Chapter 2 - Antibody Flashcards
- Which three classes have a hinge region in their Fc?
- Where exactly is the hinge region?
- The Fc region of IgG, IgA, and IgD
- Has a hinge region between the CH1 and CH2 that gives flexibility
- Describe the structure of the immunoglobulin hinge region
- What purpose does it serve?
- Region is not globular: stretch of prolines
- So paratopes have flexibility to reach the epitopes
- What are the other two classes that don’t have a hinge region?
- What do they have instead?
- IgM and IgE do not have a hinge region
- - Have an extra constant region CH4 instead
Glycosylation
- Define
- Where does it occur on each of the Ig?
- Little bit of sugar molecules added to the amino acids of the immunoglobulin
- Occurs at the CH2 of IgG, IgA, and IgD, and at the CH3 of IgM and IgE
- In comparison to other Ig, how much IgA is in the serum?
- Where is it the primary Ig?
- Describe the structure in both locations.
- Second highest in serum concentration
- IgA primary immunoglobulin in secretions
- In serum: it is a monomer
- In secretion: it is a dimer
IgA Dimer:
- Where are the monomers joined?
- What are they joined by?
- What segment does this have unique to IgA and its purpose?
- The Fc regions together and the Fab regions facing out
- Held together by a 15,000 dalton J (joining) chain
- Contains a secretory piece that is synthesized by an epithelial cell
IgA dimers joined with the J chain:
- what type of cell receptor do they bind to?
- what does that cell do with the Ig after binding?
- Bind to an epithelial cell receptor
- A precursor of the secretory piece
- The Ig is brought into the epithelial cell
- Transverses the epithelial cell
- What happens to the IgA at the secretory lumen?
- What is the final step for IgA?
- Part of the secretory piece is cleaved
- The IgA dimer attached to the remaining secretory piece (70,000 daltons) is secreted
IgA: Secretory functions
- What are they (4)?
- Prevents the entrance of pathogens
- Cross-links multiple epitopes to form aggregates
- Easily removed by the ciliated cells of the mucous membranes and by gut peristalsis
- Also functions by blocking adhesion of the bacteria, virus, or toxin
IgA Subclasses:
- what are they?
- where do you find each of them?
- IgA1
- Main component of serum IgA
- IgA2
- Main component of secreted IgA
Classes, Subclasses, and Light Chains: IgA
- Binds complement?
- Opsonic?
- Transferred through placenta?
- Does not bind complement
- It is opsonic
- Not transferred via placenta to the fetus
Classes, Subclasses, and Light Chains: IgA
- How does it transfer to a newborn?
- what else is transferred this way?
- Transferred to newborn by breast milk
- - Contains lots of IgA and other proteins, oligosaccharides, and fatty acids
Classes, Subclasses, and Light Chains: IgM
- % in the serum?
- Structure
- shape
- Fc and Fab locations
- 5–10% of the immunoglobulin in serum
- Pentamer composed of 5 of the 2 heavy chain and 2 light chain units
- Starfish-like shape
- Fc regions in the center
- Fab arms extended out
Classes, Subclasses, and Light Chains: IgM
- Size?
- what is another name for this type of Ig?
- What is a tumor called that produces IgM?
- Largest immunoglobulin
- 900,000 daltons
- Called a macroglobulin because of large molecular weight
- Tumor in which the tumor plasma cells make IgM is called a macroglobulinemia
Classes, Subclasses, and Light Chains: IgM
- what type of cells does this Ig bring together?
- good/bad at agglutination?
- good/bad at precipitation?
- Brings together cells that are slightly charged
- Repulsion due to charge is diminished over great binding distance
- Best immunoglobulin at agglutination and precipitation
Classes, Subclasses, and Light Chains: IgM
- Fixes complement?
- Opsonic?
- What type of antigens does it neutralize?
- Best at fixing complement by the classical pathway
- Opsonic
- Neutralizes toxins and viruses
Classes, Subclasses, and Light Chains: IgM
- How quickly does it respond to antigens?
- Why does it have a lower affinity?
- Does it have a high or low avidity? Why?
- First immunoglobulin produced in response to an antigen
- Produced without the somatic mutation events that improve affinity, so affinity is lower
- But Avidity can be high
- 10 paratopes on a pentameter, as opposed to 2 on a monomer
Classes, Subclasses, and Light Chains: IgM in newborns
- made or acquired?
- what does it mean if it’s seen in a newborn?
- First immunoglobulin produced in a newborn
- Elevations in IgM after birth indicate an infection
- the baby was exposed after birth
Classes, Subclasses, and Light Chains: IgM in newborns
- does it cross the placenta?
- does it cross into extravascular spaces?
- what is the half-life?
- Does not cross the placenta
- Does not enter extravascular spaces
- Half-life is 10 days
Classes, Subclasses, and Light Chains: IgM on B cells
- describe the structure
- what region is different compared to serum IgM?
- Monomeric not pentameric
- Slightly different Fc region
- Transmembrane and cytoplasmic regions
Classes, Subclasses, and Light Chains: IgM on B cells
- where is most surface IgM found?
- what are some other cells it is found on?
- Immature B cells
- Mature B cells
- Most surface IgM is found on immature and mature B cells
- Plasma cells
- Memory B cells
Classes, Subclasses, and Light Chains: IgM on B cells
- what does the antigen bind to on the B cell?
- what does it do to the cell once it binds?
- what does the B cell then become?
- Antigen binding to surface IgM
- Sends signals into B cell
- Activates, proliferates
- Becomes memory or plasma cell
Classes, Subclasses, and Light Chains: IgD
- % in serum?
- what cells found on?
- what role does it serve on that cell?
- what is its main function?
- Only ~ 0.2% of serum immunoglobulin
- On the surface of mature B cells
- Involved in antigen-specific B cell activation and is a maturation marker for the B cell
- Functions as a specific antigen receptor
Classes, Subclasses, and Light Chains
- what two Ig appear on a B cell and in what order?
- what does the addition of the second Ig help the B cell to do (2)?
IgM appears on the surface of B cells first, then IgD
- IgD:
- Helps the B cell respond to signals from T cells
- Helps the B cell switch to synthesis of IgG, IgA, or IgE
Classes, Subclasses, and Light Chains: IgD
- Binds complement?
- Opsonic?
- Transferred through placenta?
- Does not bind complement
- Not opsonic
- Not transferred to the fetus through placenta
Classes, Subclasses, and Light Chains: IgE
- concentration in serum
- what notable reaction in the body is it responsible for?
- molecular size?
- why is it that size?
- what cells are responsible for producing it?
- Lowest in concentration
- Responsible for immediate type hypersensitivity
- ~ 190,000 daltons
- due to extra CH region which binds mast cells
- Made by plasma cells along respiratory tract, the skin, and alimentary tract
Classes, Subclasses, and Light Chains: IgE
- what cells does it bind to?
- what happens to those cells once binding occurs?
- Binds to mast cells
- Binding of the antigen will cause mast cell degranulation
Classes, Subclasses, and Light Chains: IgE
- What granules are released upon mast cell binding
- What symptoms does that illicit in the body?
- Releases histamine, heparin, and chemotactic factors
- Substances cause the classic symptoms of allergy, hay fever, asthma, vomiting, diarrhea, hives, shock, and anaphylactic death
Classes, Subclasses, and Light Chains: IgE
- in what instance does this Ig serve in a protecting role?
- How does it do this?
- Protective role for things that have penetrated the mucosa, such as parasites
- Triggers inflammatory response
- Brings eosinophils, neutrophils to the area
Classes, Subclasses, and Light Chains: IgE
- Binds complement?
- Opsonic?
- Transferred through placenta?
- does not bind complement
- does not enhance phagocytosis
- does not pass through the placenta
Classes, Subclasses, and Light Chains: Light chains
- what are the two types?
- what ratio are they found in?
- what does it mean when they are found in urine?
- what are they called then?
- Two types: kappa (k) and lambda (λ)
- No functional differences between types
- Present in roughly a 2:1 ratio
- Found in the urine of patients with myeloma
- One of the first diagnostic markers of a tumor
- Called Bence-Jones proteins
- What happens when an animal is inoculated with human Ig?
- will result in the production of antibodies to different regions of the immunoglobulin.
Vaccination of an animal with human immunoglobulin:
- What are isotypic determinants?
- What are allotypic determinants?
- What is the significance of the idiotype?
- Isotypic determinants, heavy chain type - difference is related to which constant region is involved
- Allotypic determinants, different on different members of the same species - difference is inherited from mom/dad
- May regulate immune response
- What is the clonal selection theory?
- What is the key idea behind it?
- Proposes how the huge and diverse immunoglobulin repertoire could exist
- Key idea: lymphocytes that can only react with one antigen, before any encounter with antigen has occurred. When these lymphocytes interact with antigen they proliferate and make a clone of cells that respond only to that antigen
- What is the conservation of DNA theory?
- - what are the three pieces that make up the theory?
- diversity theory
- Antigen-independent random recombinational events of DNA gene segments during B-cell maturation
- Antigen-dependent clonal deletion of self-reactive B cells
- Antigen-dependent somatic mutation and affinity maturation
Antigen-Independent Diversity
- define
- what three genes are the heavy chain variable regions
encoded by?
– what happens after the genes go through recombination?
- Random recombinational events of DNA gene segments during B-cell maturation
- Encoded by three gene segments: V, D, and J genes
- Gene segments after recombination are joined to the heavy chain constant region
Antigen-Independent Diversity
- what two genes are the light chain variable regions
encoded by?
– what happens after the genes go through recombination?
- Encoded by two gene segments: V and J genes
- Gene segments are joined to the light chain constant region after a recombinational event
Antigen-Independent Diversity: Tonegawa discovery
- what chromosome are the genes that make the following components located on?
- heavy chains
- kappa light chains
- lambda light chains
- heavy chains made by genes from chromosome 14
- kappa light chains are made by genes from chromosome 2
- lambda light chains are made by genes from chromosome 22
Antigen-Dependent Clonal Deletion
- what purpose does it serve?
- Decreases diversity in a mechanism
- - Helps maintain the self–non-self recognition system of the acquired immune response
Antigen-Dependent Clonal Deletion
- when does maturational arrest occur?
- what happens to the “arrested” cell?
- Occurs if a maturing B cell meets and binds with its antigen prior to maturation
- Does not become a mature B cell
Antigen-Dependent Clonal Deletion
- in this particular process, how does apoptosis occur?
- the B cell, after receiving certain signals, produces enzymes that degrade its own DNA to commit cellular suicide
Antigen-Dependent Somatic Mutation and Affinity Maturation
- what happens when a B or T-cell binds antigen (4)?
- Rapid proliferation of the cell occurs
- Initially each offspring cell is identical in binding to the original parental cell
- Mutation occurs during this rapid proliferation
- Cells that have increased affinity of binding are selected and proliferate more
Antibody Purification
- what characteristics must be taken into account when trying to purify proteins (4)?
- Solubility characteristics
- Molecular weight
- Binding affinities
- Charge
Antibody Purification
- what are the two methods of purifying antibody?
- Ammonium sulfate precipitation
- Affinity purification of antibody
