M1-C4-L6 --> Complements
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- What mediates the activation of complement proteins of the immune system?
- Microbial surfaces or by antibody-antigen complexes.
- What are the three complement activation pathways?
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1. Classical
2. MB-Lectin
3. Alternative - In classical activation pathway, what causes C1s to become an activated enzyme?
- Binding of C1q, C1r, and C1s to antigen and IgG (or IgM)
- In classical activation pathway, what does C1s active enzyme do?
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Cleaves C2 in to C2a and C2b.
Cleaves C4 in to C4a and C4b. - In classical activation pathway, what cleaves C3?
- C4b2a enzyme
- What is the C3 convertase in Classical activation pathway?
- C4b2a
- In classical pathway, what happens to C3 convertase after it cleaves C3?
- Binds with C3b to form C4b2a3b.
- In classical pathway, what does C4b2a3b do?
- Cleaves C5 into C5a and C5b
- What is similar about all three pathways?
- C5b will recruit C6, C7, C8, and C9 into a self-assembled complex. C9 of this complex will "drill" a transmembrane pore inducing cell lysis.
- In classical pathway, what is the C5 convertase?
- C4b2a3b
- In classical pathway, what is required?
- Antibody (acquired immunity)
- In MB-lectin pathway, what is initially required?
- A mannan-binding lectin must bind to a mannose on microbial surface.
- In MB-lectin pathway, a complex of mannose and MB-lectin leads to what?
- Binding of MASP I and MASP II.
- In MB-lectin pathway, what do the MASP's do?
- Cleave C2 (into C2a and C2b) and C4 (into C4a and C4b)
- In MB-lectin pathway, what happens after MASP cleavage?
- Formation of C4b2a
- In MB-lectin pathway, what is the C3 convertase?
- C4b2a
- What does the C3 convertase do and what is the final product in the MB-lectin pathway?
- C3 convertase cleaves C3 into C3a and C3b. This forms C4b2a3b.
- In MB-lectin pathway, what is the C5 convertase?
- C4b2a3b
- In the alternative pathway, what must occur initially?
- Slow spontaneous hydrolysis of the thioester in C3.
- In the alternative pathway, what happens after C3 is hydrolyzed?
- Factor B comes in and gets attached.
- In the alternative pathway, what does Factor D do and what is the resultant product?
- Cleaves Factor B on the C3B complex to Ba and Bb. This results in C3Bb complex.
- In the alternative pathway, what is the C3 convertase?
- C3bBb
- In the alternative pathway, what happens to C3Bb and what is the result product?
- Cleaves the C3 on itself into C3a and C3b leading to the formation of C3bBb
- In the alternative pathway, what is the event immediately following formation of C3bBb?
- C3bBb forms many molecules of C3b which attach to the microbe.
- In the alternative pathway, what does C3bBb bind to?
- An additional C3b to form C3bBb3b.
- In the alternative pathway, what does C3bBb3b bind to?
- Factor P
- In the alternative pathway, what is the C5 convertase?
- C3bBb3bP
- Describe the properties of C5a
- Vasoactive and chemotactic properties.
- Describe the properties of C3a.
- Increases vasodilation and vascular permeability contributing to inflammation
- In the MB-lectin pathway, what is the stabilizing event?
- The binding to microbial surfaces.
- In the alternative pathway, what is the stabilizing event?
- Factor P (properdin) binding to C3bBb3b.
- How is systemic activation prevented in the complement pathways?
- As activated components move farther ways from sites of activation, they are more likely to be susceptible to inhibitors.
- What can be said about disorders of complement proteins?
- Very rare.
- What is the difference between primary vs secondary immune deficiency diseases?
- Primary's are congenital and secondary's are disorders associated with induced molecules or cells such as complements.
- List three classes of lipid mediators derived from arachidonic acid.
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1. Prostaglandins
2. Leukotrienes
3. Thromboxanes - NSAID's inhibit what precursor of what lipid mediator(s)?
- Inhibits cyclooxygenase thus inhibiting prostaglandins and thromboxanes
- Effects of prostaglandins. x 3
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1. Increase vasodilation
2. Increase vascular permeability.
3. Increase pain perception - Effects of thromboxanes x 2
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1. Increases platelet aggregation
2. Increases vasoconstriction - Effects of Prostacyclins x 2
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1. Inhibits platelet aggregation
2. Increases vasodilation - The peptide, Bradykinin, causes what in what condition?
- Mild inflammation in the absence of infection.
- What is the peptide, Bradykinin, activated by?
- Blood clotting.
- Bradykinin acts through what receptors?
- B1 and B2 receptors.
- What are the vascular effects of Bradykinin?
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1. Increase vasodilation
2. Increase vascular permeability. - What are the effects of serotonin and histamine? x 2
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1. Increase vasodilation
2. Increase vascular permeability - Where are serotonin and histamine derived from? x 4
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Basophils
Eosinophils
Mast cells
Platelets - What does nitric oxide increase in responsive cells?
- cyclic GMP
- Nitric Oxide is produced by three enzymes. Name two.
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1. iNOS (NOS1)
2. eNOS (NOS3) - Where is iNOS made and what does it do?
- Made in macrophage and produces anti-microbial effects.
- What is eNOS and what does it do?
- Endothelial NO synthase. Increases vasodilation and increases vascular permeability.
- Are cytokines local or systemic?
- Local
- What do cytokines do in general?
- Act on receptors to alter cell function
- Constituitively expressed chemokine receptors generally involved in what?
- Trafficking
- Inducible chemokine receptors involved in what?
- Inflammation
- What are the co-receptors of HIV-1? x 2
- CCR5 and CXCR4