Immunology lecture 22 Immunodeficiency diseases
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- What are some of the causes of immunodeficiencies
- Infectious agents, genetic defect, malnutrition, neoplasia, iatrogenic, toxins
- How can immunodeficiency etiologies be classified
- Primary (genetic) and secondary (all the others)
- What are the genetics of primary immunodeficiencies
- Many caused by recessive gene defects, and can be mapped to the X chromosome
- How is B cell function evaluated
- Measuring concentration in blood, Ig levels, and antibody response to pokeweed mitogen
- How is T cell function evaluated
- Concentration in blood, Skin test DTH, Proliferation in response to antigens
- How is phagocyte function evaluated
- Nitro blue tetrazolium uptake, blood concentration
- What are the characteristics of Severe combined immunodeficiency
- B cells and T cells are affected; rare; history of recurrent infections; increased susceptibility to a broad range of pathogens
- Give three examples of Severe combined immunodeficiency (SCID)
- Adenosine Deaminase deficiency, X-linked SCID, Bare lymphocyte syndrome
- Describe adenosine deaminase deficiency
- 50% of SCID patients, Autosomal recessive; Toxic dATP accumlates-lymphocytes are especially sensitive
- Describe X-linked SCID
- Recessive mutation in the common gamma chain, on the X chromosome; B+ T-NK-; impaired humoral immunity because of no T cell help
- Describe bare lymphocyte syndrome
- Autosomal recessive; Inability to express MHC class II; reduced numbers of CD4 T cells, so no DTH responses or T-dependent responses
- What are the characteristics of B cell immunodeficiencies
- Specific abnormality of B cell development; susceptible to encapsulated bacteria and enteric infections (lack of IgA)
- What are three examples of B cell immunodeficiencies
- X-linked Agammaglobulinemia; X-linked Hyper-IgM Syndrome; Common variable immunodeficiency
- Describe X-linked Agammaglobulinemia
- Mutation in a tyrosine kinase required for B-cell development in bone marrow; B-T+NK+; no germinal centers or plasma cells; non-random inactivation of X chromosome in B cells of female carriers
- Describe X-linked Hyper-IgM Syndrome
- Defective Ig class switching; Susceptiblility to bacteria and enteric infections; Mutation in CD40L, so defective T Cell help; random pattern of X chromosome inactivation
- Describe Common Variable Immunodeficiency
- Deficit in plasma cell differentiation, Ig deficiency
- What are the characteristics of T cell immunodeficiencies
- Deficits in cell-mediated immunity, and increased susceptibility to viruses and intracellular bacteria
- Describe Congenital Thymic Aplasia (DiGeorge Syndrome or anomaly)
- Hypoplasia or aplasia of the thymus, so T cells are reduced or absent
- Give 4 examples of defects in innate immunity
- Leukocyte adhesion deficiency type 1; Chediak-Higashi syndrome; Chronic granulomatous disease; Complement deficiencies
- Describe Leukocyte adhesion deficiency Type 1 (LAD-1)
- Mutation in LFA-1 and Mac-1, leads to reduced adherence to endothelium, poor chemotaxis, phagocytosis, cytotoxicity, and lymphocyte APC interactions; autosomal recessive
- Describe Chediak-Higashi syndrome
- Phagocyte abnormality-increased fusion of lysosomes resulting in giant cytoplasmic granules
- Describe chronic granulomatous disease
- Phagocyte abnormality affecting components of phagocyte oxidase. Nitroblue tetrazolium dye is used to test phagocyte oxidase activity; Because bacteria and fungi are not controlled, chronic activation of T cells and macrophages results
- Describe complement deficiencies
- C3 deficiency results in frequent and serious pyogenic bacterial infections
- Describe Wiskott-Aldrich Syndrome
- X linked recessive; loss of WASP, resulting in disruption of neutrophil, macrophage, lymphocyte and platelet trafficking; progressive and non-treatable
- Describe Ataxia-telangiectasia
- Autosomal recessive, involved with DNA repair. May affect both T and B cells, Thymus may be hypoplastic