What is Hypersensitivity reaction – Type III
Hypersensitivity means that the body responds to a particular substance (called allergens) in an exaggerated fashion, where it does not happen in normal circumstances. There are 4 types of hypersensitivity reaction, type I, II, III and IV. They are different in terms of the disease manifestation and pathological processes. However, only type III hypersensitivity reaction will be discussed here.
In type III hypersensitivity, soluble antibodies bind to antigens to form immune complexes in the blood. These complexes travel through the blood stream and get deposited in various organs. Hence this can occur in many parts of the body. Generally, common sites of deposition include:
- skin
- kidney
- joints
- blood vessels
- lungs
One example of a Type III hypersensitivity is serum sickness, a condition that may develop when a patient is injected with a large amount of antitoxin that was produced in an animal. The image below is that of serum sickness:
Statistics on Hypersensitivity reaction – Type III
The cases of different diseases vary widely. Certain diseases can be common, such as rheumatoid arthritis. Diseases such as systemic lupus erythematosus can have the figure of 1.8-7.6 cases per 100,000 per year. Note that systemic lupus erythromatosus is a disease of mixed hypersensitivity – type II and III hypersensitivity reaction occur in this disease.
Risk Factors for Hypersensitivity reaction – Type III
Depending on the manifestations of different type III hypersensitivity diseases, there are different risk factors as well.
There are some gender differences between diseases of type II hypersensitivity. Some diseases are more common in women such as rheumatoid arthritis.
As different diseases are included in type III hypersensitivity, ethnicity and geographical location can have impact on the disease cases.
Progression of Hypersensitivity reaction – Type III
Type III hypersensitivity reaction is induced by antigen-antibody complexes. By the various biochemical mechanisms, the end result are tissue damage to the body. The antigens can either be from the body itself or from outside the body (for example, bacteria or microorganisms that infect the body). It must be remembered that the formation of antigen-antibody complex in the circulation does not indicate the presence of type III hypersensitivity diseases. It is the capability of these complexes to mount a reaction leading to tissue damage that is the cause of diseases themselves.
Depending on the different type of diseases, some general investigations may be necessary. Basic routine investigations may include looking at the blood function, liver function, thyroid function and kidney function.
Prognosis of Hypersensitivity reaction – Type III
Type III hypersensitivity diseases can be self-limited or long-standing depending on different disease patterns. Condition such as systemic lupus erythomatus (SLE) can have very poor prognosis if kidney involvement is severe.
How is Hypersensitivity reaction – Type III Treated?
There is no cure for these diseases, the treatment aims at symptom control only. Because of the pathogenesis of these diseases are antibody in origin, a lot of treatment options are aimed at that. Depending on the severity of the hypersensitivity reaction, different treatment approaches are applied. Treatment options, either given alone or in combination, include the following:
- steroids: these drugs include prednisolone, dexamethasone, etc. In type II hypersensitivity diseases, sometimes high dose steroids are used. Depending on the diseases, steroid could become a long-term medication. In such cases, long term use will need medical supervision for monitoring of potential side effects.
There are other treatment methods all aiming at altering the body’s immuune response, this include:
- other drugs: interferon, cyclophosphamide, cyclosporin
- many of these drugs are still on research at the moment.
Hypersensitivity reaction – Type III References
- Braunwald E et al. Harrison’s principles of internal medicine. 15th ed. New York; McGraw-Hill; 2001.
- Cotran, Kumar, Collins. Robbins Pathologic Basis of Disease. 6th ed. WB Saunders Company. New York. 1999.
- Davidson A, Diamond B: Autoimmune diseases. N Engl J Med 2001 Aug 2; 345(5): 340-50.
- Middleton E Jr, Reed CE, Ellis EF, et al, eds: Allergy: Principles and Practice. 5th ed. St. Louis, Mo: Mosby-Year Book; 1998.
- Roitt IM: Essential Immunology. 9th ed. Oxford, UK; Blackwell Scientific; 1998.
- The Merck Manual: Disorders with Type III Hypersensitivity Reactions [online]. 2005. [Cited 2005 October 9th]. Available from: //www.merck.com/mrkshared/mmanual/section12/chapter148/148b.jsp
- Up to Date: Clinical features of rheumatoid arthritis [online]. 2005. [Cited 2005 October 9th]. Available from: //www.utdol.com/application/topic.asp?file=rheumart/3022&type=A&selectedTitle=1~209
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Type III, or immune-complex, reactions are characterized by tissue damage caused by the activation of complement in response to antigen-antibody (immune) complexes that are deposited in tissues. The classes of antibody involved are the same ones that participate in type II reactions—IgG and IgM—but the mechanism by which tissue damage is brought about is different. The antigen to which the antibody binds is not attached to a cell. Once the antigen-antibody complexes form, they are deposited in various tissues of the body, especially the blood vessels, kidneys, lungs, skin, and joints. Deposition of the immune complexes causes an inflammatory response, which leads to the release of tissue-damaging substances, such as enzymes that destroy tissues locally, and interleukin-1, which, among its other effects, induces fever. Immune complexes underlie many autoimmune diseases, such as systemic lupus erythematosus (an inflammatory disorder of connective tissue), most types of glomerulonephritis (inflammation of the capillaries of the kidney), and rheumatoid arthritis. Type III hypersensitivity reactions can be provoked by inhalation of antigens into the lungs. A number of conditions are attributed to this type of antigen exposure, including farmer’s lung, caused by fungal spores from moldy hay; pigeon fancier’s lung, resulting from proteins from powdery pigeon dung; and humidifier fever, caused by normally harmless protozoans that can grow in air-conditioning units and become dispersed in fine droplets in climate-controlled offices. In each case, the person will be sensitized to the antigen—i.e., will have IgG antibodies to the agent circulating in the blood. Inhalation of the antigen will stimulate the reaction and cause chest tightness, fever, and malaise, symptoms that usually pass in a day or two but recur when the individual is reexposed to the antigen. Permanent damage is rare unless individuals are exposed repeatedly. Some occupational diseases of workers who handle cotton, sugarcane, or coffee waste in warm countries have a similar cause, with the sensitizing antigen usually coming from fungi that grow on the waste rather than the waste itself. The effective treatment is, of course, to prevent further exposure. The type of allergy described in the preceding paragraph was first recognized as serum sickness, a condition that often occurred after animal antiserum had been injected into a patient to destroy diphtheria or tetanus toxins. While still circulating in the blood, the foreign proteins in the antiserum induced antibodies, and some or all of the symptoms described above developed in many subjects. Serum sickness is now rare, but similar symptoms can develop in people sensitive to penicillin or certain other drugs, such as sulfonamides. In such cases the drug combines with the subject’s blood proteins, forming a new antigenic determinant to which antibodies react. The consequences of antigen-and-antibody interaction within the bloodstream vary according to whether the complexes formed are large, in which case they are usually trapped and removed by macrophages in the liver, spleen, and bone marrow, or small, in which case they remain in the circulation. Large complexes occur when more than enough antibody is present to bind to all the antigen molecules, so that these form aggregates of many antigen molecules cross-linked together by the multiple binding sites of IgG and IgM antibodies. When the ratio of antibody to antigen is enough to form only small complexes, which can nevertheless activate complement, the complexes tend to settle in the narrow capillary vessels of the synovial tissue (the lining of joint cavities), the kidney, the skin, or, less commonly, the brain or the mesentery of the gut. The activation of complement—which leads to increased permeability of the blood vessels, release of histamine, stickiness of platelets, and attraction of granulocytes and macrophages—becomes more important when the antigen-antibody complexes are deposited in blood vessels than when they are deposited in the tissues outside the capillaries. The symptoms, depending on where the damage occurs, are swollen, painful joints, a raised skin rash, nephritis (kidney damage, causing blood proteins and even red blood cells to leak into the urine), diminished blood flow to the brain, or gut spasms. The formation of troublesome antigen-antibody complexes in the blood can also result from subacute bacterial endocarditis, a chronic infection of damaged heart valves. The infectious agent is often Streptococcus viridans, normally a harmless inhabitant of the mouth. The bacteria in the heart become covered with a layer of fibrin, which protects them from destruction by granulocytes, while they continue to release antigens into the circulation. These can combine with preformed antibodies to form immune complexes that can cause symptoms resembling those of serum sickness. Treatment involves eradication of the heart infection by a prolonged course of antibiotics.