Chapter 19: Immunodeficiency Diseases

Question 1

Immunodeficiencies

Answer 1

○ Disorders in which part of the immune system is missing or dysfunctional
○ Decreased ability to defend against infections and more susceptible to developing cancer

Question 2

Primary immunodeficiencies (PIDs)

Answer 2

○ Inherited
○ X-linked, autosomal recessive, autosomal dominant

Question 3

Secondary immunodeficiencies

Answer 3

Acquired as a result of other conditions, such as infection (e.g., HIV), autoimmune disease, malignancy, immunosuppressive therapy

Question 4

Humoral immunity affected by PID

Answer 4

Caused by defects in B cells or Th cells

Question 5

Cell-mediated immunity affected by PIDs

Answer 5

○ Involves T-cell deficiencies
○ Patients susceptible to intracellular pathogens and cancers

Question 6

Innate immunity affected by PIDs

Answer 6

○ Neutrophils or macrophages
○ Complement

Question 7

Nine Categories of PIDs

Answer 7

○ 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

Question 8

Predominantly Antibody Deficiencies (category 3)

Answer 8

○ 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

Question 9

X-linked Bruton’s tyrosine kinase (Btk) deficiency

Answer 9

○ 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

Question 10

Transient hypogammaglobulinemia of infancy

Answer 10

○ Delayed development in Ig production (especially IgG)
○ Normal numbers of B cells but delayed Th maturation

Question 11

Selective IgA deficiency

Answer 11

Low IgA levels, perhaps because of impaired differentiation to IgA plasma cells

Question 12

IgG subclass deficiencies

Answer 12

Caused by mutations in IgG heavy chain genes

Question 13

CD154 deficiency

Answer 13

Decreased levels of IgG, IgA, and IgE as a result of defect in B cell switching

Question 14

Combined Immunodeficiencies(Category 1)

Answer 14

○ Involve a T-cell deficiency
○ Complex; affect cell-mediated immunity and humoral immunity
○ Possible treatment: bone marrow transplant to reconstitute immune function

Question 15

Severe Combined Immunodeficiency Disease (SCID)

Answer 15

○ Group of very serious PIDs
○ All involve a defect in normal T-cell development
○ X-linked recessive form caused by IL2RG gene mutation

Question 16

Wiskott-Aldrich Syndrome

Answer 16

○ Rare, X-linked recessive PID
○ Defective T-cell function
○ Characterized by: Immunodeficiency, Thrombocytopenia, Eczema
○ Decreased IgM, normal IgA and IgG, increased IgE

Question 17

DiGeorge Anomaly

Answer 17

○ Developmental abnormality in third and fourth pharyngeal pouches in embryo
○ Most patients have deletion in chromosome 22

Question 18

DiGeorge Anomaly results in?

Answer 18

○ Underdevelopment of thymus and decreased T cells
○ Cardiac abnormalities
○ Abnormal facial features
○ Mental retardation

Question 19

Ataxia-Telangiectasia (AT)

Answer 19

○ 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

Question 20

Defect in Phagocytic Cell Function (category 5)

Answer 20

○ Group of disorders inherited as X-linked recessive or autosomal recessive
○ Neutrophils unable to generate oxidative burst

Question 21

Complement Deficiencies (category 8)

Answer 21

○ 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

Question 22

Screening for Suspected Immunodeficiency

Answer 22

○ Patient history
○ CBC and WBC differential
○ Serum levels of IgG, IgM, IgA, and IgG subclasses
○ Antibody response after vaccination

Question 23

Confirmatory Tests for Immunodeficiency

Answer 23

○ 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

Question 24

Evaluation of Immunoglobulins

Answer 24

○ Quantitative measurement by nephelometry or radial immunodiffusion (RID)
○ Serum protein electrophoresis (SPE)
○ Immunofixation electrophoresis (IFE)