Flashcards in Hereditary Immune Deficiency Diseases Deck (13):
What is the clinical phenotype of granulocyte deficiencies?
-skin, lymph node, or deep tissue infections, esp with S. aureus, Serratia (gram - organisms), and Aspergillus
-mechanism: ubiquitous organisms, specific antibody not required for opsonization, innate responses essential-need neutrophils
What is an example of granulocyte deficiency?
Chronic granulomatous disease
-x linked recessive mainly
-recurrent infections by staph aureus, serrate, candida, aspergillus
-CBC looks normal, normal neutrophil morphology, phagocytosis and chemotaxis
-however no bactericidal activity by neutrophils due to NADPH oxidase (Phox) dysfunction
-Diagnosis: via Phox activity
-usually in kids < 1 years old
What is the clinical phenotype of hyposplenism?
-primary or secondary, secondary can be due to sickle cell
-recurrent bacterial sepsis due to S. pneumoniae, H. influenzae, type b (encapsulated organisms)
-Mechanism: encapsulated organisms need antibody and complement opsonization
-spleen has unique ability to generate very rapid natural antibodies via B cells, IgM, to blood borne microbes
What are the clinical phenotypes of T cell deficiencies?
-DiGeorge Anomaly phenotype
-Opportunistic infections: viral, fungal, mycobacterial
-severe seborrhea like dermatitis
-mechanisms: multiple mutations in t cell maturation and signaling pathways, deficient t cell mediated immune response, deficient B cell help
What is DiGeorge syndrome? What is the phenotype?
-autosomal dominant, associated with del22q11.2
-variable spectrum of organ system involvement:
--cardiovascular: conotruncal malformations
--thymic: t cell deficiency
-T cell deficiency varies from asymptomatic to thymic a genesis with absence of t cells
What is severe combined immune deficiency? (SCID)
-clinical syndrome/phenotype characterized by infections which reflect combined deficiencies/dysfunctions of T-cells and B-cells
-Maturation defects: e.g. DiGeorge with absent thymus
-Signaling defects: ineffective TCR fxn
What is the clinical phenotype of B-cell deficiencies?
-Respiratory tract infection with usual bacterial pathogens
-Granulocytopenia or JRA like arthritis as presenting signs
-Mechanism: multiple mutations in B cell maturation and signaling, deficient antigen specific antibody required for efficient opsonization of encapsulated organisms, deficiency may be systemic or local
What is X-linked Aggamaglobulinemia (XLA)?
-B cell maturation genetic defect
-mutations in Bruton Tyrosine Kinase results in maturation block beyond pre-B cells
-absent mature B cells
-Absent IgM, IgG, and IgA antibodies
-normal T cell number and function
What is selective IgA deficiency?
-Most common primary immune deficiency
-variable genetic patterns
-likely a signaling defect resulting in failure of isotope switch to IgA
-clinical spectrum: asymptomatic mostly, atopic disease, recurrent infections, autoimmune disorders
-IgG defends lower respiratory tract, so infections in upper resp tract
What is common variable immune deficiency?
-Group of immunodeficiencies with:
-recurrent bacterial infections
-impaired antigen specific antibody responses
-normal number of B cells
What is a primary immune deficiency?
-documented or presumed genetic mutations in immune response pathways
What is the SCID newborn screening program in CA?
-all newborns screened without needing consent
-TREC is quantified by PCR (TREC are by products of TCR gene rearrangement and is surrogate for number of t cells)
-abnormal screens are sent for CBC+diff and lymphocytes subset analysis by flow cytometry
-Survival improved if BMT/HSCT done before complicating infections