Congenital Immunodeficiencies Flashcards
Defect in BTK gene
X linked agammaglobulinemia (bruton)
Defect in a tyrosine kinase leading to decreased immunoglobulins
X linked agammaglobulinemia (bruton)
What age does X linked agammaglobulinemia (bruton) present?
After 6 months when the maternal IgG in circulation wanes
What changes in T cells, B cells, and Ig’s will you observe in X linked agammaglobulinemia (bruton)?
Absent B cells in peripheral Blood (scant lymphoid tissue)
Normal T cells
Low Ig’s across the board
Low levels of mature B cells (which express CD19, CD20, and CD21) in addition to recurrent episodes of respiratory and gastrointestinal tract infections when a child is older than 6 months (when the maternal IgG has decreased) are highly suggestive of…
X linked agammaglobulinemia (bruton)
A mutation in the Bruton tyrosine kinase (BTK) gene causes X-linked agammaglobulinemia (XLA). BTK is a signal transduction molecule found on…
B cells
Although recurrent infections are a feature of many immunodeficiency disorders, the physical finding of__________________________ (due to low B-cell volume), as seen in this patient, is especially suggestive of XLA.
tonsillar hypoplasia
Although recurrent infections are a feature of many immunodeficiency disorders, tonsillar hypoplasia (due to low B-cell volume), as seen in this patient, is especially suggestive of XLA.
The diagnosis of XLA is confirmed by flow cytometry that shows ___________________________________________________________________
The diagnosis of XLA is confirmed by flow cytometry that shows reduced levels of B cells (marked by CD19, CD20, and CD21) and normal levels of T cells.
Kid has the shits and stool shows this
GIARDIA!
An oval-shaped cyst with a prominent, double-layered wall is visible in the center of the image. The cytoplasm contains four nuclei, which are identifiable as spherical structures. It also contains an axostyle, a fibrillary structure from which the flagella of the trophozoite arises.
Increased susceptibility to giardia is seen in ….
B cell disorders including IgA deficiency, Xlinked agammaglobulinemia, and CVID.
Hypersentivity reaction to blood products
selective IgA deficiency
Examples include Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella, and Group B streptococcus.
encapsulated bacteria
When does IgA deficiency normally present?
20-35
Why do we see recurrent sinopulm and GI infections in IgA selective immunodeficiency?
Recurrent sinopulmonary (mostly caused by encapsulated bacteria) and gastrointestinal infections (e.g., giardiasis) are typical in selective IgA deficiency, as secretory IgA antibodies are a crucial part of MUCOSAL DEFENSE!
B or T or Both: X linked agammaglobulinemia
B
B or T or Both: selective IgA
B
B or T or Both: CVID
B common variable immunodef
B or T or Both: Thymic aplasia as in Digeorge and Velocardiofacial syndrome
T
B or T or Both: IL-12 R def
T
B or T or Both: Hyper Ig-E (Job)
T
B or T or Both: chronic mucocutaneous candidiasis
T
Candida infections are common in those with problems of
T cells
B or T or Both: Severe Combined ID
B and T
B or T or Both: Ataxia telandgienctasia
B and T
B or T or Both: Hyper-IgM
Both B and T
B or T or Both: Wiskott-Aldrich
Both B and T
Defect in B cell differentiation leading to low IgG and IgM
CVID
Gastric adenocarcinoma is a potential complication of…
Gastric adenocarcinoma is a potential complication of common variable immunodeficiency (presumably due to alterations of p53 and Helicobacter pylori infection). As with most immunodeficiencies, CVID causes recurrent infection, including pyogenic upper respiratory infections and chronic diarrhea.
Patients with ___________________ usually have a history of recurring, often pyogenic infections (e.g., otitis media, pneumonia) starting after 6 months of age, which is when transplacental IgG-mediated passive immunity subsides.
X linked agammaglobulinemia (bruton)
Low T cells, Low Calcium, and low PTH and characteristic of…
DiGeorge Syndrome
Failure to develop 3rd and 4th pharyngeal pouches
digeorge
Tetrallogy of fallot, abnormal facies, thymic hypoplasia–> recurrent viral and fungal infections,, cleft palate, hypocalcemia secondary to hypoplastic parathyroid
digeorge
22q11.2
digeorge
Digeorge is B or T cell or both deficiency?
T cells
Deficiency of Th17 cells due to STAT3 mutation
Hyper IgE (Job)
Cold staph abscesses, retained baby teeth, exczema
Job (Hyper IgE)
Deficient Th17 cells seen in Job syndrome (hyper IgE) leads to what?
impaired recruitment of neutrophils to site of infection, elevated IgE, and elevated eos
Deficient Th1 response leading to lower INFgamma response
IL-12 Deficiency
Why are individuals with IL-12 receptor deficiency susceptible to intracellular pathogens?
Decreased IFN-γ levels are a diagnostic feature of IL-12 receptor deficiency, a congenital T-cell immunodeficiency. Normally, antigen-presenting macrophages release IL-12, which triggers T-helper cells to transform to T1 type. T1-helper cells then release IFN-γ to activate macrophages. If IL-12 receptors on naive T cells are defective, T-helper cells will not transform to T1-helper cells and will not release IFN-γ; the lack of IFN-γ results in decreased macrophage activation. If macrophages are not activated, they will not trigger cytotoxicity in cells infected with intracellular pathogens such as mycobacteria and salmonella. Patients with IL-12 receptor deficiency often present with features of disseminated disease (such as miliary tuberculosis), sepsis, and DIC.
Decreased interferon gamma is characteristic of…
IL-12 R deficiency
B or T or Both: IL-12 R def
T
Most common cause of mendelian susceptibility to mycobacterial disease
IL-12 R def
presents between 1-3 years old; typically present with mycobacterial infections and salmonellosis as well as mucocutaneous candidiasis.
IL-12 R def
Risk for disseminated TB
IL-12 R def
Impaired Th1 response
IL-12 R def
X-linked immunodeficiency caused by a defect in T-cell receptor signaling (most commonly from a defect in CD40 ligand) that renders T cells unable to activate immunoglobulin class switching in B cells.
Type 1 hyper-IgM syndrome
Actin filament assembly in leukocytes and platelets is impeded in
Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency that manifests in early infancy with recurrent sinopulmonary infections (e.g., Pneumocystis pneumonia) and failure to thrive.
Impaired neutrophil superoxide production is caused by a defect in NADPH oxidase and is seen in
chronic granulomatous disease (CGD)
Impaired thymic organogenesis resulting in thymic aplasia occurs in …
Impaired thymic organogenesis resulting in thymic aplasia occurs in severe combined immunodeficiency syndrome (SCID) and DiGeorge syndrome.
Defective microtubule polymerization and subsequent impaired phagosome-lysosome fusion in neutrophils and macrophages occur in…
Defective microtubule polymerization and subsequent impaired phagosome-lysosome fusion in neutrophils and macrophages occur in Chediak-Higashi syndrome (CHS)
mutation in the lysosomal trafficking regulator gene (LYST)
Chediak-Higashi syndrome (CHS)
Impaired B-cell maturation resulting in decreased production of all immunoglobulin classes can be caused by a mutation in the
Impaired B-cell maturation resulting in decreased production of all immunoglobulin classes can be caused by a mutation in the Bruton tyrosine kinase gene (BTK)
Decreased levels of serum IgA, IgE, and IgG should raise concern for a condition caused by defective
Decreased levels of serum IgA, IgE, and IgG should raise concern for a condition caused by defective immunoglobulin class switching.
appears on methenamine silver staining as disc-shaped cysts with central spores
Pneumocystis jirovecii
Pneumocystis jirovecii i=infections suggest a defect in what?
Cell mediated immunity! so defective T cells in T cells and B/T combo disorders
Defective Beta 2 integrin
LAD
Defective CD18
CD18=Beta 2 integrin, defective in LAD
Poor wound healing, no pus, high neutrophil count
LAD
Defective CD40 L
Recall CD40L is found on helper T cells. They assist with class switching, seen in hyper-IgM
Defective class switching
Hyper IgM
Delayed umbilical cord separation
LAD
A defect in the interleukin-2 receptor subunit gamma gene (IL2RG) is the most common mutation associated with…
severe combined immunodeficiency (SCID)
Defective microtubules due to a loss of function of the lysosomal trafficking regulator gene (LYST) is the underlying pathophysiology of…
Chediak-Higashi syndrome (CHS)
A defectively organized actin cytoskeleton
A defectively organized actin cytoskeleton due to a mutation in the WAS gene is the underlying cause of Wiskott-Aldrich syndrome (WAS)
A patient has mucocutaneous candidiasis (e.g., white oral patches, diaper rash) and features of septic shock (e.g., fever, hypotension, tachycardia) due to disseminated Candida infection. In combination with delayed separation suggests…
leukocyte adhesion deficiency.
Low levels of mature B cells (which express CD19, CD20, and CD21) in addition to recurrent episodes of respiratory and gastrointestinal tract infections when a child is older than 6 months (when the maternal IgG has decreased) are highly suggestive of…..
X-linked (Bruton) agammaglobulinemia.
A deficiency in the IL-17 receptor is associated with
chronic mucocutaneous candidiasis (CMC)
Impaired DNA repair in lymphocytes is seen in
ataxia telangiectasia (AT), an autosomal recessive disorder that occurs due to defects in the ATM gene
defects in the ATM gene
ataxia telangiectasia (AT)
retained teeth
Hyper IgE
Impaired interferon-γ secretion by Th1 cells is seen in …
Impaired interferon-γ secretion by Th1 cells is seen in IL-12 receptor deficiency, an autosomal recessive disorder.
It causes a fusion defect in granules of all cells, resulting in giant intracellular granules. In addition, a microtubule polymerization dysfunction impairs the fusion of phagosomes and lysosomes, which affects the normal immune response of neutrophils and monocytes.
Chediak-Higashi syndrome
Patients with ____________________________-are typically asymptomatic but can also develop recurrent Candida infections (e.g., oral thrush and vulvovaginal candidiasis) due to ineffective hypochlorous acid production during the oxidative burst. The nitroblue tetrazolium test is positive (normal) in these patients because NADPH oxidase function is intact and still able to reduce the dye to blue. The diagnosis is confirmed by genetic testing or immunohistochemical staining.
myeloperoxidase deficiency
myeloperoxidase
An enzyme found in neutrophil granulocytes that is involved in the production of acids with antimicrobial activity.
Class switching impaired
hyper IgM
Candida infections, defects in AIRE
chronic mucocutaneous candidiasis
A transcription factor encoded by a gene on chromosome 21 that regulates the expression of autoantigens. Facilitates the elimination of self-reactive T cells. Dysfunction is associated with chronic mucocutaneous candidiasis.
AIRE
