动物造模,自身免疫性抗体被动转运 z-bio 2023-09-13 921

　　1. The passive transport model of rabbit corneal autoimmune antibodies IgG was taken from patients with bullous pemphigoid (BP) and injected into the cornea of New Zealand rabbits. After 24 hours, the cornea showed epidermal detachment, thickening, and blister formation. The inflammatory response is dose-dependent, with IgG and C3 linear deposits visible at the junction of the epidermis. But since then, this model has been rarely used.

　　2. Passive Transport Model of Autoimmune Antibodies in Newborn Mice

　　(1) IgG was taken from patients with pemphigus vulgaris (PV) and injected intraperitoneally into newborn BALB/c mice at a daily dose of 1.5-16mg/g body weight. Within 18-72 hours, dose-dependent skin blisters or extensive epidermal collapse were observed, and IgG administration was discontinued, resulting in the cessation of skin lesion development. Because injection of F (ab) 2 fragment can also cause similar skin lesions, it suggests that Fc may not be involved in this reaction.

　　(2) IgG is taken from patients with deciduous pemphigus (PF) and administered daily at 2 doses × 10mg/g body weight was intraperitoneally injected into newborn BALB/C mice four times. Similar to PV, the skin lesions present in mice are dose-and titre-dependent.

　　(3) In the BP model, due to the lack of cross antigens between the mouse transmembrane protein BP180 and the immune domain NC16A of human BP180, it is necessary to construct a fusion protein GST mus180A. IgG was obtained by immunizing rabbits with fusion proteins, and then injected into newborn mice. Within 24 hours, the mice showed erythema and skin laxity, and histology showed epidermal vesicles and neutrophil infiltration. Direct immunofluorescence showed deposition of IgG and complement at the junction of the true epidermis.

　　(4) Mucosal pemphigus (MMP) model was established by immunizing rabbits with laminin 332 extracted from human keratinocyte culture, and then immunizing newborn mice with IgG from rabbit blood. Method: Intraperitoneal or subcutaneous injection, if the total amount exceeds 5mg/kg, tension blisters will appear within 48 hours at the skin friction or injection site. The formation of blisters is not related to complement and mast cells, indicating that Fc is not involved in pathogenesis.

　　3. Passive Transport Model of Autoimmune Antibodies in Adult Mice

　　(1) Establishment of an acquired bullous epidermal lysis (EBA) model: Rabbits were immunized with mouse NC1 immune determinant or human type VII collagen as antigen, and then immunized with the obtained rabbit polyclonal antibody. The mice were injected at a rate of 0.3-0.9mg/g body weight. After 2-4 days, dose-dependent epidermal blister formation and erosion can be observed, and histological examination reveals neutrophil infiltration and IgG/C3 deposition at the junction of the true epidermis. Among them, inbred nude mice, BALB/C, C57BL/6, and closed group SKH-1 mice are sensitive to anti type VII collagen antibodies.

　　(2) MMP model: After injection of anti human laminin 332 rabbit IgG antibody into mice, local erythema, erosion, and scab formation can be caused within 24 hours. Histology shows IgG and C3 deposition, but there are no epidermal vesicles or neutrophil infiltration.

　　The passive transport model of autoimmune antibodies in mice receiving human epidermal transplantation or humanized mice can be divided into two pathways.