Term
| Complement refers to a set of SERUM proteins that cooperates with both innate and the adaptive immune systems to |
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Definition
eliminate blood and tissue pathogens.
AND THEY CAN USE CATALYTIC CASCADES |
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Term
various complement
components bind and ____bacteria, rendering them susceptible to receptor-mediated phagocytosis by
macrophages, which express membrane receptors for complement proteins |
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Definition
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Term
Besides opsonizing ..there are other complement proteins __, interface with components of the
adaptive immune system, clear immune complexes from
the serum, and/or eliminate apoptotic cells. |
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Definition
that give an
inflammatory responses |
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Term
Besides opsonizing, and IR, ___ complement proteins that directly kills some pathogens by
creating pores in microbial membranes. |
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Definition
| a Membrane Attack Complex (MAC) assembled from |
|
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Term
“the activity of blood serum that completes the action
of antibody.” |
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Definition
| what John Ehrlich, said giving it the name complement |
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Term
Most complement components are synthesized in the ___by ___, Some by other cell types, including blood monocytes, tissue macrophages,
fibroblasts, and epithelial cells of the gastrointestinal and
genitourinary tracts. |
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Definition
|
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Term
| there are more than 30 ___ that interact in the immune system |
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Definition
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Term
Complement components can be classified into seven ( 7 )
functional categories |
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Definition
1. Inititators(C1q, MBL, ficolins)
2.Convertase activators
(C1r, C1s, C4b, C2a)and enzymatic mediators(C3 convertase, C5 convertase)
3.Opsonins 4.Anaphylatoxins
5. Membrane attack complex
6. Complement receptors Complement receptors 7. Regulatory proteins |
|
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Term
Complement components can be classified into seven ( 7 )
functional categories |
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Definition
1. Inititators(C1q, MBL, ficolins)
2.Convertase activators
(C1r, C1s, C4b, C2a)and enzymatic mediators(C3 convertase, C5 convertase)
3.Opsonins 4.Anaphylatoxins
5. Membrane attack complex
6. Complement receptors Complement receptors 7. Regulatory proteins |
|
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Term
1. Initiator complement components
functional category is what? |
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Definition
These proteins initiate their complement cascades by binding to soluble or membrane-bound molecules. Once bound to their activating ligand, they undergo conformational
alterations resulting in changes in biological activity.
The C1q complex, Mannose Binding Lectin (MBL), and the
ficolins are examples of initiator complement components. |
|
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Term
Enzymatic mediators
functional category is what? |
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Definition
Complement components like C1r, C1s, MASP2, & factor B) are proteolytic enzymes that cleave and activate other members of the complement cascade. Some are activated by binding to other macromolecules and doing shape change. Others are inactive until cleaved by another protease enzyme and are thus termed zymogens: proteins that are activated by proteolytic cleavage. The two enzyme complexes that cleave complement components C3 and C5, respectively, are called the C3
and C5 convertases and occupy places of central importance in the complement cascades. |
|
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Term
Membrane-binding components or opsonins
functional categories of complement are what ??? |
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Definition
On activation of the complement cascade, several proteins are
cleaved into two fragments, each of which then takes on a
particular role. For C3 and C4, the larger fragments, C3b
and C4b, serve as opsonins, enhancing phagocytosis by binding to microbial cells and being binding tags for
phagocytic cells bearing receptors for C3b or C4b. The larger frag of a cleaved complement component is designated with the suffi x “b,” and the smaller with the suffi x “a.” One exception to this rule: the larger, enzymatically active form of
the C2 component is named C2a. |
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Term
Inflammatory mediators
functional category of complement is what ? |
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Definition
Some small complement fragments act as inflammatory mediators..that
enhance the blood supply to the area in where released, by binding to receptors on endothelial cells lining the small blood vessels and inducing an increase in capillary diameter. They also attract other cells to the site. Because such effects can be harmful in excess, these fragments are called anaphylatoxins, mean-
ing substances that cause anaphylaxis (“against protection”). Examples include C3a, C5a, and C4a |
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Term
Membrane attack proteins
functional category of complement |
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Definition
The proteins of (MAC) insert into the cell membranes of invading microorganisms and punch holes ..
lysis of the pathogen. The complement components of the MAC are C5b, C6, C7, C8, and multiple copies of C9. |
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Term
Complement receptor proteins
functional category of complement does what? |
|
Definition
Receptor molecules on cell
surfaces bind complement proteins and signal specific cell functions. For example, some complement receptors such as CR1 bind to complement components such as C3b on the
surface of pathogens, triggering phagocytosis of the
C3-bound pathogen. Binding of the complement component C5a to C5aR receptors on neutrophils stimulates neutrophil degranulation and inflammation. Complement
receptors are named with “R,” such as CR1, CR2, and C5aR. |
|
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Term
Regulatory complement component
functional category of complement |
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Definition
Host cells are protected from complement-mediated lysis by
the presence of membrane-bound and soluble regulatory proteins. These regulatory proteins include factor I,
which degrades C3b, and Protectin, which inhibits the formation of the MAC on host cells. |
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Term
| Chapter 6...about complement you will need to know what |
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Definition
describes the components of the
complement system,
their activation via three major
pathways,
the effector functions of the molecules of the complement cascade, their interactions with other
cellular and molecular components of innate and adaptive immunity
The mechanisms that
regulate the activity of these complement components, the
evasive strategies evolved by pathogens to avoid destruction
by complement, and the evolution of the various complement proteins. |
|
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Term
| __ represent some of the most evolutionarily ancient participants in the immune response. |
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Definition
|
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Term
| the initiating event of the three pathways of complement activation is different, but they all converge in the generation of an enzyme complex capable of _____ |
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Definition
| cleaving the C3 molecule into two fragments, C3a and C3b. |
|
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Term
| The enzymes that cleave the C3 molecule into two fragments, C3a and C3b are ____ |
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Definition
|
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Term
the classical and lectin pathways use the dimer C4b2a for their ___,
while the alternative pathway uses C3bBb however, the final result is the same: ____, a centrally
located and multifunctional complement protein. |
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Definition
C3 convertase activity
a big increase in the concentration of C3b |
|
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Term
The second set of convertase enzymes of the cascade, ___, are formed by the addition of a C3b component to the C3 convertases. C5 convertases cleave C5 into the inflammatory mediator, ____, which is the initiating
factor of the MAC. |
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Definition
C5 convertases
C5a, and C5b |
|
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Term
| Complement proteins interact with one another in catalytic cascades similar to components of ____ |
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Definition
| the blood clotting system. |
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Term
| Complement proteins can do what things? |
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Definition
| opsonize bacteria, elicit IR, interface with the adaptive immune system, clear immune complexes and eliminate apoptotic cells. |
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Term
| Complement proteins can generate a __ that can directly kill some pathogens by poking holes in their plasma membranes and causing their guts to leak out. |
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Definition
membrane attack complex
MAC |
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Term
| The bacteriolytic activity requires two different substances: |
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Definition
Anti-bacterial antibodies (heat stable)
Heat sensitive lytic proteins (complement proteins) |
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Term
| Name the 6 overview Complement System Components |
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Definition
1. Initiators 2. Enzymatic Mediators 3. Opsonins 4. Inflammatory Mediators
5. Membrane Attack Proteins
6. Receptors |
|
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Term
| 1. Initiators: Complement proteins bind to soluble or membrane bound molecules and undergo ____ |
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Definition
| conformational changes resulting in biological activity. |
|
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Term
| 2. Enzymatic Mediators: Several complement components are __ that cleave and activate other members of the complement cascade. Two primary enzymatic mediators are __ |
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Definition
proteolytic enzymes
the C3 and C5 convertases |
|
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Term
| 3. Opsonins: Several complement __that are generated during the cascade serve as opsonins, enhancing phagocytosis by binding to microbial cells and serving as “tags/flags” that allow the cells to be more easily seen by phagocytes |
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Definition
|
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Term
| 4. Inflammatory Mediators: Split products of complement proteins that regulate ____and increase ____. In overabundance they act as anaphylatoxins and promote anaphylaxis |
|
Definition
endothelial cells
capillary diameter |
|
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Term
| 5. Membrane Attack Proteins: Complement components __form a complex that pokes holes into target membranes. |
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Definition
|
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Term
| 6. Receptors: Complement receptors on cells such as phagocytes recognize ____and respond by initiating phagocytosis. |
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Definition
| complement labeled target cells |
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Term
| Three Major Pathways of Complement Activation are__ |
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Definition
| classical pathway , lectin pathway , alternative pathway |
|
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Term
Activation of all three pathways leads to the generation of ____ C3 convertase cleaves and activates C3 and C5 convertase cleaves and activates C5.
• C5 convertase splits C5 into C5a and C5b. C5b then leads to generation of the MAC. |
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Definition
| a C3 convertase and a C5 convertase. |
|
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Term
C3 convertase cleaves and activates__ and C5 convertase cleaves and activates __.
• C5 convertase splits C5 into C5a and C5b. C5b then leads to generation of the MAC. |
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Definition
|
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Term
Classical Pathway
Begins with formation of soluble __or the binding ____ |
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Definition
antigen/??antibody complexes
of antibody to antigen on a target cell. |
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Term
| IgM, IgG1, IgG2, IgG3 can activate complement via their __ receptors. |
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Definition
|
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Term
| Initial stage of activation of the classical path involves ____ components |
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Definition
|
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Term
| In the classical path, binding of antibody to antigen induces conformational changes in the Fc portion of the antibody molecule, exposing a binding for the ____ |
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Definition
|
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Term
| Classical path: C1 is a macromolecular complex consisting of __. The interaction between the ___ is stabilized by Ca2+. |
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Definition
1 x C1q, 2 x C1r, and 2 X C1s = “C1qr2s2”
C1 molecules |
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Term
| Classical path: Each ___consists of 18 polypeptide chains in six collagen-like triple helices. |
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Definition
|
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Term
| Classical path: The six tips of the C1 molecules bind to the |
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Definition
CH2 domains of the antibody molecules.
C H = constant heavy |
|
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Term
| classical path: Each C1r and C1s monomer contains a ___and an __. |
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Definition
catalytic domain
interaction domain |
|
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Term
| classical path: Each C1 complex uses its __to bind at least two Fc sites to create a stable ____. This interaction induces a conformational change in C1r, converting C1r to an ___ |
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Definition
C1q globular heads
C1-antibody interaction.
active serine protease, C1r. |
|
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Term
| classical: Active C1r cleaves C1s to an active form, creating ____. |
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Definition
|
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Term
| The active C1s portion of C1qr2s2 is also a ___ and targets ___. |
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Definition
|
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Term
| Classical path: Active C1s portion of C1qr2s2 targets C4 and C2. C4 is cleaved into __ |
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Definition
|
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Term
| classical path: C4a is an __. It functions in anaphylaxis by binding to basophils and mast cells promoting their degranulation. __ doesn’t participate in the lytic phase of the complement system |
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Definition
|
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Term
| C4b attaches to the target surface near __. |
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Definition
|
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Term
| C2 attaches to the exposed site on C4b and is then cleaved by the neighboring C1s. C2b diffuses away. The result is the formation of:__ |
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Definition
| Active C4b2a = C3 convertase |
|
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Term
The C3 convertase will act on C3 to convert it into an ___.
C3 convertase ____to generate C3a and C3b. |
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Definition
active protein
hydrolyzes C3 |
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Term
| C3a is an __ that diffuses away and plays a role in regulating inflammation and can act as an __ |
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Definition
|
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Term
| A single convertase can generate a lot of C3b ... generating a lot is called __. |
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Definition
|
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Term
Part of the C3b combines with active C3 convertase (C4b2a)
to generate _____ |
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Definition
|
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Term
| The other part of C3b diffuses away and coats immune complexes and particulate antigens, functioning as an __ or promoter of phagocytosis |
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Definition
|
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Term
| C3b component of the C5 convertase binds to C5, cleaving C5 into ____ |
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Definition
|
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Term
| C5a is an ___ that diffuses away and functions in ___. |
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Definition
anaphylatoxin
anaphylaxis |
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Term
| C5b binds to C6 and initiates formation of the ___. |
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Definition
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Term
C5b6 binds to C7. The C5b67 complex undergoes a conformational change that exposes ___, which serve as binding sites for membrane phospholipids.
This reaction occurs on ___ |
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Definition
hydrophobic regions
the surface of a target cell. |
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Term
| The hydrophobic binding sites enable the C5b67 complex to insert into the ___. |
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Definition
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Term
Next C8 joins the complex, inducing a conformational change in C8 that exposes __, allowing it to interact with the membrane.
The C5b678 complex creates a __ in the cellular membrane. |
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Definition
|
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Term
| Multiple copies of C9 then binds the C5b678 complex exposing hydrophobic sites that ___. The pore that is formed allows for ions and small molecules to leak out. The cell loses osmotic stability and is killed by an influx of water. |
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Definition
|
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Term
| The end result of the 3 initiation complement pathways is formation of ___ |
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Definition
|
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Term
| for the classical pathway the C5 convertase composition is ___ |
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Definition
|
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Term
| for the alternative pathway C5 convertase is composed of __ |
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Definition
|
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Term
| the end result for all C5 convertase is_ |
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Definition
| the cleavage of C5 molecules C5b goes to the bug membrane and provides a binding site for the following MAC componenet |
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Term
| C5b is extremely liable no covalently bound and is inactive unless stabilized by binding of -- |
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Definition
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Term
| C5 initiates generation of the ____ |
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Definition
|
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Term
| when C5 binds to C6 and C7 the complex changes shape showing the ____ region on C7 which will start to stab the bug |
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Definition
|
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Term
| If the stabbing immune complex isn't on a bug. or other cellular activating surface...the hydrophobic binding sites ___ |
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Definition
|
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Term
| Released C5b67 complex can insert into membranes of nearby cells and mediate ____ |
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Definition
|
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Term
the hydrophobic domain of
C8 α β inserters into __ |
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Definition
the interior of the phospholipid membrane of the bug
C5b67 creates a small pore with the polymeration of C9 |
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Term
|
Definition
| C5b678 surrounded by poly C9 complex.. |
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Term
| The 3 main classes of complement activity are _____ |
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Definition
1. Innate defense against infections
2.Interface between innate and adaptive
3. contraction of immune response |
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Term
| The innate part is what? and by what component? |
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Definition
Lysis by MAC C5b-C9
opsonization by C3b C4b
inflammation and chemotaxis by anaphylatozins C3a, C4a, C5a and receptors on leukocytes |
|
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Term
| Interface between innate and adaptive what and who |
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Definition
^ antibody rspns by C3b and C4b and a
C3 receptors on immune cells
^ memory C3b C4b and bits bound to antigen and complex on follicular dendridic cells |
|
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Term
|
Definition
Enhancement of AP MBL, C1A, C3b, C4b C5a
Potential effects on T cells by C3, C3a, C3b, C5a |
|
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Term
| contraction activity and by who |
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Definition
clearance of complexes by C1,2,3, 4
C1q C3 C4 Loss of CD 46 triggers immune clearance |
|
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Term
| Induction of regulatory T cells by |
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Definition
|
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Term
| Activation of phagocytic cells by different ways, including anaphylatoxin increases ____X 10 |
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Definition
|
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Term
| CR 2 aka CD21 aka Epstein-Barr virus receptor. what is the ligand and when it binds and what it does |
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Definition
| liband C3d, C3dg, iC3b. B cells and FDCs enhances B cell activation..B cell co-receptor and retention of C3d-tagged immune complexes |
|
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Term
| CR1 aka CD35 on leukocytes and erythrocytes and binds with |
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Definition
| C4b C3b erythrocytes take to liver |
|
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Term
| Binding of complement-opsonized bugs via CR1 on phagocytes results in __ |
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Definition
| receptor-mediated phagocytosis and secretion of pro-inflammatory moles like IL-1 and prostaglandins |
|
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Term
CR1 on B cells mediates ____
So, CR1 acts with innate and adaptive. |
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Definition
| antigen uptake of C3b-bound antigen making C1 degrade in B cell lysosomal system & then presentation to T cells. |
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Term
| CD 21 = CR 2 is on B cells and binds to break down products of __ |
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Definition
| C3b which are iC3b, C3d, and C3dg. |
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Term
| CR 3 b can for covalent bonds with antigen so with CD 21 on B cells, it enables the B cell to ______ |
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Definition
| bind antigen via both the B cell receptor and the CD1. |
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Term
| Deficiencies in CD21 have been found in people with ____ |
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Definition
| autoimmune disease such as SLE. |
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Term
| C3aR C5aR C5L2 are member of ____ |
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Definition
| G protein coupled receptors ( GPCR ) family C3a$ and C5aR mediate inflammatory functions after binding to anaphylatoxins C3a and C5a. |
|
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Term
| complement proteins defend by |
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Definition
| forming MAC, opsonizing, inflammation to guide leukocytes to site |
|
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Term
| MAC inducted apoptosis is also called __ |
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Definition
|
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Term
| When high concentrations of complement are present |
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Definition
| MACs can overwhelm the host defenses against MAC attack and induce autoimmunity.. complement damage is a problem in several autoimmune diseases |
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Term
| antibodies and complement pay and important role in defenses against viruses and |
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Definition
| contain viral spread in an acute attack and protect against reinfection |
|
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Term
| bacteria not susceptible to MAC attack |
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Definition
| Gm + repel complement assault .. complement proteins cannot penetrate |
|
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Term
|
Definition
| antibodies and complement coat antigen that can then be seen by Fc receptor for antibodies or complement receptors on phagocytic cells. |
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Term
| complement -mediated lysis directed by tumor specific antibodies can be rendered ineffective by |
|
Definition
| endocytosis or shedding of the MAC |
|
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Term
| binding of complement coated antigen..and seen by phagocytic cells results in |
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Definition
| complement receptor mediated phagocytosis and antigen destruction.. so, a tagged bug draws the phago. and bug is eaten. |
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Term
| opsonization with antibody and complement is very important especially with ___ |
|
Definition
|
|
Term
C3b and C4b ____
C5b in _____ |
|
Definition
opsonize
makes MAC page 206 |
|
|
Term
WHAT acts as a protease required t0 generate the
ALTERNATIVE PATHWAY C3 CONVERTASE |
|
Definition
Factor D to generate C3 convertase
in the alternative pathway |
|
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Term
| WHAT are the components of the C3 convertase for the ALTERNATIVE PATHWAY OF COMPLEMENT? |
|
Definition
|
|
Term
What are the components of the
C5 convertase for the alternative pathway of complement? |
|
Definition
|
|
Term
What are the components of the
C3 convertase for the
lectin pathway of complement? |
|
Definition
|
|
Term
| What complement fixation pathway can be initiated by a soluble C3 convertase |
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Definition
| The alternative pathway of complement |
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|
