Immunoglobulins + Phagocytic and Complement deficiencies Flashcards
IgG
- 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
IgM
- first responder
- in pentamer form w/ J chain
- 5 day t 1/2
- fetus makes own at 5 months
- activates complement
IgE
- t 1/2 is 2 days
- helminth reaction
- binds Fcer1 on mast cells, basophils, eosinophils, induces release of chemical mediators
- type 1 hyper sensitivity
IgA
- 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
Opsonins
C4b
c3b
Anaphylaxotins (mast cell degranulation)
C3a, C5a
Chemotactic (neutrophils)
c5a
Myeloid progenitor cells
CFU- GM…Monocytes (blood)…macrophages, dendritic, mast cells
CFU-GM…Granulocytes…basophils, eosinophils, neutrophils
CFU- Meg…megakaryocytes…platelets
CFU- E…erythrolblasts
Lymphoid Progenitor
T precuror…T cells and NK
B precursor…B cells
Hereditary Angioneurotic Edema (HAE)
• 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
Paroxysmal Nocturnal Hemoglobinuria
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
Deficiency in C1, C2, C4 or CR1
Impaired immune complex clearance results in autoimmune diseases such as SLE
Recurrent bacterial infections by pyogenic bacteria such as streptococcus, and staphylococcus, Neisseria
C3 deficiency
Defects in opsonization and immune complex clearance
recurrent bacterial infections, glomerulonephritis
susceptable to encapsulated bacteria
Deficiency in components of MAC (C5,6,7,8,9)
- Defect in complement mediated lysis
* Recurrent meningococcal and gonococcal infections caused by Neisseria
Leukocyte Adhesion Deficiency (LAD I Deficiency)
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
LAD II
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
Chronic Granulomatous Disease
Defect in respiratory burst due to NADPH oxidase mutation, defective cell killing, granuloma formation, Nitroblue tetrazolium test (NBT)
Chediak Higashi Syndrome
Defective fusion of lysosomes with phagosomes, impaired intracellular killing, albinism
Autosomal recessive
defect in granule exocytosis leading to impaired exocytosis killing
Bruton’s X linked agammaglobulinemia
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
Selective IgA
Defect in maturation of IgA B cells, increased sinopulminary infections
- most common Immunodef disease
Common Variable
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
Job’s Syndrome (Hype IgE)
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
DiGeorge Syndrome
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
Wiskop Aldrich Syndrome
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
Ataxia Telangiectasia
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
