Immune Responses Flashcards
What type of disorder is x-linked (Bruton) agammaglobulinemia?
B-cell disorder
What type of disorder is selective IgA deficiency?
B-cell disorder
What type of disorder is common variable immunodeficiency?
B-cell disorder
What is the defect in x-linked (Bruton) agammaglobulinemia?
Defect in BTK, a tyrosine kinase gene → no B-cell maturation. X-linked recessive (↑ in Boys).
What are the B-cell immunodeficiencies?
- X-linked (Bruton) agammaglobulinemia
- Selective IgA deficiency
- Common variable immunodeficiency
How does x-linked (Bruton) agammaglobulinemia present?
Recurrent bacterial and enteroviral infections after 6 months (↓ maternal IgG).
What is the defect in selective IgA deficiency?
Unknown. Most common 1° immunodeficiency.
What are the findings in x-linked (Bruton) agammaglobulinemia?
Absent B cells in peripheral blood, ↓ Ig of all classes. Absent/scanty lymph nodes and tonsils.
How does selective IgA deficiency present?
- Majority Asymptomatic.
- Airway infections
- GI infections
- Autoimmune disease
- Atopy
- Anaphylaxis to IgA-containing products.
What are the findings in selective IgA deficiency?
↓ IgA with normal IgG, IgM levels.
What is the defect in common variable immunodeficiency?
Defect in B-cell differentiation. Many causes.
How does common variable immunodeficiency present?
Can be acquired in 20s–30s;
↑ risk of autoimmune disease,
bronchiectasis,
lymphoma,
sinopulmonary infections.
What are the findings in common variable immunodeficiency?
↓ plasma cells
↓ immunoglobulins.
What are the T cell immunodeficiencies?
- Thymic aplasia (DiGeorge syndrome)
- IL-12 receptor deficiency
- Autosomal dominant hyper-IgE syndrome (Job syndrome)
- Chronic mucocutaneous candidiasis
What is the defect in thymic aplasia (DiGeorge syndrome)?
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches → absent thymus and parathyroids.
How does thymic aplasia (DiGeorge syndrome) present?
- tetany (hypocalcemia)
- recurrent viral/fungal infections (T-cell deficiency)
- conotruncal abnormalities (e.g., tetralogy of Fallot, truncus arteriosus).
What are the findings in thymic aplasia (DiGeorge syndrome)?
- ↓ T cells
- ↓ PTH
- ↓ Ca2+
- Absent thymic shadow onCXR.
- 22q11 deletion detected by FISH.
What is the defect in IL-12 receptor deficiency?
↓ Th1 response. Autosomal recessive.
How does IL-12 receptor deficiency present?
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.
What are the findings in IL-12 receptor deficiency?
↓ IFN-γ
What is the defect in autosomal dominant hyper-IgE syndrome (Job syndrome)?
Deficiency of Th17 cells due to STAT3 mutation → impaired recruitment of neutrophils to sites of infection.
How does autosomal dominant hyper-IgE syndrome (Job syndrome) present?
FATED:
- coarse Facies
- cold (noninflamed) staphylococcal Abscesses
- retained primary Teeth
- ↑ IgE
- Dermatologic problems (eczema).
What are the findings in autosomal dominant hyper-IgE syndrome (Job syndrome)?
↑ IgE
↓ IFN-γ
What is the defect in chronic mucocutaneous candidiasis?
T-cell dysfunction. Many causes.
How does chronic mucocutaneous candidiasis present?
Noninvasive Candida albicans infections of skin and mucous membranes.
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.
What are the B- and T-cell disorders?
- Severe combined immunodeficiency (SCID)
- Ataxia-telangiectasia
- Hyper IgM syndrome
- Wiskott-Aldrich syndrome
What is the defect in severe combined immunodeficiency (SCID)?
Several types including:
- defective IL-2R gamma chain (most common, X-linked)
- adenosine deaminase deficiency (autosomal recessive).
How does severe combined immunodeficiency (SCID) present?
- failure to thrive
- chronic diarrhea
- thrush
- Recurrent viral, bacterial, fungal, and protozoal infections.
Treatment: bone marrow transplant (no concern for rejection).
What are the findings in severe combined immunodeficiency (SCID)?
- ↓ T-cell receptor excision circles (TRECs)
- absence of thymic shadow (CXR)
- absence of germinal centers (lymph node biopsy)
- absence of T cells (flow cytometry).
What is the defect in ataxia-telangiectasia?
Defects in ATM gene → failure to repair DNA double strand breaks → cell cycle arrest.
How does in ataxia-telangiectasia present?
Triad:
1. cerebellar defects (Ataxia)
- spider Angiomas (telangiectasia)
- IgA deficiency
What are the findings in t in ataxia-telangiectasia?
- ↑ AFP.
- ↓ IgA, IgG, and IgE
- Lymphopenia
- cerebellar atrophy
What is the defect in hyper-IgM syndrome?
Most commonly due to defective CD40L on Th cells → class switching defect; X-linked recessive.
How does hyper-IgM syndrome present?
- Severe pyogenic infections early in life
- opportunistic infection with Pneumocystis
- Cryptosporidium
- CMV
What are the findings in hyper-IgM syndrome?
- ↑ IgM
- ↓ ↓ IgG, IgA, IgE
What is the defect in Wiskott-Aldrich syndrome?
Mutation in WAS gene (X-linked recessive); T cells unable to reorganize actin cytoskeleton.
How does Wiskott-Aldrich syndrome present?
WATER: Wiskott-Aldrich:
- Thrombocytopenic purpura
- Eczema
- Recurrent infections
- ↑ risk of autoimmune disease and malignancy
What are the findings in Wiskott-Aldrich syndrome?
- ↓ to normal IgG, IgM
- ↑ IgE, IgA
- Fewer and smaller platelets
What are the phagocyte dysfunction immunodeficiencies?
- Leukocyte adhesion deficiency (type 1)
- Chediak-Higashi syndrome
- Chronic granulomatous disease
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.
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)
What are the findings in leukocyte adhesion deficiency (type 1)?
- ↑ neutrophils
- absence of neutrophils atinfection sites
What is the defect in Chédiak-Higashi syndrome?
Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive.
How does Chédiak-Higashi syndrome present?
- Recurrent pyogenic infections by staphylococci and streptococci
- partial albinism
- peripheral neuropathy
- progressive neurodegeneration
- infiltrative lymphohistiocytosis
What are the findings in Chédiak-Higashi syndrome?
- Giant granules in granulocytes and platelets
- Pancytopenia
- Mild coagulation defects
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.
How does chronic granulomatous disease present?
↑ susceptibility to catalase ⊕ organisms (Need PLACESS):
- Nocardia
- Pseudomonas
- Listeria
- Aspergillus
- Candida
- E. coli
- S. aureus
- Serratia
What are the findings in chronic granulomatous disease?
Abnormal dihydrorhodamine (flow cytometry) test.Nitroblue tetrazolium dye reduction test is ⊝.
↓ T cells cause these bacterial infections:
Sepsis
↓ T cells cause these viral infections:
- CMV
- EBV3. JCV
- VZV
- Chronic infection with respiratory/GI viruses
↓ T cells cause these fungal/parasitic infections:
- Candida (local)
- PCP
↓ B cells cause these bacterial infections:
Encapsulated:
- Streptococcus pneumoniae
- Haemophilus influenzae type B
- Neisseria meningitidis
- Escherichia coli
- Salmonella
- Klebsiella pneumoniae
- group B Strep
(SHiNE SKiS)
↓ B cells cause these viral infections:
- Enteroviral encephalitis
- Poliovirus (live vaccine contraindicated)
↓ B cells cause these fungal/parasitic infections:
GI giardiasis (no IgA)
↓ granulocytes cause these bacterial infections:
- Staphylococcus
- Burkholderia cepacia
- Pseudomonas aeruginosa
- Serratia
- Nocardia
↓ granulocytes cause these viral infections:
N/A
