Lecture 6 - Antibodies and Antigens Flashcards
What functions do Abs have? (7)
L6 S4
- immunomodulation
- reduce inflammatory damage to host
- organization of T-cell response
- opsonization
- activation of complement
- toxin neutralization
- direct antibacterial activity
What is the general structure of an Ab (IgG)?
L6 S5
Two heavy chains:
- variable region (VH); contains antigen binding site
- constant regions (CH1, CH2, and CH3)
- hinge region with disulfide bond linking the two heavy chains
- intrachain disulfide bridge every 90 AA creating 110 AA loop
- determines class of Ab
Two light chains:
- variable region (VL); contains antigen binding site
- intrachain disulfide bridge every 90 AA creating 110 AA loop
- constant region (CL)
Fab fragment:
- consists of: VH, VL, CH1, and CL (one per fragment but two fragments per Ab)
- contains antigen binding region
Fc fragment:
- consists of: CH2, CH3 and hinge region (two per fragment and one fragment per Ab)(all parts from heavy chains)
- biologic activity region (complement binding sites)
- determines class of Ab
What effect do papain and pepsin have on Abs?
L6 S6-7
Papain:
-results in two separate Fab portions and a Fc portion with the hinge region
Pepsin:
- results in bivalent antigen-binding fragment consisting of two Fab sections connected by hinge section
- Fc section degraded
Both result in loss of function due to separation or destruction of Fc portion from Fab portion
What types of determinants on Ags are recognized by Abs?
L6 S12
Conformational determinants:
-region consists of several different segments of Ag that are near each other in native conformation but not denatured/linear conformation
Linear determinant:
- region consists of single, linear portion of Ag
- may be accessible in native conformation; always accessible in denatured/linear structure
Neoantigenic determinant:
-region only present after proteolysis at a certain location
What does Ab affinity refer to?
How do the Ab affinities of primary and memory responses differ?
L6 S13
Ab affinity refers to the tightness of Ab binding; the higher the affinity, the less likely the Ab is to dissociate.
Abs in primary responses typically have a lower affinity than Abs in memory responses.
What is Ab valency?
L6 S14
The number of antigenic determinants that an Ab can bind to.
Ex. IgG has two Fab regions, can bind two Ags, and therefore has a valence of two
What is Ab avidity?
How does it relate to affinity and valence?
L6 S14
Avidity is the overall strength of an Ab-Ag complex and it is directly related to both affinity and valence
An Ab with low affinity, such as IgM, can have a high avidity because it has a high valence due to having additional Fab regions.
What is the pattern of Ig expression in B cell development?
L6 S18
Pre-B cell:
-cytosolic heavy chain and membrane pre-B receptor
Immature B cell:
-membrane IgM
Mature B cell:
-membrane IgM and IgD
Activated B cell:
-Ig secretion and reduced membrane Ig
What changes occur in Abs produced by plasma cells?
L6 S19
Affinity maturation:
-mutations in variable region result in increased affinity
Transition from membrane to secreted Ab:
-loss of transmembrane region
Isotype switching:
-replacement of heavy chain to change Ig class
What are the different classes of Ig and where are each primarily seen?
L6 S20
- IgG (plasma/tissues)
- IgD (B cells)
- IgE (mast cells)
- IgA (mucosal secretions)
- IgM (plasma)
What cytokines induce Ab production and what classes of Ab are induced by each cytokines?
L6 S22
IFN-γ:
- IgG3
- IgG2a
TGF-β:
- IgA
- IgG2b
IL-4:
- IgE
- IgG1
IL-2, IL-4, and IL-5:
-IgM
What are the different functions of Igs and what classes are related to each function?
L6 S24
Neutralization:
-IgG1, IgG2, IgG3, IgG4, and IgA
Opsonization (Phagocytosis):
-IgG1 and IgG3
Sensitization of NK cells:
-IgG1 and IgG3
Sensitization of mast cells:
-IgE
Activation of complement:
-IgM, IgG1, IgG3
What Ig has the highest serum level?
What Ig most common in the body?
L6 S25-26
IgG is most common in serum.
IgA is most common as it is found in epithelial mucosa.
What barriers can Abs cross and what classes of Ab can cross each barrier type?
L6 S25
Epithelium:
-IgA
Placenta:
-IgG1, IgG3, and IgG4
Vascular endothelium:
-IgG1, IgG2, IgG3, IgG4, IgA
What are the characteristics of IgG?
L6 S27-28
- most abundant in blood
- responsible for majority of immunity to bloodborne pathogens
- two heavy and two light chains
- able to cross the placenta (via FcRn receptors present only in the placenta) and give passive immunity to fetus/infant
