Hyper-IgM Syndrome In a normal immune response to protein antigen, IgM antibodies are produced first, followed by the sequential

elaboration of IgG, IgA, and IgE antibodies. As we discussed earlier in this chapter, the orderly appearance of different antibody types is called heavychain class (isotype) switching and is important for generating classes of antibody that can effectively activate complement and/or opsonize bacterial pathogens. The ability of IgM-producing B cells to turn on the transcription of genes that encode other Ig isotypes depends on certain cytokines, as well as contact-mediated signals from CD4+ helper T cells. The contact-dependent signals are provided by interaction between CD40 molecules on B cells and CD40L (also known as CD154), expressed on activated helper T cells. Patients with the hyper-IgM syndrome produce normal (or even supranormal) levels of IgM antibodies to antigens but lack the ability to produce the IgG, IgA, or IgE isotypes; the underlying defect is an inability of T cells to induce B-cell isotype switching. The most common genetic abnormality is mutation of the gene encoding CD40L. This gene is located on the X chromosome; consequently, in approximately 70% of the cases, hyper-IgM syndrome is X-linked. In the remaining patients, the mutations affect CD40 or other molecules involved in class switching, notably an enzyme called activation-induced deaminase. Although the disease is diagnosed and named because of the antibody abnormality, there is also a defect in cell-mediated immunity because the CD40-CD40L interaction is critical for helper T cell-mediated activation of macrophages, the central reaction of cell-mediated immunity. Male patients with the X-linked form of hyperIgM syndrome present with recurrent pyogenic infections due to low levels of opsonizing IgG antibodies. These patients are also susceptible to a variety of intracellular pathogens that are normally combated by cell-mediated immunity, including Pneumocystis jiroveci (formerly called P. carinii).

Pathophysiology
IgM is the form of antibody that all B cells produce initially, before they undergo class switching due to exposure to a recognized antigen. Healthy B cells efficiently switch to other types of antibodies as needed to attack invading bacteria, viruses, and other pathogens. Generally, in people with hyper IgM syndromes, the B cells keep making IgM antibodies because they can't switch to a different kind of antibody. This results in an overproduction of IgM antibodies and an underproduction of all other types, IgA, IgG, and IgE.

Class-switch recombination (CSR, also called class-switching), whereby the immunoglobulin mu heavy chain is replaced by other heavy chain isotypes with distinct biologic properties, resulting in production of immunoglobulin isotypes other than IgM. Somatic hypermutation (SHM), by which somatic mutations are introduced in the variable region of actively transcribed immunoglobulin genes, thereby allowing production of high-affinity antibodies. Generation of memory B cells.

Thymic Hypoplasia: DiGeorge Syndrome DiGeorge syndrome results from a congenital defect in thymic development with deficient T-cell maturation. T cells are absent in the lymph nodes, spleen, and peripheral blood, and infants with this defect are extremely vulnerable to viral, fungal, and protozoal infections. Patients are also susceptible to infection with intracellular bacteria, because of defective T-cell-mediated immunity. B cells and serum immunoglobulins are generally unaffected.

Tetany or tetany seizure is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disease or other conditions that increase the action potential frequency. Tetanus (from Ancient Greek: tetanos "taut", and teinein "to stretch") by a prolonged contraction of skeletal muscle fibers.
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is a medical condition characterized

Causes
The usual cause of tetany is lack of calcium. An excess of phosphate (high phosphate-to-calcium ratio) can also trigger the spasms. Milk-and-alkali tetany is an example of this imbalance. Underfunction of the parathyroid gland can lead to tetany.