immunodeficiencies

Question 1

T cell disorders

Answer 1

thymic aplasia (DiGeorge syndrome)
chronic mucocutaneous candidiasis
IL-12 receptor deficiency

Question 2

B cell disorders

Answer 2

bruton agammaglobulinemia

selective immunoglobulin deficiencies

Question 3

combined T + B cell disorders

Answer 3

severe combined immunodeficiency (SCID)
ataxia telangiectasia
Wiskott-Aldrich syndrome
Hyper-IgM syndrome

Question 4

phagocyte disorders (esp neutrophils)

Answer 4

chronic granulomatous disease
Chediak-Higashi disease
hypermmnoglobulin E (Job syndrome)
luekocyte adhesion deficiency syndrome

Question 5

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

Answer 5

thymic aplasia (DiGeorge syndrome)

Question 6

common infections if have thymic aplasia (DiGeorge syndrome)

Answer 6

recurrent viral+ fungal + protazoal infections

Question 7

associated with 22q11 deletion (detected by FISH)

Answer 7

thymic aplasia (DiGeorge syndrome): 90% cases

Question 8

treatment of chronic mucocutaneous candidiasis

Answer 8

ketoconazole

Question 9

common infections if have IL-12 receptor deficiency

Answer 9

mycobacterial + fungal infections

Question 10

X-linked (boys)
defective TK (tyrosine kinase) gene → low levels of ALL immunoglobulins

Answer 10

bruton agammaglobulinemia

Bruton = Boy

Question 11

signs of hypocalcemia

Answer 11

CHvostek sign: tap on CHeek - facial muscle spasm

Trousseau sign: Tighten bp cuff on arm for 1 min → carpopedal spasm

Question 12

T cell dysfunction that causes recurrent c. albicans infections

Answer 12

chronic mucocutaneous candidiasis

Question 13

naive helper To cells are missing IL-12 receptor (don’t respond to IL-12 from macrophages)→ no Th1 cells

Answer 13

IL-12 receptor deficiency

Question 14

recurrent bacterial infections in a boy after 6 mo of age (before 6 mo: protected by mom IgG)

Answer 14

bruton agammaglobulinemia:
Bruton
Boys
Bacterial infections
B cell deficiency

Question 15

healthy-appearing individual with recurrent sinus + lung infections
sinusitis: 3-4/year
young with recurrent pneumonia

Answer 15

IgA deficiency (most common selective Ig deficiency)

Question 16

associated with atopic dermatitis and asthma

Answer 16

IgA deficiency

Question 17

possible anaphylaxis to blood transfusions and blood products with IgA

Answer 17

IgA deficiency

Question 18

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

Answer 18

severe combined immunodeficiency (SCID)

Question 19

no thymic shadow on newborn CXR

Answer 19

severe combined immunodeficiency (SCID): absence of thymus

DiGeorge Sydnrome: thymic aplasia

Question 20

defect in early stem cell differentiation
one possible gene defect: adenosine deaminase deficiency
only defense available: NK cells (no B cells, T cells)

Answer 20

severe combined immunodeficiency (SCID)

Question 21

IgA and T cell deficiency →

sinus + lung infections

Answer 21

Ataxia-Telangiectasia (igA, Ataxia, ↑AFP, T cell deficiency)

Question 22

presentation of ataxia-telangiectasia

Answer 22

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

Question 23

presentation of Wiskott-Aldrich syndrome

Answer 23

WAITER - boy (x-linked)
Wiskott
Aldrich
Immunodeficiency
Thrombocytopenia + purpura
Eczema on TRUNK (not on usual flexural areas: knees, elbows, hands)
Recurrent pyogenic infections

Question 24

x-linked immunodeficiencies

Answer 24

bruton agammaglobulinemia
WACH
Wiskott-aldrich syndrome
Agammaglobulinemia - bruton
Chronic granulomatous disease (majority) 
Hyper-IgM syndrome (majority)

Question 25

No IgM against bacterial capsular polysaccharides low IgM high IgA

Answer 25

Wiskott-Aldrich syndrome

Question 26

``` 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 ```

Answer 26

hyper IgM syndrome

Question 27

phagocytes don't have NADPH oxidase → no superoxide free radicals → phagocytes can't destroy catalase-positive microbes → recurrent to s. aureus + aspergillus (granulomatous lesions)

Answer 27

chronic granulomatous disease

Question 28

diagnosis of chronic granulomatous disease

Answer 28

negative nitroblue tetrazolium (NBT) test add NBT to blood: phagocytes engulf dye → no yellow to blue/black oxidation

Question 29

treatment of chronic granulomatous disease

Answer 29

prophylactic TMP-SMX + itraconazole | IFN-gamma is also helpful

Question 30

phagocytes have no NADPH oxidase

Answer 30

chronic granulomatous disease

Question 31

defective LYST gene (need for transport of enzymes into lysosomes) → defective phagocyte lysosomes → giant cytoplasmic granules in PMNs are diagnostic (phagocytosed material not digested)

Answer 31

Chediak-Higashi syndrome

Question 32

present with triad: partial albinism recurrent respiratory tract + skin infections neurologic disorders (peripheral neurpathy, ataxia, seizures)

Answer 32

Chediak-Higashi syndrome

Question 33

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)

Answer 33

hyper IgE syndrome (Job syndrome)

Question 34

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

Answer 34

hyper IgE syndrome

Question 35

retained primary teeth resulting in 2 rows of teeth on top + bottom

Answer 35

hyper IgE syndrome

Question 36

abnormal integrins (leukocyte extravasation: help leukocytes to exit blood and integrate into interstitium ) → inability of phagocytes to exit circulation

Answer 36

leukocyte adhesion deficiency syndrome

Question 37

delayed separation of umbilical cord (stays on for few mos, example of impaired wound healing)

Answer 37

leukocyte adhesion deficiency syndrome (type I)