动物造模,自身免疫性主动激活 z-bio 2023-09-13 929

　　1. Self activated lymphocyte transfer

　　(1) The earliest research was on PV: Dsg3 deficient mice were immunized by intraperitoneal injection of recombinant mouse Dsg3 and adjuvant. After 32 days of first immunization, 1 was removed from the spleen of the mice × After intravenous injection of 10 to the 7th power lymphocytes into Rag2-/- mice, anti Dsg3 antibodies were detected in Rag2-/- mice after 4 days. Circulating antibodies can also bind to the skin or mucosa of the mouse, leading to severe clinical manifestations.

　　(2) Similar example: mCol17-/- mice backcross with Rag2-/- mice to produce Rag2-/- mCol17-/- hCol17+/+mice. These mice received activated lymphocytes (from the spleen of wild-type mice immunized with mCol17-/- hCol17+/+mouse skin grafts). Can produce BP skin lesions similar to humans.

　　2. After transplanting the skin of transgenic mice expressing type 17 collagen into wild-type mice of the same gender and strain, the latter will produce specific antibodies. In this active BP model, the production of antibodies is often accompanied by the deposition of IgG and C3 at the junction of the true epidermis, followed by a large number of neutrophil infiltration, dermal edema, and epidermal blisters, ultimately leading to transplant failure. The production of antibodies depends on the expression of MHC-2, indicating that the interaction between MHC-2 and CD4+T cells is crucial for antibody production in this model.

　　3. Compulsory Immune Model

　　(1) Initially, rabbits were immunized with a peptide segment encoding one epitope of BP230 to generate a BP model, but the results were unsuccessful. After improvement, UV irradiation was added to the local skin for treatment. Subsequently, deposition of IgG and C3 was observed at the irradiation site, followed by neutrophil infiltration. This model can last for 14-28 days.

　　(2) Herpetiform dermatitis has a strong correlation with HLA-DQ8, and DQ8 transgenic mice backcross with NOD mice (susceptible to autoimmune diseases). Subsequently, DQ8 transgenic NOD mice were immunized with crude gluten and Freund's complete immune adjuvant (pre treated with pertussis toxin), and 1/6 of the mice developed epidermal blisters. At the same time, IgA deposits at the junction of the epidermis and neutrophil infiltration. But interestingly, through a gluten free diet, this symptom can be completely reversed. Genetically modified or NOD background alone cannot produce herpetiform dermatitis. Unlike human manifestations, the animal model of herpetiform dermatitis has no small intestinal lesions.