Immunology

·         Most allergens are proteins that have molecular weights of 10-70 kd. Molecules smaller than 10 kd would not bridge adjacent IgE antibody molecules on the surface of mast cells or basophils. Most molecules larger than 70 kd would not pass through mucosal surfaces needed to reach antigen-presenting cells for stimulation of the immune system.

·         Puncture skin test > Intradermal skin test > RAST

·         The CH50 assay is a screening test for complement defects and is not recommended for the initial evaluation of immunodeficiency unless there is history of infection with encapsulated organisms. This test assesses the ability of an individual's serum (in varying dilutions) to lyse sheep red blood cells after those cells are sensitized with rabbit IgM anti-sheep antibody. The CH50 is an arbitrary unit that indicates the quantity of complement necessary for 50% lysis of the red blood cells in a standardized setting. Test results are usually expressed as a derived reciprocal of the test dilution needed for 50% lysis. The test is relatively insensitive because major reductions in individual complement components are necessary before the CH50 is altered. Therefore, determination C3 and C4 levels are often included in the initial screening of a child with a suspected complement deficiency.

·         The Candida skin test is a cost-effective test of T-cell function. The absolute lymphocyte count and flow cytometry measure T-cell numbers and subsets but not function.

·         Abscess formation is not characteristic of Tcell immune deficiency, even though Serratia marcescens is an unusual cause of infections in children. S. marcescens abscess suggests chronic granulomatous disease (CGD).

The management of chronic granulomatous disease includes lifelong treatment with interferon- and also trimethoprimsulfamethoxazole, as well as additional antimicrobial therapy as needed for acute infections.

Because of chronic or recurrent infections, most patients with CGD demonstrate hypergammaglobulinemia.

The nitroblue tetrazolium (NBT) is the classic test for chronic granulomatous disease. The NBT test measures the neutrophils' ability to generate superoxide anion and thereby kill ingested bacteria. It is being rapidly replaced by a more accurate flow cytometry fluorescence assay using dihydrorhodamine 123 (DHR).

·         X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is suggested by low concentrations of all Ig classes. Affected patients are also unable to respond to immunizations, unlike infants with transient agammaglobulinemia of infancy. Virus to which Patients with XLA most susceptible to Enteroviral infections (polio, ECHO, and coxsackie).( REM: ITS MC VIRUS< NOT MC ORG-S.aureus)

·         The genetic defect for X-linked lymphoproliferative (XLP) syndrome also predisposes to severe primary EBV infection, which is associated with 50% mortality in affected patients.

·         In persons with DiGeorge syndrome, the absolute lymphocyte count is usually only moderately low for age. Lymphocyte responses to mitogen stimulation are absent, reduced, or normal, depending on the degree of thymic deficiency.

·         Individuals with inherited deficiency in macrophage receptors for IFN or lymphocyte receptors for IL-12, or in IL-12 itself, suffer a severe, profound, and selective susceptibility to infection by nontuberculous mycobacteria such as Mycobacterium avium or bacilli Calmette-Guérin (BCG). About half of these patients have had disseminated Salmonella infection. These abnormalities are now grouped under the term leukocyte mycobactericidal defects.

·         Eosinophilia is associated with tissueinvasive helminthic parasites but not parasitic infections that are solely intraluminal, such as giardiasis (Giardia lamblia) or pinworm infestation (Enterobius vermicularis).

·         Schwachman-Diamond syndrome is an autosomal recessive disorder characterized by digestive abnormalities and leukopenia.

·         Persons with leukocyte adhesion deficiency have impaired transendothelial migration. The circulating neutrophil count with infection is typically above 30,000/mm3 and can surpass 100,000 per mm3, with a paucity of neutrophils in the infected tissues.

·         CYCLIC NEUTROPENIA: 21± 3 days, Severe infections including pneumonia and life-threatening sepsis, notably with Clostridium perfringens, may occur.

·         Chronic graft versus host disease resembles a multisystem autoimmune process with  maculopapular rash, hyperbilirubinemia, and diarrhea, usually after 100 days after transplantation.

·         In response to protein antigens, IgG1 and IgG3 subclasses predominate, whereas IgG2 and IgG4 are typically noted with polysaccharide antigens.

·         Autoimmune lymphoproliferative syndrome (also known as Canale-Smith syndrome) is the first immune disorder to involve a congenital defect in programmed cell death (apoptosis). Patients display a nonmalignant, noninfectious lymphoproliferation with splenomegaly, chronic lymphadenopathy, and, often, hepatomegaly. Lymphocytes persist that normally would die. Diagnosis rests on increases in alpha/beta T-cell antigen receptor positive, CD4-CD8-(i.e., double negative) T cells, and defective in vitro Fas-mediated lymphocyte apoptosis.

·         "Bubble boy": Adenosine deaminase (ADA) deficiency.