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59 Cards in this Set

  • Front
  • Back
What are the Multiple Activities of Complement?
Lysis,
Opsonization,
Activation of Inflammatory Response,
Clearance of Immune Complexes
What are complement components?
Soluble proteins and glycoproteins
What produces complement proteins?
Hepatocytes
Blood monocytes
Tissue Macrophages
GI and Genitourinary epithelial cells
Are complement proteins synthesized as an active or inactive form?
Inactive
When a complement protein is cleaved, what is the designation of the larger fragment?
"b" (such as C3b)
exception is C2a which is a larger fragment
In classical pathway, what does C1q bind to?
Ag-bound Ab (IgM or IgG)
In classical pathway, what happens to C1r?
C1r becomes autocatalitically activated. Also, 2C1r molecules activate 2C1s
In Classical Pathway, What does C1s do while it is in the C1qr2s2 molecule?
It cleaves C4 and C2.
In Classical Pathway, What happens to C4b?
It binds to the cell near the C1 complex
In Classical Pathway, What happens to C2a?
It binds to C4b producing the C4b2a complex which is also known as C3 convertase.
In Classical Pathway, What does C3 convertase do?
It hydrolyzes many C3.
In Classical Pathway, What happens to C3b?
It combines with C3 convertase to produce C5 convertase which is also known as C4b2a3b.
In Classical Pathway, What does C5 convertase do?
It cleaves C5.
In Classical Pathway, What does C5b do?
It binds to C6 and eventually forms the MAC complex.
How can C3b bind to a cell membrane?
C3 convertase must cleave C3 to form C3b which causes it to activate a thioester bond which will form a covalent bond to a free hydroxyl or amino group on the cell membrane.
When does the Alternate pathway occur?
In the presence of foreign cell surfaces.
In the Alternate pathway, what happens to C3?
C3 hydrolyzes spontaneously and C3b attaches to the cell surface.
In the Alternate pathway, What does Factor B do?
It binds C3b and exposes the site acted on by Factor D.
In the Alternate pathway, What does Factor D do?
It cleaves the Factor B, forming C3bBb.
In the Alternate pathway, what is so special about C3bBb?
It has C3 convertase activity.
In the Alternate pathway, how does properdin affect the C3 convertase?
It stabilizes the C3 (C3bBb) complex.
In the Alternate pathway, What does the C3 convertase (C3bBb) do?
It generates C3b.
In the Alternate pathway, What does C3b do to C3 convertase?
It binds to C3 convertase, activating C5 convertase (C3bBbC3b)
In the Alternate pathway, What does C5 convertase do?
It cleaves C5 to C5b.
In the Alternate pathway, What does C5b bind to?
To antigenic surface.
In the Alternate pathway, what does C5b recruit?
It recruits C678 which recruits C9 to form MAC which forms pores.
What are the two main initiators of the alternative pathway?
Pathogens and Particles of microbial origin. AND. Nonpathogens
What are some of the initiators of alternative pathway that are pathogens and particles of microbial origin?
Strains and LPS of Gm-neg bacteria
Strains and Teichoic acid of Gm-pos bacteria
Zymosan from Fungal and Yeast walls
Some Viruses and virus-infected cells
Some tumor cells (Raji)
Parasite (tyrpanosomes)
What are some of the initiators of the alternative pathway that are nonpathogens?
Human IgG, IgA, and IgE in complexes
Rabbit and guinea pig IgG in complexes
Cobra venom factor
Heterologous erythrocytes (rabbit, chicken, mouse)
Anionic polymers (Dextran sulfate)
Pure carbohydrate (agarose, insulin)
What does the Mannose-Binding Lectin Pathway consist of?
Mannose-Binding proteins
What do activated Macrophages secrete?
IL-1, IL-6, TNF-alpha
In the Mannose-Binding Lectin Pathway, what does IL-6 do?
It acts on hepatocytes to secrete mannose-binding proteins as acute phase proteins.
What are Mannose-binding proteins structurally similar to?
C1q
What does mannose-binding proteins generate?
I generates activated C1-like complex.
In the Mannose-Binding Lectin Pathway, what does the C1-like complex do?
It cleaves C4 and C2.
What can mannose-binding proteins activate when in association with serine protease?
the classical pathway.
What is the major amplification step in all three pathways?
The cleavage of C3 to C3b
Before assembly of C3 convertase, what does C1 inhibitor (C1inh) do?
It binds to C1r2s2, causing dissociation from C1q.
Before assembly of C3 convertase, what can block the association of C4b and C2a?
C4b-binding protein (C4bBP), complement receptor type I, or membrane cofactor protein (MCP)
Before assembly of C3 convertase, what is inhibitor-bound C4b cleaved by?
Factor I
Before assembly of C3 convertase, In the alternative pathway, what prevents binding of C3b to factor B?
CR1, MCP, or Factor H
Before assembly of C3 convertase, what is inhibitor bound C3b cleaved by?
Factor I.
After assembly of C3 convertase, C3 convertases are dissociate by what?
C4bBP, CR1, Factor H, and decay-accelerating factor (DAF)
After assembly of C3 convertase, what happens to the remaing C4b and C3b?
It is cleaved by Factor I
In the regulation of MAC, S protein does what?
It prevents insertion of C5b67 MAC component into the membrane.
In the regulation of MAC, what binds C5b678 and prevents assembly of poly-C9 and blocking formation of MAC?
Homologous restriction factor (HRF), or membrane inhibitor of reactive lysis (MIRL or CD59)
Which pathway does C1 inhibitor (C1inh) affect?
Classical
Which pathway does C4b-binding protein (C4bBP) affect?
Classical and Lectin
Which pathway does Factor H affect?
Alternative
Which pathway does CR1 or MCP affect?
(Complement Receptor 1 or Membrane-cofactor protein)
Classical, Alternative, and Lectin
Which pathway does DAF affect?
Classical, Alternative, and Lectin
Which pathway does Factor I affect?
Classical, Alternative, and Lectin
Which pathway does S protein affect
Terminal
Which pathway does HRF (aka MIRL) affect?
Terminal
Which pathway does Anaphylatoxin inactivator affect?
Effector
What are the anaphylotoxins?
C3a, C4a, and C5a
What do the Anaphylotoxins do?
Bind receptor on mast cells/basophils and cause degranulation. Histamine is released and causes vasodilation and smooth muscle contraction.
Anaphylotoxins also cause smooth muscle contraction and increase vascular permeability.
Allows influx of Abs and phagocytic cells to site of Ag entry
What are anaphylatoxins controlled by?
serum protease (carboxypeptidase N)
What do C3a, C5a, and C5b67 do?
They induce monocytes and PMNs to adhere to vascular endothelium, extravasate and migrate towards site.