deck_3459396 Flashcards
1
Q
What type of disorder is x-linked (Bruton)agammaglobulinemia?
A
B-cell disorder
2
Q
What type of disorder is selective IgA deficiency?
A
B-cell disorder
3
Q
What type of disorder is common variable immunodeficiency?
A
B-cell disorder
4
Q
What is the defect in x-linked (Bruton) agammaglobulinemia?
A
Defect in BTK, a tyrosine kinase gene → no B-cell maturation. X-linked recessive (↑ in Boys).
5
Q
What are the B-cell immunodeficiencies?
A
- X-linked (Bruton) agammaglobulinemia- Selective IgA deficiency- Common variable immunodeficiency
6
Q
How does x-linked (Bruton) agammaglobulinemia present?
A
Recurrent bacterial and enteroviral infections after 6 months (↓ maternal IgG).
7
Q
What is the defect in selective IgA deficiency?
A
Unknown. Most common 1° immunodeficiency.
8
Q
What are the findings in x-linked (Bruton) agammaglobulinemia?
A
Absent B cells in peripheral blood, ↓ Ig of all classes. Absent/scanty lymph nodes and tonsils.
9
Q
How does selective IgA deficiency present?
A
- Majority Asymptomatic.2. Airway infections3. GI infections4. Autoimmune disease5. Atopy6. Anaphylaxis to IgA-containing products.
10
Q
What are the findings in selective IgA deficiency?
A
↓ IgA with normal IgG, IgM levels.
11
Q
What is the defect in common variable immunodeficiency?
A
Defect in B-cell differentiation. Many causes.
12
Q
How does common variable immunodeficiency present?
A
Can be acquired in 20s–30s;↑ risk of autoimmune disease,bronchiectasis,lymphoma,sinopulmonary infections.
13
Q
What are the findings in common variable immunodeficiency?
A
↓ plasma cells↓ immunoglobulins.
14
Q
What are the T cell immunodeficiencies?
A
- Thymic aplasia (DiGeorge syndrome)- IL-12 receptor deficiency- Autosomal dominant hyper-IgE syndrome (Job syndrome)- Chronic mucocutaneous candidiasis
15
Q
What is the defect in thymic aplasia (DiGeorge syndrome)?
A
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches → absent thymus and parathyroids.
16
Q
How does thymic aplasia (DiGeorge syndrome) present?
A
- tetany (hypocalcemia)2. recurrent viral/fungal infections (T-cell deficiency)3. conotruncal abnormalities (e.g., tetralogy of Fallot, truncus arteriosus).
17
Q
What are the findings in thymic aplasia (DiGeorge syndrome)?
A
- ↓ T cells2. ↓ PTH3. ↓ Ca2+4. Absent thymic shadow onCXR.5. 22q11 deletion detected by FISH.
18
Q
What is the defect in IL-12 receptor deficiency?
A
↓ Th1 response. Autosomal recessive.
19
Q
How does IL-12 receptor deficiency present?
A
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.
20
Q
What are the findings in IL-12 receptor deficiency?
A
↓ IFN-γ
21
Q
What is the defect in autosomal dominant hyper-IgE syndrome (Job syndrome)?
A
Deficiency of Th17 cells due to STAT3 mutation → impaired recruitment of neutrophils to sites of infection.
22
Q
How does autosomal dominant hyper-IgE syndrome (Job syndrome) present?
A
FATED:- coarse Facies- cold (noninflamed) staphylococcal Abscesses- retained primary Teeth- ↑ IgE- Dermatologic problems (eczema).
23
Q
What are the findings in autosomal dominant hyper-IgE syndrome (Job syndrome)?
A
↑ IgE↓ IFN-γ
24
Q
What is the defect in chronic mucocutaneous candidiasis?
A
T-cell dysfunction. Many causes.
25
How does chronic mucocutaneous candidiasis present?
Noninvasive Candida albicans infections of skin and mucous membranes.
26
What are the findings in chronic mucocutaneous candidiasis?
- Absent in vitro T-cell proliferation in response to Candida antigens.- Absent cutaneous reaction to Candida antigens.
27
What are the B- and T-cell disorders?
- Severe combined immunodeficiency (SCID)- Ataxia-telangiectasia- Hyper IgM syndrome- Wiskott-Aldrich syndrome
28
What is the defect in severe combined immunodeficiency (SCID)?
Several types including:1. defective IL-2R gamma chain (most common, X-linked)2. adenosine deaminase deficiency (autosomal recessive).
29
How does severe combined immunodeficiency (SCID) present?
1. failure to thrive2. chronic diarrhea3. thrush4. Recurrent viral, bacterial, fungal, and protozoal infections.Treatment: bone marrow transplant (no concern for rejection).
30
What are the findings in severe combined immunodeficiency (SCID)?
1. ↓ T-cell receptor excision circles (TRECs)2. absence of thymic shadow (CXR)3. absence of germinal centers (lymph node biopsy)4. absence of T cells (flow cytometry).
31
What is the defect in ataxia-telangiectasia?
Defects in ATM gene → failure to repair DNA double strand breaks → cell cycle arrest.
32
How does in ataxia-telangiectasia present?
Triad:1. cerebellar defects (Ataxia)2. spider Angiomas (telangiectasia)3. IgA deficiency
33
What are the findings in t in ataxia-telangiectasia?
1. ↑ AFP.2. ↓ IgA, IgG, and IgE3. Lymphopenia4. cerebellar atrophy
34
What is the defect in hyper-IgM syndrome?
Most commonly due to defective CD40L on Th cells → class switching defect; X-linked recessive.
35
How does hyper-IgM syndrome present?
1. Severe pyogenic infections early in life2. opportunistic infection with Pneumocystis3. Cryptosporidium4. CMV
36
What are the findings in hyper-IgM syndrome?
1. ↑ IgM2. ↓ ↓ IgG, IgA, IgE
37
What is the defect in Wiskott-Aldrich syndrome?
Mutation in WAS gene (X-linked recessive); T cells unable to reorganize actin cytoskeleton.
38
How does Wiskott-Aldrich syndrome present?
WATER: Wiskott-Aldrich:1. Thrombocytopenic purpura2. Eczema3. Recurrent infections4. ↑ risk of autoimmune disease and malignancy
39
What are the findings in Wiskott-Aldrich syndrome?
1. ↓ to normal IgG, IgM2. ↑ IgE, IgA3. Fewer and smaller platelets
40
What are the phagocyte dysfunction immunodeficiencies?
- Leukocyte adhesion deficiency (type 1)- Chediak-Higashi syndrome- Chronic granulomatous disease
41
What is the defect in leukocyte adhesion deficiency (type 1)?
Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive.
42
How does leukocyte adhesion deficiency (type 1) present?
- recurrent bacterial skin and mucosal infections- absent pus formation- impaired wound healing- delayed separation of umbilical cord (> 30 days)
43
What are the findings in leukocyte adhesion deficiency (type 1)?
1. ↑ neutrophils2. absence of neutrophils atinfection sites
44
What is the defect in Chédiak-Higashi syndrome?
Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive.
45
How does Chédiak-Higashi syndrome present?
1. Recurrent pyogenic infections by staphylococci and streptococci2. partial albinism3. peripheral neuropathy4. progressive neurodegeneration5. infiltrative lymphohistiocytosis
46
What are the findings in Chédiak-Higashi syndrome?
1. Giant granules in granulocytes and platelets2. Pancytopenia3. Mild coagulation defects
47
What is the defect in chronic granulomatous disease?
Defect of NADPH oxidase → ↓ reactive oxygen species (e.g., superoxide) and ↓ respiratory burst in neutrophils; X-linked recessive most common.
48
How does chronic granulomatous disease present?
↑ susceptibility to catalase ⊕ organisms (Need PLACESS):- Nocardia- Pseudomonas- Listeria- Aspergillus- Candida- E. coli- S. aureus- Serratia
49
What are the findings in chronic granulomatous disease?
Abnormal dihydrorhodamine (flow cytometry) test.Nitroblue tetrazolium dye reduction test is ⊝.
50
↓ T cells cause these bacterial infections:
Sepsis
51
↓ T cells cause these viral infections:
1. CMV2. EBV3. JCV4. VZV5. Chronic infection with respiratory/GI viruses
52
↓ T cells cause these fungal/parasitic infections:
1. Candida (local)2. PCP
53
↓ B cells cause these bacterial infections:
Encapsulated:1. Streptococcus pneumoniae2. Haemophilus influenzae type B3. Neisseria meningitidis4. Escherichia coli5. Salmonella6. Klebsiella pneumoniae7. group B Strep(SHiNE SKiS)
54
↓ B cells cause these viral infections:
1. Enteroviral encephalitis2. Poliovirus (live vaccine contraindicated)
55
↓ B cells cause these fungal/parasitic infections:
GI giardiasis (no IgA)
56
↓ granulocytes cause these bacterial infections:
1. Staphylococcus2. Burkholderia cepacia3. Pseudomonas aeruginosa4. Serratia5. Nocardia
57
↓ granulocytes cause these viral infections:
N/A
58
↓ granulocytes cause these fungal/parasitic infections:
1. Candida (systemic)2. Aspergillus
59
↓ complement causes these bacterial infections:
1. Encapsulated species with early component deficiencies2. Neisseria with late component (MAC) deficiencies
60
↓ complement causes these viral infections:
N/A
61
↓ complement causes these fungal/parasitic infections:
N/A
62
General rules about B and T cell deficiency infections:
B-cell deficiencies tend to produce recurrent bacterial infections, whereas T-cell deficiencies produce more fungal and viral infections.
63
Autograft
from self
64
Syngeneic graft (isograft)
from identical twins or clone
65
Allograft
from nonidentical individual of same species
66
Xenograft
from different species
67
Hyperacute transplant rejection onset
within minutes
68
Acute transplant rejection onset
weeks to months
69
Chronic transplant rejection onset
months to years
70
Graft vs. host disease onset
varies
71
Hyperacute transplant rejection pathogenesis
Pre-existing recipient antibodies react to donor antigen (type II hypersensitivity reaction), activate complement.
72
Acute transplant rejection pathogenesis
Cellular: CD8+ T cells activated against donor MHCs.Humoral: similar to hyperacute, except antibodies develop after transplant.
73
Chronic transplant rejection pathogenesis
CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC .Both cellular and humoral components.
74
Graft vs. host disease pathogenesis
Grafted immunocompetent T cells proliferate in theimmunocompromised host and reject host cells with “foreign” proteins → severe organ dysfunction.
75
Hyperacute transplant rejection features
Widespread thrombosis of graft vessels → ischemia/necrosis. Graft must be removed.
76
Acute transplant rejection features
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate. Prevent/reverse with immunosuppressants.
77
Chronic transplant rejection features
Recipient T cells reactand secrete cytokines → proliferation of vascular smooth muscle and parenchymal fibrosis. Dominated by arteriosclerosis.
78
Graft vs. host disease rejection features
* Maculopapular rash
* jaundice
* diarrhea
* hepatosplenomegalyUsually in bone marrow and liver transplants (rich in lymphocytes). Potentially beneficial inbone marrow transplant for leukemia (graft-versus-tumor effect).
79
What is the autoantibody associated with this disorder?myasthenia gravis
Anti-ACh receptor
80
What is the autoantibody associated with this disorder?Goodpasture syndrome
Anti-basement membrane
81
What is the autoantibody associated with this disorder?SLE, antiphosphlipid syndrome
Anticardiolipin, lupus anticoagulant
82
What is the autoantibody associated with this disorder?Limited scleroderma (CREST syndrome)
Anticentromere
83
What is the autoantibody associated with this disorder?Pemphigus vulgaris
Anti-desmosome (anti-desmoglein)
84
What is the autoantibody associated with this disorder?SLE
Anti-dsDNA, anti-Smith
85
What is the autoantibody associated with this disorder?Type I diabetes mellitus
Anti-glutamic acid decarboxylase (GAD-65)
86
What is the autoantibody associated with this disorder?bullous pemphigoid
Antihemidesmosome
87
What is the autoantibody associated with this disorder?drug-induced lupus
Anti-histone
88
What is the autoantibody associated with this disorder?Polyomositis, dermatomyositis
Anti-Jo-1, anti-SRP, anti-Mi-2
89
What is the autoantibody associated with this disorder?Hashimoto thyroiditis
Antimicrosomal, antithyroglobulin
90
What is the autoantibody associated with this disorder?Primary biliary cirrhosis
Antimitochondrial
91
What is the autoantibody associated with this disorder?SLE, nonspecific
Antinuclear antibodies
92
What is the autoantibody associated with this disorder?Pernicious anemia
Antiparietal cell
93
What is the autoantibody associated with this disorder?Scleroderma (diffuse)
Anti-Scl-70 (anti-DNA topoisomerase I)
94
What is the autoantibody associated with this disorder?Autoimmune hepatitis
Anti-smooth muscle
95
What is the autoantibody associated with this disorder?Sjogren syndrome
Anti-SSA, anti-SSB (anti-Ro, anti-La)
96
What is the autoantibody associated with this disorder?Graves disease
Anti-TSH receptor
97
What is the autoantibody associated with this disorder?Mixed connective tissue disease
Anti-U1 RNP (ribonucleoprotein)
98
What is the autoantibody associated with this disorder?Celiac disease
IgA anti-endomysial, IgA anti-tissue transglutaminase
99
What is the autoantibody associated with this disorder?Microscopic polyangiitis, eosinophilic granulomatosis with polyangiitsi (Churg-Strauss syndrome)
MPO-ANCA/p-ANCA
100
What is the autoantibody associated with this disorder?Granulomatosi with polyangiitis (Wegener)
PR3-ANCA/c-ANCA
101
What is the autoantibody associated with this disorder?Rheumatoid arthritis
Rheumatoid factor, anti-CCP (more specific)
102
Examples of a type I hypersensitivity disorder
Allergic and atopic disorders Anaphylaxis
103
What are examples of allergic and atopic disorders?
- rhinitis - hay fever - eczema- hives- asthma
104
What can cause anaphylaxis?
- bee sting- some food/drug allergies
105
Examples of a type II hypersensitivity reaction
* Acute hemolytic transfusion reactions
* Autoimmune hemolytic anemia
* Bullous pemphigoid
* Erythroblastosis fetalis
* Goodpasture syndrome
* Graves disease
* Guillain-Barré syndrome
* Idiopathic thrombocytopenic purpura
* Myasthenia gravis
* Pemphigus vulgaris
* Pernicious anemia
* Rheumatic fever
106
How does a type I allergic reaction present?
Immediate, anaphylactic, atopic
107
What type of hypersensitivity disorder?Allergic and atopic disorders
Type I
108
What type of hypersensitivity disorder? Anaphylaxis
Type I
109
How does a type II alergic reaction present?
Disease tends to be specific to tissue or site where antigen is found
110
What type of hypersensitivity reaction is this?Acute hemolytic transfusion reactions
Type II
111
What type of hypersensitivity reaction is this? Autoimmune hemolytic anemia
Type II
112
What type of hypersensitivity reaction is this? Bullous pemphigoid
Type II
113
What type of hypersensitivity reaction is this? Erythroblastosis fetalis
Type II
114
What type of hypersensitivity reaction is this? Goodpasture syndrome
Type II
115
What type of hypersensitivity reaction is this? Graves disease
Type II
116
What type of hypersensitivity reaction is this?Guillain-Barré syndrome
Type II
117
What type of hypersensitivity reaction is this?Idiopathic thrombocytopenic purpura
Type II
118
What type of hypersensitivity reaction is this? Myasthenia gravis
Type II
119
What type of hypersensitivity reaction is this?Pemphigus vulgaris
Type II
120
What type of hypersensitivity reaction is this?Pernicious anemia
Type II
121
What type of hypersensitivity reaction is this?Rheumatic fever
Type II
122
Examples of a type III hypersensitivity reaction
* Arthus reaction (e.g., swelling and inflammation following tetanus vaccine)
* SLE
* Polyarteritis nodosa
* Poststreptococcal glomerulonephritis
* Serum sickness
123
How does a type III hypersensitivity reaction present?
Can be associated with vasculitis and systemic manifestations
124
What type of hypersensitivity reaction is this?Arthus reaction
Type III
125
What type of hypersensitivity reaction is this? SLE
Type III
126
What type of hypersensitivity reaction is this? Polyarteritis nodosa
Type III
127
What type of hypersensitivity reaction is this? Poststreptococcal glomerulonephritis
Type III
128
What type of hypersensitivity reaction is this?Serum sickness
Type III
129
Examples of a type IV hypersensitivity reaction
* Contact dermatitis (e.g., poison ivy, nickel allergy)
* Graft-versus-host disease
* Multiple sclerosis
* PPD (test for M. tuberculosis)
130
What can cause contact dermatitis?
poison ivy and nickel allergy
131
How does a type IV hypersensitivity reaction present?
Response is delayed and does not involve antibodies (vs. types I, II, and III)
132
What type of hypersensitivity reaction is this? Contact dermatitis
Type IV
133
What type of hypersensitivity reaction is this?Graft-versus-host disease
Type IV
134
What type of hypersensitivity reaction is this? Multiple sclerosis
Type IV
135
What type of hypersensitivity reaction is this?PPD
Type IV
136
What is the pathogenesis of a transfusion allergic reaction?
Type I hypersensitivity reaction against plasma proteins in transfused blood.
137
How does a transfusion allergic reaction present?
* Urticaria
* pruritus
* wheezing
* fever Treat with antihistamines.
138
What is the pathogenesis of a transfusion anaphylactic reaction?
Severe allergic reaction. IgA-deficient individuals must receive blood products without IgA.
139
How does a transfusion anaphylactic reaction present?
* dyspnea
* bronchospasm
* hypotension
* respiratory arrest
* shockTreat with epinephrine.
140
What is the pathogenesis of a febrile nonhemolytic transfusion reaction?
Type II hypersensitivity reaction. Host antibodies against donor HLA antigens and WBCs.
141
How does a febrile nonhemolytic transfusion reaction present?
* fever
* headaches
* chills
* flushing
142
What is the pathogenesis of an acute hemolytic transfusion reaction?
Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs).
143
How does an acute hemolytic transfusion reaction present?
* Fever
* hypotension
* tachypnea
* tachycardia
* flank pain
* hemoglobinuria (intravascular hemolysis)
* jaundice (extravascular)
