Hereditary immune deficiency diseases Flashcards Preview

Blood > Hereditary immune deficiency diseases > Flashcards

Flashcards in Hereditary immune deficiency diseases Deck (16):

Immune deficiency disorders

-Characterized by recurring infection, with an increased susceptibility to cancer or autoimmunity (onset at any age)
-Primary immune deficiency (ID): genetic mutations that induced immunocompromise (IC)
-Secondary ID: acquired (extrinsic), or factor induced IC due to infections, malnutrition, dugs/radiation
-Natural ID: normal developmental processes of IC (newborns and geriatrics)


Granulocyte (PMN) deficiencies

-Skin, lymph node, deep tissue infections with staph, GN bacterial, aspergillus/candida
-May show hepatosplenomegaly/lymphadenopathy
-Due to neutropenia
-Underlying genetic deficiency could be chronic granulomatous disease
-Deficiency in innate immunity


Chronic granulomatous disease (CGD)

-Usually (60%) X linked recessive, onset generally in 1st year of life
-Recurrent infections of staph, GN, fungi
-Have normal neutrophil morphology, phagocytosis, chemotaxis
-Phagocytes deficient in NADPH oxidase gene (Phox), leads to inability to destroy phagocytosed pathogens
-Dx: assessment of Phox activity via NBT test



-Can be primary congenital or secondary to various ID diseases (such as SCID), deficiency in innate immunity
-Have recurrent bacterial sepsis due to S pneumo and H influenzae
-Both of these bacteria require Ab opsonization
-Normally within hours of infection B cells in spleen will produce IgM Abs against these organisms
-Without these Abs the organisms are able to rapidly proliferate


Deficiencies in adaptive immune system

-Defects in lymphocyte maturation
-Defects in lymphocyte signaling and effector functions


DiGeorge phenotype

-Recurrent opportunistic infections of viruses, fungi, and mycobacteria
-Often have infections in GI, thrush, dermatitis (epithelial barriers), also have hepatosplenomegaly and lymphadenopathy
-Mechanisms of ID: multiple mutations in T cell maturation and signaling pathways, deficient T cell mediated immune response, deficient help for B cells to mature


DiGeorge syndrome

-Autosomal dominant trait that has varying degrees of deficiency (some are asymptomatic, some have no T cells at all)
-Characterized by lack of functioning thymus, and therefore severe T cell deficiency
-Other malformations may exist: craniofacial, cardiovascular, parathyroid (hypocalcemia)
-Deletion on chrom 22


SCID: severe combined immune deficiency

-Characterized by recurrent infections that reflect combined dysfunction of T and B cells
-Defects primarily affecting T cells: complete DiGeorge syndrome (absent thymus), gc-deficiency (IL2/7 dysfunction preventing development of T cells from stem cells, X linked SCID)
-Signaling defects: ineffective TCR function
-Every newborn in CA is screened for SCID
-Common feature of most SCID: largely decreased T cell count, normal B cell/NK cell number (but decreased B cell function due to lack of CD4s)


Phenotypes of B cell deficiencies

-U and L RT infections (IgA/IgG, respectively), GI infections (IgA)
-Can be from multiple mutations in B cell maturation and signaling, or deficient Ag-specific Ab required for efficient opsonization of encapsulated organisms (may be systemic or local)


Selective IgA deficiency

-Most common primary immune deficiency, variable genetic patterns
-Most likely a signaling defect resulting in failure of isotype switch to IgA
-Undetectable IgA in serum
-Broad clinical spectrum (possible compensation): asymptomatic, atopic disease, recurrent infections, autoimmune disorders (AID)


X linked agammaglobulinemia

-X linked genetic defect in B cell maturation, due to mutation in bruton tyrosine kinase (BTK)
-This blocks the B cell maturation beyond pre-B cells
-Absent mature B cells, absent IgM/IgG/IgA
-Normal T cell number and function


Common variable immune deficiency (CVID)

-Variable clinical features: Ig's affected, age of onset, degree of T cell abnormalities, genetic mutations
-Have recurrent bacterial infections, hypogammaglobulinemia, impaired Ag-specific Ab responses, but have normal number of B cells


Rx of immune deficiency disorders

-Correct secondary pathology (infection, malnutrition)
-Enhance support of existing immune responses: INFg (CGD), hematopoietic GFs (neutropenia), ILs
-Replacement of missing/dysfunctional factors: BM/SC transplant, IVIG
-Correction of primary genetic defect via gene therapy: X linked SCID, CGD, ect


T cell receptor excision circles (TREC)

-Small circles of T cell DNA, by products of TCR genetic rearrangement during generation of Ag-specific TCR in thymus
-They are stable, detectable, and quantifiable
-Are a surrogate for # of T cells in body


T cell subset analysis

-Specific CDs (cluster of differentiation) are what define each subset of T cells
-These can be measured by flow cytometry and Ag-specific monoclonal Abs
-TREC + flow cytometry allow us to distinguish what type of SCID a child has
-SCID is fatal but can be cured w/ timely HSC/BM transplant (only done once SCID is detected via screening)


T cell dysregulation in CVID

-Able to switch from IgM->IgE but not IgM->IgG or IgA means T cell dysregulation
-Chronic respiratory infections means B cell/Ab deficiency
-AID means T cell dysregulation
-Rx of B cell/Ab deficiency is IVIG (IgG only)
-Some features of CVID: T cell dysregulation, Ab deficiency (but w/ normal # of B cells)