Immune deficiency disorders

Question 1

X-linked agammaglobulinemia (Bruton disease)
Defect:
Presentation:

Answer 1

Defect: BTK - a tyrosine kinase gene - no B cell maturation
Presentation: recurrent bacterial and enteroviral infections after 6 months

Question 2

Selective IgA deficiency
Defect:
Presentation:

Answer 2

Defect: Unknown (most common primary immunodeficiency)
Presentation: Asymptomatic (most); Airway and GI infections

Question 3

Common variable immunodeficiency
Defect:
Presentation:

Answer 3

Defect: Defect in B-cell differentiation
Presentation: Acquired in 20s-30s; increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections

Question 4

Thymic aplasia (DiGeorge syndrome)
Defect:
Presentation:

Answer 4

Defect: 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches
Presentation: Tetany (hypocalcemia), recurrent infections, conotruncal abnormalities

Question 5

IL-12 receptor deficiency
Defect:
Presentation:

Answer 5

Defect: Decreased Th1 response, Autosomal recessive
Presentation: Disseminated mycobacterial and fungal infections; decreased IFN-gamma

Question 6

Autosomal dominant hyper-IgE syndrome
Defect:
Presentation:

Answer 6

Defect: Deficiency of Th17 cells due to STAT3 mutation leads to impaired recruitment of neutrophils to site of infection
Presentation: Coarse Facies, cold staphylococcal Abscesses, retained primary teeth, Increased IgE, Dermatologic problems

Question 7

Chronic mucocutaneous candidiasis
Defect:
Presentation:

Answer 7

Defect: T cell dysfunction
Presentation: non-invasive candida albicans infections of skin and mucous membranes

Question 8

SCID
Defect:
Presentation:

Answer 8

Defect: Defective IL-2R gammaa chain (most common); Adenosine deaminase deficiency
Presentation: Failure to thrive; chronic diarrhea, thrush, recurrent infections

Question 9

Ataxia-telangiectasia
Defect:
Presentation:

Answer 9

Defect: Defects in ATM gene lead to DNA double strand breaks and cell cycle arrest
Presentation: Cerebellar defects, spider angiomas, IgA deficiency (increased AFP)

Question 10

Hyper-IgM syndrome
Defect:
Presentation:

Answer 10

Defect: Defective CD40L on Th cells = class switching defect (X-linked recessive)
Presentation: Severe pyogenic infections early in life (pneumocystitis, cryptosporidium, CMV)

Question 11

Wiskott-Aldrich syndrome
Defect:
Presentation:

Answer 11

Defect: Mutation in WAS gene; T cells unable to reorganize actin cytoskeleton
Presentation: WATER: Wiskot-Aldrich; Thrombocytopenic purpura, Eczema, Recurrent infections

Question 12

Leuckocyte adhesion deficiency (type 1)
Defect:
Presentation:

Answer 12

Defect: Defect in LFA-1 integrin (CD1) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive
Presentation: Recurrent bacterial skin and mucosal infections; delayed separation of umbilical cord

Question 13

Chediak-Higashi syndrome
Defect:
Presentation:

Answer 13

Defect: Defect in lysosomal trafficking regulator gene; microtubule dysfunction in phagosome-lysosome fusion
Presentation: Recurrent pyogenic infectiouns by staphyloccoci and streptococci, partial albinism, peripheral neuropathy, lymphohistiocytosis

Question 14

Chronic granulomatous disease
Defect:
Presentation:

Answer 14

Defect: Defect of NADPH oxidase leads to decreased reactive oxygen species and absent respiratory burst
Presentation: Increased susceptibility to catalase positive organisms

Question 15

What type of transplant rejection is seen within minutes of transplant? (what type of reaction, what happens to the graft)

Answer 15

Type II reaction

Widespread thrombosis of graft vessels

Question 16

What type of transplant rejection occurs within weeks/months? (type of cells, what happens to graft)

Answer 16

CTLs against donor MHCs and humoral response

Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate

Question 17

What type of transplant rejection occurs after months/years? (What makes this the worse type of host response to graft)

Answer 17

Recipient T-cells perceive donor MHC as recipient MHC and react against donor antigens presented - irreversible and organs specific (Heart, Lungs, Liver, Kidney)
Obliterative vascular fibrosis, parenchyma atrophy