immunodeficiencies

Question 1

Chronic Granulomatous Disease

Answer 1

mech: reduced levels NADPH oxidase (makes o2-). can’t kill catalase+ bacteria
cells: phagocytes
symptoms: chronic inflammation and granuloma formation in lung, liver, brain. bone and skin infections

Question 2

Leukocyte adhesion defect LAD

Answer 2

mech: defective integrin/CD18
cells: increase neutrophil bc can’t get to tissue
symptoms: recurrent bacterial infections w/o pus
treatment: SCT

Question 3

Chediak-Higashi syndrome

Answer 3

mech: defect in phagosome lysosome fusion
cells: abnormal NK cells

symptoms: pyogenic bacterial and viral infections
albinism
abnormal platelets

Question 4

complement defect

Answer 4

mech: lack C2 and C4 or C2 and C3 early proteins
can also lack C5-9

symptoms: AI disease
increase encapsulated bacteria infections
NESSERIA INFECTIONS

Question 5

defective TLR signaling

Answer 5

mech: can’t get proper pro-inflammatory cytokines
cells: No IL-1, IL-6, TNF-a, IL-12
symptoms: severe viral or pyogenic bacterial infections w/o inflammation

Question 6

SCID X-linked

Answer 6

mech: mutation in gene for common gamma chain for IL-2, 4, 7, 9, 15, 21
cells: defective T and NK cells (need 7 and 15). B cells fine

Question 7

SCID - general

Answer 7

absent T cell or function
may affect B and NK cells
B cells present but can’t fully function
get early onset bacterial, viral and fungal pathogens

Question 8

SCID - defective purine metabolism

Answer 8

mech: ADA and PNP deficiency create toxic metabolites to T, B and NK
cells: low T, B and NK cells
treatment: enzyme replacement

Question 9

SCID - VDJ

Answer 9

mech: defect in RAG-1 or 2. lymphocyte development blocked

cells: lack B and T cells.
normal NK cells

Omenn syndrome - residual RAG activity. Abnormally activated T cells

Question 10

SCID - bare lymphocyte syndrome

Answer 10

mech: loss of MHC II
no development of CD4 T cells

cells: no CD4 T cells

Question 11

SCID - T cell signaling

Answer 11

mech: defect expression of TCR/CD3 or transduction cascade

Rare

Question 12

DiGeorge

Answer 12

mech: 22q11 deletion. defects in 3rd and 4th pharyngeal pouches -> impaired thymus, parathyroid, heart
cells: T cell deficiency
symptoms: similar to SCID

Question 13

Hyper IgM - X-linked

Answer 13

mech: mutation on CD40L on T cells
cells: increased IgM but no other Ig
symptoms: opportunistic infections, neutropenia, liver disease, sclerosing cholagitis, liver and biliary tree tumor

Question 14

Hyper IgM - autosomal recessive

Answer 14

mech: defect in CD40 gene

Question 15

Hyper IgM - enzymes

Answer 15

mech: mutation in AID and UNG needed for isotype switching and affinity maturation
cells: cells all seem fine. no other Ig
symptoms: lymphoid hyperplasia and AI disease

Question 16

XLA

Answer 16

mech: defect in BTK
cells: no B cells
symptoms: infections from encapsulated bacteria, otitis media, sinusitis, pneumonia
treatment: Ab replacement

Question 17

Selective IgA def

Answer 17

mostly asymptomatic

recurrent sinopulm infections, AI and allergies

Question 18

CVID

Answer 18

mech: impaired Ab production
cells: low IgG and other Ig

symptoms: encapsulated bacteria - otitis media, sinusitis, pneumonia
lymphoid hyperplasia, granulomatous lesions, lymphoma, AI, IBD

Question 19

WAS

Answer 19

mech: X linked mutation in WASP
cells: abnormal platelets and leukocytes
symptoms: eczema, reduced platelets, immunodef