Term
| What are two antibacterial enzymes produced by epithelial cells? |
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Definition
lysozyme and secretory phospholipase A2
. Lysozyme selectively cleaves the (1,4 beta glycosidic linkage). Phospholipase A2 is a highly basic enzyme that can enter the bacterial cell wall, hydrolyze phospholipids in the cell membrane, killing the bacteria. |
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Term
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Definition
| specialized epithelial in the base of the crypts in the small intestine |
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Term
| What are the three classes of antimicrobial peptides in mammals? |
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Definition
| defensins, cathelicidins, histatins |
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Term
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Definition
30-40 amino acid peptides
have three disulfide bonds
"first responders" to to disrupt hydrophobic region of bilayer |
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Term
| What are the three subfamilies of defensins?Which forms to humans make? |
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Definition
| alpha, beta, and theta. Humans only make alpha and beta |
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Term
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Definition
| made by neutrophils and macrophages that are made in response to an infection to keratinocytes in skin cells. Originally produced in a propeptide. Activated when two granules are cleaved by neutrophil elastase. Stored and processed in lamellar bodies |
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Term
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Definition
| lipid rich secretory organelles in the lungs |
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Term
| Which antimicrobial peptides, when proteolyzed, release an amphipathic antimicrobial peptide? |
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Definition
| alpha defensins, beta defensins, cathelicidins, RegIII |
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Term
| What is the mechanism of defensins? |
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Definition
| Defensins interact with the charged surface of the cell membrane of microbes. They become inserted into the lipid bilayer. They from a pore in the membrane and cause loss of membrane integrity |
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Term
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Definition
| a type of bactericidal proteins made by epithelia for carbohydrate binding proteins. Bacterial version is called RegIIIgamma... |
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Term
| What is the human form of RegIII gamma ? |
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Definition
| HIP/PAP...kills bacteria directly by forming a hexametric pore in the bacterial membrane. |
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Term
| other than killing bacteria invading the body, what do anti microbial peptides do? |
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Definition
| They bind liposaccharides, which trigger the release of pro inflammatory cytokines |
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Term
| What happens when antimicrobial peptides bind LPS? |
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Definition
| inflammation is down regulating of inflammation |
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Term
| True or False. Antimicrobial proteins can act as chemoattractants. |
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Definition
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Term
| What is the significance of lectins? |
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Definition
| They bind carbohydrate containing surface molecules. For example, it is able to bind to glycoprotein 120 on cell surfaces, and keeps HIV from binding to the CD4 molecule. |
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Term
| how do antimicrobial proteins aid in wound healing? |
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Definition
| they stimulate collagen production and angiogenesis |
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Term
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Definition
| lectins that require calcium for the binding activity of their carbohydrate-recognition domain |
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Term
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Definition
| a system of plasma proteins--about 30 proteins, heat sensitive at 56 degrees. Makes up about 10% of serum proteins. Widely distributed throughout the body. |
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Term
| What is the difference between plasma and serum? |
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Definition
Plasma: Fluid portion of noncoagulated blood containing proteins, carbohydrates, minerals and fats
Serum: Fluid portion of coagulated blood without fibrinogen and other clotting factors |
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Term
| IS complement part of the innate or adaptive immunity? |
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Definition
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Term
| Who produces complement proteins? |
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Definition
– Monocytes/macrophages
– Fibroblasts
– Hepatocytes
– Epithelial cells (especially in GI tract) |
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Term
| What is the general mechanism of action of complement proteins? |
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Definition
| they stimulate a cascade of proteolytic reactions and protein aggregation on the microbial surface. initiates opsonization. forms pores on the microbial surfaces to kill |
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Term
| True or false. Complement proteins can only work through inflammation and phagocytosis mechanisms to kill the pathogen. |
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Definition
| False. Not only can complement proteins work through both mechanisms of inflammation and phagocytosis, they can also attack the membrane |
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Term
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Definition
| They are like "pro-enzymes" which are proteolytic enzymes that only become active after cleavage. Once one is cleaved, a positive feedback loop is amplified, as one activated protease cleaves another. |
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Term
| What is the terminology for each type of protein in the complement system? What does each signify? |
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Definition
C# = inactive precursors
C#b = active serine proteases
C#a = distinct acting bioactive molecule |
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Term
| What are the three different pathways of the complement system? What is the common goal of all three pathways? |
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Definition
| Lectin, Classical, alternative. All three pathways have a common goal of producing a C3 convertase, which cleaves C3, leaving C3b on the microbial surface and releasing C3a |
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Term
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Definition
| initiated by soluble carbohydrate-binding proteins ---mannose binding proteins--mannose-binding lectin and the ficolins |
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Term
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Definition
| intimated when the complement component C!, which comprises a recognition protein (c1q) associated with proteases either recognizes microbial surface directly or binds to antibodies already bound to the pathogen. |
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Term
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Definition
| can be intiated by spontaneous hydrolysis and activation of the complement component C3, which can bind directly to microbial surfaces. |
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Term
| What is the main effector molecule of the complement system? |
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Definition
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Term
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Definition
| a small peptide that binds to specific receptors and helps induce inflammation. |
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Term
| How does C3b act like opsin? |
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Definition
| covalently binds to the microbial surface and enables phagocytes that carries receptors for complement to take up and destroy the C3b-coated microbes. |
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Term
| How is the covalent bond formed between C3b and a microbe? |
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Definition
| a highly reactive thirster bond is hidden inside the folded C3 protein and cannot react until the C3 is cleaved . When C3 is cleaved, the C3a fragment is released and a conformation change is induced in C3b that allows the thioester bond to react with a hydroxyl or amino group on a nearby microbial surface. |
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Term
| What happens is C3 is cleaved, and there is no available hydroxyl or amino group? |
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Definition
| The thioester bond is rapidly hydrolyzed, inactivating C3b, which is one way that alternative pathway is inhibited in healthy individuals. |
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Term
| When the C3b is bound to the surface of a pathogen, which chain is closer to the thioester group? |
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Definition
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Term
| how do the extracellular glycoproteins of yeast differ from glycoproteins of humans? |
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Definition
| yeasts contain many terminal mannose residues, whereas human glycoproteins have terminal silica acid residues. |
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Term
| Which two domains make up mannose -binding lectin (MBL) ? Which pathway is it in? |
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Definition
| Found in the lectin pathway, MBL has an amino-terminal collagen-like domain and a carboxyl-terminal C-type lectin domain. It is part of a group called collections. |
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Term
| What is the structure of MBL ? (mannose binding lectin) |
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Definition
| trimers, assemble into oligomers through disulfide bonds through cysteine rich residues. |
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Term
| how does MBL show specificity for microbes over humans? |
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Definition
| its carbohydrate recognition domain has a low affinity for mannose, focus, and NAG--> which are common in microbes and not humans. |
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Term
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Definition
| the total binding strength |
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Term
| Even though MBL is present in low concentrations in plasma, when does it get unregulated? |
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Definition
| during the acute-phase response (innate) |
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Term
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Definition
| pattern recognition molecules used by the lectin pathway. |
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Term
| What is the structure of ficolins? |
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Definition
| they have a fibrinogen-like domain, rather than a lectin domain attached to a collagen like stalk. |
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Term
| What does ficolin have a specificity for? |
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Definition
| for oligosaccharides containing acetylated sugars, but does not bind mannose-containing carbohydrates |
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Term
| How many ficolins do humans have and where are they produced? |
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Definition
| 3, L, M, and H ficolin. L-ficolin and H-ficolin are synthesized by the liver and circulate in the blood; M-ficolin is synthesized and secreted by lung and blood cells |
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Term
| Name three MBL-associated serine proteases. They are not active when bound to MBL. What does that make them? |
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Definition
| MASP-1, MASP-2, and MASP-3. They are zymogens. |
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Term
| Explain the process of the lectin pathway in terms of how MBL activates the C3 convertsase? |
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Definition
| MBL associates with the MASP-1 serine protease. Within the same complex, MASP[-1 cleaves MASP-2. MASP-2 cleaves C4 and C2. Upon cleaving C4, C4a is released and conformationally changes C4b. C4b covalently binds to the microbial surface via thioester bond. C4b also binds C2. MASP-2 also cleaves C2, releasing C2b. C2a remains bound to C4b, creating a complex like C3 convertase called C4b2a. C4b2a cleaves MANY C3 MOLECULES into C3a and C3b C3b binds to microbe, C3a causes inflammatory response |
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Term
| What happens when someone is deficient in MBL or MASP-2? |
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Definition
| they experience more respiratory infections by common extracellular bacteria during early childhood. |
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Term
| What is the pathogen sensor known in the classical pathway? |
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Definition
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Term
| What are the two serine proteases associated with the C1 complex in the classical pathway? |
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Definition
|
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Term
| what is the structure of C1q? |
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Definition
| hexameter of trimers..contains an amino -terminal globular domain.....carboxyl terminal of collagen domain |
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Term
| how many trimers form together to make a C1q molecule? |
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Definition
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Term
| Explain the steps of the classical pathway when two or more of the globular C1q heads interact with a ligand.. |
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Definition
| Once the globular heads of C1r come into contact with a ligand, then C1r becomes active and cleaves C1s to become active. C1s acts on C4 and C2 and cleaves both of them. C4b binds to the pathogen and also binds to C2a. This produces the active form of C3 convertase C4b2a. |
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Term
| What is another name for the C4b2a molecule? |
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Definition
| "classical C3 convertase" |
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Term
| What are two ways that C1q (classical) can attach itself to the surface of pathogens? |
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Definition
1. attaching directly to surface components on some bacteria, including certain proteins bacterial cell walls and polyanionic structures
2. binding to C-reacitve protein, an acute phase protein in human plasma that binds to phosphocholine residues in bacterial surface molecules |
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Term
| What is the main function of C1q in an immune response? |
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Definition
| to bind to the Fc constant regions of antibodies, thus linking the effector functions of complement to recognition provided by adaptive immunity. |
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Term
| Which class of antibody is the most efficient at binding C1q? |
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Definition
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Term
| What is the C3 convertase called for the alternative pathway? |
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Definition
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Term
| Why is the alternative pathway referred to as an "amplification loop" |
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Definition
| Once some C3b has been formed, by whichever pathway, the alternative pathway can act as an application loop to increase C3b production rapidly. |
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Term
| What are the two ways that the alternative pathway can be initiated? |
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Definition
| The C3b generated by either of lectin or classical pathways----OR the spontaneous hydrolysis of C3 to C3(H2O) |
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Term
| If the alternative pathway is triggered by the C3b from the lectin or classical pathways, how does it go? |
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Definition
| C3b will bind factor B enabling plasma protein factor D to cleave B into Ba and Bb. Bb then remains with C3b to form C3bBb convertase. |
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Term
| If the alternative pathway is activated through the hydrolysis of the thioester bond in C3 to form C3(H2O), how does it go? |
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Definition
| it's called the ticker: Once C3(H2O) is formed, it binds to factor B, which is then cleaved by factor D, producing a short lived fluid-phase C3 convertase, C3(H2O)Bb. This molecule can cleave many molecules of C3 to C3a and C3b. Much of the C3b produced is inactivated by hydrolysis, but some of it attaches to microbes via its thioester bond. |
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Term
| Since Bb is very short lived in the alternative pathway, how are they stabilized? |
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Definition
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Term
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Definition
|
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Term
| What happens if patients are lacking properdin? |
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Definition
| Properdin deficient patients are more susceptible to Neisseria meningitis infections |
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Term
| What does Factor B do in the alternative pathway? |
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Definition
| Bb is the active fragment of the C3 convertase C3 C3bBb |
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Term
| is properdin a postive or negative regulatory protein? |
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Definition
| positive regulatory protein, by stabilizing C3bBb |
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Term
| What is the most abundant complement protein in the plasma membrane? |
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Definition
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Term
| What is the initiating serine protease in the alternative, lectin, and classical pathway? |
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Definition
Alternative: Factor D
Classical: C1s
Lectin: MASP |
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Term
| Which complement protein binds to the cell surface in all three pathways? |
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Definition
alternative: C3b
Lectin/Classical: C4b |
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Term
| What is the C3/C5 convertase in each pathway? |
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Definition
alternative: Bb
Lectin/Classical: C2a |
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Term
| What is the role of negative regulatory proteins? |
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Definition
| to protect health host cells from the injurious effects of inappropriate complement activation. They interact with C3b and either prevent the convertase from forming or promote its rapid dissociation. |
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Term
| What are some negative regulatory proteins that regulate the stability of C3 convertases? |
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Definition
-decay accelerating factor (DAF) (competes for factor B binding to C3b and can displace Bb from a convertase that has already formed)
-Factor I and MCP can cleave C3b to an inactive derivative iC3b |
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Term
| How would you form a C5 convertase (what are they) in each pathway? |
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Definition
Classical and lectin: A C5 convertase is formed by binding of C3b to C4b2a to yield C4b2a3b
Alternative pathway: The C5 convertase is formed by binding C3b to C3bBb to form C3b(2)Bb |
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Term
| What happens when C5 binds to a C5 convertase enzyme? |
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Definition
| It is cleaved in C5a and C5b |
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Term
| The C5a receptor is an example of what type of protein? |
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Definition
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Term
| What is the functional role of C3a and C5a? |
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Definition
| recruit phagocytic cells to the site of infection and promote inflammation. |
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Term
| What is the functional role of C3b? |
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Definition
| When pathogens have C3b bound to the surface, receptors for C3b on phagocytes will bind and ingest the bacteria |
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Term
| Where would you find CR1 expressed? What does it bind? |
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Definition
| on phagocytic immune cells...C3b |
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Term
| What happens when C3b is bound to its receptor, CR1? |
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Definition
| nothing....it can be phagocytsized until C5a comes along to tell it to! |
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Term
| What is the order for reactivity for C5a, C4a, and C3a? |
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Definition
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Term
| When C5a and C3a are systematically injected, what happens? What do we classify C5a and C3a as? |
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Definition
| smooth muscle contractions and an increase in vascular permeability (anaphalaxins) |
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Term
| How does a pore get made into the lipid bilayer of the pathogen? |
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Definition
| C5b binds C6 and C7. This is called the C5b67. C8 also binds and inserts its hydrophobic domain into the lipid bilayer. around 10-16 C9 molecules binds to the complex and polymerize. |
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Term
|
Definition
|
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Term
|
Definition
| inhibits the binding of C9 to C5b678 complex |
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Term
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Definition
| C1 inhibitor; binds to active enzymes C1r:C1s and causes them to dissociate from C1q, which remains bound to pathogen. By this mechanism, C1INH limits the spontaneous activation of C1 in plasma |
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Term
| What is the active C3 convertase for the lectin and classical pathways? |
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Definition
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Term
| In the lectin and classical pathways, what displaces C2a from the C4b2a ? |
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Definition
|
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Term
|
Definition
| protease I --cleaves to C4c and C4d |
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Term
| What complement factor displaces C3b? |
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Definition
| CR1 and H. Protease I cleaves it |
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Term
| How is the membrane attack complex regulated? |
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Definition
| CD59 prevents the membrane attack at the C8 C9 polymerization phase |
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Term
| Which microbes have membrane and secreted proteins to evade complement |
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Definition
| N. meningitidis, B. burgdorferi, S. pneumoniae, S. aureus |
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Term
|
Definition
| a microbe mechanism to cleave Ig |
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Term
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Definition
| binds Fc regions, blocks C1 activation |
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Term
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Definition
| inactivates bound C3b (microbe mechanism to fight back) |
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Term
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Definition
| inhibits convertase activity (microbe mechanism to fight back) |
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Term
| What is the receptor for C3a and C5a? |
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Definition
| "c3a receptor" and "C5a receptor" |
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Term
| difference between function of C3a and C3b? |
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Definition
c3a = cell activaton , chemotaxis
c3b = increase in phagocytosis, transport of immune complexes |
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