1. Complement system gets rid of primarily what?
(The Complement System)
1. A series of ~20 heat labile plasma proteins synthesized where and by what?
2. Complement functions in a cascade to attack what?
(3-5). They do this via what three things?
1. in the liver by Kupffer cells and hepatocytes
2. extracellular pathogens
3. lysing bacteria
4. opsonizing bacteria
5. recruiting inflammatory cells
(1-3). Complement proteins are present inactive forms in the serum and are triggered via either of 3 mechanisms (+ what they are)
4. Complement system provides for amplication of what?
5. Is complement highly regulated?
1. classical pathway - activated by IgG or IgM antibodies binding to surface
2. Alternate pathway - spontaneous activation in the blood or bacterial surfaces
3. Lectin Pathway - activated by opsonins binding to bacterial cell surface
4. the cascade
- C plus a number; thus C4 is complement factor 4
1. When the proteins are cleaved during activation, the smaller fragment is labeled a or b? What do we get after C4 is cleaved?
2. Some Cleavage products from C3 and C5 are what
3. For proteins that are not also part of the classical pathway, they are designated how? Thus B is what?
- When celaved during activation, they acquire a lower case a or b as in the classical. Thus, Bb is complement component B, active form
1. a, (so larger is b); C4a and C4b
2. opsonins (what you stick on something to signal)
3. with a letter only; complement component B
(Classical and Alternate Pathways)
1. The early events of both pathways involve as series of what type of reaction? what do these reactions provide?
2. All pathways form a what? what does it do?
3. After C3/C5 convertase formation, the pathways do what?
1. cleavage reactions; provide proteas enzyme for the enxt substrate in the series
2. C3/C5 convertase; cleaves and activates C3 and C5
3. overlap and use the same proteins
the colored text is the three main things the complement system does
(Initiation of Complement Cascades)
HE SAID NOT TO WORRy TO MUCH ABOUT REMEMBERING SPECIFIC NUMBERS
1. when you have two IgG's next to each other, what can bind those? what happens to it?
2. After it cleaves what will it bind? What stays? What leaves?
3. This combines with what? what stays? what leaves? What can this formed complex now do?
4. What happens to cleaved C3 parts? What can it do now?
5. What happens at this point?
- Just look at picture on ipad
What starts in each pathway?
6. classical pathway
7. lectin pathway
8. alternative pathway
1. C1; becomes activated and self cleaves
2. C4; C4b; C4a
3. C4b combines with C2; C2b; C2a; cleave a bunch of C3
4. C3a leaves and C3b sticks around; cleave C5
5. Can now cleave a lot of C3 or C5
7. lectin-binding proteins
8. spontaneous activation on surface of bacterial cell
1. The classical complement pathway initiates after what attaches to the surface of a particle such as a bacterium or virus?
2. The C4bC2a is the what? This can do what?
3. C3b (lots of it!) binds to what?
1. IgM or IgG
2. the C3/C5 convertase; can cleave alot of C3
3. binds covalently to bacterical surface
1. C3a acts as a what?
2. C3b binds to pathogen surface and act as whats? Also helps cleave what?
1. peptide mediator of inflammation
2. opsonins; C5
(Lectin Pathway of Complement Activation)
1. What is the major difference between classical and lectin pathway?
2. What are the two major host-derived serum proteins that bind to bacterial surfaces to start the cascade?
(Mannose Binding Lectin)
3. bind to what?
4. produced by what?
5. bind to what?
6. Present at higher levels in serum and maybe more important than MBLs?
7. Both bind what that do what?
1. the intial protein used
2. Mannose binding lectin and Ficolins
3. mannose residues on pathogen cells
4. liver in low quantities (acute phase protein)
5. carbohydrate structures on bacterial and fungal cells
7. Serine proteases that cleave C4 and C2
1. Is the end result the same as for the classical pathway?
2. What is C3bBb?
just read the rest (on ipad) - he didnt talk about it very much
2. the C3/C5 convertase!
also read this one - also spent very little time talking about this one
(Proteins of the Alternative Pathway)
1. which fragment is the active enzyme of the C3/C5 convertase?
2. Which is a plasma serine protease, cleaves B when it is bound to C3b to Ba and Bb?
3. What is the plasma protein that stabilizes the C3bBb convertase on bacterial cells?
3. P (Properdin)
(The C5 convertase)
1. Does the classical and lectin pathways generate a different C5 convertase than the alternate pathway?
2. C5 binds to C3b compnent, allowing cleavage by what in classical and what in alternate?
3. Does C5b bind surfaces covalently? Does it initiate formation of the membrane attack complex?
DO NOT MEMORIZE PICTURE - JUST USE TO GET YOU R BEARINGS - on ipad
2. C2b (classical) or Bb (alternate)
3. no, yes
(Membrane Attack Complex)
1. Once C3b is attached, what can form? Is this the same regardless of how the complement cascade was initiated? What is the outcome?
2. C5b will bind C6 and C7 causing it to released from C3b. This complex attaches and binds C8 and many C9. What does C9 do? What is the target cell usually?
1. the membrane attack complex; yes; lysis of the cell
2. forms a ring structure causing a pore to form (many bacteria are resistant to this though); bacteria
1. What is the most important action of complement deposition onto bacterial surfaces? What dos ths do?
2. what are the most important complement receptors? where are they found?
3. (extra) are antibodies opsonins?
maybe look at this slide a little - don't really need to know anything off of it but I can't help myself
1. OPSONIZATION; enhances uptake by phagocytes
2. CR1 and CR3; esentially on phagocytes
1. Are antibodies opsonins? What isn't so great about them vs. complement system?
2. Complement eposition assists in what?
1. yes; they are much slower than complement system
2. the uptake of bacteria
1. Several complement cleavage fragments (C5a, C3a, and C4a a little bit) are what that promote what?
2. Increase vascular what?
3. Trigger mast cells to release what? which does what to vasculatare?
4. increase adherence of phagocytes to what?
5. What is the result of all this?
1. ANAPHYLATOXINS that promote inflammation locally
2. vascular permeability
3. granules (containing histamine); makes vasculature leaky (vasodilation)
4. to blood vessel endothelial cells
(Complement and Inflammation)
1. The generation of complement cleavage products amplifies the inflammatory response - what are the two main ones that do this?
2. This is mediated by what 5 things?
1. C5a and C5b (I don't think this is right - look at picture)
2. 1. smooth muslce contraction
2. mast cell degranulation
3. vasodilation of blood vessels
4. activation of phagocytes (neutrophils and macrophages)
5. establishing a chemotactic gradient to recruit immune cells
(Regulation of Complement)
- Because it's not specific to an antigen - the complement can bind to host cell membrane
1. Why don't you get damage to your own tissues is because of what? that do what?
*regulatory proteins can protect host cells from complement mediated damage that occurs secondary to inflammation
2. Regulatory proteins can be associated with which two spots?
3. What does decay accelerating factor do?
4. What does CD59 do?
* these are both regulatory proteins by the way
JUST LOOK AT LAST FEW PAGES - he didn't seem to keen on us flat memorizing all of this
1. presence of regulatory proteins; interrupt complement cascade at different points
2. host cell surface or secreted in serum
3. displaces Bb or C2b (convertase dissociation)
4. prevents formation of membrane attack complex
1. What are the examples?
1. C3 deficiency in Brittney Spaniels
2. C3 receptor deficiency in cattle (bovine luekocyte adhesion deficiency) - bascially C3 couldn't be used as an opsonin
Summary slide BAM