Lecture 3 Flashcards
How are the 2 binding sites on each antigen determined?
by “hand shape”
There are 10^16 different possibilities
What is the FAb region?
Variable region of a B cell Ab
It binds the Ag
What is the FAc region of an Ab?
The constant region - there are 5 different regions within it (MDGEA)
What do V, D and J stand for?
V = variable (54) D = diversity (16) J = joining
Describe the antibody structure
Looks liek the letter Y
4 polypep chains: 2 heavy and 2 light
Ag binding arms = FAb fragment
The rest of the body is the constant region (FAc)
Describe VDJ recombination
Each combination is specific for only one Ag
a palindrome
The V portion has a complementary sequence on the D and the D has a complementary sequence within J
VDJ rearrangement matches up with Ab so each Ab only has 1 Ab specificity
What is allelic exclusion?
Each cell has 2 genes (maternal and paternal)
You only make protein from one gene at a time, excluding the other
–> The chosen gene undergoes VDJ rearrangement
The rearranged Ab is put on cell membrane
It is tested to see if it is specific for self or foreign Ag
What is receptor editing?
If original Ab on B cell is specific for self, the Ab is internalized and the second allele is rearranged
2nd rearrangement is put on cell surface and tested for self-reactivity
*Each cell gets 2 chances to make Ab
What is Somatic Hypermutation?
If an Ab on the surface of the B cell comes into contact with its antigen, it can go back to its DNA and make a point mutation
Goal: to have a higher affinity for Ag
*A point mutation that increases affinity
What is class switching?
VDJ is attached to the Ab's constant regions (MDGEA) Depending on the type of Ab needed, is can switch between these letter types. It must switch forward, however; it cannot go backwards The Fc region is generated by class switching
Why are antibody functions related to their constant regions?
because the constant regions bind to Fc receptors
Where do you find Fc receptors?
cells have receptors for the Fc portions of the Ab
Ex. Fc portion attaches to macrophage –> it can aid in phagocytosis
Also, it can act as an opsinin to coat the bacteria with Ab so that the macrophage can come along and bind the bacteria
What is B cell tolerance and how does it happen?
It is how auto reactive B cells kill themselves
Binding soluble Ag in the bone marrow: ANERGY (non-responsive, but not dead)
Binding particulate self-Ag in the bone marrow: APOPTOSIS
How is a B cell activated?
An Ab on the surface of a B cell binds an Ag
What happens after a B cell is activated?
Where does this occur?
B cells become plasma cells (Ab secreting cells) –> all Abs will have the same specificity
Secretion of the Ab toward the Ag
This usually happens in lymph node germinal center
Ab binds Ag, internalizes it and breaks down Ag into peptides that can bind in MHC
What are the functions of Ags?
- Opsinization
- Mast Cell Activation
- Antibody Dependent Cellular Cytotoxicity (ADCC)
- Neutralization
- Activates the complement cascade (“fixing complement”)
Describe opsinization
Ab binds bacteria
Fc portion binds to receptor on macrophage
Fc receptor is phosphorylated –> sends signal to macrophage to start making ROS
Macrophages have Fc gamma receptor for IgG
Describe Mast Cell Activation
Mast cells have Fcepsilon receptors for IgE (and so do eosinophils)
–> IgE is associated with allergies
If IgE specific for an allergen is bound to a mast cell, and the allergen is encountered, the mast cell degranulates (releases histamine)
Describe Antibody Dependent Cellular Cytotoxicity (ADCC)
Assoc. with Natural Killer Cells
Have Fcgamma receptor for IgG
occurs during viral infections (virus enters nucleus –> integrates genome–> makes proteins/new viruses –> puts viral coat proteins on surface)
Ab binds to viral Ag proteins
Natural Killer Cells come in and kill the cell
Describe neutralization
Neutralization occupies active sites of bacterial toxins
Describe the Ag function of activating the complement cascade
called “fixing complement”
Ab can initiate the complement cascade –> cascade comes and sits on the cell and kills it
What are the monomer forms of all constant regions on an Ab?
M - pentomeric D - monomeric G - monomeric E - monomeric A - monomeric OR dimeric
What cytokine triggers each of the Ab class types?
IgM - IL2 IgD - ? IgG - IFNgamma IgE - IL4 IgA - TGFbeta
What is the 1/2 life for each Ab class type?
IgM: 2 - 7 days IgD: 3 days IgG: 23 days! IgE: 2 days IgA: 3 days
What is the main location for each Ab class type?
IgM: blood IgD: blood IgG: blood and serum (most abundant) IgE: blood IgA: secretions
What is the type of antigen that each Ab class type is reactive for?
IgM: infection IgD: ? IgG: infection (viral or bacterial) IgE: worms, parasites and allergens IgA: Foods, Microbes associated with mucus
Which Ab class type can be made after only 5 months of gestation?
IgM
Which Ab class type is always made 1st?
IgM
Which Ab class type can cross the placenta?
IgG
Which Ab class type can protect a new born for up to 6 weeks?
IgG
Which Ab is associated with:
Th1?
Th2?
Th3?
Th1: IgG
Th2: IgE
Th3: IgA
Which Ab is most likely the first one encountered during an infection?
IgA because it lines mucosal membranes
