Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ID Board Review > Primary Immunodeficiency Disorders > Flashcards

Primary Immunodeficiency Disorders Flashcards

1
Q

Defect in Severe Combined Immunodeficiency (SCID)

A

Fully or mostly absent T cells that do not function

->functionally deficient B cells given lack of T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Diagnosis of SCID

A

T cell count <300 microL
AND
absence of T-cell responses to mitogens (<10% response compared to control)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Hypomorphic SCID

A

Reduced number of T cells for age (or normal number with reduced diversity)
AND
<30% T-cell function compared to control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

SCID Newborn screening

A

T-cell receptor excision circles - marker of T cell receptor development (>99% sensitive for classic and hypomorphic SCID)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Wiskott-Aldrich Syndrome Defect

A

Mutation in WAS protein (WASP) expressed in all hematopoetic cells, which is important for cell mobility, cell-cell interactions and platelet function
-> Leads to poor T cell function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

WAS Triad

A

Thrombocytopenia (with decreased MPV)
Eczema
Recurrent infections
(also with predisposition to malignancy, autoimmunity and childhood mortality)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Most common etiology for Hyperimmunoglobulin (Ig) M Syndrome

A

CD40 Ligand deficency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CD40 Ligand Deficiency genetics

A

X-linked

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

HyperIgM Syndrome (NOT CD40 Ligand deficiency) genetics

A

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

CD40 Ligand Function

A

Expressed on all B cells - Pivotal for B-cell growth, survival and differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CD40 Ligand Deficiency Labs

A 
High IgM (or normal)
Low or absent IgG, IgA, IgE due to inability to class switch
Lack of specific IgG production
CD4 count is normal, but non-functioning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CD40 Ligand Deficiency Presentation

A

Present like CD4 deficient (AIDS) patients - PJP, cryptosporidum, cryptococcus

No lymphadenopathy (unlike AR-HyperIgM, which can have excessive LAD since production defect is downstream)

GI disease (diarrhea, liver dysfunction) is common

High risk for malignancy (especially lymphomas and liver cancer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

GATA2 Deficiency age of onset

A

Teens to late adulthood (median 20 years)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

GATA2 Deficiency Lab findings

A

Decreased B and NK cells
Monocytopenia (>80%)
Occasional CD4 lymphopenia and neutropenia (50%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

GATA2 Deficiency Infections (4)

A

Recalcitrant, severe HPV
Disseminated NTM
EBV viremia
HSV outbreaks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

GATA2 Deficiency Non-infectious presentation (4)

A

Antibody-negative pulmonary alveolar proteinosis
Hematologic malignancies (MDS/AML)
Sensorineural hearing loss
Lymphedema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Familial Hemophagocytic Lymphohistiocytosis etiology

A

Prolonged, excessive activation of antigen-presenting and cytotoxic cells due to inability to clear inciting pathogen

Cytokine storm from APCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Diagnostic Criteria for FHLH:

A

5 of 8:

  • Fever
  • Splenomegaly
  • Cytopenias (Hgb <9, PLT <100, ANC <1000)
  • Hypertriglyceridemia (>265)
  • Low fibrinogen (<150)
  • High ferritin (>500)
  • High soluble IL-2 receptor (>2400) - marker of T-cell activation
  • Low or absent NK-cell activity
  • Hemophagocytosis on pathology

(Also transaminitis and HSM, but not part of criteria)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

IgA Deficiency diagnosis

A

Undetectable IgA in blood and secretions without other immunoglobulin deficiencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

IgA deficiency presentation

A

Most have on illness
25-50% have recurrent infections, especially involving mucosal surfaces (ear infections, sinusitis, bronchitis, pneumonia)
May also have GI manifestations and chronic diarrhea
Autoimmune diseases and allergies may be more common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

T-cell defects (5)

A
  1. SCID - most common severe PID
  2. Wiksot-Aldrich Syndrome
  3. CD40 Ligand Deficiency - most common etiology for hyperIgM syndrome
  4. GATA2 Deficiency - later onset
  5. Familial HLH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

B Cell defects (3)

A
  1. IgA deficiency - most commonly found primary immune deficiency, especially among caucasians (?1/500)
  2. X-linked agammaglobulinemia
  3. CVID - very common, mainly in adults
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

X-linked agammaglobulinemia defect

A

Deficiencies in Bruton’s Tyrosine Kinase leading to severely decreased B-cell numbers and absence of serum Ig

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

X-linked agammaglboulinemia infections

A

Bacterial respiratory and GI infections: H flu, S aureus, S pneumonia

Chronic enteroviral infections, can cause meningoencephalitis

Monoarticular arthritis, usually aseptic and responds to high-dose gammaglobulin treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Common variable immune deficiency (CVID) lab findings

A

Low levels of serum Ig with decreased specific antibody responses

Small subset also have minor T-cell defects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

CVID presentation

A

Mostly adults, very common (1/25,000)

Recurrent respiratory and GI tract infections

Subset present with autoimmunity, including IBD, granulomas, endocrinopathies

May be at higher risk of developing cancer (esp. lymphoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Chronic granulomatous disease (CGD) defect

A

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase defects leading to inability to produce superoxide anions

Inflamed tissue around uncleared pathogens creates granulomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

CGD Diagnosis

A

Dihydrorhodamine testing (DHR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Most common (and most severe) genetic defect for CGD

A

CYBB - X-linked

30
Q

CGD prognosis

A

Without diagnosis - fatal within 1st year
With diagnosis and adequate prophylaxis:
-X-linked median life-expectancy: 20-25 years
-AR: 30-40 years

31
Q

CGD infections

A

Most common is GI disease (can mimic colitis, IBD)
Fungal - mostly aspergillus - ubiquitous and most common cause of death
Sepsis from uncommon catalase-positive organisms:
-Granulibacter bethesdensis
-Chromobacterium violaceum
-Francisella philomiragia
-Burkholderia cepacia
-Nocardia (not 2/2 steroids)

32
Q

Phagocytic defects (5)

A
  1. CGD
  2. Severe congenital neutropenia
  3. X-linked neutropenia
  4. Shwachman-Diamond Syndrome
  5. Leukocyte adhesion deficiency (LAD)
33
Q

Severe congenital neutropenia:

  1. Inheritance
  2. age of onset
  3. Presentatoin
A
  1. AD
  2. Variable, typically childhood
  3. Severe neutropenia, cyclic neutropenia, neutropenic infections (bacterial, fungal), MDS/leukemia
34
Q

X-linked neutropenia:

  1. Age of onset
  2. Presentation
A
  1. Childhood

2. Gain-of-function mutation in Wiskott gene -> myeloid maturation arrest

35
Q

Schwachman-Diamond syndrome

  1. Inheritance
  2. Age of onset
  3. Presentation
A
  1. AR
  2. 0-18y
  3. Neutropenia, pancytopenia, exocrine pancreatic insufficiency, skeletal abnormalities
36
Q

Leukocyte adhesion deficiency (LAD)

  1. Inheritance
  2. Age of onset
  3. Presentation
A
  1. AR
  2. Infancy
  3. Delayed umbilical cord separation, omphalitis, gingivitis, periodontitis, bacterial and fungal mucous membrane infections without pus
37
Q

Complement defect infections

A

Recurrent sinopulmonary infections, bacteremia, and/or meningitis (mild to moderate severity)

Encapsulated bacteria - S. pneumoniae, H. influenza type B, N. meningitidis

Recurrent pyogenic infections when other components of immune system are normal

38
Q

Complement defect associated syndromes (2):

A
  1. SLE

2. atypical hemolytic uremic syndrome

39
Q

Folate metabolism Defects (3)

A
  1. Hereditary folate malabsorption
  2. Methylenetetrahydrofolate dehydrogenase (MTHFD1) Deficiency
  3. Hyper IgE (Job’s) Syndrome
40
Q

Hereditary folate malabsorption defect

A

Defect in proton-coupled folate transporter leading to decreased intestinal absorption of folate and folate intake through blood-brain-barrier

41
Q

Hereditary folate malabsorption presentation

A

Megaloblastic anemia
Pancytopenia -> T-cell lymphocytopenia -> SCID-like infections (PJP most common)
Also with hypogammaglobulinemia

Other symptoms include diarrhea, oral mucositis, failure to thrive, developmental delay, seizures

42
Q

Hereditary folate malabsorption diagnosis

A

Serum and CSF folate concentrations

Can have normal serum folate but elevations in total homocysteine

43
Q

Hereditary folate malabsorption treatment

A

Folinic acid (NOT folic acid, which interferes with active folinic acid transport)

44
Q

Hyper IgE (Job’s) Syndrome defect

A

AD mutation in STAT3

45
Q

Hyper IgE Presentation

A

Newborn eosinophilic pustulosis followed by eczematoid dermatitis

Cold skin abscesses (without inflammatory reaction)

Formation of pneumoatceles following lung infections

Retained primary teeth, scholiosis, fractures under minimal trauma, joint laxity, increased nasal widgth

46
Q

Adult-onset (or diagnosis) immunodeficiency syndromes (5)

A 
GATA2 Deficiency
Familial HLH
IgA deficiency
CVID
Complement defects?
47
Q

Adult-onset/diagnosis immunodeficiency-like syndromes (4)

A

Good’s syndrome
Atypical hemolytic uremic syndrome
Pulmonary alveolar proteinosis
Adult-onset susceptibility to mycobacteria

48
Q

Good’s Syndrome:

  1. Inheritance
  2. Age onset
  3. Manifestations
A
  1. Unknown
  2. 40-70
  3. Hypogammaglobulinemia with thymoma, severe opportunistic infections (CMV, PJP)
49
Q

Atypical hemolytic uremic syndrome

  1. Inheritance
  2. Age onset
  3. Manifestations
A
  1. AD, AR, autoimmune
  2. 10-60
  3. Fever with hemolytic anemia, thrombocytopenia and renal failure
50
Q

Pulmonary alveolar proteinosis

  1. Inheritance
  2. Age onset
  3. Manifestations
A
  1. Autoimmune
  2. 20-40
  3. Antibodies to GM-CSF, cryptococcal meningitis, Nocardia, PAP
51
Q

Adult-onset susceptibilty to mycobacteria

  1. Etiology
  2. Age onset
  3. Manifestations
A
  1. Autoimmune, antibodies to IFN-gamma
  2. 30-60
  3. Infections with mycobacteria, fungi, salmonella, VZV
52
Q

T cell defects

  1. Main issue
  2. Age at presentation
  3. Most common organisms
  4. Most commonly affected organs
A
  1. Cellular immunity
  2. Infancy (<6 mo if classic)
  3. Intracellular, viruses, fungi, protozoa
    (Herpesviridae, pneumocystis, candida, cryptococcus, histoplasma)
  4. Systemic
53
Q

B cell defects

  1. Main issue
  2. Age at presentation
  3. Most common organisms
  4. Most commonly affected organs
A
  1. Antibodies
  2. 6-12 months (after waning of maternal Ab)
  3. Encapsulated bacteria (staph, strep pneumo, H. flu)
  4. Respiratory (sinus, pneumonias, GI/diarrhea)
54
Q

Phagocytic defects

  1. Main issue
  2. Age at presentation
  3. Most common organisms
  4. Most commonly affected organs
A
  1. Dysfunctional phagocytosis
  2. First 2 years of life
  3. Catalase positive bacteria (staph, serratia, nocardia) and fungi (aspergillus)
  4. Skin, GI, GU, dental
55
Q

Complement defects

  1. Main issue
  2. Age at presentation
  3. Most common organisms
  4. Most commonly affected organs
A
  1. Opsonization, cell lysis
  2. Childhood (opsonization) to adulthood (terminal complement)
  3. Bacteria (Neisseria, streptococcus)
  4. Central nervous system (meningitis)
56
Q

Disseminated infections with mycobacteria, TB, salmonella predisposition (3)

A

IL-12 deficiency (AR)
IL-23 deficiency (AR)
Interferon-gamma receptor deficiency (AR/AD)

57
Q

Familial candidiasis predisposition (1)

A

CARD9 deficiency (AR)

58
Q

Chronic mucocutaneous candidiasis (CMC) predisposition (2)

A

IL-17 deficiency (AR) - affects skin, scalp, mucosa, nails; +/- staph skin infections

Autoimmune polyendocrine candidiasis ectodermal dystrophy (APECED) syndrome (AR/AD) - CMC, Addison Disease, hypoparathyroidism, metaphyseal dysplasia

59
Q

Predisposition to chronic cholangitis and hepatic cirrhosis due to cryptosporidium infection (1)

A

IL-21 receptor deficiency (AR)

60
Q

Predisposition to EBV (chronic viremia, EBV-lymphoproliferative disorder, dysgammaglobulinemia) (5)

A 
ITK deficiency (AR)
MAGT1 deficiency (XL)
STK4 deficiency (AR)
CD27 deficiency (AR)
Coronin-1A deficiency (AR)
61
Q

Predisposition to HPV with disseminated wart-like papules with malignant potential

A

Epidermodysplasia veruciformis (AR)

62
Q

Predisposition to HPV with myelokathexis (retention of neutrophils in bone marrow), hypogammaglobulinemia and warts

A

CXCR4 deficiency (AD)

63
Q

DOCK-8 deficiency

A 
(AR)
Hyperimmunoglobulin E
Eosinophilia
Severe viral skin infections (HPV)
Recurrent staph infections
Lack of connective tissue or skeletal involvement
64
Q

Predisposition to herpes encephalitis

A

Toll-like receptor 3 deficiency (AD, incomplete penetrance)

65
Q

Predisposition to mucocutaneous HSV

A

Caspase 8 (AR)

66
Q

Diagnosis of complement deficiency

A

CH50

67
Q

PJP prophylaxis

A

All PID with low CD4 (SCID) or CD4 dysfunction (CD40L deficiency)

68
Q

Anticandidal prophylaxis

A

Severe T-cell defects (SCID)

69
Q

Anti-aspergillus prophylaxis

A

CGD

Prolonged, nonbenign neutropenia

70
Q

CGD prophylaxis

A

Aspergillus
TMP-SMX
Interferon-gamma

ID Board Review (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions