Lecture 6 - Antibody Structure and Function Flashcards
B Cells
- B cells arise from bone marrow stem cells
- Mature B cells exit bone marrow and enter circulation.
- B cells continuously circulate in search of antigen.
Functions of Antibodies
— Neutralization of microbes and tozins
— Opsonization and phagocytosis of microbes
— Antibody-dependent cellular cytotoxcicity
— Lysis of microbes
— Phagocytosis of microbes opsonized with complement fragments (eg. C3b)
— Inflammation
— Complement activation
Antigen-Antibody/BCR Interactions
- BCR detect three-dimensional antigens.
- B cells are active only against extracellular antigens
BCR/TCR Activation
- Antigen receptors associate with cellular signaling proteins in the BCR or TCR complex.
- When adjacent receptors bind two or more antigens the receptors are pulled together into an aggregate.
- Cross-linking brings signaling proteins together and initiates signal transduction.
- As the signaling proteins are the same in each clone, the transduced signal is also the same
Clonally distributed antigen receptors
Each clone has a unique receptor distinct from all other receptors
Clone
A parental lyphocyte and all its progeny
B cell antibody production
- Each B cell encodes its own unique BCR with its own unique antigen specificity. The antigen receptor is membrane bound on a naïve B cell.
- Antigen plus second signal stimulate the B cell and initiate antibody production.
The BCR and corresponding antibody share IDENTICAL antigen specificities
Antibody (Ab)
Aka immunoglobulin (Ig)
A type of glycoprotein produced by B lymphocytes
Antibodies bind antigen with a high degree of specificity and affinity.
Antibodies recognize a variety of three-dimensional shapes (amino acids, lipids, carbohydrates, etc)
Ig
Immunoglobulin (aka antibodies)
Antibody Structure
Four polypeptides:
- two light chains and two identical heavy chains form a Y-shaped molecule.
- two heavy chains connected to the light chains by a disulfide bond. The two heavy chains are connected to each other by two disulfide bonds
The tips of the light and heavy chains are the variable region (functional domain: antigen binding)
The rest is the constant region (bilogical activity)
Antibody Light Chain
Contains one V domain and one C domain
Antibody Heavy Chain
Contains one V domain and at least three C domains
Antibody functional domain
- The variable (V) region varies between clones and is involved in antigen recognition.
- The constant (C) region is conserved among clones and is required for structural integrity and effector functions
Epitope
The parts of an antigen recognized by an antibody are called epitopes. Epitopes can be recognized on the basis of sequence or shape
Affinity
The strength with which one antigen binding surface of an antibody binds an antigen
Antibody-mediated Antigen Recognition
- Antibodies recognize a large array of 3D structures.
- Each clone is specific for a single antigen.
- Antigen recognition is mediated by specific domains of the antibody.
- Signaling triggers B lymphocyte activation
Antibody (immunoglobulin) isotypes
IgG, IgE, IgD, IgM, IgA
They differ in their C region and their physical/biological properties and effector functions
IgA
Antibody isotype involved in mucosal immunity and neonatal passive immunity
Diamer: consists of two IgA molecules joined by a J chain.
The J chain facilitates transport of IgA across mucosal epithelia and facilitates transfer of IgA to newborns to confer neonatal passive immunity
IgD
Antibody isotype
Found on naïve B cells; acts as a marker for B cell development
Function poorly understood; restricted to membrane and barely expressed on active B lymphocytes and IgD knock-out mice do not have any major defects.
IgE
Antibody isotype involved in mast cell activation (immediate hypersensitivity)
Secreted as a monomer
Binds the Fcε receptor on mast/basophilic cells
Functions:
— Binds allergens and facilitates degranulation
— Facilitates protection against parasites
— Possible role in cancer immunity
IgG
Antibody isotype involved in opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity, neonatal immunity, and feedback inhibition of B cells
Secreted as a monomer
Most abundant antibody in bodily fluids
Can transfer to fetus
Functions:
— Neutralization of toxins
— Opsonization for inducing phagocytosis via complement system
— Facilitates antibody-dependent cytotoxicity on NK cells
Opsonization
Ig binding promotes microbe internalization
Presentation process for IgG
- Opsonization: Ig binding promotes microbe internalization
- IgG-Ag binds the Fcγ receptor of macrophages.
- Ag is internalized through phagocytosis.
- Microbe is degraded in the phagolysosome.
- Microbial peptides are presented on Class II MHC molecules CD4 T cell activation
ADCC
Antibody-Dependent Cellular Cytotoxicity
Mediated by Fc receptors
ADCC mediation by Fc receptors with IgG
- IgG binds Ag on surface of target cell
- Fcγ Receptors on Natural Killer cells bind Fc of Ig
- Cross-linking of Fc receptors signals to the Natural Killer cell to kill the target.
- Target cell dies by apoptosis
IgM
Antibody Isotype thats involved with naive B cell antigen receptors and complement activation
Pentamer with 10 different Ag binding sites
Has a J chain for secretion
IgM is the first antibody expressed in mature B cells.
Important for activation of the complement pathway (neutralization, phagocytosis)
Appears early after infection and usually not seen upon re-infection
Affinity
strength of binding of antigen by a single Ab binding site
Avidity
The combined strength of multiple binding site interactions an Ab can make with antigen. IgM has greater avidity than IgD as it can bind MORE epitopes at once than IgD can
