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22 Cards in this Set
- Front
- Back
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What is the first event in complement pathway activation?
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Direct or indirect binding of complement proteins to surface of cell or pathogen.
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What initiates the alternate pathway?
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The alternative pathway is initiated if C3, a complement protein, binds directly to the surface of a bacterial cell.
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What initiates the lectin pathway?
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The lectin pathway is activated when MBL binds to the surface of a cell or pathogen and then eventually recruits C2 and C4.
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What event initiates the classical pathway?
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The classical pathway is initiated if antibodies (IgG, IgM), CRP, or SAP bind to the surface of a cel or pathogen and then eventually recruits the C1 complex.
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What is the C1 complex and what is its role in the classical pathway?
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The C1 complement protein + antibodies (IgG, IgM), CRP, or SAP = C1 complex
The C1 complex splits C4 and C2 |
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What is the second major event in complement pathways?
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The formation of C3 convertase.
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What is the function of C3 convertase? How is it formed in the classical and lectin pathways? How is it formed in the alternative pathway?
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C3 convertase cleaves C3 into C3a and C3b. In the classical and lectin pathways, C4b and C2b serve as the C3 convertase. In the alternative pathway, however, C3b and Bb form the C3 convertase.
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What does C3a do?
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C3a will stimulate inflammation by binding to complement receptors (CR) on mast cells, neutrophils and macrophages.
C3b binds covalently to surface of cell or pathogen to opsonize the cell (or to serve as a component of C3 in the alternative pathway or ). |
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What are the four functions of C3b?
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1. Opsonizes cell or pathogen for phagocytosis
2. Component of C3 convertase in alternative pathway (note positive feedback loop) 3. Component of C5 convertase in all complement pathways 4. Further cleavage of C3b produces C3d (which binds to CR2 on B cells); initiating proliferation/differentiation/humoral immunity 5. It also stimulates inflammatory reactions: Proteolysis of C3, C4 and C5 releases C3a, C4a and C5a which recruit/activate leukocytes for the destruction of microbes by leukocytes. |
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If the cell is not phagocytosed, what is the next major event in the complement pathway?
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The formation of C5 convertase, which cleaves C5 to produce C5a and C5b.
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What are two innate defenses for intracellular pathogens that can enter into host cells?
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1. Cytokines: make the host intracellular environment unfavorable for pathogen reproduction
2. Natural killer cells: Destroy the infected host cell |
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What are PAMPs?
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Different classes of microbes (ex: gram positive bacteria, dsRNA viruses) share certain structures known as PAMPs (which stands for pathogen associated molecular patterns). They serve as ligands for recognition receptors or innate proteins like lysozyme, complements etc.) Some examples include LPS, peptidoglycan or dsRNA.
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What are some receptors that cells/plasma proteins use to "recognize" a pathogen?
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Examples:
1. Toll like receptors (TLRs) -- (extracellular) bacterial cells 2. Toll like receptors (TLRs) -- (endosomal membrane) nucleic acids of ingested microbes 2. Lectin -- microbial polysaccharide; cytosolic 3. NOD-like receptor -- bacterial peptidoglycans and products of damaged cells; cytosolic 4. Lectin -- microbial polysaccharide; extracellular |
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How is the formation of C5 convertase different in the alternative pathway compared to the lectin/classical pathways?
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When C3b binds to the microbe in alternative complement pathways, it initiates the formation of C5 convertase ( --[C3b + Bb + C3b] + C5 --> C5a + C5b).
In classical/lectin pathways, C4b binds to the microbe and initiates the format of C5 convertase (--[C4b+Bb+C3b] + C5 --> C5a + C5b) |
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What does C5a do?
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Stimulates inflammation by binding to complement receptors (CR) on mast cells, neutrophils and macrophages (M&M)
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What does C5b do?
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Covalently binds to surface of cell or pathogen:
1. Initiates formation of Membrane attack complex (MAC) 2. Leads to osmotic lysis of the cell the complement proteins are attached to. |
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Describe how the covalent binding of C5b to the surface of the cell or pathogen leads to osmotic lysis of the cell the complement proteins are attached to.
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The process works like a "hole punch." After C5 convertase releases C5a to stimulate inflammation, C5b remains and binds to the cell surface, along with C6, C7, and C8...as well as C9. Together, they form the "Membrane Attack Complex." This complex allows water to rush in through the membrane and the cell explodes.
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What is properdin?
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Stabilizes the C3 convertase (C3bBb) on microbial surfaces (alternative pathway)
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What is factor D?
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Plasma serine protease which cleaves Factor B when it is bound to C3b.
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What is factor B?
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Bb is a serine protease and the active enzyme of C3 and C5 convertases. (alternative pathway)
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If the pathogen is extracellular and complement pathways fail to destroy it, what are the body's next two defenses?
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1. Capture of pathogens by phagocytic leukocytes:
- Macrophages - Dendritic cells - Neutrophils - Eosinophils 2. Activation of non-phagocytic leukocytes - Mast cells |
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Describe the general cascade of the classical and lectin complement pathways.
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When MBL (lectin), IgG, IgM, CRP or SAP bind to a pathogens surface, a complex called C1 is formed.
C4 and C2 then, as a result, split and C4b and C2b form the C3 convertase which splits C3 into C3a and C3b. the C3b binds to the pathogen surface where it (1) opsonizes and (2) becomes part of the C5 convertase. The C5 convertase is composed of C3b+Bb+B3b+C5. It splits C5 into C5a and C5b. C5a leaves to promote inflammation, but C5b stays on the pathogen surface to form the Membrane attack complex with C6-C9. The MAC allows water to rush into the cell, causing it to lyse. |
