Innate Immunodeficiencies

Question 1

Asplenia

Answer 1

susceptibility: encapsulated extracellular bacteria (H. influenza, S. pneumonia, Neisseria)
Clincal: vaccinate against encapsulated and prophylactic antibiotics before dental surgery and when showing signs of respiratory infection and fever

Question 2

C3 deficiency

Answer 2

can’t activate any complement cascade
susceptibility: bacterial infection, esp. encapsulated bacteria
MORE serious than Factor I deficiency

Question 3

Paroxysmal nocturnal hemoglobinuria

Answer 3

gene: mutations in genes involved in phosphatidylinositol glycan biosynthesis
immune defect: lack of DAF, HRF, CD59
CD59 and DAF: control proteins that interfere with MAC formation
susceptibility: lysis of erythrocytes by complement
Clinical: hemolytic anemia, red urine, thrombosis
Tx: bone marrow transplant; eculizumab (Soliris): C5 specific; reduces need for blood transfusions

Question 4

X-linked hypohidrotic ectodermal dysplasia and immunodeficiency

Answer 4

gene: NEMO or IKK gamma deficiency
immune defect: impaired activation of NFkB (Toll-like receptors activate NFkB->cytokines)
susceptibility: chronic bacterial and viral infections (mycobacterium is common)
developmental defects: deep set eyes, sparse or fine hair, conical or missing teeth, incontinentia pigmenti (blistering and color change in skin)
Tx: gamma globulin injections; bone marrow transplant

Question 5

Chronic granulomatous disease

Answer 5

mutation results in non-functional p91 protein
gene: NADPH oxidase
immune defect: impaired neutrophil function-can’t killed phagocytosed bacteria
susceptibility: organisms that make catalase (S. aureus, E. coli, Klebsiella, Aspergillus, Serratia marcescens, Nocordia, Candida); chronic bacterial and fungal infections; granulomas
MUST test infants with skin or bone infection with SERRATIA MARCESCENS
Dx: negative DHR (dihydroorhodamine) test or negative nitroblue tetrazolium dye test
Tx: prophylactic TMP-SMX (antibiotic), itraconazole, IFN-gamma

Question 6

MBL deficiency

Answer 6

MBL-> MASP->lectin pathway

susceptibility: severe recurrent infections; Neisseria meningitidis

Question 7

NK-cell deficiency

Answer 7

Genetic Deficiency: perforin, defective formation of cytoplasmic granules, or development in bone marrow
susceptibility: herpes virus, VZV, CMV, EBV, mycobacterium avium/intracellulare, trichophytan (hair, skin, and nail fungal infections)

Question 8

Leukocyte adhesion deficiency

Answer 8

Defective CD18
defective migration of phagocytes into infected tissues
Susceptibility: fungal and bacterial infections; especially capsulated bacteria
clinical: delayed sloughing of umbilical cord

Question 9

Glucose-6-phosphate dehydorgenase (G6PD) deficiency

Answer 9

defective respiratory burst (can’t produce superoxide or hydrogen peroxide)- impaired killing of phagocytosed bacteria
susceptibility: bacterial and fungal infections
clinical: anemia
low levels of C3 and factor B (complement gets used up)

Question 10

Myeloperoxidase deficiency

Answer 10

Normal function; catalyze production of HOCl
deficiency: impaired production of toxic oxygen species in neutrophil granules and macrophage lysosomes
impaired killing of phagocytes bacteria
susceptibility: bacterial and fungal infections
Anemia

Question 11

Chediak-Higashi syndrome

Answer 11

gene: LYST
defect in vesicle fusion
impaired phagocytosis due to inability of endosomes to fuse with lysosomes
susceptibility: bacterial infections, granulomas
Clinical: albinism, recurrent pyogenic infection (strep and staph), neurological disorders
Dx: poorly organized and larger than normal azurophilic granules in neutrophils
Tx: bone marrow transplant (or will develop fatal lymphoma-like proliferating disease)

Question 12

Neutropenia

Answer 12

neutrophil count of <500 cells/ul
susceptibility: bacterial and fungal infections, including normal flora
slow response to infection and slow to resolve

Question 13

Kostmann syndrome

Answer 13

severe congenital neutropenia (AR)

gene: G-CSF (stimulates granulocyte growth) or receptor

Question 14

cyclic neutropenia

Answer 14

neutropenia every 2-4 weeks (AD)

gene: ELA-2

Question 15

benign chronic neutropenia

Answer 15

low but not life threatening neutropenia

asymptomatic

Question 16

immunodeficiencies that have high incidence of associated nuetropenia

Answer 16

X-linked hyper-IgM syndrome
X-linked agammaglobulinemia (XLA)
WHIM syndrome
Griselli Syndrome

Question 17

susceptibility when C3b deposition is reduced

Answer 17

bacterial infections

Question 18

Deficiency of C5-C9

Answer 18

No MAC formation
susceptibility: Neisseria
C5 deficiency is more serious than C6-9

Question 19

Deficiency of C1, C2, C4

Answer 19

immune complex disease

– usually immune complexes (Ab-antigen)are opsonized by activation of classical complement cascade

Question 20

Deficiency of Factor D

Answer 20

critical component of alternative pathway

susceptibility: capsulated bacteria and Neisseria

Question 21

Factor P deficiency

Answer 21

susceptibility: capsulated bacteria and Neisseria

Question 22

Factor I

Answer 22

similar to C3 deficiency: final result depletion of C3b

• • reduced cleavage of C3b or C4b-> abnormally high amounts of C3 converts-> uses up all of C3
    susceptibility: capsulated bacteria

Question 23

C1INH deficiency

Answer 23

disease: HANE (hereditary angioneurotic edema)

C1 inhibitor: binds to activated C1r: C1s forcing them to dissociate from C1q (controls spontaneous activation of C1)