Primary Immunodeficiency

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What is the #1 reason for secondary immunodeficiency? Malnutrition (protein/ calorie malnutrition)
Most primary immunodeficiencies are due to what? Single gene autosomal recessive mutations
List some common Clinical Presentations of Immunodeficiency (non-specific) Recurrent sino-pulmonary infection; absence of lymph tissue; failure to thrive; oral or perineal candidiasis (fungal/thrush); chronic diarrhea and malabsorption; skin lesions (eczema,pyoderma, telangiectasia)
List some common Clinical Presentations of Immunodeficiency (non-specific) Recurrent sino-pulmonary infection; absence of lymph tissue; failure to thrive; oral or perineal candidiasis (fungal/thrush); chronic diarrhea and malabsorption; skin lesions (eczema,pyoderma, telangiectasia)
Which immunodeficienty category tend to involve common "bugs" such as pnewmococcus, staphylococcus, H. influenza, pseuomonas? Humoral Immunodeficiency
Which immunodeficiency category often involves opportunistic infections such as TB, Intestinal parasitosis, oralpharyngeal candidiasis? Cellular Immunodeficiency
Name the major primary immunodeficiency syndromes (1) Selective IgA deficiency (2) Common Variable (3) SCID (4) X-Linked (5) CGD (chronic granuloma disease)
What % of SCID disorders are X-linked? What percent are ADA deficiency? 48% are X-linked, the rest are autosomal recessive, including ADA deficiency which makes up 14%.
Which cells are deficient in X-linked SCID? No T cells (T- , B+)
Which cells are deficient in ADA deficiency, RAG deficiency and Omenn SCID? No T cells or B cells (T-, B-)
What is molecularly defective in X-linked SCID (T-, B+) Defect in gamma c (common gamma chain) which is the transmembrane portion of receptor for multiple cytokines. Receptor interacts with JAK3 and critical for T cell and NK development.
What is the most common Primary Immunodeficiency? IgA Deficiency. Serum IgA<10 mg/cc. Many cases also associated with IgG subclass deficiency. Many pt's asymptomatic. Associated with recurrent sinopulmonary infections, autoimmune, GI and endocrine disorders.
Transient hypogammaglobulinemia Occurs in infancy. Resolves spontaneously by age 4. Typically does not require replacement therapy.
Common Variable Immunodeficiency Heterogenous group of disorders. Pyogenic (pus) infections. Reduced B cells 50%. Increased risk of malignancy.
X-linked agammaglobulinemia Pre-B cell maturational defect. FATAL if not detected and TREATED in early childhood. Pyogenic infections prominent and absent circulating mature B cells.
X-linked Hyper IgM Syndrome Defect in gene encoding CD40. (recall CD40 simulates AID for SHM and isotype switching). IgG, A, E low: IgM High
IgG Subclass Deficiency Any of the 4 subclasses can be affected but current deficiencies found in IgG 1,2,3. Recurrent pyogenic infections. Many affected are asymptomatic. Associated with IgA deficiency. Significance uncertain.
Complement Deficiency Inability to generate C3 Convertase; deficiency in C3 component; deficiency in lytic phase (C5-9); deficiency in regulatory proteins
Defect in C5-C9 (lytic phase) is associated with susceptibilty to what? Infection by Neisseria
Which is the most common complement defect? Defect in C2
Early component deficiency in the complement pathway may be associated with what symptoms? Pyogenic infection and connective tissue disease
What causes paroxysmal nocturnal hemoglobinuria? Deficiency of DAF which normally breaks down C3 convertase on RBCs. Results in red cell lysis.
What causes herditary angioedema? C1 esterase inhibitor is absent or nonfunctional. The greatest clinical concern is edema closing off airway.
In this disease, the phagocytes can engulf the pathogens, but can not kill them do to deficiency in ROS (superoxide) formation Chronic granulomatous disease
Lazy leukocyte syndrome PMNs do not respond to chemotactic signals
Treatment of Immunodeficiency (1) Antibiotic suppression (2) Intramuscular gammaglobulin (Ig) (3) I.V. gammaglobulin (4) Bone marrow transplantation (5) Specific compponent replacement
What is the half-life of IgG? 3 weeks