Immune maturation

B cells Type of lymphocyte responsible for antibody-mediated immunity mature in the bone marrow and circulate in the circulatory and lymph systems where they transform into antibody-producing plasma cells when exposed to antigens. 

Figure 9.1-3 Key in utero immune maturation events and toxicant disruption. Seven in utero critical immune maturation events in the rodent are shown with developmental immunotoxicants known to disrupt those processes. In some cases, the processes are blocked by the xenobiotics while in others the integrity of the process may be compromised by early-life exposure. Arrows are not designed to indicate precise in utero timing but rather general periods of prenatal development. CsA = cyclosporin A CY = cyclophosphamide DEX = dexamethasone EPS = lipopolysaccharide. Adapted from Dietert and Piepenbrink (2006a).

In addition to their endocrine disrupting properties, it must be appreciated that many of the chemicals in question possess more general toxic properties, which may be potentiated by metabolism by the organism. Several PAHs, PCBs and PCDDs are carcinogenic, while certain phthalate esters can enhance the excretion of zinc, potentially leading to zinc deficiency. Zinc, an essential element, plays a vital role in spermatogenesis and mature T-cell production. Deficiency may result in abnormalities of the male reproductive system, depletion of spermatogenesis and suppression of the immune system. 

Hematopoietic (blood) cells transport oxygen and carbon dioxide, contribute to host immunity, and facilitate blood clotting [1], A complex, interrelated, and multistep process, called hematopoiesis, controls the production as well as the development of specific marrow cells from immature precursor cells to functional mature blood cells. This well-regulated process also allows for replacement of cells lost through daily physiologic activities. The proliferation of precursor cells, the maturation of these into mature cells, and the survival of hematopoietic cells require the presence of specific growth factors. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

NF-kB is also crucial for the proper functioning of the adaptive immune system not only by acting on the immune cells themselves but also by participating in the development and organization of the secondary lymphoid organs (lymph nodes, spleen, and Peyer s patches), in which both B and T lymphocytes undergo maturation and activation. NF-kB proteins have an important role in lymphocyte development and... 

The key end result of TLR signalling is the induction of cytokines. Cytokines are proteins produced during an immune response that allow the maturation, activation and differentiation of effector cells in the immune system. The activation of NFkB and AP-1 by the MyD88 and the TREF dependent pathways leads to the production of proinflammatory cytokines such as IL-6, TNF-a and various chemokines. This pathway can also activate IRF-7 via TLR-7and TLR-9 allowing Type-I interferons to be produced. 

B cells play a large role in the humoral immune response. In humans, B cells are produced and mature in the bone marrow. However, the abbreviation B does not stand for bone marrow. It stands for the bursa of Fabricius, an organ unique to birds, where B cells originally were discovered to mature. 

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