Chapter 19: Immunodeficiency Diseases Flashcards
Immunodeficiencies
○ Disorders in which part of the immune system is missing or dysfunctional
○ Decreased ability to defend against infections and more susceptible to developing cancer
Primary immunodeficiencies (PIDs)
○ Inherited
○ X-linked, autosomal recessive, autosomal dominant
Secondary immunodeficiencies
Acquired as a result of other conditions, such as infection (e.g., HIV), autoimmune disease, malignancy, immunosuppressive therapy
Humoral immunity affected by PID
Caused by defects in B cells or Th cells
Cell-mediated immunity affected by PIDs
○ Involves T-cell deficiencies
○ Patients susceptible to intracellular pathogens and cancers
Innate immunity affected by PIDs
○ Neutrophils or macrophages
○ Complement
Nine Categories of PIDs
○ Combined immunodeficiencies
○ Combined immunodeficiencies with associated or syndromic features
○ Predominantly antibody deficiencies
○ Diseases of immune dysregulation
○ Congenital defects of phagocyte number, function, or Both
○ Defects in innate immunity
○ Autoinflammatory disorders
○ Complement deficiencies
○ Phenocopies of primary immunodeficiencies
Predominantly Antibody Deficiencies (category 3)
○ Low levels of serum Igs: agammaglobulinemia
○ Involve genetic defects in B-cell maturation or defective interactions between B and T cells
○ May involve all Ig isotypes or one (sub)class
X-linked Bruton’s tyrosine kinase (Btk) deficiency
○ Arrested maturation at pre-B-cell stage
○ Lack of mature CD19+ B cells in blood and plasma cells in lymphoid tissues
○ Treated with gamma globulins
Transient hypogammaglobulinemia of infancy
○ Delayed development in Ig production (especially IgG)
○ Normal numbers of B cells but delayed Th maturation
Selective IgA deficiency
Low IgA levels, perhaps because of impaired differentiation to IgA plasma cells
IgG subclass deficiencies
Caused by mutations in IgG heavy chain genes
CD154 deficiency
Decreased levels of IgG, IgA, and IgE as a result of defect in B cell switching
Combined Immunodeficiencies(Category 1)
○ Involve a T-cell deficiency
○ Complex; affect cell-mediated immunity and humoral immunity
○ Possible treatment: bone marrow transplant to reconstitute immune function
Severe Combined Immunodeficiency Disease (SCID)
○ Group of very serious PIDs
○ All involve a defect in normal T-cell development
○ X-linked recessive form caused by IL2RG gene mutation
Wiskott-Aldrich Syndrome
○ Rare, X-linked recessive PID
○ Defective T-cell function
○ Characterized by: Immunodeficiency, Thrombocytopenia, Eczema
○ Decreased IgM, normal IgA and IgG, increased IgE
DiGeorge Anomaly
○ Developmental abnormality in third and fourth pharyngeal pouches in embryo
○ Most patients have deletion in chromosome 22
DiGeorge Anomaly results in?
○ Underdevelopment of thymus and decreased T cells
○ Cardiac abnormalities
○ Abnormal facial features
○ Mental retardation
Ataxia-Telangiectasia (AT)
○ Rare autosomal-recessive syndrome
○ Ataxia: involuntary muscle movements
○ Telangiectasias: capillary swelling and red blotches on skin
○ Low number of T cells and defective antibody responses
○ Involves mutation in AT gene on chromosome 11
Defect in Phagocytic Cell Function (category 5)
○ Group of disorders inherited as X-linked recessive or autosomal recessive
○ Neutrophils unable to generate oxidative burst
Complement Deficiencies (category 8)
○ Most are inherited as autosomal recessive
○ Deficiencies in early C’ components- C2 deficiency most common
○ Deficiencies in late C’ components
○ Deficiency in C1 esterase inhibitor
Screening for Suspected Immunodeficiency
○ Patient history
○ CBC and WBC differential
○ Serum levels of IgG, IgM, IgA, and IgG subclasses
○ Antibody response after vaccination
Confirmatory Tests for Immunodeficiency
○ Immunophenotyping and flow cytometry: determines numbers of B cells, helper T cells, cytotoxic T cells, NK cells
○ Genetic testing
○ Mitogen assays for T- or B-cell proliferation
○ Other assays for T-cell activation: QuantiFERON TB and T-Spot
○ Cylex ImmuKnow assay
Evaluation of Immunoglobulins
○ Quantitative measurement by nephelometry or radial immunodiffusion (RID)
○ Serum protein electrophoresis (SPE)
○ Immunofixation electrophoresis (IFE)
