Lecture 10 Flashcards
(28 cards)
Which is the main Ig class in blood and for mucosal secretions?
- Blood: IgG
- mucosal secretion: IgA
How are J-chain containing IgA dimers transcytosed across EC into lumens?
polymeric Igreceptor
Colostrum is rich in which Ig?
IgA
Which Ig can cross the placenta by transcytosis?
IgG after binding to neonatal Fc receptor (FcRn) in placenta and confers passive immunity
How is IgG protected from lysosomal degradation?
- FcRn binds to Fc region of IgG which has been endocytosed by cells
- this contributes to IgG’s long half-life in blood (3 weeks)
What is the function of the complement system?
- kill and opsonize microbes
- clear immune complexes
- initiate inflammation
- recruit neutrophils and monocytes to infected/inflamed tissue sites
What are the three complement pathways?
- alternative pathway-spontaneously activated
- lectin pathway-activated by binding 1st component, mannose binding lectin (MBL), to terminal mannose residues on microbes
- classical pathway- activated by binding C1 to C1 binding sites on Fc regions of IgM and IgG antibodies
Where do the three complement pathways converge?
-C3 complement component to generate membrane attack complexes (MACs) of C5b-C9 on microbial surfaces
Which two convertase does MAC formation require?
-C3 convertase and C5 convertase to cleave C3 and C5 into a fragments that diffuse away and b fragments that become covalently bound to microbial surface
How are C1 and MBL components activated?
- when binding of at least 2 of C1q or MBL heads engaged by complementary ligands
- carbs on microbes or Fcs of antigen bound IgM or IgG
Why is IgM a better complement activator than IgG?
-IgM has 5 Fcs but a higher density of IgG is needed for close proximity of two IgG Fcs
What is C3 convertase comprised of for classical pathway?
C4b2b
What is C3 convertase comprised of for alternative pathway?
- slow hydrolysis of C3 into C3a and C3b
- followed by binding of Factor B to some of bound C3b and cleavage of Factor B by Factor D
- generate C3 convertase comprised of C3bBb
MAC formation involves association of which components?
- C6-C8 with bound C5b and polymerization of C9 to form hole in microbial membrane
- this leads to osmotic lysis of cell
(T/F) Gram negative bacteria-outer membrane susceptible to complement lysis
True
What is the role of C3b?
Helps in elimination of microbes by covalently attaching to microbes and immune complexes, then binds to C3b receptors
Which are the main cell type for clearance of immune complexes from blood?
Erythrocytes
Which soluble fragments are responsible for initiating/amplifying inflammation on mast cells and basophils?
C5a and C3a cause degranulation
What are examples of membrane and soluble regulators?
- membrane regulator: decay accelerating factor (DAF)-bind to C3 convertase and accelerate dissociation (block complement activation on host cells)
- soluble regulator: factor 1 inactivates bound C3b by clearing into smaller fragments that diffuse away leaving behind covalently bound C3d
- C1 inhibitor-prevent spontaneous activation of C1 proteases
DAF deficiency leads to what types of issues?
-excessive inflammation and complement mediated lysis of erythrocytes-leads to anemia
paraoxysmal nocturnal hemoglobinuria (PNH)
-Hb released from lysed RBC excreted in urine (red appearance)
C1 inhibitor deficiency (hereditary angioedema)
- swelling episodes around face and GI tract and cause abdominal pain
- treat with C1 inhibitor
Symptoms of C3 deficiency
- infection with pyogenic and encapsulated bacteria
- predispose to immune complex disease
C4, C2 deficiency
-susceptible to immune complex disease since C3b also becomes defective
