From conception to old age, the major histocompatibility complex (MHC) is at the centre of immune responses that aid survival, fitness and adaptation of mammalian species to the environment. Its main function is that of controlling adaptive immunity, particularly T-cell-mediated immunity towards pathogens. In several species, including humans, the MHC is also able to elicit T-cell-mediated immune responses to allogeneic MHC antigens (non-self MHC antigens expressed by another individual from the same species). Although this phenomenon was originally identified in mice by the somewhat unnatural means of tissue transplantation, it was soon realized that it may also play an important role in the natural state, since the mammalian fetus in the maternal uterus is semi-allogeneic, due to the presence of MHC genes inherited from the father. Thus, during normal pregnancy the maternal immune system undergoes changes that lead to tolerance of the fetus. The MHC can play a dual role in the reproduction process: firstly influencing mating choice in some species, affecting the mother-father MHC matching; and secondly influencing the development of the fertilized ovum during the preimplantation period. In this review we examine the role of the MHC at three distinct levels: (i) MHC expression in gametes and its role in fertilization; (ii) MHC expression in placental tissue; and (iii) MHC expression in embryonic tissue. We suggest that the MHC plays a pleiotropic role, both in fitness (survival and reproductive success) and in development, thereby ensuring the survival of the species in future generations.
The lysophospholipid (LPL) growth factors sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are generated by macrophages, dendritic cells, mast cells, and platelets, which leads to lymph and plasma concentrations of 0.1-1 microM. Distinctive profiles of G protein-coupled receptors (GPCRs) for S1P and LPA are expressed by each type of immune cell and are regulated by cellular activation. At 1-100 nM, S1P signals T cells through their principal S1P(1) GPCRs with consequent protection from apoptosis, enhancement of chemotaxis, and facilitation of optimal regulatory activity of CD4(+)25(+) T cells. At 0.3-3 microM, S1P inhibits T cell chemotaxis and to a lesser extent other functions. These S1P-S1P(1) GPCR signals suppress homing of blood and spleen T cells to secondary lymphoid tissues. S1P(1) GPCR antagonists evoke lymphopenia by permitting blood T cells to enter lymph nodes and blocking S1P(1) GPCR-dependent T cell efflux from lymph nodes. Inversely, there is a decrease in lymphoid tissue traffic of T cells in transgenic mice, which overexpress lymphocyte S1P(1) GPCRs. The immunotherapeutic activity of S1P(1) GPCR antagonists, which limits T cell access to organ grafts and autoimmune antigens, does not reduce other functional capabilities of T cells. LPLs and their GPCRs thus constitute an immunoregulatory system of sufficient prominence for pharmacological targeting in transplantation, autoimmunity, and immunodeficiency.
Transforming growth factor-β (TGF-β) has been shown to play an essential role in the suppression of inflammation, yet recent studies have revealed the positive roles of TGF-β in inflammatory responses. For example, TGF-β induces Foxp3-positive regulatory T cells (iTregs) in the presence of interleukin-2 (IL-2), while in the presence of IL-6, it induces pathogenic IL-17 producing Th17 cells. TGF-β inhibits the proliferation of immune cells as well as cytokine production via Foxp3-dependent and -independent mechanisms. Little is known about molecular mechanisms involved in immune suppression via TGF-β; however, Smad2/3 have been shown to play essential roles in Foxp3 induction as well as in IL-2 and IFN-γ suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Interaction between TGF-β and other cytokine signaling is important in establishing the balance of immunity and tolerance.
OBJECTIVE: To determine the most frequent food allergens causing immediate hypersensitivity reactions in Swiss children of different age groups and to investigate the clinical manifestation of IgE-mediated food allergies in young patients.
PATIENTS AND METHODS: The study was a prospective analysis of children referred for assessment of immediate type I food hypersensitivity reactions. The diagnostic strategy included a careful history, skin prick tests with commercial extracts and native foods, in vitro determination of specific IgE to food proteins and food challenges when appropriate. A total of 278 food allergies were identified in 151 children with a median age of 1.9 years at diagnosis.
RESULTS: Overall, the most frequent food allergens were hen’s egg (23.7%), cow’s milk (20.1%), peanut (14.0%), hazelnut (10.4%), wheat (6.1%), fish (4.3%), kiwi and soy (2.2% each). In infancy, cow’s milk, hen’s egg and wheat were the most common allergens. In the second and third year of life however, the top three food allergens were hen’s egg, cow’s milk and peanut, whereas above the age of 3 years, peanut was number one, followed by hen’s egg and fish. Overall, urticaria (59.0%) and angioedema (30.2%) were the most frequent clinical manifestations. Gastrointestinal symptoms were found in 25.9% and respiratory involvement in 25.2%. There were 13 cases (4.7%) of anaphylaxis to peanut, fish, cow’s milk, hen’s egg, wheat and shrimps.
CONCLUSIONS: A total of eight allergens account for 83% of IgE-mediated food allergies in Swiss infants and children, with differences in the distribution and order of the most frequently involved food allergens between paediatric age groups.
Obesity alt ers adipose tissue metabolic and endocrine function and leads to an increasedrelease of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68