Immunodeficiencies

Question 1

Bruton agammaglobulinemia - defect

Answer 1

defect in BTK, a tyrosine kinase gene -> no B-cell maturation
insufficient opsonization of pathogens with IgG
X-linked recessive

Question 2

Bruton agammaglobulinemia - presentation

Answer 2

recurrent extracellular encapsulated bacterial and enteroviral infections after 6mo (decrease maternal IgG)

Question 3

Bruton agammaglobulinemia - findings

Answer 3

absent B cells in peripheral blood
decrease Ig of all classes
Absent/scanty lymph nodes and tonsils
LIVE VACCINES CONTRAINDICATED

Question 4

Selective IgA deficiency - defect

Answer 4

unknown

most common primary immunodeficiency

Question 5

Selective IgA deficiency - presentation

Answer 5

majority: asymptomatic
can see airway and GI infections
autoimmune disease
atopy
anaphylaxis to IgA-containing products

Question 6

Selective IgA deficiency - findings

Answer 6

decrease IgA with normal IgG, IgM levels

increase susceptibility to GIARDIASIS

Question 7

Common variable immunodeficiency - defect

Answer 7

defect in B-cell differentiation

cause is unknown in most cases

Question 8

Common variable immunodeficiency - presentation

Answer 8

usually presents after age 2 and may be considered delayed

increase risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections

Question 9

Common variable immunodeficiency - findings

Answer 9

decrease plasma cells

decrease immunoglobulins

Question 10

thymic aplasia (DiGeorge syndrome) - defect

Answer 10

22q11 deletion

failure to develop 3rd and 4th pharyngeal pouches -> absent thymus and parathyroids

Question 11

thymic aplasia (DiGeorge syndrome) - presentation

Answer 11

tetany (hypocalcemia)
recurrent viral/fungal infections, intracellular bacteria (T-cell deficiency) 
cotruncal abnormalities (tetralogy of Fallot, truncus arteriosus)

Question 12

thymic aplasia (DiGeorge syndrome) - findings

Answer 12

decrease T cells, decrease PTH, decrease Ca2+

thyme shadow absent on CXR

Question 13

IL-12 receptor deficiency - defect

Answer 13

decrease Th1 response

autosomal recessive

Question 14

IL-12 receptor deficiency - presentation

Answer 14

disseminated mycobacterial and fungal infections

may present after administration of BCG vax

Question 15

IL-12 receptor deficiency - findings

Answer 15

decrease IFN-gamma

Question 16

autosomal dominant hyper-IgE syndrome (Job syndrome) - defects

Answer 16

deficiency of Th17 cells due to STAT3 mutation -> impaired recruitment of neutrophils to sites of infection

Question 17

autosomal dominant hyper-IgE syndrome (Job syndrome) - presentation

Answer 17

FATED: 
coarse Facies
cold (non inflamed) staphylococcal Abscesses
retained primary Teeth
increased IgE
Dermatologic problems (eczema)

bone fractures from minor trauma

Question 18

autosomal dominant hyper-IgE syndrome (Job syndrome) - findings

Answer 18

increase IgE

increase eosinophils

Question 19

chronic mucocutaneous candidiasis - defect

Answer 19

T-cell dysfunction

can result from congenital genetic defects in IL-17 or IL-17 receptors

Question 20

chronic mucocutaneous candidiasis - presentation

Answer 20

noninvasive Candida albicans infections of skin and mucous membranes

Question 21

chronic mucocutaneous candidiasis - findings

Answer 21

absent in vitro T-cell proliferation in response to candida antigens
absent cutaneous reaction to candida antigens

Question 22

severe combined immunodeficiency - defect

Answer 22

several types including:
defective IL-2R gamma chain (most common, XR)
adenosine deaminase deficiency (AR)

Question 23

severe combined immunodeficiency - presentation

Answer 23

failure to thrive, chronic diarrhea, thrush
recurrent viral, bacterial, fungal, and protozoal infections
treatment: avoid live vax, give antimicrobial prophylaxis and IVIG; BONE MARROW TRANSPLANT = curative

Question 24

severe combined immunodeficiency - findings

Answer 24

decrease T-cell receptor excision circles (TRECs)

absence of thymic shadow (CXR), germinal centers (lymph node biopsy), and T cells (flow cytometry)

Question 25

ataxia-telangiectasia - defect

Answer 25

defects in ATM gene -> failure to detect DNA damage -> failure to halt progression of cell cycle -> mutations accumulate AR defect in DNA ds repair enzyme

Question 26

ataxia-telangiectasia - presentation

Answer 26

``` triad: cerebellar defects (ataxia) spider angiomas (telangiectasia) IgA deficiency ```

Question 27

ataxia-telangiectasia - findings

Answer 27

increase AFP decrease IgA, IgG, and IgE lymphopenia, cerebellar atrophy increase risk of lymphoma and leukemia

Question 28

Hyper-IgM syndrome - defect

Answer 28

``` most commonly due to defective CD40L on Th cells -> class switching defect XR ```

Question 29

Hyper-IgM syndrome - presentation

Answer 29

severe pyogenic infections early in life | opportunistic infection with Pneumocystis (fungal), cryptosporidium, CMV

Question 30

Hyper-IgM syndrome - findings

Answer 30

normal or increase IgM marked decrease IgG, IgA, IgE failure to make germinal centers

Question 31

Wiskott-Aldrich syndrome - defect

Answer 31

mutation in WASp gene leukocytes and platelets unable to reorganize actin cytoskeleton -> defective antigen presentation XR

Question 32

Wiskott-Aldrich syndrome - presentation

Answer 32

``` WATER: Wiskott-Aldrich: Thrombocytopenia Eczema Recurrent (pyogenic) infections increase risk of autoimmune disease and malignancy ```

Question 33

Wiskott-Aldrich syndrome - findings

Answer 33

decrease to normal IgG, IgM increase IgE, IgA fewer and smaller platelets

Question 34

Leukocyte adhesion deficiency type 1 - defect

Answer 34

Defect in LFA-1 integrin (CD18) protein on phagocytes impaired migration and chemotaxis AR

Question 35

Leukocyte adhesion deficiency type 1 - presentation

Answer 35

recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing, delayed (>30d) separation of umbilical cord

Question 36

Leukocyte adhesion deficiency type 1 - findings

Answer 36

increase neutrophils in blood | absence of neutrophils at infection sites

Question 37

Chediak-Higashi syndrome - defect

Answer 37

defect in lysosomal trafficking regulator gene (LYST) microtubule dysfunction in phagosome-lysosome fusion AR decrease phagocytosis

Question 38

Chediak-Higashi syndrome - presentation

Answer 38

``` PLAIN: Progressive neurodegeneration Lymphobistiocytosis Albinism (partial) recurrent pyogenic Infections by staphylococci and streptococci (gram +, gram -, fungal) peripheral Neuropathy ```

Question 39

Chediak-Higashi syndrome - findings

Answer 39

giant granules in granulocytes and platelets pancytopenia mild coagulation defects

Question 40

chronic granulomatous disease - defect

Answer 40

defect in NADPH oxidase -> decrease ROS (e.g. superoxide) and decrease respiratory burst in neutrophils X-linked most common

Question 41

chronic granulomatous disease - presentation

Answer 41

increase susceptibility to catalase + organisms | - staph aureus, pseudomonas, klebsiella, aspergillus

Question 42

chronic granulomatous disease - findings

Answer 42

``` abnormal dihydrorhodamine (flow cytometry) test (decrease green fluorescence) nitroblue tetrazolium dye reduction test (obsolete) fails to turn blue ```

Question 43

early complement deficiencies

Answer 43

C1-C4 increased risk of severe, recurrent pyogenic sinus and respiratory tract infections increased risk of SLE

Question 44

terminal complement deficiencies

Answer 44

C5-C9 | increased susceptibility to recurrent Neisseria bacteremia

Question 45

C1 esterase inhibitor deficiency

Answer 45

causes hereditary angioedema d/t unregulated activation of kallikrein -> increase bradykinin characterized by decreased C4 levels ACEi CONTRAINDICATED

Question 46

paroxysmal nocturnal hemoglobinuria

Answer 46

defect in PIGA gene preventing the formation of anchors for complement inhibitors (decay-accelerating factor [DAF/CD55] and membrane inhibitor of reactive lysis [MIRL/CD59]) causes complement-mediated lysis of RBCs