Medical brain notes 15

  HYPERSENSITIVITY REACTIONS   (This material is included here for reinforcement. It is also covered in the Immunol-ogy Lecture Notes.) Type I (immediate) hypersensitivity  reactions (anaphylactic type) are character-ized by IgE-dependent release of chemical mediators from mast cells and basophils. Cross-linking of IgE bound to antigen to IgE Fc receptors on the surface of mast cells and basophils causes degranulation. This binding triggers release of chemi-cal mediators that include histamine and heparin; eosinophil chemotactic factor; leukotriene B4 and neutrophil chemotactic factor; and prostaglandin D4, platelet-activating factor (PAF), and leukotrienes C4 and D4. Influx of eosinophils amplifies and perpetuates the reaction. Effects may be systemic (anaphylaxis, as for example due to bee stings or drugs) or localized (food allergies, atopy, and asthma). Type II hypersensitivity reactions (antibody-mediated)  are mediated by IgG or IgMantibodies directed against a...

  AUTOIMMUNE DISEASES Systemic lupus erythematosus  (SLE) is a chronic systemic autoimmune diseasecharacterized by loss of self-tolerance and production of autoantibodies. Females are affected much more often than males (M:F = 1:9); peak incidence is age 20–45; and African Americans are affected more often than Caucasians. The mechanism of injury in lupus is a mix of type II and III hypersensitivity reactions. ·                Important  autoantibodies  that may be detected in the sera from lupus patients include antinuclear antibody (ANA) (>95%); anti-dsDNA (40–60%); anti-Sm (20–30%); antihistone antibodies; nonhistone nuclear RNA  proteins; and blood cells. ·                SLE affects  many organ systems o       Hematologic (type II hypersensitivity reaction) manifestations can include hem...

  PRIMARY IMMUNE DEFICIENCY SYNDROMES X-linked agammaglobulinemia of Bruton  is an immunodeficiency characterized bya developmental failure to produce mature B cells and plasma cells, resulting in agammablobulinemia. The condition occurs because of loss of function mutations of B-cell Bruton tyrosine kinase (BTK). Clinically, the disease affects male infants who have recurrent infections beginning at 6 months of life due to the loss of passive maternal immunity. Common infections include pharyngitis, otitis media, bronchi-tis, and pneumonia; common infecting organisms include  H. influenza, S. pneumo-coccus , and  S. aureus . Common variable immunodeficiency  is a group of disorders characterized by defectsin B-cell maturation that can lead to defective IgA or IgG production. Clinically, both sexes are affected with onset in childhood of recurrent bacterial infections and with increased susceptibility to  Giardia lamblia . Complications include increased fr...

  SECONDARY IMMUNE DEFICIENCY SYNDROMES Systemic diseases  that can cause secondary immunodeficiency include diabetesmellitus, collagen vascular disease (e.g., systemic lupus erythematosus), and chronic alcoholism. Secondary immunodeficiency is more common.

  ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) AIDS can be diagnosed when a person is HIV- positive and has CD4 count <200 cells/mL,  or  when a person is HIV-positive and has an AIDS-defining disease. Males are affected more frequently than females. The  human immunodeficiency virus  (HIV) is an enveloped RNA retrovirus that contains reverse transcriptase. HIV infects CD4-positive cells, including CD4+ T lymphocytes, all macrophages, lymph node follicular dendritic cells, and Langer-hans cells. The mechanism of infection is by binding of CD4 by the viral gp120, followed by entry into cell by fusion, which requires gp41 and coreceptors CCR5 (β-chemokine receptor 5) and CXCR4 (α-chemokine receptor). Transmission of HIV  can occur by many mechanisms, including sexual contact(most common mode, including both homosexual transmission and an increasing rate of heterosexual transmission, with important cofactors including herpes and syphilis infection); parenteral...

  IMMUNOLOGY OF TRANSPLANT REJECTION Rejection is caused largely by differences in HLA alleles between donor and recipi-ent. Immunosuppressive agents are used to prevent and mitigate rejection. ·                Hyperacute rejection  occurs within minutes to hours due to preformed anti-bodies in the recipient. Lymphocyte cross-matching has almost eliminated this problem.   ·                Acute rejection  occurs in the first 6 months and may be cellular (CD8+ Tlymphocytes kill graft cells) or antibody-mediated.   ·                Chronic rejection  occurs after months or years and may be cell-mediated orantibody-mediated. The vasculature components are targeted, and the histo-pathologic changes depend on the organ involved.