Quiz 3 Part 3 Flashcards
What is the 1st antibody to be produced in an antibody response
IgM
What are the 2 antibodies on the B cell surface
IgM and IgD (BOTH CANT BE ON SAME ANTIBODY —- 1 OR THE OTHER)
What genes are transcribed FIRST
C mu and C delta
What is allelic exclusion?
allelic exclusion refers to the fact that we only want to make ONE type of antibody at a time, so 1 chromosome is suppressed and one is activated.
1 type of antibody to a single antigen
Where does the uniqueness exist between antibodies?
ALWAYS IN VDJ
However, the idea is that we can attach different constant regions to work with different kinds of effector molecules
Explain the process of making IgM and IgD and how they get to the surface of the B cell
VDJ has already been joined
transcription occurs through C mu and C delta. Through alternate splicing, either C mu or C delta is chosen to be attached to the VDJ region.
Attached to VDJ and the C mu or C delta is a AAA region. this AAA makes a molecule that has a hydrophobic transmembrane domain to stick into the plasma membrane of the B cell
After the antibody is formed, it has issues getting to the surface of the B cell. Iga and IgB deliver the B cell receptor (the antibody) to the membrane. Iga and IgB have tails that allow for intracellular signaling
When IgM/IgD is being spliced to attach to VDJ, is the DNA being spliced or mRNA?
mRNA is being spliced
What happens when B cell receptors bind to an antigen?
this binding triggers proliferation and differentiation of B cells into antibody secreting plasma cells
What is somatic hypermutation?
somatic hypermutation introduces POINT MUTATIONS (addition/deletion/changing of a single base) throughout rearranged variable regions.
If this mutation increases affinity for the antigen, the B cell is selected to mature into plasma cells that begin secreting antibodies
Somatic hypermutation is dependent on…..
AID activity (activation-induced cytidine deaminase)
Activation-induced cytidine deaminase is ONLY produced in proliferating B cells (those that have been activated by antigen)
Due to somatic hypermutation, antibodies of increasingly higher affinity for the antigen are produced. what is the term for this?
AFFINITY MATURATION
Explain the difference between the B cell receptor IgM and the secreted IgM
the B cell receptor IgM is a monomer while the secreted form is a circular pentamer
the secreted IgM is not very effective. It is a bulky molecule with low-affinity sites. It has a small hinge region, and is so big that it has issues moving around efficiently
Secreted (pentameric) IgM coordinates with….
J chain
Is IgM heavily involved in the antibody response?
no — it is really only a receptor.
the secreted version is too bulky to be involved
What part of an antibody gives it the ability to interact with different effector molecules?
the constant region
What is isotype switching
Switching IgM for something more useful
When does isotype switching occur? What is isotype switching dependent on?
isotype switching ONLY occurs in B cells in response to an antigen.
like somatic hypermutation, it is also dependent on AID ( activation-induced cytidine deaminase)
In isotype switching, is the variable region being changed?
NO—–only the constant region (C region)
Isotype switching is regulated by….
cytokine signaling.
Cytokines stimulate different transcription factors. They stimulate SPECIFIC transcription
VDJ ALWAYS GIVES…..
antigen specificity
In somatic hypermutation, AID causes the ___ to become ____
C’s to become U’s
Explain how isotype switching is done
CYTOKINES turn promoters in the switch region ON. This causes AID to add in the U’s at the switch regions which causes a break in the DNA. a loop is formed and a circular piece of all the unneeded things breaks off and the new constant region is now attached to VDJ and transcription occurs
is isotype switching done on DNA or RNA
DNA
Is spacing a concern in isotype switching?
NO
When is spacing a concern? (frameshift mutations)
in junctional diversity (RAG complex)
DJ joining
What are 3 mechanisms for antibodies to clear pathogens
neutralization —- directly inactivate the pathogen or toxin
opsonization — coating with antibody to enhance phagocytosis. (phagocytes express Fc receptors)
complement activation — binding of C1 complement protein
can antibodies trigger complement
yes —- the binding of C1 complement protein
How does opsonization of a pathogen by an antibody help to enhance phagocytosis
phagocytes express Fc receptors (Fc = tail region of proteased antibody)
Which type of immunoglobulin is best at neutralization and opsonization and is also most plentiful in our serum
IgG1,2,3
Which immunoglobulin is involved in giving maternal antibodies to the fetus through the placenta
IgG1
Which immunoglobulins have the ability to activate complement
IgG and IgM
Are IgM’s mainly found in the blood or tissues?
BLOOD — they’re too big to enter tissues
What is the function of IgA
to keep the commensal bacterial population in check. this is the MOST PRODUCED OF ANY ISOTYPE. predominantly made in MALTS
What is the function of IgE
to mediate allergic reactions. involved in the recruitment of mast cells, eosinophils and basophils.
Cells have a very high affinity for which immunoglobulin receptor?
IgE (mediate allergic reactions)
What is the function of IgD
to protect mucosal surfaces (found in upper airways of the bronchial tract)
Which cells have a high affinity IgD receptor
basophils
What is the most abundant immunoglobulin in internal bodily fluids
the 4 subclasses of IgG — 1-4
Which immunoglobulin has a high degree of conformational flexibility
IgG
Explain how IgG has a high degree of conformational flexibility
Fab and Fc regions move in a partly independent matter which enhances binding ability
However, the flexible hinge of IgG is also subject to proteolysis
Name the 4 things that IgG can do that shows flexibility
WAVE – the fab arms
WAG – the Fc tail
ROTATE – the Fab arm
BEND – the Fab elbow
Which class of IgG has the largest hinge
which has the second largest
IgG3 – largest by far
IgG2– secon largest hinge
