subcategory of Type 2.org/wiki/Hypersensitivity . http://en. [5] Instead of binding to cell surface components. which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand. These conditions are more frequently classified as Type 2.

the free encyclopedia Type IV hypersensitivity Classification and external resources MeSH D006968 Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three days to develop. which stimulates the proliferation of further CD4+ Th1 cells. it is not antibody mediated but rather is a type of cell-mediated response. proteolipid protein)    Rheumatoid arthritis Antigen in synovial membrane (possibly type II collagen)     Some peripheral neuropathies Schwann cell antigen . CD4+ T cells secrete IL-2 and interferon gamma. transform into multinucleated giant cells. whereas activated macrophages produce hydrolytic enzymes and.Type IV hypersensitivity From Wikipedia. Activated CD8+ T cells destroy target cells on contact. The antigen-presenting cells in this case are macrophages that secrete IL-12. further inducing the release of other Th1 cytokines. thus mediating the immune response. Unlike the other types. [edit]Examples Disease Target antigen Effects Diabetes mellitus type 1 Pancreatic beta cell proteins (possibly insulin. CD4+ helper T cells recognize antigen in a complex with Class 2 major histocompatibility complex. on presentation with certain intracellular pathogens. Glutamate decarboxylase)    Insulitis Beta cell destruction Demyelinating disease Perivascular inflammation Paralysis Ocular lesions Chronic arthritis Destruction of articular cartilage and bone Neuritis Paralysis Multiple sclerosis Oligodendrocyte proteins (myelin basic protein.

nickel  Tuberculin [1]  The pathophysiology of the Tuberculin reaction is explained thus: M. After several weeks.preserving mechanism peculiar to TB it is able to block the fusion of the phagosome within which it is existing with the lysosome which would destroy it.wikipedia. on stimulation with IFN-gamma.org/wiki/Type_IV_hypersensitivity . the macrophages become capable of killing M. Hashimoto's Thyroiditis Thyroglobulin antigen   Crohn's disease Contact dermatitis Mantoux test* (diagnostic) Unless else specified in boxes. These cells differentiate into epithelioid histiocytes which wall off the infected cells.Mantoux test not taken from [1] Hypothyroidism Hard goiter Follicular thymitis Chronic inflammation of ileum and colon Dermatitis with usually short-lived itching Skin induration indicates TB exposure Unknown  Environmental chemicals.g. but at the cost of significant inflammation and local damage. Some other clinical examples:        Temporal arteritis Hashimoto's thyroiditis Symptoms of leprosy Symptoms of tuberculosis Coeliac disease Graft-versus-host disease[2] Chronic transplant rejection http://en. e. So it can continue existing and replicating within the immune cell designed to destroy it. but due to a self. However unfortunately the hyper-activated macrophages secrete TNF which recruits multiple monocytes into the battle. poison ivy. tuberculosis are engulfed by macrophages after being identified as foreign. then ref is: * . tuberculosis by forming phagolysosomes and nitric oxide radicals. the immune system somehow [ mechanism as yet unexplained] ramps up and.

and glomeruli. These immune complexes insert themselves into small blood vessels. When these antigens bind antibodies.Type III hypersensitivity From Wikipedia. formed in the slight excess of antigen. these medium-sized complexes. Unlike the free variant. the free encyclopedia Type III hypersensitivity Classification and external resources Immune complex MeSH D007105 Type III hypersensitivity occurs when antigen-antibody complexes that are not adequately cleared by innate immune cells accumulate. . joints. leading to small immune complexes being formed that do not fix complement and are not cleared from the circulation. a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement. causing symptoms. Large complexes can be cleared by macrophages but macrophages have difficulty in the disposal of small immune complexes. immune complexes of different sizes form[1]. are viewed as being highly pathogenic[2]. giving rise to an inflammatory response and attraction of leukocytes. It is characterized by solvent antigens that are not bound to cell surfaces (which is the case in type II hypersensitivity). [edit]Presentation Type III hypersensitivity occurs when there is little antibody and an excess of antigen.

leading to blotchy hemorrhages.[3] and can cause damage wherever they precipitate. when the deposited immune complexes can precipitate an inflammatory response. along with notable eosinophilic deposition (fibrinoid necrosis). this is an example of IgA involvement in a nephropathy The reaction can take hours. as seen in Henoch-Schönlein purpura. glomerulonephritis and arthritisare commonly-associated conditions as a result of type III hypersensitivity responses[5]). Hence. acute necrotizing vasculitis within the affected tissues is observed concomitant to neutrophilic infiltration. immunofluorescence microscopy can be used to visualize the immune complexes [6] ). Often.g. can cause localized clot formation. kidney glomeruli and joint tissues respectively) bear the brunt of the damage. This typifies the response to injection of foreign antigen sufficient to lead to the condition of serum sickness[7]. sites of urinary and synovial fluid formation. Platelet aggregation. Skin response to a hypersensitivity of this type is referred to as an Arthus reaction. especially in microvasculature. or even weeks to develop. mediate the induction of granule release from mast cells (from which histamine can cause urticaria). and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action. [edit]Examples Some clinical examples: Disease Target antigen   Main effects Systemic lupus erythematosus Nuclear antigens Nephritis Skin lesions . Because of the nature of the antibody aggregation. The cause of damage is as a result of the action of cleaved complement anaphylotoxins C3a and C5a.Such depositions in tissues often induce an inflammatory response. As observed under methods of histopathology. respectively. tissues that are associated with blood filtration at considerable osmotic and hydrostatic gradient (e. Immune Complex Glomerulonephritis. which. leading to tissue damage through frustrated phagocytosis by PMNs and macrophages)[4]. clinical features emerge a week following initial antigen challenge. and is characterized by local erythema and some induration. Typically. days. vasculitis. depending on whether or not there is immunlogic memory of the precipitating antigen.

g. blood vessels (e. aspergillosis).. rheumatoid arthritis) or other organs.g.g. serum sickness) or may involve individual organs including skin (e. Serum sickness (arthus reaction) . Arthus reaction)..g.wikipedia. then ref is: [8] Arthritis Nephritis Systemic vasculitis Acute arthritis Arthritis Vasculitis Nephritis Cutaneous vasculitis Alveolar inflammation Purpura Glomerulonephritis Various  Inhaled antigens (often mould or hay dust)  Unknown.org/wiki/Type_III_hypersensitivity Hypersensitivity Type 3 Type III hypersensitivity is also known as immune complex hypersensitivity. joints (e. lungs (e. lupus nephritis).. systemic lupus erythematosus.g. polyarteritis).. kidneys (e. This reaction may be the pathogenic mechanism of diseases caused by many microorganisms. likely respiratory pathogen   http://en..The reaction may be general (e..g. Post-streptococcal glomerulonephritis Streptococcal cell wall antigens Polyarteritis nodosa Reactive arthritis Hepatitis B virus antigen Several bacterial antigens     Serum sickness Various   Arthus reaction Farmer's Lung Henoch–Schönlein purpura Unless else specified in boxes.

They are mostly of the IgG class. or endogenous (non-organ specific autoimmunity: e. so that only preformed complexes can bind to the low affinity FcgammaRIII. It is mediated by soluble immune complexes. systemic lupus erythematosus.The reaction may take 3 . The antigen is soluble and not attached to the organ involved. The antigen may be exogenous (chronic bacterial. . although IgM may also be involved. viral or parasitic infections).g. It is now thought that this form of hypersensitivity has a lot in common with type I except that the antibody involved is IgG and therefore not prebound to mast cells. Macrophages infiltrating in later stages may be involved in the healing process. The damage is caused by platelets and neutrophils.10 hours after exposure to the antigen (as in Arthus reaction). 4a and 5a). Primary components are soluble immune complexes and complement (C3a. The lesion contains primarily neutrophils and deposits of immune complexes and complement.. SLE).

Watch Type 3 hypersensitivity animation .

It is easy to demonstrate experimentally by subcutaneous injection of any soluble antigen for which the host has a significant IgG titre. In the normal animal these complexes fix complement but experiments in animals genetically deficient in C3 or C4 have shown that complement is not required for pathology to be observed following antibody-antigen complex challenge. These antigen-antibody complexes lodge in the capillaries between the endothelial cells and the basement membrane. and consequently more diffuse. Because the FcgammaRIII is a low affinity receptor and because the threshold for activation via this receptor is considerably higher than for the IgE receptor the reaction is slow compared with a type I reaction. Complement is not required for the Arthus reaction. triggering a type III reaction in the lung. This leads to tissue death and hemorrhage. The leukocytes then discharge their killing agents and promote massive inflammation. The antigen-antibody complexes activate the classical complement pathway and complement proteins and antigen-antibody complexes attract leukocytes to the area. Systemic reaction of type 3 hypersensitivity The presence of sufficient quantities of soluble antigen in circulation to produce a condition of antigen excess leads to the formation of small antigen-antibody complexes which are soluble and poorly cleared. typically maximal at 4-8hrs. for example in 'pigeon fanciers lung' where the antigen is pigeon proteins inhaled via dried faeces. but may modify the symptoms. The deposited immune complexes trigger neutrophils to discharge their granule contents with consequent damage to the surrounding . The Arthus reaction The Arthus reaction is the name given to a local type III hypersensitivity reaction.Large quantities of soluble antigen-antibody complexes form in the blood and are not completely removed by macrophages. The condition extrinsic allergic alveolitis occurs when inhaled antigen complexes with specific IgG in the alveoli. The major pathology is due to complex deposition which seems to be exacerbated by increased vascular permeability caused by mast cell activation via FcgammaRIII. This is also example of autoimmunity.

Another form of delayed hypersensitivity is contact dermatitis (poison ivy. epitheloid and giant cells. etc.) This is the only class of hypersensitive reactions to be triggered by antigen-specific T cells. neutrophils as well as TNFbeta and IFNgamma.etc.Common examples of generalised type III reactions are postinfection complications such as arthritis and glomerulonephritis. chemicals. heavy metals. blastomycosis. histoplasmosis. etc. The lesion is characterized by induration and erythema (abnormal redness and inflammation of skin) Type IV hypersensitivity is involved in the pathogenesis of many autoimmune and infectious diseases (tuberculosis. The classical example of this hypersensitivity is tuberculin (Montoux) reaction which peaks 48 hours after the injection of antigen (PPD or old tuberculin).endothelium and basement membranes. The complexes may be deposited in a variety of sites such as skin. lepromin. other T cells and. . leishmaniasis.) in which the lesions are more papular. toxoplasmosis. poison ivy. kidney and joints. etc. The consequences are a cellular infiltrate in which mononuclear cells (T cells and macrophages) tend to predominate. followed by macrophages.) intradermal (tuberculin. processed it and displayed appropriate peptide fragments bound to class II MHC is contacted by an antigen specific TH1 cell patrolling the tissue. It is usually maximal in 48-72 hours. leprosy. fibrosis Antigen and site epidermal ( organic chemicals.Delayed hypersensitivity reactions Type contact tuberculin granuloma Reaction time 48-72 hr 48-72 hr 21-28 days Clinical appearance Histology eczema local induration hardening lymphocytes. typically a tissue dendritic cell which has picked up antigen.) and granulomas due to infections and foreign antigens. edema of epidermis lymphocytes. leprosy. Type IV hypersensitivity can be classified into three categories depending on the time of onset and clinical and histological presentation Table 3 . Delayed type hypersensitivity results when an antigen presenting cell. Type 4 hypersensitivity Type IV hypersensitivity is also known as cell mediated or delayed type hypersensitivity. monocytes. etc. to a lesser extent. The resulting activation of the T cell produces cytokines such as chemokines for macrophages.) persistent antigen or foreign body presence (tuberculosis. heavy metals. macrophages macrophages.

Despite the fact that "memory T cells". An incubation period of two to 12 weeks is usually necessary after exposure to the TB bacteria in order for the PPD test to be positive. do circulate through tissues. which have been sensitized by prior infection. Result Interpretation . and recruitment of other types of inflammatory cells to the area.The tuberculosis skin test is a test used to determine if someone has developed an immune response to the bacterium that causes tuberculosis (TB). there is some doubt that a single T cell could initiate the event. fibrin deposition. raised area with clearly defined margins at and around the injection site) through local vasodilation (expansion of the diameter of blood vessels) leading to fluid deposition known as edema. called T cells.The problem which this explanation faces is the rarity of antigen-specific T cells. Due to the nature and kinetics of the reaction it is still believed that activation of memory TH1 cells is primarily responsible for propagating the reponse. This PPD material is used for skin testing for tuberculosis. The classical example of delayed type hypersensitivity is in tuberculosis. One theory is that limited IgM-antigen complexes in local capilliaries may lead to a limiting. tuberculosis bacterium produces a delayed-type hypersensitivity skin reaction to certain components of the bacterium. The answer to this conundrum may lie in the recent observations that at least some Type IV reactions absolutely require the presence of 'natural' IgM antibody for initiation. are recruited by the immune system to the skin site where they release chemical messengers called lymphokines. Reaction in the skin to tuberculin PPD begins when specialized immune cells. The tuberculin skin test is based on the fact that infection with M. The components of the organism are contained in extracts of culture filtrates and are the core elements of the classic tuberculin PPD (also known as purified protein derivative). but initiation may require IgM and probably also complement. unlike naive T cells. localised complement activation within the vessel activating the vascular endothelium and thus recruiting inflammatory cells including memory T cells. These lymphokines induce induration (a hard.

If blisters are present (vesiculation). phagocytes fluid and protein to site of antigen injection causes visible lesion . the test is also considered positive. In a healthy person whose immune system is normal. Recruitment of T cells. Positive test tuberculin: 18mm Summary of type 4 hypersensitivity 1. Antigen is injected into the subcut tissue and processed by local APC 2.A tuberculin reaction is classified as positive based on the diameter of the induration in conjunction with certain patient-specific risk factors. induration greater than or equal to 15 mm is considered a positive skin test. A Th1 effector cell recognizes antigen and releases cytokines which act on vascular epithelium 3.

html .TH1 Influence of immune response http://drainameducci.com/2011/08/hypersensitivity.blogspot.