Some clinical examples:

Other examples are:

- Subacute bacterial endocarditis

- Symptoms of malaria

Type III hypersensitivity occurs when there is an excess of antigen, leading to small immune complexes being formed that fix complement and are not cleared from the circulation. It involves soluble antigens that are not bound to cell surfaces (as opposed to those in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form. Large complexes can be cleared by macrophages but macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as being highly pathogenic.

Such depositions in tissues often induce an inflammatory response, and can cause damage wherever they precipitate. The cause of damage is as a result of the action of cleaved complement anaphylotoxins C3a and C5a, which, respectively, 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, leading to tissue damage through frustrated phagocytosis by PMNs and macrophages).

The reaction can take hours, days, or even weeks to develop, depending on whether or not there is immunological memory of the precipitating antigen. Typically, clinical features emerge a week following initial antigen challenge, when the deposited immune complexes can precipitate an inflammatory response. Because of the nature of the antibody aggregation, tissues that are associated with blood filtration at considerable osmotic and hydrostatic gradient (e.g. sites of urinary and synovial fluid formation, kidney glomeruli and joint tissues respectively) bear the brunt of the damage. Hence, vasculitis, glomerulonephritis and arthritis are commonly associated conditions as a result of type III hypersensitivity responses.

As observed under methods of histopathology, acute necrotizing vasculitis within the affected tissues is observed concomitant to neutrophilic infiltration, along with notable eosinophilic deposition (fibrinoid necrosis). Often, immunofluorescence microscopy can be used to visualize the immune complexes. Skin response to a hypersensitivity of this type is referred to as an Arthus reaction, and is characterized by local erythema and some induration. Platelet aggregation, especially in microvasculature, can cause localized clot formation, leading to blotchy hemorrhages. This typifies the response to injection of foreign antigen sufficient to lead to the condition of serum sickness.

The Arthus reaction involves the in situ formation of antigen/antibody complexes after the intradermal injection of an antigen. If the animal/patient was previously sensitized (has circulating antibody), an Arthus reaction occurs. Typical of most mechanisms of the type III hypersensitivity, Arthus manifests as local vasculitis due to deposition of IgG-based immune complexes in dermal blood vessels. Activation of complement primarily results in cleavage of soluble complement proteins forming C5a and C3a, which activate recruitment of PMNs and local mast cell degranulation (requiring the binding of the immune complex onto FcγRIII), resulting in an inflammatory response. Further aggregation of immune complex-related processes induce a local fibrinoid necrosis with ischemia-aggravating thrombosis in the tissue vessel walls. The end result is a localized area of redness and induration that typically lasts a day or so.

Arthus reactions have been infrequently reported after vaccinations containing diphtheria and tetanus toxoid. The CDC's description:

Arthus reactions (type III hypersensitivity reactions) are rarely reported after vaccination and can occur after tetanus toxoid–containing or diphtheria toxoid–containing vaccines. An Arthus reaction is a local vasculitis associated with deposition of immune complexes and activation of complement. Immune complexes form in the setting of high local concentration of vaccine antigens and high circulating antibody concentration. Arthus reactions are characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally by necrosis. These symptoms and signs usually occur 4–12 hours after vaccination. ACIP has recommended that persons who experienced an Arthus reaction after a dose of tetanus toxoid–containing vaccine should not receive Td more frequently than every 10 years, even for tetanus prophylaxis as part of wound management.

An example of a tuberculosis (TB) infection that comes under control: "M. tuberculosis" cells are engulfed by macrophages after being identified as foreign, but due to an immuno-escape mechanism peculiar to mycobacteria, TB bacteria are able to block the fusion of their enclosing phagosome with lysosomes which would destroy the bacteria. Thereby TB can continue to replicate within macrophages. After several weeks, the immune system somehow [mechanism as yet unexplained] ramps up and, on stimulation with IFN-gamma, the macrophages become capable of killing "M. tuberculosis" by forming phagolysosomes and nitric oxide radicals. The hyper-activated macrophages secrete TNF-α which recruits multiple monocytes to the site of infection. These cells differentiate into epithelioid cells which wall off the infected cells, but results in significant inflammation and local damage.

Some other clinical examples:

- Temporal arteritis

- Leprosy

- Coeliac disease

- Graft-versus-host disease

- Chronic transplant rejection

In immunology, the Arthus reaction (, ) is a type of local type III hypersensitivity reaction. Type III hypersensitivity reactions are immune complex-mediated, and involve the deposition of antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium), and glomeruli. This reaction is usually encountered in experimental settings following the injection of antigens.

Some examples:

- Allergic asthma

- Allergic conjunctivitis

- Allergic rhinitis ("hay fever")

- Anaphylaxis

- Angioedema

- Urticaria (hives)

- Eosinophilia

- Penicillin allergy

- Cephalosporin allergy

- Food allergy

- Sweet itch

Treatment usually involves adrenaline (epinephrine), antihistamines, and corticosteroids.

If the entire body is involved, then anaphylaxis can take place, which is an acute, systemic reaction that can prove fatal.

Risk factors for drug allergies can be attributed to the drug itself or the characteristics of the patient. Drug-specific risk factors include the dose, route of administration, duration of treatment, repetitive exposure to the drug, and concurrent illnesses. Host risk factors include age, sex, atopy, specific genetic polymorphisms, and inherent predisposition to react to multiple unrelated drugs (multiple drug allergy syndrome).

A drug allergy is more likely to develop with large doses and extended exposure.

Some of the drugs associated with serum sickness are:

- allopurinol

- barbiturates

- captopril

- cephalosporins

- griseofulvin

- penicillins

- phenytoin

- procainamide

- quinidine

- streptokinase

- sulfonamides

- rituximab

- ibuprofen

- infliximab

Chronic stress can aggravate allergic conditions. This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of interleukin 12 by both the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. Stress management in highly susceptible individuals may improve symptoms.

Serum sickness can be developed as a result of exposure to antibodies derived from animals. These sera or antitoxins are generally administered to prevent or treat an infection or envenomation.

Hypersensitivity (also called hypersensitivity reaction or intolerance) is a set of undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over- reaction of the immune system and these reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. They are classified in four groups after the proposal of P. G. H. Gell and Robin Coombs in 1963.

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

CD4+ T1 helper T cells recognize antigen in a complex with the MHC class II major histocompatibility complex on the surface of antigen-presenting cells. These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T1 cells. CD4+ T cells secrete IL-2 and interferon gamma, inducing the further release of other T1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including allergic asthma, atopic dermatitis, allergic rhinitis and several ocular allergic diseases. Allergic reactions may generally be divided into two components; the early phase reaction, and the late phase reaction. While the contribution to the development of symptoms from each of the phases varies greatly between diseases, both are usually present and provide us a framework for understanding allergic disease.

The early phase of the allergic reaction typically occurs within minutes, or even seconds, following allergen exposure and is also commonly referred to as the immediate allergic reaction or as a Type I allergic reaction. The reaction is caused by the release of histamine and mast cell granule proteins by a process called degranulation, as well as the production of leukotrienes, prostaglandins and cytokines, by mast cells following the cross-linking of allergen specific IgE molecules bound to mast cell FcεRI receptors. These mediators affect nerve cells causing itching, smooth muscle cells causing contraction (leading to the airway narrowing seen in allergic asthma), goblet cells causing mucus production, and endothelial cells causing vasodilatation and edema.

The late phase of a Type 1 reaction (which develops 8–12 hours and is mediated by mast cells) should not be confused with delayed hypersensitivity Type IV allergic reaction (which takes 48–72 hours to develop and is mediated by T cells). The products of the early phase reaction include chemokines and molecules that act on endothelial cells and cause them to express Intercellular adhesion molecule (such as vascular cell adhesion molecule and selectins), which together result in the recruitment and activation of leukocytes from the blood into the site of the allergic reaction. Typically, the infiltrating cells observed in allergic reactions contain a high proportion of lymphocytes, and especially, of eosinophils. The recruited eosinophils will degranulate releasing a number of cytotoxic molecules (including Major Basic Protein and eosinophil peroxidase) as well as produce a number of cytokines such as IL-5. The recruited T-cells are typically of the Th2 variety and the cytokines they produce lead to further recruitment of mast cells and eosinophils, and in plasma cell isotype switching to IgE which will bind to the mast cell FcεRI receptors and prime the individual for further allergic responses.

Although genetic factors govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. Several hypotheses have been identified to explain this increased rate; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise. The hygiene hypothesis maintains that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from T1 type responses, leading to unrestrained T2 responses that allow for an increase in allergy.

Changes in rates and types of infection alone however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, "Toxoplasma gondii", and "Helicobacter pylori" (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%, and an increased rate of parasitic infections has been associated with a decreased prevalence of asthma. It is speculated that these infections exert their effect by critically altering T1/T2 regulation. Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.

When a medication causes an allergic reaction, it is called an allergen. The following is a short list of the most common drug allergens:

- Antibiotics

- Penicillin

- Sulfa drugs

- Tetracycline

- Analgesics

- Codeine

- Non-steroidal anti-inflammatory drugs (NSAIDs)

- Antiseizure

- Phenytoin

- Carbamazepine

This is an additional type that is sometimes (especially in the UK) used as a distinction from Type 2.

Instead of binding to cell surfaces, the antibodies recognise and bind to the cell surface receptors, which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling.

Some clinical examples:

- Graves' disease

- Myasthenia gravis

The use of Type 5 is rare. These conditions are more frequently classified as Type 2, though sometimes they are specifically segregated into their own subcategory of Type 2.

In type II hypersensitivity (also tissue-specific, or cytotoxic 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 (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.

An example of type II hypersensitivity is the ABO blood incompatibility where the red blood cells have different antigens, causing them to be recognized as different; B cell proliferation will take place and antibodies to the foreign blood type are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens. That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.

Type II reactions can affect healthy cells. Examples include red blood cells in autoimmune hemolytic anemia and acetylcholine receptors in myasthenia gravis.

Another example of type II hypersensitivity reaction is Goodpasture's syndrome where the basement membrane (containing collagen type IV) in the lung and kidney is attacked by one's own antibodies.

Another form of type II 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 cells (NK) 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.

NSAID or nonsteroidal anti-inflammatory drug hypersensitivity reactions encompasses a broad range of allergic or allergic-like symptoms that occur within minutes to hours after ingesting aspirin or other NSAID nonsteroidal anti-inflammatory drugs. Hypersensitivity drug reactions differ from drug toxicity reactions in that drug toxicity reactions result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual (see nonsteroidal anti-inflammatory drugs section on adverse reactions for NSAID-induced toxic reactions); hypersensitivity reactions are idiosyncratic reactions to a drug. Although the term NSAID was introduced to signal a comparatively low risk of adverse effects, NSAIDs do evoke a broad range of hypersensitivity syndromes. These syndromes have recently been classified by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity. The classification organizes the hypersensitivity reactions to NSAIDs into the following five categories:

- 1) NSAIDs-exacerbated respiratory disease (NERD) is an acute (immediate to several hours) exacerbation of bronchoconstriction and other symptoms of asthma (see aspirin-induced asthma) in individuals with a history of asthma and/or nasal congestion, rhinorrhea or other symptoms of rhinitis and sinusitis in individuals with a history of rhinosinusitis after ingestion of various NSAIDs, particularly those that act by inhibiting the COX-1 enzyme. NERD does not appear to be due to a true allergic reaction to NSAIDs but rather at least in part to the more direct effects of these drugs to promote the production and/or release of certain mediators of allergy. That is, inhibition of cellular COX activity deprives tissues of its anti-inflammatory product(s), particularly prostaglandin E2 while concurrently shuttling its substrate, arachidonic acid, into other metabolizing enzymes, particularly 5-lipoxygenase (ALOX5) to overproduce pro-inflammatory leukotriene and 5-Hydroxyicosatetraenoic acid metabolites and 15-lipoxygenase (ALOX15) to overproduce pro-inflammatory 15-Hydroxyicosatetraenoic acid metabolites, including eoxins; the condition is also associated with a reduction in the anti-inflammatory metabolite, lipoxin A4, and increases in certain pro-allergic chemokines such as eotaxin-2 and CCL7.

- 2) NSAIDs-exacerbated cutaneous disease (NECD) is an acute exacerbation of wheals and/or angioedema in individuals with a history of chronic urticaria. NECD also appears due to the non-allergic action of NSAIDs in inhibiting the production of COX anti-inflammatory metabolites while promoting the production 5-lipoxygenase and 15-lipoxygenase pro-inflammatory metabolites and the overproduction of certain pro-allergic chemokines, e.g. eotaxin-1, eotaxin-2, RANTES, and interleukin-5.

- 3) NSAIDs-induced urticarial disease (NEUD) is the acute development of wheals and/or angioedema in individuals with no history of chronic NSAIDs-induced urticaria or related diseases. The mechanism behind NEUD is unknown but may be due to the non-allergic action of NSAIDs in promoting the production and/or release of allergy mediators.

- 4) Single NSAID-induced urticarial/angioedema or anaphylaxis (SNIUAA) is the acute development of urticarial, angioedema, or anaphylaxis in response to a single type of NSAID and/or a single group of NSAIDs with a similar structure but not to other structurally unrelated NSAIDs in individuals with no history of underlying relevant chronic diseases. SNIUAA is due to a true IgE-mediated allergy reaction.

- 5 Single NSAID-induced delayed reactions (SNIDR) are a set of delayed onset (usually more than 24 hour) reactions to NSAIDs. SNIDR are most commonly skin reactions that may be relatively mild moderately severe such as maculopapular rash, fixed drug eruptions, photosensitivity reactions, delayed urticaria, and contact dermatitis or extremely severe such as the DRESS syndrome, acute generalized exanthematous pustulosis, the Stevens–Johnson syndrome, and toxic epidermal necrolysis (also termed Lyell's syndrome). SNIDR result from the drug-specific stimulation of CD4+ T lymphocytes and CD8+ cytotoxic T cells to elicit a delayed type hypersensitivity reaction.

It is estimated that 2—3 percent of hospitalised patients are affected by a drug eruption, and that serious drug eruptions occur in around 1 in 1000 patients.

Atopic reactions are caused by localized hypersensitivity reaction to an allergen. Atopy appears to show a strong hereditary component. One study concludes that the risk of developing atopic dermatitis (3%) or atopy in general (7%) "increases by a factor of two with each first-degree family member already suffering from atopy". As well, maternal stress and perinatal programming is increasingly understood as a root cause of atopy, finding that "...trauma may be a particularly robust potentiator of the cascade of biological events that increase vulnerability to atopy and may help explain the increased risk found in low-income urban populations.”

Environmental factors are also thought to play a role in the development of atopy, and the 'hygiene hypothesis' is one of the models that may explain the steep rise in the incidence of atopic diseases, though this hypothesis is incomplete and in some cases, contradictory to findings. This hypothesis proposes that excess 'cleanliness' in an infant's or child's environment can lead to a decline in the number of infectious stimuli that are necessary for the proper development of the immune system. The decrease in exposure to infectious stimuli may result in an imbalance between the infectious-response ("protective") elements and the allergic-response ("false alarm") elements within the immune system.

Some studies also suggest that the maternal diet during pregnancy may be a causal factor in atopic diseases (including asthma) in offspring, suggesting that consumption of antioxidants, certain lipids, and/or a Mediterranean diet may help to prevent atopic diseases.

The multicenter PARSIFAL study in 2006, involving 6630 children age 5 to 13 in 5 European countries, suggested that reduced use of antibiotics and antipyretics is associated with a reduced risk of allergic disease in children.

The culprit can be both a prescription drug or an over-the-counter medication.

Examples of common drugs causing drug eruptions are antibiotics and other antimicrobial drugs, sulfa drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), biopharmaceuticals, chemotherapy agents, anticonvulsants, and psychotropic drugs. Common examples include photodermatitis due to local NSAIDs (such as piroxicam) or due to antibiotics (such as minocycline), fixed drug eruption due to acetaminophen or NSAIDs (Ibuprofen), and the rash following ampicillin in cases of mononucleosis.

Certain drugs are less likely to cause drug eruptions (rates estimated to be ≤3 per 1000 patients exposed). These include: digoxin, aluminum hydroxide, multivitamins, acetaminophen, bisacodyl, aspirin, thiamine, prednisone, atropine, codeine, hydrochlorothiazide, morphine, insulin, warfarin, and spironolactone.

The cause of allergic conjunctivitis is an allergic reaction of the body's immune system to an allergen. Allergic conjunctivitis is common in people who have other signs of allergic disease such as hay fever, asthma and eczema.

Among the most common allergens that cause conjunctivitis are:

- Pollen from trees, grass and ragweed

- Animal skin and secretions such as saliva

- Perfumes

- Cosmetics

- Skin medicines

- Air pollution

- Smoke

- Dust mites

- Balsam of Peru (used in food and drink for flavoring, in perfumes and toiletries for fragrance, and in medicine and pharmaceutical items for healing properties)

- Eye drops

Most cases of seasonal conjunctivitis are due to pollen and occur in the hay fever season, grass pollens in early summer and various other pollens and moulds may cause symptoms later in the summer.

There is a strong genetic predisposition toward atopic allergies, especially on the maternal side. Because of the strong familial evidence, investigators have tried to map susceptibility genes for atopy. Genes for atopy (C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1/IL18R1, TLR1/TLR6/TLR10, LPP, MYC/PVT1, IL2/ADAD1, HLA-B/MICA) tend to be involved in allergic responses or other components of the immune system. C11orf30 seems to be the most relevant for atopy as it may increase susceptibility to poly-sensitization.

Allergic conjunctivitis occurs more frequently among those with allergic conditions, with the symptoms having a seasonal correlation.

Allergic conjunctivitis is a frequent condition as it is estimated to affect 20 percent of the population on an annual basis and approximately one-half of these people have a personal or family history of atopy.

Giant papillary conjunctivitis accounts for 0.5–1.0% of eye disease in most countries.

The Allergic Alсоhоl from the original on 30 April 2012. Retrieved 2010-04-08.