动物造模,自身免疫,药效评价 z-bio 2024-07-25 382

　　1. Self activated lymphocyte metastasis

　　(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 the first immunization, 1 × 10 7th power lymphocytes were taken from the spleen of the mice and intravenously injected into Rag2-/- mice. After 4 days, Rag2-/- mice were detected to produce anti-Dsg3 antibodies. Circulating antibodies can also bind to the skin or mucosa of the mouse, leading to severe clinical manifestations.

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

　　2. After transplanting transgenic mouse skin expressing type 17 collagen into wild-type mice of the same gender and lineage, 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 dermis, leading to massive neutrophil infiltration, dermal edema, subepidermal vesicles, and ultimately resulting in 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. Mandatory immune model

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

　　(2) There is a strong correlation between herpetic dermatitis and HLA-DQ8, and DQ8 transgenic mice are backcrossed with NOD mice (susceptible to autoimmune diseases). Subsequently, DQ8 transgenic NOD mice were immunized with coarse grain gum 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 is deposited at the junction of the true epidermis and infiltrated by neutrophils. But interestingly, this symptom can be completely reversed through a gluten free diet. Transgenic or NOD background alone cannot produce herpetic dermatitis. Unlike human performance, animal models of herpetic dermatitis have no small intestinal lesions.