Immunology 2 (Kyle) Flashcards
1. Describe the basic structure of antibody molecules 2. Distinguish the structural difference between isotypes of an antibody 3. Catalog the functional difference between isotypes of an antibody 4. Recognize the characteristics of epitopes
What is an antibody?
Antibodies are identical to what? (On the surface of the Bcell that secreted it)
Antibodies (Ab) are globular proteins (immunoglobulins) that are produced by B Cells. Ab’s are the primary component of humoral immunity
The B Cell receptor.
What do antibodies bind to?
Ab’s bind to antigens and interact with the host system and cells to promote clearance of infectious agents.
What is the main component of B cell surface receptors?
What is an immunoglobulin that is secreted from a B cell?
Membrane integrated forms of Ab molecules
An antibody
What is the common structure of an antibody?
All Ab’s consist of a common core of two identical light chains (24 Kd) and two identical heavy chains (55 or 70 kD)
How are the heavy chains and light chains connected?
One of the two light chains is attached to each heavy chain, and the heacy chains are attached to each other. These attachments are formed by intrachain disulfide bonds.
Are the heavy and light chains transcribed from the same genes?
NO Heavy and light chains are encoded on different genes.
What are the similar (But not identical) regions of the heavy and light chains?
Immunoglobulin domains (Ig domains)
How are Ig domains formed and what are the regions within the Ig domains?
IG domains fold independently are are formed from disulfide bonds. The animo-terminal Ig domain of each chain is the VARIABLE region ( V- region ) and is highly variable between Ab molecules. The CONSTANT region ( C-region) is conserved throughout many Ab molecules.
Where do Ab molecules perform their function?
In the extracellular space in the presence of an infection.
What allows Ab molecules to withstand the variations in Ph, Salt conc, and proteolytic enzymes that are encountered in the extracellular space?
Their unique 3 degree structure.
What is the primary difference between the C and V domains of the immunoglobin molecule?
V domain is larger and contains an extra loop of polypeptide chain.
What forms the antigen binding domain?
The localized region of both heavy and light chain V domains form the antigen-binding site of each “arm” of an antibody molecule.
What is similar about the C and V domains?
Both the C and V domains are roughly cylindrical shape and are formed by two adjacent B-Sheets structures that are covalently linked by a disulfide bonds.
What forms immunoglobulin folds?
The adjacent B-Sheets in the C and V domains.
What is a hypervariable region?
Hypervairable regions are three distinct regions in the V chains of an Ab molecule designated HV1, HV2, and HV3. They are formed from the loops between B-Sheets and form the ANTIGEN BINDING SITES
What is a framework region?
A framework region is a low variable region between the hypervariable regions.
What do framework regions actually do?
The framework region of both the heavy and light chains from the B-Sheets that provide the structural framework of the domains.
What is the function of the Ab molecule?
The function of Ab’s is to bind to microorganisms and facilitate their destruction and removal from the body/
What is an EPITOPE?
The portion of any particular antigen that an antibody binds to is called an antigenic determinant or and EPITOPE
Complex macromolecules typically have multiple epitopes each of which can be bound by a separate antibody molecule, such molecules are called…?
Multivalent antigens
What chemical forces bind an Ab molecule to an antigen?
Noncovalent forces
The antigen-binding region of an Ab molecule is normally rich in what type of AA?
Aromatic
What determines how long an Ab stays bound to an antigen?
Binding affinity
What are the two types of antigenic determinants that antibodies can bind?
Continuous epitopes- formed by a linear structure of amino acids.
Discontinuous epitopes- Formed by AA from different parts of the protein brought together via protein folding.
What aspect of antibody structure allows them to be divided into five isotypes?
Isotypes of antibodies are determined by the structure of the heavy chain.
What portion of an antibody contains the V or HV regions?
The amino terminal ends of both the heavy and light chains.
What are the two types of light chains?
Kappa and Lambda. These are found in all five types isotypes of antibody
What are the 5 isotypes of antibody molecules?
What two can be divided further into two subtypes?
IgA, IgD, IgE, IgG, IgM
IgA and IgD
Which antibody molecules can exist as multimeric structures?
IgM and IgA
What are the two major structural regions of an Ab?
- The variable region/ antigen binding sites
2. The stem portion of antibody molecules (Fc portion)
What is an Idiotype?
An AA sequence within the variable region of an antibody molecule. This sequence forms the mirror- image of the epitope that the Ab recognizes.
What does the variable region / antigen-combining sites do?
Interacts with the epitope of the antigen
What does the stem or (Fc region) do?
The Fc region interacts with the complement components and with the macrophages and NK cells to promote clearance of antigen and activation of subsequent immune responses.
What two Ab molecules have a hinge region?
IgG and IgA
Is the hinge region ever subjected to proteolytic cleavage?
Yes
What two enzymes cleave the hinge region of IgG and IgA?
Papain and Pepsin
How does Papain cleave the hinge region of IgG and IgA?
Papain cleavage yields a single Fc fragment and two Fab fragments. Each Fab fragment contains a single antigen binding site.
How does Pepsin cleave the IgG and IgA Ab’s ?
Pepsin cleavage produces a F9ab)2 fragment that contains two antigen -binding domains and a single pFc fragment. Since the F(ab)2 fragment contains a single antigen-binding sites it binds antigens more avidly than does a Fab fragment.
What determines the Ab’s role in effector mechanisms?
Interaction with the host cell and complement proteins
What initiates the complement cascade?
The Fc portion of antibody-antigen complexes
What portion of the Ab molecule facilitates delivery to areas of the cell that it would not reach without active transport?
The Fc portions
What are immunoglobins?
The antigen binding molecules of B Cells. they can be on the surface of the B cell as a receptor or secreted as antibodies.
What determines the specificity of a secreted Ab molecule?
Ab’s are identical to the immunoglobulin component of the B-Cell receptor
Will two Ab’s secreted from the same B-Cell have the same specificity for an antigen?
YES, all antigens produced by the same B-Cell will have the same specificity for an antigen.
What type of cell produces Ab’s ?
B-Cells but more specifically a fully mature B-cell that produces antigens is a plasma cell
Describe the Clonal Hypothesis (This has been in two different lectures)
- During development progenitor cells give rise to a large number of lymphocytes (Bcells) each with a different specificity.
- During infection lymphocytes with receptors that recognize the pathogen are activated
- Proliferation and differentiation of pathogen activated lymphocytes give rise to effector cells that terminate the infection.
What happens when a B-cell is activated?
It differentiates into a plasma cell and releases Ab’s
What is an antigen?
Any molecule that is bound by an antigen or T cell receptor
What is the portion of an antigen bound by an antibody molecule?
EPITOPE
How would you characterize the nature of antigen binding?
Noncovalent
Which two Ab isotypes can exist as multimeric structures?
IgA and IgM
What stabilizes IgA-IgM multimers?
Joining Chain ( J-Chain ) 15kD polypeptide that joins the tain regions of the Ab isotypes
Which Ab isotype can be found in mucosal secretions ? How is this possible?
IgA. IgA is covalently bound with a secretory component which is noncovalently bound to the dimer. This secretpry component, which is produced by the epithelial surface of mucosal tissues. This secretory component is what actually transports IgA through the epithelial membrane.
Individuals deficient in IgA experience what problem?
In increase in the prevalence of respiratory infections.
Where is IgA found?
Serum and Exocrine secretions (Colostrum, breast milk, intestinal and respiratory secretions, saliva, tears, and other secretions.
What are the different forms of IgA
Monomeric, Dimeric, and Tetrameric.
Which Ab isotype exists primarily as membrane IgD and serves with IgM as an antigen receptor on early B cells?
IgD
Which Ab is bound to receptors on mast cells where they serve as receptors for allergens and parasite antigens.
IgE
What happens if sufficient Ag binds to IgE on mast cells?
The mast cells degranulate releasing histamine, prostoglandins, platelet-activating factors and cytokines.
Which Ab is important for both paracitic infection and anaphylactic hypersensitivity ?
IgE
What is the principle Ab isotype in the anemnestic (memory) immune response ?
Also crosses the placenta
IgG
What composes 85% of Ab isotypes in adults?
IgG
Along with IgM, ____ is found on the surface of all niave B cells. It is large and cannot pass through membrane.
IgM
Which Ab isotype is important for immunity to polysaccharide antigens?
IgM.
