immunodeficiencies Flashcards
T cell disorders
thymic aplasia (DiGeorge syndrome) chronic mucocutaneous candidiasis IL-12 receptor deficiency
B cell disorders
bruton agammaglobulinemia
selective immunoglobulin deficiencies
combined T + B cell disorders
severe combined immunodeficiency (SCID)
ataxia telangiectasia
Wiskott-Aldrich syndrome
Hyper-IgM syndrome
phagocyte disorders (esp neutrophils)
chronic granulomatous disease
Chediak-Higashi disease
hypermmnoglobulin E (Job syndrome)
luekocyte adhesion deficiency syndrome
3rd + 4th branchial pouches don’t develop (endodermal):
no thymus: no mature T cells
no parathyroid: no PTH → hypocalcemia → tetany
congenital defects: heart/great vessels
thymic aplasia (DiGeorge syndrome)
common infections if have thymic aplasia (DiGeorge syndrome)
recurrent viral+ fungal + protazoal infections
associated with 22q11 deletion (detected by FISH)
thymic aplasia (DiGeorge syndrome): 90% cases
treatment of chronic mucocutaneous candidiasis
ketoconazole
common infections if have IL-12 receptor deficiency
mycobacterial + fungal infections
X-linked (boys) defective TK (tyrosine kinase) gene → low levels of ALL immunoglobulins
bruton agammaglobulinemia
Bruton = Boy
signs of hypocalcemia
CHvostek sign: tap on CHeek - facial muscle spasm
Trousseau sign: Tighten bp cuff on arm for 1 min → carpopedal spasm
T cell dysfunction that causes recurrent c. albicans infections
chronic mucocutaneous candidiasis
naive helper To cells are missing IL-12 receptor (don’t respond to IL-12 from macrophages)→ no Th1 cells
IL-12 receptor deficiency
recurrent bacterial infections in a boy after 6 mo of age (before 6 mo: protected by mom IgG)
bruton agammaglobulinemia: Bruton Boys Bacterial infections B cell deficiency
healthy-appearing individual with recurrent sinus + lung infections
sinusitis: 3-4/year
young with recurrent pneumonia
IgA deficiency (most common selective Ig deficiency)
associated with atopic dermatitis and asthma
IgA deficiency
possible anaphylaxis to blood transfusions and blood products with IgA
IgA deficiency
presents with this triad:
1) severe recurrent infections: chronic mucocutaneous candidiasis, fatal or recurrent viral infections: RSV, VZV, HSV, measles, flu, parainfluenza, pneumocystitis jirovecii (PCP) pneumonia
2) chronic diarrhea
3) failure to thrive
severe combined immunodeficiency (SCID)
no thymic shadow on newborn CXR
severe combined immunodeficiency (SCID): absence of thymus
DiGeorge Sydnrome: thymic aplasia
defect in early stem cell differentiation
one possible gene defect: adenosine deaminase deficiency
only defense available: NK cells (no B cells, T cells)
severe combined immunodeficiency (SCID)
IgA and T cell deficiency →
sinus + lung infections
Ataxia-Telangiectasia (igA, Ataxia, ↑AFP, T cell deficiency)
presentation of ataxia-telangiectasia
ATAXIA Ataxia + poor smooth pursuit Telangiectasia (> 5 ho) Acute leukemia, lymphoma (↑ risk) Xray sensitivity (avoid) IgA deficiency + T cell deficiency AFP elevated (> 8 mo age): helpful for screening in toddler with poor smooth pursuit average age of death: 25 yo
presentation of Wiskott-Aldrich syndrome
WAITER - boy (x-linked) Wiskott Aldrich Immunodeficiency Thrombocytopenia + purpura Eczema on TRUNK (not on usual flexural areas: knees, elbows, hands) Recurrent pyogenic infections
x-linked immunodeficiencies
bruton agammaglobulinemia WACH Wiskott-aldrich syndrome Agammaglobulinemia - bruton Chronic granulomatous disease (majority) Hyper-IgM syndrome (majority)
No IgM against bacterial capsular polysaccharides
low IgM
high IgA
Wiskott-Aldrich syndrome
high IgM (other isotypes decreased) if AR disorder: B cells don't have CD40 (binds to CD40-L on Th1 cells to promote Ig class switching: only have IgM production) if X-linked disorder (more common): Th1 cells don't have CD40-L
hyper IgM syndrome
phagocytes don’t have NADPH oxidase → no superoxide free radicals → phagocytes can’t destroy catalase-positive microbes → recurrent to s. aureus + aspergillus (granulomatous lesions)
chronic granulomatous disease
diagnosis of chronic granulomatous disease
negative nitroblue tetrazolium (NBT) test
add NBT to blood: phagocytes engulf dye →
no yellow to blue/black oxidation
treatment of chronic granulomatous disease
prophylactic TMP-SMX + itraconazole
IFN-gamma is also helpful
phagocytes have no NADPH oxidase
chronic granulomatous disease
defective LYST gene (need for transport of enzymes into lysosomes) → defective phagocyte lysosomes → giant cytoplasmic granules in PMNs are diagnostic (phagocytosed material not digested)
Chediak-Higashi syndrome
present with triad:
partial albinism
recurrent respiratory tract + skin infections
neurologic disorders (peripheral neurpathy, ataxia, seizures)
Chediak-Higashi syndrome
mutation in gene for STAT3 signaling protein (part of JAK-STAT pathway) leads to:
impaired differentiation of Th17 cells in mucosa → impaired recruitment of neutrophils to fight opportunistic infections (staph, candida)
high IgE + eosinophils (mechanism for elevation not understood)
hyper IgE syndrome (Job syndrome)
present with triad:
eczema
recurrent COLD (walled infection, no neutrophils to area) S. aureus abscesses (boils like Job in bible)
coarse facial features: broad nose, frontal bossing, deep-set eyes, thick “doughy” skin
hyper IgE syndrome
retained primary teeth resulting in 2 rows of teeth on top + bottom
hyper IgE syndrome
abnormal integrins (leukocyte extravasation: help leukocytes to exit blood and integrate into interstitium ) → inability of phagocytes to exit circulation
leukocyte adhesion deficiency syndrome
delayed separation of umbilical cord (stays on for few mos, example of impaired wound healing)
leukocyte adhesion deficiency syndrome (type I)
