Type III hypersensitivity disease

Introduction to type III hypersensitivity disease Type III hypersensitivity antibodies are similar to antibodies in type II hypersensitivity reactions, mainly IgG and IgM antibodies, but the difference is that these antibodies bind to the corresponding soluble antigens to form antigen-antibody complexes (immune complexes). And, under certain conditions, deposited in tissues such as the glomerular basement membrane, blood vessel wall, skin or synovium. The immune complex activates the complement system, producing anaphylatoxins and attracting local infiltration of neutrophils; polymerizing platelets, releasing vasoactive amines or forming thrombi; and activating M to release cytokines such as IL-1. The result is an inflammatory response and tissue damage characterized by hyperemia, local necrosis and neutrophil infiltration. This type of hypersensitivity is also known as immune complex-mediated hypersensitivity. basic knowledge The proportion of illness: 0.003%-0.004% Susceptible people: no special people Mode of infection: non-infectious Complications: shock

Type III hypersensitivity disease etiology

Regarding the pathogenesis of autoimmune responses, in many cases, there is more understanding of the mechanisms of autoimmune antibody production. In some autoimmune hemolytic anemia, erythrocytes are coated with cytotoxic (type II) autoantibodies. Thus, the complement system interacts with complexes formed by cell surface antigens and antibodies, such as heterologous particles that are coated with antibodies, causing red blood cells to be phagocytosed and dissolved.

Autoimmune renal damage can be the result of antibody-mediated (type II) or immune complex (type III) responses, and antibody-mediated responses are seen in Goodpasture syndrome, where lung and kidney diseases are associated with the presence of anti-basement membrane antibodies. Systemic lupus erythematosus with nephritis is a well-known best example of autoimmune damage associated with soluble antigen-antibody complexes (immune complexes), another example is an immune complex containing renal tubular antigens. Types of membranous glomerulonephritis, glomerulonephritis after streptococcal infection may be due in part to streptococcal-induced cross-reactive antibodies, but this view has not been confirmed.

In systemic lupus erythematosus and other systemic (and organ-specific) autoimmune diseases, there are various antibodies, blood-forming antibodies and autoimmune hemolytic anemia, thrombocytopenia. It may also be related to leukopenia; anticoagulant antibodies can cause bleeding problems, and the nuclear substance antibodies cause the resulting immune complex to deposit not only in the glomerulus, but also in the vascular tissue and the junction of the dermis and the epidermis, rheumatoid joints. At the time of inflammation, a complex of condensed IgG-like rheumatoid factor (RF) and complement is deposited on the synovium. The rheumatoid factor is usually an IgM globulin specific for the receptor on the constant region of its own IgG heavy chain (occasionally IgG or IgA), IgG-RF-complement polymer can also be found in neutrophils, where it causes lysosomal enzyme release, resulting in joint inflammation, a large number of plasma cells in the joint, and the synthesis of anti-IgG Antibodies, T cells and lymphokines are also found in rheumatoid joints and may also be involved in the inflammatory process. The process leading to immune changes is unclear, possibly due to bacterial or viral infections. Reducing serum complement concentration reflect the occurrence of systemic lupus erythematosus in a wide range of immune responses; and rheumatoid arthritis are different, but normal serum complement intrasynovial complement concentration.

In pernicious anemia, autoantibodies that neutralize internal factors appear in the gastrointestinal tract, and autoantibodies against the microsomal components of the gastric mucosa are more common. There is a hypothesis that cell-mediated autoimmunity attacks parietal cells. Lead to atrophic gastritis, thereby reducing the production of internal factors, but still can absorb a sufficient amount of vitamin B12 to prevent the occurrence of primitive giant red cell anemia. If the internal factor autoantibodies in the gastrointestinal cavity are also developing, the absorption of vitamin B 12 will Stop, and pernicious anemia will develop.

Hashimoto's thyroiditis is associated with autoantibodies against thyroglobulin, thyroid epithelial microsomes, thyroid cell surface antigens, and secondary colloidal antigens. It mediates tissue production through the cytotoxicity of microsomal antibodies and the activity of specific mission T cells. Injury and eventual mucus edema, patients with primary mucinous edema can also detect low titers of antibodies, suggesting that it is the result of an unidentified autoimmune thyroiditis, as well as exophthalmia (Graves disease) Autoimmunity is involved, about 10% of patients eventually develop mucinous edema spontaneously, and mucinous edema occurs after partial thyroidectomy. Another antibody specific to Graves disease is called thyroid stimulating antibody, and they are thyroid stimulating hormone in the thyroid gland. The (TSH) receptor reacts and acts on thyroid cell function in the same way as normal TSH.

Type III hypersensitivity disease prevention

Autoimmunity is a complex, multi-factor effect of natural phenomena, in addition to boundary effects (such as drug haptens, microbial infections), but also closely related to the body's own genetic factors, especially in the main tissue compatibility system. The immune response gene and/or the immunosuppressive gene are abnormal, so the most important aspect of prevention is to avoid contact with allergens.

Type III hypersensitivity disease complications Complications

The common complication of this disease is shock.

Symptoms of type III hypersensitivity disease Common symptoms Joint swelling and pain Lymph node enlargement Similar to urticaria skin... Red spot nodules dyspnea

Common type III hypersensitivity disease

(1) Inflammatory damage caused by locally formed immune complexes

1. Arthus reaction Maurice Arthus was immunized with horse serum for several weeks, and repeated injections of the same serum showed redness and swelling in the injection. The reaction reached a peak in 3 to 6 hours, and the degree of redness increased with the increase of the number of injections. After 5-6 injections, apoptotic necrosis occurs locally, and the reaction can self-resolve or heal. This is the Arthus reaction. The mechanism is that the injected antigen binds to the intravascular antibody to form a soluble immune complex and is deposited at the injection site. On the wall of the small arteries, immune complex-mediated vasculitis is caused. The anaerobic toxin produced rapidly after complement activation causes degranulation of mast cells, platelet aggregation and release of vasoactive amines, which intensifies redness and swelling, and a large number of polymorphonuclear nucleus in lesions. Leukocyte infiltration.

2. Response to inhaled antigens Intrapulmonary Arthus-type responses to inhaled exogenous antigens are associated with many hypersensitivity diseases in humans, and they are often manifested as occupational-related hypersensitivity pneumonia, such as inhaled thermophiles in peasant lung patients. Severe dyspnea occurs within 6-8 hours after actinomycetes spores or hyphae, which is caused by the combination of inhaled antigen and specific IgG antibody into immune complex. There are many similar lung type III supertypes in clinical practice. Sensitive reaction, and according to the patient's occupation or the nature of the sensitizing antigen, the corresponding disease name, such as the pigeon breeder's disease (due to inhaling the serum protein in the pigeon's dung), the dry milk washer's lung (due to the inhalation of penicillium spores), Cane pneumoconiosis, leather lungs (inhalation of bovine protein), peeling maple bark disease (inhalation of Cryptostrama spores), red pepper disease and grass roof disease, etc., these are due to repeated inhalation of antigenic substances in the working environment The resulting antigen-antibody complex mediates occupational diseases.

3. Response to endogenous antigens Locally released antigens often cause type III hypersensitivity reactions, such as dead worms in lymphatic vessels causing inflammatory reactions, impeding lymphatic flow, in patients with high levels of antibodies, treatment Sudden release of antigen to produce immune complex-mediated type III hypersensitivity reactions, such as the treatment of erythema nodules on the skin after treatment of patients with nodular leprosy with Dapsone, and the treatment of Jarisch-Herxheimer reaction in patients with syphilis treated with penicillin (treatment) After the syphilis increased the reaction) and so on.

(2) Diseases caused by circulating immune complexes

1. Serum disease is different from Arthus reaction, which is a systemic type III hypersensitivity disease caused by circulating immune complexes. It is passively immunized with horse anti-diphtheria or tetanus toxoid antisera to prevent and treat these diseases. Severe diseases are still an important means to this day. Some patients have elevated body temperature 7 to 10 days after injection of animal antiserum, systemic urticaria, swollen lymph nodes, joint swelling and pain, and some may have mild acute Glomerulonephritis and myocarditis, serum levels of complement decreased, because the disease is mainly caused by injection of serum from heterologous animals, it is called serum disease, anti-venom antibody is used to treat snake bites, and murine monoclonal antibody is used to treat malignant tumors. Or autoimmune disease, serum disease can also occur when anti-lymphocyte or anti-thymocyte serum is used to treat transplant rejection. After stopping the injection of the above serum, the symptoms are generally resolved without treatment.

Due to the injection of a large number of heterologous protein antigens, the serum disease is called acute serum disease, which is characterized by a large amount of immune complex deposition. The repeated injection of heterologous protein antigens is called chronic serum disease, and the complex formation is less, and Often deposited in the kidneys, arteries and lungs.

The pathogenesis of serum disease is due to the excessive amount of antigen injected, so that there are still more injected antigens in the blood circulation when the corresponding antibodies are produced in the body. Once the antigens and antibodies meet, a soluble complex of different proportions is formed. When the equal size complex is not phagocytosed by the mononuclear phagocytic system, it attaches to the skin, joints, kidneys, and heart. The exact mechanism of why immune complexes are particularly easy to deposit in a certain part is still unknown, but recently One mechanism for generating a complex at a particular location is that the tissue already has an antigen deposited locally before the start of antibody synthesis, and thus the antibody binds to the antigen present on the tissue, in which case the complex is local rather than Formed in the blood circulation.

2. Immune complex glomerulonephritis In the case of chronic infection and autoimmunity, the deposition of immune complexes persists due to the persistence of antigens. Many glomerulonephritis is associated with circulating immune complexes, such as systemic lupus erythematosus. There are DNA/anti-DNA/complement deposits in the patient's kidney, most notably kidney disease caused by infection with certain strains of nephritogenic streptococcus and nephrotic syndrome in Nigerian children associated with three-day malaria, virus Complex nephritis can also occur during chronic infection, such as glomerulonephritis in mice infected with meningitis virus, which is a representative model of many glomerulonephritis in humans.

3. The deposition of the complex in other parts of the body is a major filtration site, which is also conducive to the accumulation of immune complexes. This is the cause of central nervous system symptoms in patients with systemic lupus erythematosus. C4 levels in cerebrospinal fluid often decrease. In the nervous tissue of patients with subacute sclerosing panic encephalitis, there is a complex deposition of measles antigen and corresponding antibodies. In the rash of serum disease and systemic lupus erythematosus, there are lg and C3 on the basement membrane connected to the epidermis and the dermis. Sedimentation, recently reported that the nodular polyarteritis lesion contains hepatitis B virus immune complex, and the drug such as penicillin binds to human protein and has antigenicity. The complex with the corresponding antibody can also cause type III. Hypersensitivity reaction.

Examination of type III hypersensitivity diseases

Circulating antibodies against horse serum, hepatitis antigen, DNA, denatured IgG (rheumatoid factor) and some fungal spores are another evidence to support type III response. For example, during the period of systemic lupus erythematosus, Increased antibody to self-denatured double-stranded DNA and decreased serum complement. If the antigen is unknown, the total serum complement concentration and the concentration of the first few complement components (C1, C4 or C2) can be determined. Complement activation also indicates that a type III response is occurring.

In the allergic pulmonary aspergillosis, the Aspergillus intravitreal antigen test can cause IgE-mediated wheal blush reaction, followed by Arthus-like reactions.

Up to now, serum immune complexes can be detected by cryoprecipitation (using the nature of precipitation of certain complexes in cold environments). Soluble complexes can also be detected using precision instruments for analytical ultracentrifugation and sucrose density gradient centrifugation. The complex reacts with the complement component (such as the C1q binding assay) and inhibits the reaction of the monoclonal rheumatoid factor with IgG. The Raji cell assay interacts with the cellular receptor based on the immune complex containing the complement component (eg The principle of the C3 receptor on the surface of Raji cells is established. There are also some methods of measurement, but the above three are the most commonly used. No single test can detect all immune complexes, so these methods are limited to use in clinical medicine. Monitor the level of activity of certain diseases.

Diagnosis and diagnosis of type III hypersensitivity diseases

Judgment can be made based on medical history, clinical performance and laboratory data.

Differential diagnosis

Type I hypersensitivity: also known as allergic allergy or immediate allergic reaction, because the antigen interacts with antibodies (usually IgE) on the medium-releasing cells, so that the Fo of IgE on the cells is bridged by fibers, causing cell activation. The membrane of the intracellular granule fuses with the membrane to form a conduit, which releases some active mediators such as histamine, serotonin, and slow-reacting substance-A (SPS-A). These mediators can cause smooth muscle contraction, telangiectasia, and transparency. Increased sex and increased glandular secretion, depending on the target cells affected by these active substances, respiratory allergic reactions, digestive tract allergic reactions, skin allergic reactions or anaphylactic shock, common type I hypersensitivity reactions with penicillin allergic reactions, drugs Caused by drug eruption, food-induced allergic gastroenteritis, allergic rhinitis caused by pollen or dust, bronchial asthma, etc.

Type II hypersensitivity reaction: also known as cytolysis allergy or cytotoxic allergy, when the antigen on the cell binds to the antibody, the cell is destroyed due to the action of complement, phagocytic or K cell, such as blood transfusion reaction The hemolytic reaction of the newborn and the hemolytic anemia caused by the drug belong to the type II hypersensitivity reaction.

Type IV hypersensitivity: Also known as delayed allergic reaction, a pathological manifestation of cell-mediated immunity, which is mediated by T cells. A common type is that chemicals (such as dyes) bind to skin proteins or Change its composition to become an antigen, which can sensitize T cells. After re-exposure to the antigen, T cells become killer cells or release lymphokines causing contact dermatitis. Another type is called infectious allergic reaction, which is caused by certain pathogens. As a result of antigenic stimulation, it is found in tuberculosis, syphilis, etc. In addition, rejection of organ transplantation, encephalomyelitis after vaccination, and certain autoimmune diseases belong to this type.

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