immunodeficiency Flashcards
(75 cards)
1
Q
generally, T-cells deficiencies vs B cell deficiencies according to risk for infections
A
generally, B-cells deficiencies –> recurrent bacterial infection
generally, T-cells deficiencies –> fungal and viral infection
2
Q
Immunodeficiencies are divided to
A
- B-cells disorders
- T-cells disorders
- B and T cell disorders
- Phagocyte dysfunction
3
Q
Immunodeficiencies - B-cells disorders - types
A
- X-linked (Bruton) agammaglobulinemia
- Selective IgA deficiency
- Common variable immunodeficiency
4
Q
X-linked (Bruton) agammaglobulinemia - defect
A
Defect in BTK, a tyrosine kinase gene –> no B cell maturation (X-linked recessive –> boys)
5
Q
X-linked (Bruton) agammaglobulinemia - mechanism of inheritance
A
X-linked recessive –> boys
6
Q
X-linked (Bruton) agammaglobulinemia - presentation
A
Recurrent bacterial and enteroviral infection after 6 months (after maternal IgG protection)
7
Q
X-linked (Bruton) agammaglobulinemia - findings
A
- Absent B cells in peripheral blood
- Low Ig of classes
- Absent/scanty lymph nodes and tonsils
8
Q
Selective IgA deficiency - defect
A
unknown
9
Q
Selective IgA deficiency - presentation
A
5 As
- Majority asymptomatic
- airway and GI infections
- autoimmune diseases
- Atopy
- Anaphylaxis to IgA-containing products
10
Q
Selective IgA deficiency - findings
A
- low IgA
2. normal IgG, IgM levels
11
Q
Common variable immunodeficiency - defect
A
defect in B-cells differentiation (many causes)
12
Q
Common variable immunodeficiency - presentation
A
Can be acquired in 20s-30s
- high risk of autoimmune disease
- bronchiectasis 3. lymphoma
- sinopulmonary infections
13
Q
Common variable immunodeficiency - can be acquired in
A
20-30s
14
Q
Common variable immunodeficiency - findings
A
- low plasma cells
2. low immunoglobulins
15
Q
T-cell disorders - types
A
- Thymuc aplasia (DiGeorge syndrome)
- IL-12 receptor deficiency
- Autosomal dominant hyper-IgE syndrome (Job syndrome)
- Chronic mucocutaneous candidiasis
16
Q
Thymuc aplasia is AKA
A
DiGeorge syndrome
17
Q
Thymuc aplasia (DiGeorge syndrome) - defect
A
22q11 deletion –> failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids
18
Q
Thymuc aplasia (DiGeorge syndrome) - presentation
A
- Tetany (hypocalcemia)
- reccurent viral/fungal infections
- conotruncal abnormalities (ef. tetralogy of Fallot, truncus arteriosus)
19
Q
Thymuc aplasia (DiGeorge syndrome) - findings
A
- decreased T-cells
- decreased Parathormone –> decreased calcium
- absent thymic shadow on CXR
- 22q11 deletion detected by FISH
- not well developed lymph node paracortex
20
Q
IL-12 receptor deficiency - defect
A
low Th1 response
21
Q
IL-12 receptor deficiency - mode of inheritance
A
AR
22
Q
IL-12 receptor deficiency - presentation
A
Disseminated mycobacterial and fungal infections
- may present after BCG vaccine administration
23
Q
IL-12 receptor deficiency - may present after
A
BCG vaccine administration
24
Q
IL-12 receptor deficiency - findings
A
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
