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Flashcards in immunodeficiency Deck (75):
1

generally, T-cells deficiencies vs B cell deficiencies according to risk for infections

generally, B-cells deficiencies --> recurrent bacterial infection
generally, T-cells deficiencies --> fungal and viral infection

2

Immunodeficiencies are divided to

1. B-cells disorders
2. T-cells disorders
3. B and T cell disorders
4. Phagocyte dysfunction

3

Immunodeficiencies - B-cells disorders - types

1. X-linked (Bruton) agammaglobulinemia
2. Selective IgA deficiency
3. Common variable immunodeficiency

4

X-linked (Bruton) agammaglobulinemia - defect

Defect in BTK, a tyrosine kinase gene --> no B cell maturation (X-linked recessive --> boys)

5

X-linked (Bruton) agammaglobulinemia - mechanism of inheritance

X-linked recessive --> boys

6

X-linked (Bruton) agammaglobulinemia - presentation

Recurrent bacterial and enteroviral infection after 6 months (after maternal IgG protection)

7

X-linked (Bruton) agammaglobulinemia - findings

1. Absent B cells in peripheral blood
2. Low Ig of classes
3. Absent/scanty lymph nodes and tonsils

8

Selective IgA deficiency - defect

unknown

9

Selective IgA deficiency - presentation

5 As
- Majority asymptomatic
- airway and GI infections
- autoimmune diseases
- Atopy
- Anaphylaxis to IgA-containing products

10

Selective IgA deficiency - findings

1. low IgA
2. normal IgG, IgM levels

11

Common variable immunodeficiency - defect

defect in B-cells differentiation (many causes)

12

Common variable immunodeficiency - presentation

Can be acquired in 20s-30s
1. high risk of autoimmune disease
2. bronchiectasis 3. lymphoma
4. sinopulmonary infections

13

Common variable immunodeficiency - can be acquired in

20-30s

14

Common variable immunodeficiency - findings

1. low plasma cells
2. low immunoglobulins

15

T-cell disorders - types

1. Thymuc aplasia (DiGeorge syndrome)
2. IL-12 receptor deficiency
3. Autosomal dominant hyper-IgE syndrome (Job syndrome)
4. Chronic mucocutaneous candidiasis

16

Thymuc aplasia is AKA

DiGeorge syndrome

17

Thymuc aplasia (DiGeorge syndrome) - defect

22q11 deletion --> failure to develop 3rd and 4th pharyngeal pouches --> absent thymus and parathyroids

18

Thymuc aplasia (DiGeorge syndrome) - presentation

1. Tetany (hypocalcemia)
2. reccurent viral/fungal infections
3. conotruncal abnormalities (ef. tetralogy of Fallot, truncus arteriosus)

19

Thymuc aplasia (DiGeorge syndrome) - findings

1. decreased T-cells
2. decreased Parathormone --> decreased calcium
3. absent thymic shadow on CXR
4. 22q11 deletion detected by FISH
5. not well developed lymph node paracortex

20

IL-12 receptor deficiency - defect

low Th1 response

21

IL-12 receptor deficiency - mode of inheritance

AR

22

IL-12 receptor deficiency - presentation

Disseminated mycobacterial and fungal infections
- may present after BCG vaccine administration

23

IL-12 receptor deficiency - may present after

BCG vaccine administration

24

IL-12 receptor deficiency - findings

low INF-γ

25

INF-γ is secreted by .... / actions

It is secreted by NK cells and T cells in response to il-12 from macrophages. actions:
1. stimulates macrophages to kill phagocytosed pathogens
2. Inhibits differentiation of Th2
3. activates NK cells to kill virus infected-cells
4. increases MHC expression and antigen presentation by all cells

26

Autosomal dominant hyper-IgE syndrome is also called

Job syndrome

27

Autosomal dominant hyper-IgE syndrome (Job syndrome) - defect / mode of inheritance

Deficiency of Th17 cells due to STAT3 mutation --> impaired recruitment of neutrophils to site of mutation
AD

28

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

FATED
1. coarse Facies
2. cold (noninflammed) staphylococcal Abscess
3. retained primary Teeth
4. IgE
5. Demratoligic problems (eczema)

29

Autosomal dominant hyper-IgE syndrome (Job syndrome) - fingings

high IgE
low IFN-γ

30

Chronic mucocutaneous candidiasis - defect

T-cell dysfunction (many causes)

31

Chronic mucocutaneous candidiasis - presentation

Noninvasive Candida ablicans infection of skin and mucous membranes

32

Chronic mucocutaneous candidiasis - findings

1. absent in vitro T-cell proliferation in response to Candida ablicans
2. Absent cutaneous reaction to Candida ablicans

33

B and T cell disorders - types

1. Severe combined immunodeficiency
2. Ataxia-telangiectasia
3. Hyper-IgM syndrome
4. Wiskott-Aldrich syndrome

34

Severe combined immunodeficiency - defect

several types:
a. defective IL-2R gamma chain (MC, X-linked)
b. adenosine deaminase deficinecy (AR)

35

Severe combined immunodeficiency - presentation

1. Failure to thrive
2. chronic diarrhea
3. thrush
4. Reccurent viral, bacterial, fungal and protozoal infections

36

Severe combined immunodeficiency - treatment

bone marrow transplant (no concern for rejection)

37

Severe combined immunodeficiency - findings

1. decreased T-cell receptor excision circles (TRECs)
2. absence of thymic shadow on CXR
3. absence of germinal centers (lymph node biopsy)
4. absence of T cells (flow cytometry)

38

T-cell receptor excision circles (TRECs) are

small circles of DNA created in T-cells during their passage through the thymus as they rearrange their TCR genes --> indication of T-cell maturation

39

Ataxia-telangiectasia - defect

defects in ATM gene --> failure to repair DNA double strand breaks --> cell cycle arrest

40

Ataxia-telangiectasia - presentation

triad: 1. cerebellar defects (Ataxia)
2. spider angiomas (telangiectasia)
3. IgA deficiency

41

Ataxia-telangiectasia - findings

1. increased AFP
2. low IgA, IgG and IgE
3. Lymphopenia
4. cerebellar atrophy
5. normal level of IgM

42

Hyper-IgM syndrome - defect

MC due to defective CD40L on Th cells --> class switching defect
XR

43

Hyper-IgM syndrome - mode of inheritance

XR

44

Hyper-IgM syndrome - presentation

1. severe puogenic infection early in life
2. opportunistic infection with Pneumocystis, Cryptospridium, CMV

45

Hyper-IgM syndrome - opportunistic infection with

1. Pneumocystis
2. Cryptospridium
3. CMV

46

Hyper-IgM syndrome - findings

1. normal of increased IgM
2. low IgG, IgA, IgE

47

Wiskott-Aldrich syndrome - defect

mutation of was gene --> T cells unable to reorganize actin cytoskeleton
XR

48

Wiskott-Aldrich syndrome - mode of inheritance

XR

49

Wiskott-Aldrich syndrome - presentation

Mneominic: WATER + autoimmune + malignancy
1. Thrmobocytopenia
2. Eczema
3. Reccurent infections
4. High risk of autoimmune disease and malignancy

50

Wiskott-Aldrich syndrome - findings

1. low/normal IgG, IgM
2. High IgE, IgA
3. Fewer and smaller platelets

51

B and T cell disorders - types and mode of inheritance

1. Severe combined immunodeficiency --> X or AR
2. Ataxia-telangiectasia --> -
3. Hyper-IgM syndrome --> XR
4. Wiskott-Aldrich syndrome --> XR

52

Phagocyte dysfunction - types and mode of inheritance

1. Phagocyte adhesion deficiency (type 1) --> AR
2. Chediak-Higashi --> AR
3. Chronic granulomatous disease --> XR

53

Leukocyte adhesion deficiency (type 1) - defect

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

54

Leukocyte adhesion deficiency (type 1) - mode of inheritance

AR

55

Leukocyte adhesion deficiency (type 1) - presentation

1. reccurent bacterial skin and mucosa infection
2. absent pus formation
3. impaired wound healing
4. delayed separation of umbilical cord (>30 days)

56

Leukocyte adhesion deficiency (type 1) - findings

1. increased neutrophils
2. no neutrophils at infection site

57

Chediack-Hisgashi syndrome - mechanism

Defect in lysosomal trafficking regulator gene (LYST) --> microtubule dysfunction in phagosome-lysosome fusion
AR

58

Chediack-Hisgashi syndrome - Mode of inheritance

AR

59

Chediack-Hisgashi syndrome - presentation

1. reccurent pyogenic infections by staphyococci and streptococci
2. partial albinism
3. peripheral neuropathy
4. progressive neurodegeneration
5. infiltrative lymphohistiocytosis

60

Chediack-Hisgashi syndrome - findings

1. giant granules in granulocytes and platelets
2. pancytopenia
3. Mild coagulation defects

61

Chronic granulomatous disease - mechanism

Defect of NADPH oxidase --> decreased ROS and respiratory burst in neutrophils
XR

62

Chronic granulomatous disease - mode of inheritance

XR

63

Chronic granulomatous disease - presentation

high susceptibility to CAT + organism

64

CAT + bugs?

CATs Need PLACESS to Belch their Hairballs
Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, Staphylococci, Seratia, B. cepacia, H. pylori

65

Chronic granulomatous disease - findings

Abnormal dihydrorhodamine (flow cytometry) test (decreased green fluorescence)
Nitroblue tetrazolium dye reduction test obsolete (if + --> less blue)

66

MC immunodeficiency

Selective IgA deficiency

67

infections in immunodeficiencies (bacteria, viruses, Fungi/parasaties) - decreased T cells

bacteria: sepsis
Viruses: CMV, EBV, JCV, VZV, chronice infection with respiratory/GI viruses
fungi/paratsites: Candida (local) PCP

68

infections in immunodeficiencies (bacteria, viruses, Fungi/parasaties) - decreased B cells

bacteria: encapsulated
viruses: enteroviral encephalitis, poliovirus (live vaccine contraindicated)
fungi/paratsites: giardias (if no IgA)

69

infections in immunodeficiencies (bacteria, viruses, Fungi/parasaties) - decreased granulocytes

bacteria 1. staphylococcus 2. Burkholderia cepacia
3. Pseudomonas aeruginosa 4. Serratia 5. Nocardia
viruses: no
fungi/parasites: Candida (systemic), aspergillus, mucormycosis

70

infections in immunodeficiencies (bacteria, viruses, Fungi/parasaties) - low complement

bacteria --> encapsuled species with early compoment deficiencies, Neisseria with late compoment deficiencies

71

Immunodeficiency disorder with low INF-γ

1. Il-12 deficiency
2. AD hyper-IgE syndrome (Job syndrome)

72

Immunodeficiency disorder with cold abscess

AD hyper-IgE syndrome (Job syndrome)

73

Immunodeficiency disorder with fewer and smaller platelets

Wiskott-Aldrich syndrome

74

Immunodeficiency disorder with delayed separation of umbilical cord

Leukocyte adhesion deficiency

75

Immunodeficiency disorder with infiltrative lymphohistiocytosis

Chediak-Higashi syndrome