Immunoglobulins + Phagocytic and Complement deficiencies

Question 1

IgG

Answer 1

• 23 day t 1/2
• crosses placenta
• in breast milk
• most common in blood and ECF
• Neutralization and Complement activation
• Binds Fc region on macrophages, PMNs, NK
• four subtypes

Maternal IgG detected in fetus at 2 months • Fetus doesn’t synthesize its own IgG
• Maternal IgG increases in last trimester
• Maternal IgG declines at birth as infants begins to synthesize their own IgG
• Total IgG in infant is greater at birth than at 23 months due to presence of maternal IgG

Question 2

IgM

Answer 2

• first responder
• in pentamer form w/ J chain
• 5 day t 1/2
• fetus makes own at 5 months
• activates complement

Question 3

IgE

Answer 3

• t 1/2 is 2 days
• helminth reaction
• binds Fcer1 on mast cells, basophils, eosinophils, induces release of chemical mediators
• type 1 hyper sensitivity

Question 4

IgA

Answer 4

• mucus surfaces, transported across gut epithelium–transcytosis
• Major Ig in secretions such as saliva, mucus, sweat, gastric fluid, and tears (secreted as dimer with J chain), monomer in blood (76-390 mg/dl)
• dimer with J chain
• GI infections
• breast milk
• IgA1 has long hinge region allows for flexibility (twice as long as IgA2)
• 2 subclasses
• neutralization,
• weakly does complement activation and opsonization
• T 1/2 is 5.5 days

Question 5

Opsonins

Answer 5

C4b

c3b

Question 6

Anaphylaxotins (mast cell degranulation)

Answer 6

C3a, C5a

Question 7

Chemotactic (neutrophils)

Answer 7

c5a

Question 8

Myeloid progenitor cells

Answer 8

CFU- GM…Monocytes (blood)…macrophages, dendritic, mast cells
CFU-GM…Granulocytes…basophils, eosinophils, neutrophils
CFU- Meg…megakaryocytes…platelets
CFU- E…erythrolblasts

Question 9

Lymphoid Progenitor

Answer 9

T precuror…T cells and NK

B precursor…B cells

Question 10

Hereditary Angioneurotic Edema (HAE)

Answer 10

• Autosomal dominant
•Deficiency in C1 inhibitor;
Lack of inhibitor of kinin and bradykinin pathways , increase in vascular permeability
- C1 esterase Inhibitor (C1INH) serine protease inhibitor which dissociates C1r2s2 from C1q preventing activation of C4 and C2
• Localized edema

Question 11

Paroxysmal Nocturnal Hemoglobinuria

Answer 11

DAF and HRF are absent from the host cell membrane

HRF (Homologous Restriction Factor),
• membrane protein which bind to C5b678 on autologous cells and block binding of C9
DAF– accelerates C3 convertase disassociation in classic and alternative pathway
• Constitutive activation of complement leading to RBC lysis
• Breakdown of RBCs in urine leads to hemoglobin release & dark urine

Question 12

Deficiency in C1, C2, C4 or CR1

Answer 12

Impaired immune complex clearance results in autoimmune diseases such as SLE

Recurrent bacterial infections by pyogenic bacteria such as streptococcus, and staphylococcus, Neisseria

Question 13

C3 deficiency

Answer 13

Defects in opsonization and immune complex clearance

recurrent bacterial infections, glomerulonephritis
susceptable to encapsulated bacteria

Question 14

Deficiency in components of MAC (C5,6,7,8,9)

Answer 14

• Defect in complement mediated lysis

* Recurrent meningococcal and gonococcal infections caused by Neisseria

Question 15

Leukocyte Adhesion Deficiency (LAD I Deficiency)

Answer 15

DEFECT IN ADHESION/INTEGRINS
• Autosomal recessive
• Defect in β chain (CD18) of integrin family members such as CR3, CR4, &; LFA-1; defect in rolling of leukocytes prior to transmigration
• Impaired recruitment of neutrophils to site of infection
• Impaired phagocytosis of bacteria
• Absence of pus formation
• Recurrent pyogenic infections and impaired wound healing

Defect in beta chain of CD18 of LFA-1 integrin, impaired tight interaction with ICAM on endothelial cells

Question 16

LAD II

Answer 16

DEFECT IN ROLLING/SELECTINS

Defect in fucosylated ligands of E selectins, Impaired rolling of neutrophils along endothelial surface

impaired wound healing,
lack of pus, decreased transendothelial migration

Question 17

Chronic Granulomatous Disease

Answer 17

Defect in respiratory burst due to NADPH oxidase mutation, defective cell killing, granuloma formation, Nitroblue tetrazolium test (NBT)

Question 18

Chediak Higashi Syndrome

Answer 18

Defective fusion of lysosomes with phagosomes, impaired intracellular killing, albinism

Autosomal recessive
defect in granule exocytosis leading to impaired exocytosis killing

Question 19

Bruton’s X linked agammaglobulinemia

Answer 19

Defect in Btk (bruton’s tyrosine kinase gene) defect in B cell maturation, depletion of all serum Igs, recurrent bacterial infections (pyogenic encapsulated)

small lymph nodes, no germinal centers
treatment w/ IgG injection

Males cannot make functional B cells..symptoms at 5-6 months

Question 20

Selective IgA

Answer 20

Defect in maturation of IgA B cells, increased sinopulminary infections
- most common Immunodef disease

Question 21

Common Variable

Answer 21

Heterogeneous group of disorders
diff for diff people

• b cells dont proliferate with antigen
• have b cells, not enough plasma cells

diminished antibody secretion/synthesis

Question 22

Job’s Syndrome (Hype IgE)

Answer 22

recurrent cold staphylococcus abcesses (no inflmation) eczema, skeletal effects, high level of Ige

Increase in TH2 cells & high level of IgE, (histamine release inhibits neutrophil chemotaxis)

failure of TH1 cells to produce IFN y (leads to diminished ability of macrophages to kill bacteria)
chrom 22

Question 23

DiGeorge Syndrome

Answer 23

congenital abnormality of thymus development; absence of T cells

• affects development of pharyngeal arches
• thyroid/parathyroid abnormal
• cleft palate, hypocalcemia, hypoparathyroidism
• t cells absent bc thymus GONE
• thymus transplant
• recurrent viral infections

Question 24

Wiskop Aldrich Syndrome

Answer 24

Defect in WAS glycoprotein, Defective Cytoskeletal organization, eczema

eczema, food allergies, bloody diarrhea

defective reorganization of actin cytoskeleton following TCR crosslinking due to defect in WASP protein

impaired t cell engagement w/ b cells and other things

impaired t cell movement, cell division, reorganization,
of cytoskeleton

poor Ab response to polysaccharides, low IgM/ High IgA/E

Question 25

Ataxia Telangiectasia

Answer 25

Mutation in DNA repair gene, defect in TCR &; BCR rearrangement somatic recombination of Ig and TCR leading to defects in lymphocyte maturation

• gait abnormalities (waddling) and telangiectasis (widened vessels) flat red marks on skin