Immunodeficiencies

Question 1

Bruton agammaglobulinema

Answer 1

Defect in BTK (tyrosine kinase gene)

No B cells

X-linked recessive

Recurrent bacterial and enteroviral infxns after 6 months old when maternal IgG decreases

Question 2

Common variable immunodeficiency

Answer 2

Defect in B cell differentiation –> increased risk of autoimmune disease, bronchiectasis, lymphoma, infxns (less Ig)

Can be acquired

Question 3

DiGeorge syndrome

Answer 3

Thymic aplasia

22q11 deletion, fail to develop 3rd and 4th pharyngeal pouches –> no thymus or parathyroids

T cell deficiency –> recurrent viral/fungal infxn

heart abnml (eg ToF)

No PTH –> hypoCa –> tetany

Question 4

Job syndrome

Answer 4

Autosomal dominant hyper-IgE syndrome

Deficiencies of Th17 cells due to STAT3 mutation –> impaired recruitment of PMNs

Increased IgE, decreased IFN-gamma

Question 5

Chronic mucocutaneous candidiasis

Answer 5

T cell dysfxn (many causes)

Question 6

Severe combined immunodeficiency

Answer 6

Several types (eg IL-2R gamma chain defect - X linked, adenosine deaminase deficiency - autosomal recessive)

Tx: bone marrow transplant

No thymic shadow, no germinal centers in ln, no T cells on flow

Question 7

Ataxia telangiectasia

Answer 7

ATM gene defect –> can’t repair DNA ds breaks –> cell cycle arrest

CBL defects, spider angiomas, Ig deficiency

Increased AFP

Question 8

Hyper-IgM syndrome

Answer 8

Defective CD40L on Th cells –> no class switching of B cells (so lots of IgM, but not much IgG, A, or E)

X-linked recessive

Lots of pyogenic infxns

Question 9

Wiskott-Aldrich syndrome

Answer 9

Mutation in WAS gene (X-linked recessive)

T cells can’t reorganize actin

WATER:

Thrombocytopenic purpura
Eczema
Recurrent infxns

Decreased IgG, Increased IgE/A, decreased, small plts

Question 10

Leukocyte adhesion deficiency (type 1)

Answer 10

Defect in LFA-1 integrin (CD18) on phagocytes –> impaired migration and chemotaxis, so have increased neutrophils but not at the site of infxn where they’re needed

Recurrent skin and mucosal bacterial infxns, delayed separation of umb cord

Autosomal recessive

Question 11

Chediak-Higashi syndrome

Answer 11

Lysosomal trafficking defect (LYST), aut recessive

Granules accumulate in granulocytes and plts

Recurrent staph and strep infxns, partial albinism, peripheral neuropathy and neruodegeneration,

Question 12

CGD

Answer 12

NADPH oxidase deficiency –> decreased ROS and increased susc to catalase pos orgs

X linked rec

Negative nitroblue tetrazolium test (stains for ROS)