Immunoglobulins Flashcards
Are antibodies proteins?
Yes
What are the aspects to antibodies?
- 4 polypeptide chains (2 light chains and 2 heavy chains)
- 4 chains held together by disulfide bonds
What is a ligand?
Any molecule that binds to a protein
What is an antigen?
Any molecule that is recognized and bound by an antibody (has components of the adaptive immune system)
What is an epitope?
The specific part of an antigen recognized by an antibody
What is another name for immunoglobulins
Antibodies
What is a bivalent antibody?
When 1 antibody binds to 2 of the same antigens (a monomer that contains 2 antigen binding sites)
What is a constant region?
AA sequence that doesnt very, very much (compared to other regions of the antibody)
What is a variable region?
Differ in AA sequence from one immunoglobulin to the other
Where do antibodies bind to their targets (= antigen)
Variable region
What type of protein structure do immunoglobulins have?
Tertiary
What type of lymphocytes make antibodies?
B-lymphocytes
What is a hypervariable region?
A region where there is greater AA sequence diversity and the area where epitopes bind to the tips of the antibodies
What occurs when an antibody is treated with papain?
Causes a cleave in the hinge region which leads to the release of 2 arms (these are called fab fragments and contain antigen binding sites)
What are the 2 functions of the FC region?
- Potentially anchor membranes in the plasma membrane
- Mediates downstream effector functions that come in to destroy pathogens
What is the hinge region on an immunoglobulin?
Area that provides flexibility to the molecule and allows the molecule to change shape, which is helpful in binding to antigens of different shapes and sizes
Where do epitopes bind?
To the tips of antibodies at their hypervariable sequences
How many heavy chain permutations?
5520 (40 V, 23 D, 6J)
How many light chain permutations?
295 (2 loci: 175 kappa + 120 lambda)
Overall purpose of B-lymphocyte development
Going from membrane bound to secreted
B-lymphocyte development
- Lymphoid progenitor cells
— Proliferation and B cell diversification in bone marrow - Different resting B cells
— About 10^12 sequence variants - Antigen binds
— Proliferation and differentiation of B-Beta cells - Antibody secreting B-Beta cells
- Secreted antibodies (they can seek out the antigen)
IgM
Membrane bound (initial antibodies from immature B cells)
IgG
Class of antibodies that actually gets secreted and released from cells
In antibody trafficking, where are proteins directed?
They are directed to the secretory pathway by a signal at their amino terminus
Antibody trafficking order
ER -> Golgi App -> Plasma Mem (fusion)
Antibody trafficking default pathway
- Proteins in the lumen of the ER are secreted from cells
*Proteins with signals that anchor them in the ER membrane can end up at the plasma membrane
What do plasma membrane protein’s (IgM) consist of?
Signal peptide + stop transfer
Where is an IgM’s heavy chain stop transfer sequence?
Within its FC domain
During B-cell maturation, why is a switch made from IgM to IgG?
Because IgG heavy chain LACK a stop transfer codon
*The switch is in the last cassette (CR) from Mu to Gamma
**Occurs so that secretion can occur (stop transfer sequence is removed)
IgA
IgA’s have a protective function when they are secreted into the saliva
Are IgA’s found in blood
NO
Where are IgA’s produced?
Connective tissue of a specialized plasma cell that is polarized and below epithelial cells
Do IgA’s form dimers?
YES
How are plasma cells and B-cells related?
Plasma cells ARE mature antibody-producing B cells
What recognizes IgA dimers?
plgR’s recognize IgA dimers and fuse with the apical surface and release the IgA’s into the saliva
What are super secondary structures?
Groupings of secondary structure elements
What are immunoglobulin folds?
Domains of super-secondary structures that hold chains together non-covalently and are repeated
What is Rituximab?
First clinically used monoclonal antibody
4 properties of an ideal tumor associated antigen (TAA)
- Expression on all tumor cells
- Expression on tumor cell surface
- Functions in tumor cell survival
- Lack of expression on normal tissues
*No current TAA’s display ALL of these ideals
What is a good target for a therapeutic antibody to treat B cell hyper-proliferative disorders?
CD20
What does Rituximab recognize?
Recognizes CD20 antigen (CD’s are names for bio markers in different cell types)
Do early progenitors express CD20?
NO (b-cell adaptive immunity can be restored after)
What interactions do super secondary structures drive?
Protein-protein interactions
What is the structure of super secondary structures?
4-stranded antiparallel beta sheet overlaying a 3-stranded antiparallel beta sheet
Types of tumor cell death
- Complement mediated lysis
- Phagocytosis
- Block protein function and kill tumor directlyy
