1. Streptococcus infection and immune response theory The etiology and pathogenesis of rheumatic fever have not been fully clarified, but it is now recognized that rheumatic fever is an autoimmune disease caused by throat infections of group A and group B streptococci.
2. Theory of viral infection In recent years, some scholars have paid more attention to the theory of viral infection, and think that rheumatic fever may be related to coxsackie B3 and B4 virus infection.
883B。 Genetic factors Genetic markers have recently been found in patients with rheumatic fever. About 72% patients with rheumatic fever are positive by serum containing allogenic antigen.
4. The change of immune function may also be involved in the occurrence of rheumatic fever.
(2) Pathogenesis
1. Pathogenesis
(1) Streptococcus infection and immune response theory: Although the etiology and pathogenesis of rheumatic fever have not been fully clarified so far, it is now recognized that rheumatic fever is an autoimmune disease caused by throat infections of group A and group B streptococci. It has been proved that human tissues and some structures of streptococcus have cross antigenicity, so the body can mistake streptococcus for "itself" and eliminate it without normal immune response; Once the immune function of the body changes, streptococcus can enter the human body as an antigen to produce corresponding antibodies. At present, many autoantibodies have been detected, such as anti-myocardial antibody, anti-M protein antibody, anti-cardiac valve polysaccharide antibody, anti-neuronal antibody and so on. These antibodies not only react with streptococcus-associated antigens, but also can act on antigens associated with myocardium, heart valve, nerve tissue and connective tissue, resulting in autoimmune reaction, damage to corresponding tissues and rheumatic fever. Cellular immune mechanism also plays an important role in the occurrence and development of rheumatic fever. Through immunohistochemical technique, it is confirmed that T lymphocyte infiltration is the main focus of rheumatic fever. Lymphocyte reaction in rheumatic fever patients is enhanced, and a series of cellular immune reaction markers are activated, such as interleukin (IL- 1, IL-2) and tumor necrosis factor -γ(TNF-γ). The inhibition of leukocyte migration is enhanced, the toxicity of natural killer cells (NK) and monocytes is enhanced, the reaction of T lymphocytes to streptococcus antigen is enhanced, phagocytes produce free radicals, and peripheral blood and heart tissues are enhanced.
(2) Theory of virus infection: In recent years, relevant scholars have paid more attention to the theory of virus infection, and think that rheumatic fever may be related to coxsackie B3 and B4 virus infection. The reasons are as follows: ① The titers of anti-Coxsackie B3 and B4 antibodies in some patients with rheumatic heart disease increased significantly; ② Cardiotropic virus was found in the left atrium and heart valve of patients with rheumatic heart disease; ③ After infected with Coxsackie B4 virus, Javanese monkeys can produce pathological changes similar to rheumatic heart disease. However, this theory is not generally accepted, and it is difficult to explain that penicillin really has a significant effect on preventing the recurrence of rheumatic fever. Many scholars believe that virus infection may create conditions for streptococcus infection and play an inducing role in the occurrence of rheumatic fever.
(3) Genetic factors: Recently, genetic markers have been found in patients with rheumatic fever. About 72% patients with rheumatic fever are positive by serum containing allogenic antigen. Monoclonal antibody D8/ 17 against B cell alloantigen has also been produced. 80% ~ 100% of patients with acute rheumatic fever were positive, while only 15% of the control group were positive. Therefore, it is possible to screen the susceptible population of acute rheumatic fever with monoclonal antibodies. Through the study of immunogenetics, it is found that there are special antigens expressed in the immune system cells of rheumatic fever patients and their relatives. It is reported that most of them are accompanied by the increase of HLA-DR4 frequency. In addition, the frequencies of some loci of HLA-DQAl and DQB 1 also increase. The progress of this study may find rheumatic fever and susceptible patients in the general population, so as to carry out targeted prevention and treatment. Most scholars believe that genetic factors can be one of the inducing factors, but the most likely cause of multiple members of the same family is related to the same living environment and easy mutual infection.
(4) Immune function: The change of immune function may also participate in the occurrence of rheumatic fever. Immunoglobulin IgG, IgA and IgM often increase in rheumatic fever and rheumatic activities; Although there are more white blood cells in the blood, the phagocytic ability is reduced. The results of lymphocyte transformation test showed that the transformation rate of lymphocytes to primitive lymphocytes decreased, indicating that the cellular immune function was defective. In addition, cell-mediated immune response is also very important in the process of this disease.
Regarding malnutrition theory, trace elements are related to rheumatic fever (zinc deficiency is found to be closely related to the immunopathological mechanism of rheumatic fever and rheumatic heart disease) and endocrine disorders. , still exploring. In a word, the pathogenesis of rheumatic fever is complex, which is the result of many factors, such as the throat infection of streptococcus and the immune state of the body.
2. Pathological rheumatic fever is systemic connective tissue inflammation, which can be divided into three stages according to the pathological process.
(1) Degeneration exudation stage: Collagen fibers in connective tissue split and swell, forming glassy and cellulose degeneration. There are inflammatory cells such as lymphocytes, plasma cells, eosinophils and neutrophils infiltrating around degenerative diseases. This period can last for 1 ~ 2 months, and it will resume or enter the second and third periods.
(2) Proliferating period: On the basis of the above lesions, rheumatic granuloma or rheumatic corpuscles appear, which is the characteristic lesion of rheumatic fever, the basis of pathological diagnosis of rheumatic fever and the index of rheumatic activity. There is cellulose-like necrosis in the center of the corpuscle, and lymphocytes and plasma cells infiltrate at its edge, and there are rheumatic cells. Rheumatoid cells are round, oval or polygonal, with abundant cytoplasm, alkalophilia, empty nucleus and obvious nucleoli. Sometimes binuclear or multinucleated cells form giant cells and enter the hardening stage. This period can last for 3 ~ 4 months.
(3) Sclerosing stage: Degenerative and necrotic substances in the center of rheumatic corpuscles are gradually absorbed, inflammatory cells oozing out are reduced, fibrous tissues proliferate, and scar tissues are formed at granulomas.
Because the disease often recurs, the development process of the above three stages can exist alternately, which takes 4 ~ 6 months. Phase 0 and phase 2 of/kloc-are often accompanied by serous exudation and inflammatory cell infiltration, which largely determines the occurrence of clinical symptoms. The lesions of joints and pericardium are mainly exudation, while the formation of scars is mainly confined to endocardium and myocardium, especially valves.
Inflammatory lesions of rheumatic fever involve collagen fibers in connective tissue of the whole body. In the early stage, joints and heart were mostly involved, and then the heart was mainly damaged. The lesions in each stage are concentrated in the affected organs, such as joints and pericardium, which form arthritis and pericarditis. After that, the exudate can be completely absorbed, but a small amount of pericardial exudate can not be completely absorbed, and polarization forms partial adhesion, mainly the proliferative lesions of myocardium and endocardium, and then scar hyperplasia is formed. Proliferative lesions and adhesions of heart valves often lead to chronic rheumatic valvular disease.