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78 Cards in this Set
- Front
- Back
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What does C1q do?
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C1q binds to the Fc region of Ab (1 molecule of IgM or 2 molecules of IgG) bound to pathogens, thus allowing autoactivation of C1r.
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What does C1r do?
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Upon autoactivation induced by C1q binding, C1r cleaves C1s to active protease.
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What does C1s do?
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C1s is a serine protease that cleaves C4 and C2.
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What does C4b do (2)?
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1. C4b binds C2 for cleavage by C1s.
2. C4b covalently binds to pathogens and opsonizes them. |
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What does C4a do?
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C4a is a peptide mediator of inflammation with weak activity (C4a is a weak anaphylatoxin).
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What does C2a do?
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C2a is the active enzyme of the classical pathway C3/C5 convertase, it cleaves C3 and C5.
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What does C2b do?
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C2b is the precursor of vasoactive C2 kinin.
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What does C3b do? (3)
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1. C3b binds C5 for cleavage by C2a.
2. C3b initiates amplification via the alternative pathway 3. Many molecules of C3b bind to pathogen surfaces and act as opsonins |
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What does C3a do?
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C3a is a peptide mediator of inflammation with intermediate activity (C3a is an intermediate anaphylatoxin).
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What is the function of C5a?
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C5a is a peptide mediator of inflammation with high activity (C5a is strong anaphylatoxin).
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What is the function of C5b?
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C5b initiates assembly of the membrane attack system/complex (MAC).
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What is the function of C6?
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C6 binds C5b, forming the acceptor for C7.
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What is the function of C7?
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C7 binds C5b6; the amphiphilic complex inserts in the lipid bilayer.
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What is the function of C8?
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C8 binds C5b67, initiating C9 polymerization.
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What is the function of C9?
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Many C9 molecules polymerize to C5b678 to form a membrane-spanning channel, lysing the cell.
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What are some general characteristics of the complement proteins?
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Complement proteins are:
1. heat-labile 2. plasma proteins 3. augment opsonization of bacteria by Ab 4. many are serine proteases 5. act in a specific order |
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What does complement interact with?
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Complement interacts with pathogens to mark them for destruction by phagocytes through opsonization or kills pathogens through formation of the membrane attack complex (MAC).
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The classical pathway is initiated by...
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The classical pathway is initiated by activation of the C1 complex (by binding to Ag-Ab complexes; 2 molecules of IgG, or 1 molecule of IgM).
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Where is complement activation largely confined to?
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Complement activation is largely confined to the surface on which it is initiated.
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What do the terminal complement proteins do?
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The terminal complement proteins polymerize to form pores in membranes that can kill certain pathogens.
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How is the host protected from the destructive effects of complement?
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Complement control proteins regulate all three pathways of the complement activation and protect the host from its destructive effects.
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What determines the extent of complement activation under different circumstances?
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Membrane and plasma proteins that regulate the formation and stability of C3 convertases determine the extent of complement activation under different circumstances.
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What is the C1 complex comprised of?
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The C1 complex is comprised of a single C1 q molecule bound to two molecules each of the two zymogens C1r and C1s.
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What is the nature of the C1q molecule?
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C1q itself is a hexamer, each subunit of which is in turn a trimer, forming a globular domain with a triple-helical collagen-like tail.
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What links the C1q hexamer together?
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In the C1q hexamer the six globular heads are linked together by their collagen-like tails, which surround the (C1r:C1s)2 complex.
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What activates the autocatalytic enzymatic activity in C1r?
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Binding of more than one of the C1q heads to a pathogen surface or to the constant/Fc region of Abs in an Ag-Ab complex causes a conformation change in the (C1r:C1s)2 complex, leading to the activation of autocatalytic enzymatic activity in C1r.
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What is the function of activated C1r?
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The active form of C1r cleaves its associated C1s to generate an active serine protease.
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Once activated, what is the function of C1s?
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Activated C1s cleaves C4 and then C2, to generate two large fragments, C4b and C2a, that together form the C3 convertase of the classical pathway.
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C1s cleaves C2 to produce the large fragment...
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C1s cleaves C2 to produce the large fragment C2a, WHICH IS ITSELF A SERINE PROTEASE.
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What functions as the C3 convertase in the classical pathway?
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C4b2a, the complex of C4b with the active serine protease C2a, remains covalently linked to the surface of the pathogen as the C3 convertase of the classical pathway.
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What is the most important function of the C3 convertase?
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The most important job of the C3 convertase is to cleave large numbers of C3 molecules to produce C3b molecules that coat the pathogen surface.
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What are the 5 main cytokines secreted by macrophages and dendritic cells?
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IL-1, IL-6, IL-8 (CXCL8), IL-12, TNF-alpha
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IL-1 is mainly produced by what two types of cells?
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Macrophages and Keratinocytes
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IL-6 is mainly produced by what two types of cells?
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Macrophages and Dendritic cells
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IL-8 (CXCL-8) is mainly produced by what two types of cells?
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Macrophages and Dendritic cells
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IL-12 is mainly produced by what two types of cells?
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Macrophages and Dendritic cells
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TNF-alpha is mainly produced by what two types of cells?
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Macrophages and Dendritic cells
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What does IL-1 act upon?
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Lymphocytes and the Liver
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What does IL-6 act upon?
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Lymphocytes and the Liver
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What does IL-8/CXCL8 act upon?
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Phagocytes
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What does IL-12 act upon?
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Naive T cells
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What effect does IL-1 have on lymphocytes?
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IL-1 enhances the response of lymphocytes.
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What effect does IL-1 have on the liver?
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IL-1 induces acute-phase protein secretion by the liver.
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What effect does IL-6 have on lymphocytes?
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IL-6 enhances responses of lymphocytes.
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What effect does IL-6 have on the liver?
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IL-6 induces acute-phase protein secretion by the liver.
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What effect does IL-8 (CXCL8) have on phagocytes?
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IL-8 acts as a chemoattractant for neutrophils.
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What effect does IL-12 have on naive T cells?
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IL-12 diverts immune response to TH1, pro-inflammatory, cytokine secretion.
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What effect does TNF-alpha have on vascular endothelium?
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TNF-alpha:
1. Induces changes in vascular endothelium (expression of cell-adhesion molecules (E- and P-selectin) 2. Changes in cell-cell junctions with increased fluid loss 3. Local blood clotting. |
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Cytokines produced by macrophages cause dilation of...
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Cytokines produced by macrophages cause dilation of LOCAL SMALL BLOOD VESSELS.
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Leukocytes move to periphery of blood vessel as a result of...
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Leukocytes move to periphery of blood vessel as a result of INCREASED EXPRESSION OF ADHESION MOLECULES.
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After leukocytes move to the periphery of blood vessels as a result of increased expression of adhesion molecules they...
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extravasate at site of infection.
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Class of mechanism (COM):
Acidification-Specific product? |
pH=~3.5-4.0, bacteriostatic or bactericidal
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Class of mechanism (COM):
Toxic oxygen-derived products-Specific product? (5) |
1. Superoxide O2-
2. Hydrogen peroxide (H2O2) 3. Singlet oxygen (1O2*) 4. Hydroxyl radical (*OH) 5. Hypohalite (OCl-) |
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Class of mechanism (COM):
Toxic nitrogen oxides-Specific products? |
Nitric oxide NO
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Class of mechanism (COM):
Antimicrobial peptides-Specific products? |
Defensins and cationic proteins
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Class of mechanism (COM):
Enzymes-Specific products? |
Lysozyme-dissolves cell walls of some Gram-positive bacteria. Acid hydrolases-further digest bacteria.
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COM: Competitors
Specific products? |
Lactoferrin (binds Fe) and vitamin B12-binding protein.
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Activated macrophages secrete a range of cytokines including...
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IL-1, IL-6, IL-8 (CXCL8), IL-12, and TNF-alpha
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What are the local effects of the cytokine IL-1?
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Local effects of IL-1 include:
1-Activates vascular endothelium 2-Activates lymphocytes 3-Local tissue destruction 4-Increases access of effector cells |
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What are the systemic effects of the cytokine IL-1?
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Systemic effects of IL-1 include:
1. Fever 2. IL-6 production |
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What are the local effects of the cytokine IL-6?
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Local effects of the cytokine IL-6 include:
1-Lymphocyte activation 2-Increased Ab production |
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Which complement proteins make up the C3 convertase of the classical pathway?
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C1q, C1r, C1s, C4b, C2a.
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What is an anaphylatoxin?
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Anaphylatoxins are peptide mediators of inflammation.
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Which complement proteins increase vascular permeability and are chemotactic for phagocytes and lymphocytes?
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C5a, C3a, and C4a.
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How do C3b and C4b attach to the cell surface?
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C3b and C4b attach to the cell surface through a reactive thioester group (w/ R-OH).
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What is the most active anaphylatoxin?
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C5a is the most active anaphylatoxin.
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Which cells are the first responders, appearing rapidly on the scene?
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Neutrophils.
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Small complement-cleavage products act on blood vessels to...
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Small complement-cleavage products act on blood vessels to INCREASE VASCULAR PERMEABILITY AND CELL-ADHESION MOLECULES.
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Increased permeability allows increased fluid leakage from blood vessels and...
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Increased permeability allows increased fluid leakage from blood vessels and EXTRAVASATION OF IMMUNOGLOBULIN AND COMPLEMENT MOLECULES.
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Cytokines are typically released in response to...
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Cytokines are typically released in response to STIMULUS SUCH AS INFECTION.
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Characteristics of cytokines (3)
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Cytokines are:
1. small protein molecules (~25kDa) produced by cells 2. usually released in response to stimulus such as infection 3. can act in an autocrine or paracrine manner. |
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What are chemokines?
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Chemokines are a class of cytokines that have chemoattractant properties.
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CRP? Made by?
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C-reactive proteins; made by the liver
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Selectins
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Selectins are adhesion molecules found on activated endothelial cells-they bind carbohydrates and initiate leukocyte-endothelial cell interactions.
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Integrins
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Integrins are adhesion molecules found on a variety of leukocytes, they bind to cell adhesion molecules and extracellular matrix (strong adhesion).
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Immunoglobulin superfamily
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The immunoglobulin superfamily is a group of adhesion molecules found on endothelial cells-they play various roles in cell adhesion and are the ligand for integrins.
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The release of TNF-alpha by macrophages induces...
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The release of TNF-alpha by macrophages induces LOCAL PROTECTIVE EFFECTS , BUT NOT WHEN RELEASED SYSTEMICALLY(fever, mobilization of metabolites and shock).
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Why doesn't complement destroy self cells (collateral damage)?
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'Cause we've got CR1, DAF, & MCP suckas!
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