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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
-GI symptoms
-Oral candidiasis
-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:
--craniofacial dysmorphisms
--cardiovascular: conotruncal malformations
--parathyroid: hypocalcemia
--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
-GI symptoms
-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


What are therapies for immune deficiency disorders?

1. correct secondary pathology
-treat infection, malnutrition
2. enhance/support existing immune responses
-interferon gamma
3. replacement of missing/dysfunctional factors
-HSC or bone marrow transplant
4. correction of primary genetic defect-gene therapy