Immune response adhesive antigens

A wide variety of novel approaches for the development of mucosal immune responses by administration of antigens in different delivery systems have been investigated, in many cases, with considerable success. These approaches include (1) the coadministration of immunogens with adjuvants active at the mucosal surface, (2) the coupling of immunogens to carrier molecules that promote their uptake at the mucosal inductive site, and (3) the expression of antigens in live attenuated bacterial or viral vectors, which can promote the colonization of mucosal tissue and the incorporation of antigens into a variety of microparticulate and adhesive vehicles, which are taken up in mucosal inductive sites. 

Hydrophilic surfactant proteins A (SP-A) and D (SP-D), secreted by type II pneumocytes, interact specifically with a wide range of microorganisms and play important roles in the innate, natural defense system of the lung [16]. Both mRNA and protein levels of SP-A and SP-D increase dramatically in response to lung infection, injury and endotoxin challenge [17]. Type II pneumocytes also express class II major histocompatibility complex (MHC) antigens and intracellular adhesion molecule (ICAM-1), which may facilitate pulmonary immune responses [15]. 

Skin is rich in dendritic cells, which are potent initiators of immune responses and possess the co-stimulatoiy and adhesion molecules required for T cell activation. In addition, dendritic cells possess a unique ability to process and present extracellular antigens in the context of both class I and class II molecules. Thus, transfection of plasmids into these cells is likely to elicit both cellular and humoral responses. Specific targeting of dendritic cells residing in the lymph nodes will likely represent an attractive strategy for providing a robust immune response with nucleic acid vaccines. 

BIRT-377 (1), a small molecule inhibitor of lymphocyte function-associated antigen 1 (LFA-1), was first discovered by Kelly and coworkers in 1999. It was shown to have potential therapeutic utility in the treatment of a variety of inflammatory and immune disorders. In binding to intercellular adhesion molecules, the cell-surface receptor LFA-1 allows many cell-cell adhesion events that control immunological functions. A lack of these synaptic functions leads to potentially life-threatening immunodeficiency diseases. In case of overactive immune responses, an LFA-1 inhibitor can be used to attenuate the inflammatory responses. These immunosuppressive activities have been tested in vitro, and early clinical trials on transplantation have already been undertaken. ... 

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