Current Immunology Reviews (Discontinued) - Volume 5, Issue 4, 2009

The mucosal surfaces of the gastrointestinal tract are constantly exposed to large quantities of commensal microbes and enteric pathogens. Highly sophisticated innate immune mechanisms are in place to recognize and prevent the establishment of infections with such pathogens. At the same time, immune responses to commensals are being donwregulated resulting in a phenomen called oral tolerance. In turn, enteric pathogens have developed a variety of mechanisms to counter the immune response including novel colonization strategies and the production of virulence factors that can downregulate recognition and elimination by the innate immune system. This review focuses on enteric infections in large animals and describes the complex interplay between the host's innate immune system and pathogenic bacteria such as Escherichia coli, Salmonella spp., Campylobacter jejuni, Yersinia spp. and Shigella spp.

Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of humans. Although causes of MS are enigmatic, underlying elements contributing to disease development include both genetic and environmental factors. Recent epidemiological evidence has pointed to viral infection as a trigger to initiating white matter damage in humans. Mouse hepatitis virus (MHV) is a positive strand RNA virus that, following intracranial infection of susceptible mice, induces an acute encephalomyelitis that later resolves into a chronic fulminating demyelinating disease. Immune cell infiltration into the central nervous system is critical both to quell viral replication and instigate demyelination. Recent efforts by our laboratory and others have focused upon strategies capable of enhancing remyelination in response to viralinduced demyelination, both by dampening chronic inflammation and by surgical engraftment of remyelination-competent neural precursor cells.

Fasciola hepatica is a trematode that affects human and domestic ruminant health, causing significant economic losses in cattle estimated at US$2000 millon per year. Juvenile parasites migrating through the host tissues, as well as adults settle in the biliary ducts, are in contact with different cells from the immune system. Despite those interactions, the persistence of the parasite in the host for many years provides evidence of its ability to prevent or downmodulate the inflammatory response in the infection site. Different strategies have been developed by the parasite to prevent potential damage being induced by the immune response, thus allowing some parasites to reach the adult stage in a safe place such as the biliary ducts. In this review we discuss how excretory-secretory products (ESP) from F. hepatica can affect the functionality of pivotal immune cells, such as eosinophils and macrophages by inducing selective apoptosis pathways and alternative activation of macrophages. Furhermore, the modulatory effects of ESP on dendritic cell activation and lymphocyte proliferation is reviewed as a strategy to facilitate F. hepatica evasion of both innate and adaptive immunity.

The discovery of new functions for CD154 and CD40 molecules has expanded our knowledge to claim that CD154 plays well beyond its postulated role in adaptive immunity. Active research in this area has outlined an important role of CD154 and its receptor CD40 in the physiopathology of autoimmunity. CD154/CD40 interactions have been shown to underlay inflammatory events characterizing autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosous, and multiple sclerosis. Besides CD40, three additional receptors were recently discovered for CD154, namely, αIIbβ3, α5β1 and Mac-1 integrins. This review gives an overview on CD154 and its receptors, and outlines the function of CD154/CD40 interactions in both normal and autoimmune states. Moreover, the potential usefulness of various CD154-interfering agents in treatment/prevention of autoimmune events is discussed.

Major histocompatibility complex (MHC) genes are involved in various mechanisms of pathogenesis and immunoediting of non-Hodgkin’s lymphoma (NHL). MHC class III polymorphisms, located within tumor necrosis factor (TNF) family gene cluster, have diverse expression in normal individuals and lymphoma patients, and their expression depends on the allelic version. Certain HLA class I and II gene products are involved in the tumor peptide presentation and ligation of specific T-cell receptors (TCR). They are involved in NHL pathogenesis either directly or as a consequence of the linkage disequilibrium (LD) with causative genes. TNF polymorphic alleles and closely located nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor like 1 (NFKBIL1) may lead to up-regulation of nuclear factor kappa B (NFκB) and adverse outcome of certain subsets of diffuse large B-cell lymphomas. In addition, HLA class I ligation to the natural killer (NK)-cell immunoglobulin-like receptors (KIR) plays a critical role in immunosurveillance of the tumors, which may result in deterioration of NHL outcome, especially when the repertoire of MHC-KIR interaction is reduced. This review summarizes clinical data of MHC allele and haplotype polymorphisms and their pleiotropic or epistatic links to the pathogenesis of NHL.

Dendritic cells (DCs) and macrophages differently contribute to the generation of coordinated immune system responses against infectious agents. They interact with microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms. Upon antigen binding, PRRs instruct DCs for the appropriate priming of natural killer cells, followed by specific T-cell responses. Once completed the effector phase, DCs reach the terminal differentiation stage and eventually die by apoptosis. By contrast, following antigen recognition, macrophages initiate first the inflammatory process and then switch to an anti-inflammatory phenotype for the restoration of tissue homeostasis. In this review we will focus on the comparison of the divergent responses of DCs and macrophages to microbial stimuli and in particular to lipopolysaccharide (LPS).