Acquired immune responses

It has already been noted that the phenotype of an acquired immune response is considered to reflect the early cytokine environment in which naive CD4+ T cells interact with antigen. Again, it has been suggested, for example, that early exposure to IL-4 can push an immune response in a Th-2 direction (Swain et al., 1990). We therefore investigated (by ELISA) whether ES-62 was able spontaneously to induce IL-4 secretion in naive murine spleen cells (48 h exposure). Ironically, given that the molecule induces a Th-2 antibody response and seems to be able to induce the release of a number of other cytokines, IL-4 was not detected (Harnett et al., 1999a). It was noted, however, that IL-4 was produced by spleen cells from mice that had been pre-exposed to ES-62. This established Th-2 phenotype is consistent with the antibody data. 

Homo sapiens (compared to Drosophila melanogaster) Large-scale gene duplications with substantial expansion of genes involved in acquired immune response (B cells, T cells, major histocompatibility complex genes, cytokines, chemokines and their receptors), plasma proteases (complement and hemostatic proteins), proteins associated with apoptotic regulation and proteins related to neuronal network formation and electrical coupling... 

Taken together, the studies cited above strongly suggest that mast cells can contribute to the sensitization phase of acquired immune responses by virtue of their ability to produce mediators that can promote migration of APCs. Furthermore, mast cells prepare LNs to become the meeting point of antigen-laden APCs and T cells (fig. 1). 

The ability of mast cells to promote and even to shape acquired immune responses was further corroborated by Maurer et al. [14] investigating host defense mechanisms in Leishmania major... 

As is implied by its name, the first TNF-a-dependent mechanism described was the induction of tumor necrosis in vivo through its role in tumor vasculature. However the mechanisms of the in vitro toxicity of TNF-a to tumor cells imply apoptosis rather than necrosis [97], Tumor necrosis in SCID (severe combined immuno-deficiency) mice treated with LPS does not lead to the rejection of tumors [98], Furthermore, necrosis and tumor regression must be dissociated since anti-IFN-y antibodies inhibit LPS-induced regression of Meth A sarcoma in mice, but not the necrotic hemorrhage attributed to TNF-a. It is now accepted that the antitumoral effect of TNF-a is indirect and dependent on acquired immune response. Matsumoto et al. [99] reported that, while TNF-a itself has no effect on hepatoma KDH-8 tumor cells in vitro, the antitumoral effect of the lipid A ONO-4007 against KDH-8 tumors in vivo is inhibited by anti-TNF-a antibodies in WKAH rat, showing an indirect effect of TNF-a. 

Three lipids A have been more intensively studied in animal models, all of them having indirect effects, mediated in vivo by the immune system. For two of them, DT-5461 and ONO-4007, TNF-a is an important mediator acting at the vascular level that provokes tumor necrosis. For the third one, OM-174, the treatment induces the accumulation of IFN-y and EL-1 P in tumors, which activate NOS II transcription in tumor cells that produce autotoxic NO, which then provokes the apoptosis of tumor cells. At the same time this treatment inhibits the production of TGF-pi by tumor cells which reduces the TGF-pi induced immunosuppression and enhances NO production. Acquired immune response, probably completes the tumor regression started by the apoptosis process and, most probably induces specific memory. 

Grimbaldeston MA, Metz M, Yu M, Galli S J. 2006. Effector and potential immunoregulatory role of mast cells in IgE-mediated acquired immune responses. Curr Opin Immunol. 18 751-760. 

IFN-y modulates a number of components of the immune response. This is the only type II IFN whereas there are more than 20 types of type I IFNs (IFN-a, IFN-(3, IFN-w and IFN-t). It is not related to type I IFNs, has separate receptors and is encoded by a different chromosomal locus. IFN-y is produced by activated T lymphocytes (THi and CD8+ cells), NK cells, B cells, NKT cells and professional APCs. It promotes the activity of cytolytic T lymphocytes, macrophages and NK cells. The cell self-activation and activation of nearby cells in part may result from IFN-y production by professional APCs, which include monocyte/macrophage and dendritic cells. The early host defense against infection is likely to utilize IFN-y secreted by NK and professional APCs. In acquired immune responses, T lymphocytes are the major source of IFN-y. 

STAT4 is induced not only by IL-12 but also by IFN-a and IL-23. IL-12 and IL-23 are produced in response to various pathogenic organisms and regulate innate and acquired immune responses. IL-12 binds to 11,-12(31 and IL-12(32 receptors. A subunit called P40 is shared by IL-12 and IL-23. IL-12 and IL-23 activate the JAKs, JAK2 and Tyk2, STAT4 and other STATs. 

Some observations have suggested that presence of microbial compounds in the environment may affect hosts immune response. For example, the children of farmers who are exposed to high levels of endotoxins exhibit increased expression of TLR2 and CD14 compared to children with less exposure. This suggests a modulation of innate immune response in the absence of an infection. How this observation corresponds to a lower incidence in allergic disease needs to be determined. Activation of TLR induces inflammatory and acquired immune response, and inhibition of one of these pathways (MyD88) results in decreased THi responses and enhanced IgE production. 

The above-mentioned observations were also described in humans by P.B. Medawar in the 1940s. Based on his observations in humans, and later in animal experiments, he concluded that the graft rejection was a result of immune response, which eventually led to the discovery of MHC. The development of acquired immune response to transplanted tissue results in the rejection of the tissue where cytotoxic T cells, inflammatory T cells and antibodies play a major role in the rejection process. 

Until recently, most of the attention regarding allograft rejection focused on T cells and acquired immune response. Pattern recognition receptors (PRRs), which sense conserved pathogen-derived molecules that differentiate infectious nonself from self... 

Figure 19.2 The acquired immune response. In response to a specific antigen there is clonal expansion of B cells and subsequent production of antibodies (Ig) specific for that antigen. Antigen presenting cells process and present antigen to T cells. Again there is clonal expansion of cells specific for that antigen.

Systemic and Acquired Immune Responses in Alzheimer s Disease... 

Tritto E, Muzzi A, Pesce I, Monaci E, Nuti S, Galli G, Wack A, Rappuoli R, Hussell T, De Gregorio E (2007) The acquired immune response to the mucosal adjuvant LTK63 imprints the mouse lung with a protective signature. J Immunol 179(8) 5346-5357 Ulrich JT, Myers KR (1995) Monophosphoryl lipid A as an adjuvant. Past experiences and new directions. Pharm Biotechnol 6 495-524... 

Siglecs are expressed abundantly on many cells of the immune system and are therefore likely to be important in both innate and acquired immune responses. The development of siglec-specific agonists and antagonists may provide new approaches for the treatment of certain autoimmune and inflammatory conditions. Moreover, the... 

The function of the innate immune system is thought to be the recognition of invading pathogens, the activation of inflammation to control the pathogen, and the subsequent activation of the acquired immune response. It constitutes the most archaic part of our immune defences and has survived through years of evolution. 

Vaccination by the nasal route produces a mucosal protection using mucus, the epithelial surface, and both innate and acquired immune responses. The innate defense mechanism plays a very important role in that it influences the type of acquired immune mechanism, which mainly responds on the basis of immune memory. The ability to attain these responses is the main principle of attaining protection from infection. 

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