Antibody Structure + F(x) Flashcards
What secretes antibodies? What do antibodies recognize?
B-lymphocytes; Antigens
What is the basic function of antibodies?
To tag particles for destruction or protection against reinfection.
Where is the antigen binding site of Ab’s?
In the N-terminus (located in the variable region Fab)
Where does the effector/phagocytic cell bind to?
Fc – in the constant region
Is the light chain located “outside” or “inside” of the heavy chain?
Outside (and is not as long as the heavy chain).
What holds the light and heavy chains together, as well as the hinge? What type of chemical bond is it?
Disulfide bond; covalent bond.
Name the 5 different antibody classes.
IgG, IgM, IgA, IgD, IgE
What is another word for an Ab class?
Isotype
Which is the first Ab produced in the immune response?
IgM
How many arms does IgM have? How many binding sites?
5 arms. 10 binding sites.
IgM is an antigen receptor of what?
Of naïve B cells.
Which Ab is used primarily as an antigen receptor on naïve B cells? It is highly secreted T/F?
IgD False, it does not circulate in the blood stream.
Which Ab is the major Ab of serum and extravascular tissues (blood)?
IgG
Which Ab can cross the placenta & provide protection to the uterus?
IgG
Which is the major Ab of secretions (mucus, saliva, milk…)?
IgA
Which Ab is important for immune defense against helminthes (worms) and causes allergic reactions (hypersensitivity)?
IgE
What does IgE cause the release of?
Granules full of histamines
IgG, major Ab for?
Serum + extravascular tissues (blood). Also, can cross the placenta + provide protection to the uterus.
What 2 events make it possible for the immune system to synthesize Ab’s against Antigens not encountered before?
Gene rearrangement. Clonal selection of B cells producing Ab specific for Ag.
What is VDJ recombination? Which combination occurs first?
Random encoding of 3 segments of heavy chain domains V, D & J. D and J initially join, then DJ complex and V. D-J –> D-J-V
Describe the diversity of Ab’s.
With VDJ combo’s creating over 10K different heavy chains X light chains and junctional diversity, there ~ 3x10^7 possibilities.
Can a B-cell make Ab’s for more than one Ag-binding specificity?
No
Where does recirculation of B-cells occur?
In the periphery, between blood, lymphoid organs and lymph.
Define Clonal Selection.
Selection with subsequent expansion of clones (occurs as a result of antigenic stimulation only of those lymphocytes bearing the appropriate receptors.)
Antibodies are secreted by what?
B-lymphocytes
Approximately how many different antibodies are their? What does this allow?
>10^9, which allows for the ability to distinguish between very similar molecules.
What types of molecules can antibodies recognize?
Proteins, polysaccharides, and lipids.
What are 2 major functions of antibodies?
Tag particles for clearance/destruction + to protect against re-infection
What are the two chains found in antibodies (specifically an IgG)?
Light chains + heavy chains
What are the two types of domains found in antibodies?
Variable domains + constant domains.
What are the two fragments in antibodies and what do they stand for?
Fab – Fragment antigen binding Fc – Fragment crystallizable (constant) binds to receptors on phagocytes
What term refers to IgG’s ability to bind antigen?
Bivalent (two binding sites)
What type of bonds hold the two heavy chains of an IgG together?
Covalent bonds.
Where is the variability of antibodies found in their structure?
In the loops in the variable domains of the heavy and light chains. (These regions are responsible for binding to antigen.)
How many amino acids make up a single domain?
110 amino acids
Which of the immunoglobulins is the most prevalent in blood?
IgG
Which of the immunoglobulins is the major secreted Ig?
IgA
What does IgM form with other IgM molecules?
IgM pentamers
What does IgA form with other IgA molecules?
IgA dimmers
1?
Antigen Binding Site
2?
Fab - Fragment Antigen Binding
3?
Fc - Fragment Crystallizable
4?
Flexible Region
5?
VH - Variable Doman of Heavy Chain
6?
CH1 - 1st Constant Domain of Heavy Chain
7?
VL - Variable Domain of Light Chain
8?
CL - Constant Domain of Light Chain
9?
CH2 - 2nd Constant Domain of Heavy Chain
10?
CH3 - 3rd Constant Domain of Heavy Chain
Describe IgM (μ)
First antibody produced in immune response. Antigen receptor (B-cell receptor, BCR) of naïve B-cells.
Describe IgD (δ)
Used primarily as antigen receptor on naïve B-cells, little secreted.
Describe IgG (γ)
Major antibody of serum and extravascular tissues. Crosses placenta to provide protection in utero.
Describe IgA (α)
Major antibody of secretions (mucous, saliva, milk, etc.)
Describe IgE (ε)
Important for immune defense against helminthes; allergy and asthma.
What does plasticity refer to in terms of the immune system?
It has the ability to synthesize antibodies to antigens that have not been encountered before.
How is it possible that the immune system can undergo plasticity? (The ability to synthesize antibodies to antigens that have not been encountered before.)
By…
- Random generation of a very diverse array of antibodies by gene rearrangement.
- Clonal selection of B-cells producing antibody for the specific antigen.
In plasticity, what is this gene rearrangement more specifically called?
V(D)J recombination
What is lymphocyte development designed to do?
To generate functional lymphocytes with useful antigen receptors that are not self-reactive.
Describe antigen recognition and clonal selection of lymphocytes.
Antigen binding to lymphocyte antigen receptors may induce proliferation of antigen-specific lymphocytes (clonal expansion; requires other signals as well.) In this process the antigen selects from a pre-existing pool of cells only those with appropriate surface Ig specificity and causes their clonal expansion.
How can Helper T-cells help in the process of antigen recognition and clonal selection of lymphocytes?
The process can occur, causing limited cell division and differentiation. However, Helper T-cells can send signals to the B-cell causing stronger cell division (clonal expansion) and cause the transformation of the B-cell into a plasma cell.
What does the induction of a T-cell dependent antibody response require that the antigen contains?
A protein component.
Do most pathogens contain T-independent antigens or T-dependent antigens?
Both.
What type of peptide does the B-cell present to the T-cell when enlisting its help?
Class II MHC peptide complex.
What is this type of T-cell also known as besides helper T-cell?
CD4+ T-cell.
How does a B cell respond to antigen(as opposed to a plasma cell)?
A B-cell uses membrane Ig (BCR) to respond to antigen and undergo clonal expansion.
How does a plasma cell respond to antigen (as opposed to a B-cell)?
A plasma cell makes the same antibody in a secreted form, releasing 10,000 antibody molecules per second.
Describe affinity maturation.
Somatic mutations are induced within the V-regions of antibody genes. By chance some B-cells mutate their antibodies to a form that binds the antigen with higher affinity. These cells are selected.
Where does affinity maturation occur?
In germinal centers within secondary lymphoid organs.
What do the high affinity B cells that are selected give rise to?
Antibody secreting plasma cells and long-lived memory B-cells.
Why does it make sense that the mutations in affinity maturation would occur in the variable domains?
Because it is in these domains that antigen binding occurs.
What organelle would a plasma cell have an abundance of?
RER
What does the 1st encounter of a B-cell with an antigen lead to?
Secretion of antigen specific IgM (primary response)
What does the 2nd encounter of a B-cell with an antigen lead to?
A more rapid, larger, and longer lasting response dominated by IgG (secondary response).
What is the improved secondary or ‘memory’ respons the result of?
Changes that persist after the 1st encounter with Ag. Some of the B-cells that respond in the primary response do not change into plasma cells but become long-lived ‘memory’ B-cells, thus increasing the frequency of B-cells specific for the antigen. Having a higher frequency of Ag-specific B-cells at the beginning of the secondary response causes the response to be larger, more rapid, and last longer.
What are hybridomas?
A fusion of an activated B-cell with a transformed plasma cell to produce a hybrid cell that produces lots of antibodies.
