Feb. 17th (Exam 2) Flashcards
What are naive B-cells?
What classes of Immunoglobulins do the naive B-cells express on their cell surfaces?
Is this the only time that a single B cell will express two isotypes on its surface?
These are circulating B-cells that have not encountered antigen.
They only express IgM and IgD
Yes.
What is the process that results in the two isotypes that we see in naive B-cells?
Can we get our other isotypes this way?
Alternative splicing of the primary transcript.
No. That requires input from antigen-activated T cells.
What is allelic exclusion?
Why is it so important?
This is the idea that a single B-cell will only express one type of heavy chain and light chain, essentially excluding out the other allele of the chromosome.
Without this, it would be possible to select for example two different V and J gene segments of the variable light chain region from different chromosomes - destroying the antigen specificity.
This ensures that B-cells are making IgM and IgD that are specific to ONE antigen.
Review: what does it take to make an antigen binding site of an immunoglobulin?
Explain all the sources of diversity for antibodies.
One light chain
One heavy chain
- Random combination of the segments in the variable regions (both light and heavy)
- Junctional Diversity
- nicking the hairpins
- adding Non somatic DNA
- Random combinatorial association of heavy and light chains.
- Somatic Hypermutation
-changes in the entire variable region that are concentrated within the CDR because of affinity maturation
- Isotype switching (does not change the antigen binding site, but gives diversity in the effects the antibodies can have.
Describe the properties of IgM and IgD heavy chains.
Their C-terminus has many hydrophobic regions so that the immunoglobulin can associate with the membrane, but they have a very short cytoplasmic region.
What are Igα and Igβ?
These are transmembrane signalling proteins that travel with IgM and IgD to the membrane.
*They are important in signal transduction
What is the B-cell Receptor Complex?
This is the Immunoglobulin IgD OR IgM and the Igα and the Igβ signalling protein.
What will eventually occur when an antigen encounters a naive B cell?
We will see proliferation and differentiation and eventual secretion of antibodies.
What are IgM antibodies generally for?
Quantity?
They are produced in high quantities and are important for protective immunity against a wide range of infections.
What are IgD antibodies generally for?
Quanitity?
They are produced mainly within the respiratory tract against the bacteria that commonly cause infections there.
Not produced in high quantities other than there.
What is the difference between a membrane bound immunoglobulin and a antibody?
How is this difference accomplished?
There is a hydrophobic sequence at the carboxyl terminus of the heavy chain for the immunoglobulin.
For the antibody, the hydrophobic sequence is replaced by a hydrophilic sequence.
This is accomplished by alternative RNA splicing of the same primary RNA transcript - no rearrangement
What is somatic hypermutation?
When does it occur?
These are single-nucleotide substitutions introduced randomly into the V domain coding sequence.
It occurs after antigen binding.
What enzyme is necessary for somatic hypermutation?
Where is it produced?
What does it do and when does it do it?
The enzyme we talked about is called Activation-Induced cytidine Deaminase (AID)
Only produced within proliferating B cells
It converts cytosine in single stranded DNA to uracil during transcription when the two strands of the immunoglobulin gene are temporarily separated.
Other enzymes that are not specific to B cells but are parts of other repair mechanisms will convert the uracil to any of the four bases
What may somatic hypermutation result in?
Affinity maturation
What is affinity maturation?
This is the idea that as the adaptive immune response to infection proceeds, antibodies of progressively higher affinity for the infecting pathogen are produced.
Kind of like evolution but sped up really fast
What is the first class of antibody that is made in the primary immune response?
IgM
What is the membrane bound IgM like?
It is monomeric - by itself
What is secreted effector IgM like?
What are its limitations?
It is a pentamer that has ten antigen binding sites.
It is bulky, and has low-affinity binding sites and is restricted in the recruitment of effector mechanisms.
What is Isotype (Class) Switching?
What does it rely on?
Where will this happen (what types of cells?)
This is further DNA recombination events that allow the V region to be used with other heavy-chain C genes.
Relies on AID
It will only occur in B-cells that are proliferating in response to antigen.
In the most simple terms, how does isotype (class) work?
What controls/regulates the patterns of switching?
The previous constant gene of the heavy chain is cleaved leaving the new C gene to be transcribed.
Cytokines that are secreted by other immune cells control the patterns of switching.
What is neutralization?
What is a neutralizing antibody?
Neutralization is the direct binding and inactivation of a pathogen/toxin that prevents it from interacting with human cells.
Any antibody that can do such action.
What is an example of a neutralizing antibody?
Where can we find it?
IgA - in the gut, saliva, tears, sweat, milk
What type of receptors do phagocytes have that is related to opsonization?
They have receptors for the Fc regions of some antibodies.
Describe the IgG antibody class and explain it using the frame of opsonization.
It is the most abundant antibody in the internal body fluids including the blood and lymph.
Similar to IgM but is smaller and more flexible which make it better at accessing pathogens in the ECM of damaged tissue.
The flexibility, due to its hinge region allows to it bind to two antigens on the surface of a pathogen and activate complement system and the Fc receptors of phagocytes - this is why it can be called an opsonin.
