Antibodies and Complements Flashcards
After injection of Antigen at time=0 days, the primary response of antibody to Antigen will occur around day ____ and will reach its peak response around day ____.
9-10
16-18
What are four important features of antibodies?
- Bind a variety of antigenic structures
- Exquisite discrimination of similar antigens
- Bind antigen with great strength
- Recognize antigen in its native form
What is the overall mission of antibodies?
Neutralize the target antigen
What are the three ways in which antibodies neutralize antigens?
- Opsonization
- Complement Fixation
- Direct Neutralization
What is opsonization?
Antibodies tag microbial organisms or infected cells for phagocytosis
What is complement fixation?
Antibody activates complement system to destroy microbial organisms or infected cells (increases opsonization and lyses some bacteria)
What is Direct Neutralization?
Antibody prevents bacterial adherence.
Antibody binds toxins in the blood and tissue, facilitating the removal of the toxins.
Which immunoglobulin makes up 70-75% of all Ig in serum?
IgG (immunoglobulin G)
What are the main functions of IgG?
- Neonatal immunity
- Role in immunological memory
- Represents the basic structure of all IgG (hinge region with flexible arms)
Which immunoglobulin is a major component of B cell surface immunoglobulin?
IgD (also referred to as B-cell receptor)
less than 1% of circulating Ig
Which immunoglobulin is very scarce in serum and is found on the surface of basophils and mast cells?
IgE
Which immunoglobulin is important for killing large parasites, such as worms?
IgE
A resting mast cell has preformed granules containing _____ and other inflammatory mediators.
histamine
An activated mast cell has multivalent antigen that crosslinks with ______ antibody (which was bound to mast surface), causing the release of _______ contents.
IgE
granule
Which immunoglobulin is secreted in saliva?
IgA
IgA is usually assembled as a ______ and its receptor transports IgA across _______ epithelium.
Dimer
Mucosal
The _________ joins the two IgA in order to form a dimer.
J chain
What are the two forms of IgA?
Membrane-Bound
Secreted
What is the structure of IgM?
Pentamer
Which immunoglobulin is the first secreted in response to the initial antigenic challenge?
IgM
five armed pentamer is effective at detecting new antigens
What is the most abundant Ig in the mouth?
IgG
(IgA is abundant in saliva but G is always most abundant)
Board Question
What is the complement system of immunity?
A part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism
*FAST
What are the principle functions of the complement system?
- Opsonization and cell activation
- Chemotaxis
- Lysis of target cells
What are the nine important complement family members?
C1, C2, C3, C4, C5, C6, C7, C8, C9
Which of the nine complement family members is the Central Component?
C3
Which of the nine complement family members are the “late components”?
C5
C6, C7, and C8
C9
Many complement components are ________.
Proenzymes (not yet in their active form)
Active sites of complement components are masked. When does activation of these components occur?
When the masking is removed: mostly by proteolytic cleavage, resulting in the exposure of the active site
________ of complement molecules are the active complements.
Fragments
What is the complement system’s role in opsonization and cell activation?
- Complement FRAGMENTS coat the surface of a target
- Immune cells bind to coated target
- Results in phagocytosis and cell activation
What role does the complement system play in chemotaxis?
- Small FRAGMENTS of complements form a concentration gradient (1/2 sticks to bacteria, 1/2 floats away)
- Stimulates immune cells to move toward the site of infection
What role does the complement system play in lysing target cells?
- MAC: complement activation results in the assembly of a Membrane Attack Complex
- the MAC inserts itself into lipid bilayers
- the MAC makes a large hole on the cell membrane to cause the cell lysis
How does opsonization help the killing of bacteria?
- A complement generates Active complement fragments through interaction with a bacterium
- Complement receptors (CR) are expressed on phagocytic cells
- CR mediates phagocytosis of the bacterium
Complement molecule C3 breaks into active fragments _____ (“find me”) and ______ (“eat me”).
C3a
C3b
How are complement molecules involved in the inflammatory response?
- C3b binds to a microbe and releases C3a
- Proteolysis of C5 causes the release of C5a
- C3a and C5a recruit(chemotaxis) and activate leukocytes
- Recruited leukocytes kill the invading microbes
- C5a is a major factor in Allergic reactions*
The formation of the MAC is initiated by which complement fragment?
C5b
What are the classical pathway activators?
Antibody-antigen complexes containing IgM or IgG1-3
Adaptive
What are the lectin pathway activators and on what surface do they act?
Terminal Mannose Groups
Microbial Surface
What are the Alternative pathway activators?
Microbial Cell Walls
Innate
Describe the steps of activation of the alternative pathway and what happens to “self surface” bound complements.
- Spontaneous cleavage of C3 into C3a and C3b (slow)
- if C3b does not attach and is in fluid, it will degrade
- C3b will covalently bind to “self surface” or “protected surface”
- Self surface bound C3b will bind to factor H (H for Host, B for bacteria)
- C3bH is deactivated by factor I
- iC3b is the inactive form
Describe the steps of activation of the alternative pathway and what happens to “protected surface” bound complements.
- Spontaneous cleavage of C3 into C3a and C3b (slow)
- Unattached C3b will be degraded
- C3b will covalently bind to “self surface” or “protected surface” <–MICROBE
- C3b bound to microbial surface will bind to factor B
- C3bB is cleaved by factor D to generate C3bBb
- C3bBb is the alternative pathway C3 Conertase
- C3 Convertase catalyzes a significant amount of cleavage
C3 Convertase is which complement molecule? It is used in which complement pathway?
C3bBb
Alternative (innate)
Which molecule is the adapter for the Classical Pathway?
C1
The Classical Pathway is an example of ______ immunity because its _____ adapter recognizes antigen-antibody complexes.
Adaptive
C1
True or False: Free antibody do not engage C1.
TRUE
only tissue-bound antibody activates C1 and generates the active C1qr2s2 form
Which of these immunoglobulins would engage C1 and activate the classical pathway?
a. Soluble IgM
b. Antigen bound IgM
c. Soluble IgG
d. Antigen bound IgG
b, d
C1 recognizes antigen-antibody complexes, NEVER free antibodies
Describe the Classical Pathway after binding of C1 to the antigen-antibody complex:
- Activated C1 molecule will cleave C2 and C4
- Formation of C4b2a
- C4b2a is the Classical Pathway “C3 Convertase”
- C3b binds to C4b2a complex and antigenic surface
- Late stage complement C5 convertase = C4b2a3b
_____ is required for the initiation of MAC.
C5b
MAC is formed by ____, ___, ___, ___, and multiple ___.
C5b, C6, C7, C8
(multiple) C9
