Lecture 6: Antibody Structure and Function Flashcards
What happens to b cells that arise from bone marrow stem 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 (7)
- Neutralization of microbes and toxins- The Ab binds to some structures on the microbe and it doesn’t allow the microbe to infect.
- Opsonization and phagocytosis of microbes
- Antibody-dependent cellular cytotoxicity
- Lysis of microbes
- Phagocytosis of microbes opsonized with complement fragments (e.g., C3b)
- Inflammation
- Complement activation
Opsonization
The Ab can act as an intermediary to improve the ability of phagocytes to ingest pathogens.
C3b
- one of the fragments of complement
- C3b is essentially acting like an Ab, because once the C3b receptor is bound with C3b & microbe, we get induction effects.
What is a complement?
- set of molecules
- If an Ab binds to a microbe, you get natural assembly of the components of complement. And they bind the conserved (Fc) portion of the Ab. This complex has the ability to lyse microbes (punches holes in the microbe)
What is the conserved portion of the antibody?
Fc
Antigen-Antibody/BCR Interactions
- BCR detect three-dimensional antigens.
- B cells are active only against extracellular antigens.
BCR/TCR Activation (steps)
- 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.
Cross-linking
Brings signaling proteins together and initiates signal transduction.
What is a clone? Why is it called a clone?
A parental lymphocyte and all its progeny
Clone because they all have the same B cell PCR specificity.
Antigen recognition drives lymphocyte activation. How does this work?
Membrane-bound receptors on B lymphocytes and T cell receptors on T lymphocytes recognize antigen.
Antigen receptors distinguish many, often chemically related, structures with _______ _________.
precise specificity
Antigen receptors are clonally distributed. What does this mean?
Each clone has a unique receptor distinct from all other receptors.
B cell and antibody production process
- Each B cell encodes its own unique BCR with its own unique antigen specificity. The antigen receptor is membrane bound on a naive B cell.
- Antigen plus second signal stimulate B cell and initiate antibody production.
The BCR and corresponding antibody share ______ antigen specificities.
identical
Antibodies (Immunoglobulin)
- are 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.)
Antibody structure
- An antibody consists of four polypeptides: two identical light chains and two identical heavy chains form a Y-shaped molecule.
- Each light chain is connected by a disulfide bond and the two heavy chains are connected by two disulfide bonds.
- Each light chain contains one V domain and one C domain.
- Each heavy chain contains one V domain and at least three C domains.
- Each domain folds into a characteristic 3-D shape: The Immunoglobulin (Ig) domain.
Variable (V) region
Antibodies bind antigens through the variable regions of the light and heavy chains.
The variable (V) region varies between clones and is involved in antigen recognition
Effector region
- determines the type/function of Ab
- conserved portion of Ab
- identical between different Abs= gonna get the same response
Each antigen receptor has two distinct functional domains:
- Each BCR/antibody has its own unique variable region.
- All BCRs/antibodies share a common constant region.
Constant (C) region
Is conserved among clones and is required for structural integrity and effector functions.
DNA have recognition binder for antibodies of different microbes. Same end results lead to __________
phagocytosis
Different variable regions bind _______________.
Identical constant regions induce _____________.
different antigens
identical responses
Antibodies bind antigens by ____________________ interactions.
reversible non-covalent
Epitope
- The parts of an antigen recognized by an antibody
- can be recognized on the basis of sequence or shape.
- where the fingers of the Ab bind.
Affinity
- the strength with which one antigen-binding surface of an antibody binds an antigen.
- how well the epitope.
High affinity= they bind so well
Low affinity= they don’t bind so well
Features of antibody-mediated antigen recognition
- Antibodies recognize a large array of 3-D 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 Classification (5)
- IgG
- IgE
- IgD
- IgM
- IgA
What are the monomeric antibodies?
IgG, IgE, IgD
What are the dimeric antibodies?
IgA
This antibody sits on the membrane. It has 5 antibodies all joined together. 10 binding sites.
IgM
Joining chain
holds the two antibodies together
IgD isotype of antibody
- function is poorly understood
- restricted to membrane and barely expressed on active B lymphocytes.
- IgD knock-out mice do not have any major defects.
- found on naive B cells; acts as a marker for B cell development.
IgE isotype of antibody
- binds the Fcε receptor on mast/basophilic cells
-secreted as a monomer
Functions:
- binds allergens and facilitates degranulation.
- facilitates protection against parasites.
- possible role in cancer immunity.
What happens to the vesicles containing the enzymes once IgE binds to the mast cells?
Vesicles containing the enzymes will be released once IgE binds
IgG isotype of antibody
- most abundant antibody in bodily fluids.
- can transfer to fetus.
- secreted as monomer.
Functions:
- neutralization of toxins.
- opsonization for inducing phagocytosis via complement system.
- facilitates antibody-dependent cytotoxicity on NK cells.
What happens when IgG binds to a macrophage?
- 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.
Fc receptors also mediate ____________________
Antibody-Dependent Cellular Cytotoxicity (ADCC)
What happens when Fc receptors mediate Antibody-Dependent Cellular Toxicity (ADCC)?
- 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 NK cell to kill the target.
- Target cell dies by apoptosis.
IgM isotype of antibody
- exists as pentamers
- 10 different Ag binding sites
- As with IgA, it has a J chain for secretion
- 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.
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.
Affinity vs. Avidity of Antibodies
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.
