Lecture 6- Immunoglobulins Flashcards
Describe the structure of an antibody
Y shaped, joined by disulfide bonds, 2 light chains, 2 heavy chains, variable and constant region, FAB and FC region
What two basic amino acid sequences encode the light chain constant region
Kappa and lambda
Do B cell antibodies produce both kappa and lamdba
Never, just 1
How are B cell lymphomas marked
Increase in frequency in 1 type of light chain
FAB
Fragment antigen binding site, smaller, readily penetrate deep into tissues, can’t generate immune response but can neutralize
CroFab
Only approved antivenin in US
FC
Fragment crystallization
Where does proteolytic cleavage by papain occur
Above disulfide bond so end up with 2 FAB regions and 1 FC
Where does proteolytic cleavage by pepsin occur
Below the disulfide bone so you get 1 FAB region (F’ab)2 and one FC region (pfc’)
How does variation occur in binding sites
Heavy and light chain recombinations and how they interact with each other leads to additional specificity
What region of antibody determines class and function
Constant region
What are the 5 classes of antibodies
IgM, IgD, IgG, IgA, and IgE
What Ig’s are important for neutralization
IgG and IgA
What Ig’s are important for opsonization
IgG
What Ig’s are important for sensitization for killing by NK cells
IgG
What Ig’s have sensitization of mast cells
IgE
What Ig’s have sensitization of basophils
IgD and IgE
What Ig’s activate complement
IgG and IgM (better)
What Ig transport across epithelium
IgA
What Ig transports across placenta
IgG
What are the two subtle differences in antibody structure
Location of disulfide bonds and different carbohydrates linked to the antibody
What is IgM
1st class of antibodies produced by B cells after activation, secreted as a pentamer so can’t penetrate tissues, J-chain promotes polymerization, binds with C1 to activate complement
What is IgG
Most abundant class of antibody, found in blood and tissues, interacts with C1 to activate complement, crosses placenta, 20 day half life
How does IgG achieve 20 day half life and why is it important
IgG is pinocytoses from plasma and binds to FcRN (neonatal receptors) within endosomes. Once bound IgG-FcRN complex directs endosome away from lysosomes, fuses with cell membrane and releasing IgG back into circulation
Monomeric IgA
Found in blood stream, engage in neutralization, BCR on memory B cells
IgA1
Activates alternative pathway, mostly found in serum
IgA2
Does not activate complement, most found in secretions
What do both isotypes of IgA do
Bind Fc receptors on phagocytic cells- initiate phagocytosis and respiratory burst
Secretory IgA
Found at mucosal surfaces- secreted across epithelium into breastmilk, tears, saliva, gut and respiratory mucosa
Neutralize antibodies
Selective IgA deficiency
Loss of IgA production, leads to increased risk of infections at mucosal surfaces
IgE
Binds with high affinity to mast cells and basophils, important in fighting parasites and allergic reactions- triggers release of histamine and interleukins
IgD
Signals for B cell activation, enhances mucosal immunity
IgY
Found in birds, reptiles and lungfish
Where is IgM found
Blood
Where is IgG found
Blood, extracellular fluid, tissues
where is IgA found
Secretions across epithelia like breastmilk
Where is IgE found
Associated with mast cells so right beneath the skin
What are the 6 antibody functions
- B cell activation
- Neutralization
- Optimization
- Complement activation
- Antibody dependent cellular toxicity
- Mast cell and basophil activation
What is B cell activation
BCR bound to CD79A and CD79B, enough binding of BCR’s will activate B cells
T cell independent, doesn’t generate memory cells
Neutralization
Virus binds to receptor on cell surface and receptor endocarditis virus and it starts releasing viral DNA
To prevent things antibody blocks binding to virus receptor and can also block fusion by binding to virus
Opsonization
Bacterium is coated with complement and IgG antibody, C3b binds to CR1 and antibody binds to Fc receptor and bacteria are phagocytosed. Macrophage membranes fuse created enclosed vesicle, the phagocyte. Lysosome fuses and degrades bacteria.
Fc receptor free antibody vs aggregation of antibodies
Free antibody does not cross link Fc receptors, binding to an aggregation of antibodies like those on bacterial surfaces activates the macrophage leading to phagocytosis
Complement activation with IgG and IgM
Both activate C1 in the classical pathway
Why is IgM more efficient in complement than IgG
IgM is more efficient because C1 can bind 1 IgM but in IgG it must bind at least 2.
Antibody dependent cell mediated cytotoxicity (ADCC)
Antibody binds antigen on surface of target cells, FC receptors on NK cells recognize bound antibody, cross linking FC receptors signals NK cell to kill target cell via toxic granules, results in apoptosis
Mast cells and basophils
Involved in mobilizing cells to site of infection, releasing histamine
Bind IgE and IgG
IgE binds and causes release of cellular contents, increases blood flow and vascular permeability, recruits neutrophils, macrophages, eosinophils, and antigen specific lymphocytes, increases lymph flow
What is the main Ig involved in primary immune response
IgM
What Ig’s are involved in complement activation
IgG and IgMw
What Ig’s are involved in neutralization
IgG, IgA, IgM
What Ig’s are involved in opsonization
IgG, IgA
What Ig’s are involved in ADCC-NK cells
IgG
What Ig’s are involved in degranulation of mast cells and basophils
IgE
