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Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system. An in vitro human tonsil tissue-based system captures key features of a functional germinal center and can be used to study humoral immune responses to vaccines, new antigens and adjuvants., Author(s): Lisa E. Wagar [sup.1] [sup.15] , Ameen Salahudeen [sup.2] [sup.16] , Christian M. Constantz [sup.3] , Ben S. Wendel [sup.1] , Michael M. Lyons [sup.1] , Vamsee Mallajosyula [sup.3] [...]

Advances in the field of cancer immunology, including studies on tumor-infiltrating [CD8.sup.+] cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, [CD4.sup.+] Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers., Introduction Studies of the immune response to late-stage cancers including the role of tumor-infiltrating [CD8.sup.+] cytotoxic T lymphocytes (CTLs) in attacking cancer cells have led to promising new cancer immunotherapeutics [...]

Migration has fascinated researchers for years and many active areas of study exist. However, the question of how migratory species stay healthy within the context of their annual cycle remains relatively unexplored. This article addresses this question using Red Knots (Calidris canutus) as a model migrant species. We review recent research on immune function in Red Knots and integrate this work with the broader eco-immunological literature to introduce a conceptual model. This model synthesizes earlier ideas about resource allocation and the costs of immunity with recent increases in our knowledge about the vertebrate immune system and then puts these concepts into the context of defense against real pathogens in environments where a myriad of factors change in time and space. We also suggest avenues for further research, which will help to test the model and better link measures of immune function to pressure from pathogens and to optimal defense against disease. doi: 10.1093/icb/icq055

The objective was to determine effects of an intratracheal Mannheimia haemolytica challenge after 72-h exposure to bovine viral diarrhea virus type lb (BVDVlb) persistently infected (PI) calves on serum antibody production, white blood cell count (WBC), cytokine concentrations, and blood gases in feedlot steers. Twenty-four steers (initial BW = 314 [+ or -] 31 kg) were randomly allocated to 1 of 4 treatments (6 steers/treatment) arranged as a 2 x 2 factorial. Treatments were 1) steers not exposed to steers PI with BVDV nor challenged with M. haemolytica (control; CON); 2) steers exposed to 2 steers PI with BVDV for 72 h (BVD); 3) steers intratracheally challenged with M. haemolytica (MH); and 4) steers exposed to 2 steers PI with BVDV for 72 h and challenged with M. haemolytica (BVD+MH). There were 12 h between exposure to PI steers and challenge with M. haemolytica. Rectal temperature was increased (P < 0.001) for MH and BVD+MH during the initial 24 h after the M. haemolytica challenge. For MH and BVD+MH, total WBC count was increased (P < 0.01) at 36 h post M. haemolytica challenge compared with CON, whereas in BVD steers, WBC count was decreased (P < 0.01). Total lymphocyte count was increased (P = 0.004) during the initial 72 h post BVDV exposure for the BVD and BVD+MH groups compared with MH and CON, and this difference remained at 96 h post M. haemolytica challenge. An increased (P < 0.001) total neutrophil count was observed during the initial 36 h for the MH group and at 72 h for the BVD+MH challenge group. Interleukin 1[beta], IL-6, and tumor necrosis factor [alpha] (TNF[alpha]) concentrations were greater (P [less than or equal to] 0.04) in BVD steers than steers not exposed to BVDV, and interferon [gamma], IL-1[beta], and TNF[alpha] were greater (P [less than or equal to] 0.02) in MH steers than in steers not challenged with M. haemolytica. There were BVD x MH interactions (P [less than or equal to] 0.04) for plasma carbon dioxide, carbonic acid, and sodium bicarbonate concentrations. Challenge with M. haemolytica decreased carbon dioxide, carbonic acid, and sodium bicarbonate concentrations to a greater extent when steers were not exposed to PI steers compared with steers exposed to BVDV. We conclude that the challenge model was successful at inducing bovine respiratory disease (BRD) associated with BVDV and M. haemolytica. Understanding the physiological changes in morbid animals will lead to improved strategies for decreasing severity and economic losses associated with BRD. Key words: bovine, bovine respiratory disease, bovine viral diarrhea virus, cytokine, immune response, Mannheimia haemolytica doi: 10.2527/jas.2009-2005

The magnitude of an adaptive immune response is controlled by the interplay of lymphocyte quiescence, proliferation, and apoptosis. How lymphocytes integrate receptor-mediated signals influencing these cell fates is a fundamental question for understanding this complex system. We examined how lymphocytes interleave times to divide and die to develop a mathematical model of lymphocyte growth regulation. This model provides a powerful method for fitting and analyzing fluorescent division tracking data and reveals how summing receptor-mediated kinetic changes can modify the immune response progressively from rapid tolerance induction to strong immunity. An important consequence of our results is that intrinsic variability in otherwise identical cells, usually dismissed as noise, may have evolved to be an essential feature of immune regulation.

Byline: D. Gammack (1), C.R. Doering (2), D.E. Kirschner (3) Keywords: Reaction-diffusion-advection; Granuloma; Mycobacterium tuberculosis; Internal states; Internal velocity; Immune response Abstract: The immune response to Mycobacteriumtuberculosis (Mtb) infection is the formation of multicellular lesions, or granolomas, in the lung of the individual. However, the structure of the granulomas and the spatial distribution of the immune cells within is not well understood. In this paper we develop a mathematical model investigating the early and initial immune response to Mtb. The model consists of coupled reaction-diffusion-advection partial differential equations governing the dynamics of the relevant macrophage and bacteria populations and a bacteria-produced chemokine. Our novel application of mathematical concepts of internal states and internal velocity allows us to begin to study this unique immunological structure. Volume changes resulting from proliferation and death terms generate a velocity field by which all cells are transported within the forming granuloma. We present numerical results for two distinct infection outcomes: controlled and uncontrolled granuloma growth. Using a simplified model we are able to analytically determine conditions under which the bacteria population decreases, representing early clearance of infection, or grows, representing the initial stages of granuloma formation. Author Affiliation: (1) Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 49109, USA (2) Department of Mathematics, Michigan Center for Theoretical Physics, University of Michigan, Ann Arbor, MI, 49109,48120, USA (3) Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 49109, USA Article History: Registration Date: 01/01/2003 Received Date: 10/12/2002 Online Date: 20/08/2003 Article note: Send offprint requests to:kirschne@umich.edu

Insects such as Drosophila melanogaster provide useful models for human immunity. Rel protein signaling cascades have been identified in the immune response of Drosophila. The signaling pathways are markedly similar in Homo and Drosophila. A combination of molecular, genetic, and genomic techniques can be used to study Drosophila immune response.

Several questions regarding the physiological rules of immunity remain unanswered, resulting in limited progress in autoimmune diseases, transplantation tolerance, allergy and chronicinfectious diseases. To provide an explanation for the plasticity of the immunesystem, it is proposed that lymphocytes possess the ability to tune and update their responsiveness to recurrent signals. In this model, suprathreshold interactions represent processes such as cellular anergy, while subthreshold interactions represent functions such as immunological memory and control of infections.

The concept of theoretical immunology is described and applied to different service and technology scenarios within the business world. Discussion focuses on immune response to not only identify problems and eliminate them but successfully inoculate the system against further incursions.

The host-parasite relationship of intravascular helminths in mammalian hosts is complex, consisting of several interrelated aspects. These organisms are often very long lived in these hosts that possess highly evolved immunie systems, which implies the existence of mechanisms in these complex parasites for evading the immune response. On the other hand, mammalian hosts appear to be very successful in limiting their worm burdens, mainly by preventing reinfection. Thus, a balance between host and parasite is often achieved. This balance extends to the immunopathological consequences of the infections as well. Especially in the schistosomes, where relatively more is known about immunopathology, it is becoming increasingly apparent that immunopathological reactions to the eggs are multifunctional and paradoxical: they cause disease, they limit disease, and they even serve the schistosome by making possible the escape of its eggs, laid deep within the tissues, from the host's body to propagate the life cycle. The comparative approach, using different species of schistosome and filarids in different mammalian hosts, has proved to be valuable for understanding the immunological basis of these complex relationships. The knowledge gained from these model systems is already being vigorously applied to the human diseases, two of the great scourges of the tropics, schistosomiasis and lymphatic filariasis, to the end of their eradication from the earth by mass immunization.

Macrophage inflammatory factor may be one of the adhesion triggers influencing the activity of integrins in promoting the adhesion of leukocytes to the endothelium of postcapillary venules. A consensus model has emerged in which members of the selectin and integrin families are part of a two-step process required for leukocyte extravasation. Selectins promote the transient adhesion of leukocytes to the epithelium by slowing their passage through postcapillary venules. This transient adhesion is then intensified by the action of integrins.