Monocyte Chemoattractant Protein-1 2518 A/G Single Nucleotide ...
The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack...
-
Upload
dorthy-chandler -
Category
Documents
-
view
213 -
download
0
Transcript of The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack...
![Page 1: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/1.jpg)
IMMUNOLOGY
Bios 328a textbook-based study of immunologySpring 2003
http://www.lehigh.edu/~sk08/Courses/Bios328/mainpage.htm
![Page 2: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/2.jpg)
The overview….
• Complement has three functions:
– Opsonin
– Chemoattractant
– Membrane Attack Complex (MAC)
• Complement functions in two (three?) systems:
– Alternative
– Classical
– Lectin-based
![Page 3: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/3.jpg)
The CLASSICAL pathwayStimulated by antibodies:
specifically: IgM and IgG (subclasses 1, 2, 3)
Start with C1q a HUGE protein (410,000 daltons!)
Composed of 18 peptides. Peptides can associate to
form trimers; six sets of trimers make C1q.
C1q has helical “stalks” and globular “heads.”
(N. B. the heads are the carboxy end and the stalks are the amino ends)
![Page 4: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/4.jpg)
The CLASSICAL pathway
Also associated with C1 are C1r and C1s which associate to make dimeric pairs (C1r2s2); the dimeric pair joins C1q to form C1qr2s2.
![Page 5: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/5.jpg)
The CLASSICAL pathway
• C1qr2s2 binds to TWO immunoglobulins.
– The complement binding sites of circulating IgM are too far apart to bind complement;
– only when IgM is bound does it fold so that C1qr2s2 can “see” nearby complement binding domains.
– IgG concentrations must be high in the vicinity of antigens for threshold levels of complement binding domains to be present.
![Page 6: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/6.jpg)
The CLASSICAL pathway
• When C1qr2s2 is bound to requisite number of immunoglobulins, C1r “autocatalytically” converts to C1[r].
• C1[r], in turn, converts C1s to C1[s].
• C1[s] cleaves C2 and C4.
• C4 is cleaved to C4a and C4b; C4b associates with its “target” which is C2.
• C2 is cleaved by C1[s] making C[4b2a] which is a C3 convertase! (Note that 2a is bigger than 2b, this nomenclature being the one exception to the convention that “a” is smaller than “b.”)
• As with the other C3 convertase, C3b can join C[4b2a] to make
C[4b2a]3b which is also a C5 convertase.
![Page 7: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/7.jpg)
The CLASSICAL pathway
![Page 8: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/8.jpg)
The CLASSICAL pathway
![Page 9: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/9.jpg)
The CLASSICAL pathway
![Page 10: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/10.jpg)
The complement pathways…
![Page 11: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/11.jpg)
The LECTIN pathway
• Lectins are proteins which bind to carbohydrates.
• Many bacteria have many mannose residues on their surface. The lectin-based complement system begins with a “mannose-binding protein” (MBP).
• MBP reacts, in turn, with a MBP-associated serine protease (MASP).
• MASP functions, in effect, like activated C1q[r2s2], that is a C3 convertase.
![Page 12: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/12.jpg)
The mostamazingcircumstance:
• Erythrocytes (!) deliver the complex of antigen –antibody – complement to the liver and spleen for consumption by phagocytes.
![Page 13: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/13.jpg)
Monoclonal Ab’s
![Page 14: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/14.jpg)
Contrast with the normal circumstance…
• The normal response to an immunogen is polyclonal Ab’s
• The immunogen most commonly has multiple epitopes
• The multiple epitopes select multiple B-cell lineages
• Multiple clones mature to produce Ab’s for the multiple epitopes
![Page 15: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/15.jpg)
Monoclonals are just what they say they are:
• Remember: a single B-cell makes a single type of antibody– or, more precisely, a single idiotype
• The B-cell is made immortal– The clone, if stable, continues to secrete the
single type of Ab
![Page 16: The overview…. Complement has three functions: –Opsonin –Chemoattractant –Membrane Attack Complex (MAC) Complement functions in two (three?) systems:](https://reader036.fdocuments.in/reader036/viewer/2022082820/56649f3a5503460f94c589f0/html5/thumbnails/16.jpg)
The scheme…• “HGPRT+” =‘s
hypoxanthine-guanine phosphoribosyl transferase
• The enzyme is used in the “salvage pathway” for DNA synthesis
• “HAT” =‘s hypoxanthine -- aminopterin -- thymidine medium
• aminopterin inhibits de novo DNA synthesis
• thymidine is needed for pyrimidine synthesis in the salvage pathway
• hypoxanthine for purines...