Pathoma 2023 PDF_p24-25.pdf

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Www.Medicalstudyzone.com y * T ' a s * 16 * FUNDAMENTALS * / OF PATHOLOGY 1. Macrophages process and present antigen via MHC class II to CD4 + helper T cells. 2. Interaction leads macrophages to secrete IL-12, inducing CD4 + helper T cells to differentiate into T H1 subtype. 3. TH1cells secrete IFN-γ, which converts macrophages to epithelioid histiocytes and giant cells. PRIMARY IMMUNODEFICIENCY I. DIGEORGE SYNDROME A. Developmental failure of the third and fourth pharyngeal pouches 1. Due to 22q11 microdeletion B. Presents with T-cell deficiency (lack of thymus); hypocalcemia (lack of parathyroids); and abnormalities of heart, great vessels, and face II. SEVERE COMBINED IMMUNODEFICIENCY (SCID) A. Defective cell-mediated and humoral immunity B. Etiologies include 1. Cytokine receptor defects - Cytokine signaling is necessary for proliferation and maturation of B and T cells. 2. Adenosine deaminase (ADA) deficiency - ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products; buildup of adenosine and deoxyadenosine is toxic to lymphocytes. 3. MHC class II deficiency - MHC class II is necessary for CD4 + helper T cell activation and cytokine production. C. Characterized by susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines D. Treatment is sterile isolation ('bubble baby') and stem cell transplantation. Ill. X-LINKED AGAMMAGLOBULINEMIA A. Complete lack of immunoglobulin due to disordered B-cell maturation 1. Pre- and pro-B cells cannot mature. B. Due to mutated Bruton tyrosine kinase; X-linked C. Presents after 6 months of life with recurrent bacterial, enterovirus (e.g., polio and coxsackievirus), and Giardia lamblia infections; maternal antibodies present during the first 6 months of life are protective. D. Live vaccines (e.g., polio) must be avoided. IV. COMMON VARIABLE IMMUNODEFICIENCY (CVID) A. Low immunoglobulin due to B-cell or helper T-cell defects Fig. 2.2 Granuloma. A, Noncaseating. B, Caseating. Fig. 2.3 Angioedema. (Courtesy of James Heilman, MD, Wikipedia)  Www.Medicalstudyzone.com Inflammation, Inflammatory Disorders, and Wound Healing 17 B. Increased risk for bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood C. Increased risk for autoimmune disease and lymphoma V. IgA DEFICIENCY A. Low serum and mucosal IgA; most common immunoglobulin deficiency B. Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic. VI. HYPER-IgM SYNDROME A. Characterized by elevated IgM B. Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells) 1. Second signal cannot be delivered to helper T cells during B-cell activation. 2. Consequently, cytokines necessary for immunoglobulin class switching are not produced. C. Low IgA, IgG, and IgE result in recurrent pyogenic infections (due to poor opsonization), especially at mucosal sites. VII. WISKOTT-ALDRICH SYNDROME A. Characterized by thrombocytopenia, eczema, and recurrent infections (defective humoral and cellular immunity); bleeding is a major cause of death B. Due to mutation in the WASP gene; X-linked VIII. COMPLEMENT DEFICIENCIES A. C5-C9 deficiencies-increased risk for Neisseria infection (N gonorrhoeae and N meningitidis) B. Cl inhibitor deficiency-results in hereditary angioedema, which is characterized by edema of the skin (especially periorbital, Fig. 2.3) and mucosal surfaces AUTOIMMUNE DISORDERS I. BASIC PRINCIPLES A. Characterized by immune-mediated damage of self tissues 1. US prevalence is 1%-2%. B. Involves loss of self-tolerance 1. Self-reactive lymphocytes are regularly generated but develop central (thymus and bone marrow) or peripheral tolerance. 2. Central tolerance in thymus leads to T-cell (thymocyte) apoptosis or generation of regulatory T cells. i. AIRE mutations result in autoimmune polyendocrine syndrome. 3. Central tolerance in bone marrow leads to receptor editing or B-cell apoptosis. 4. Peripheral tolerance leads to anergy or apoptosis of T and B cells. i. Fas apoptosis pathway mutations result in autoimmune lymphoproliferative syndrome (ALPS). 5. Regulatory T cells suppress autoimmunity by blocking T-cell activation and producing anti-inflammatory cytokines (IL-10 and TGF-β ). i. CD25 polymorphisms are associated with autoimmunity (MS and type 1DM). ii. FOXP3 mutations lead to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked). C. More common in women; classically affects women of childbearing age 1. Estrogen may reduce apoptosis of self-reactive B cells. D. Etiology is likely an environmental trigger in genetically-susceptible individuals. 1. Increased incidence in twins