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immunoglobulins and antibodies
cmbm exam III
53
Chemistry
Graduate
01/10/2010

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Term
what is the definition of an antigen? what are they made of, does this change their compatibility with T or B cells? is there anything morphologically that improves them?
Definition
an ANtibody GENerator. essentially any molecule capable of binding specifically to B or T cell antigen receptors. usually protein, esp if bound to T cell receptors, but can also be carbohydrate, lipid or nucleic acid for B cells, (however function is improved if conjugated with protein). for T cells, antigen must be proteins because they are processed and presented by MHCs. generally the larger, (more epitopes), and more complex, (more diverse), the better
Term
what is an immunogen? how does it differ from an antigen?
Definition
an immunogen is any agent capable of inducing an immune response by T ot B cells. all immunogens are antigens, but not all antigens are immunogens, (you can bind to a receptor and still not generate a response).
Term
what is an epitope? how are they shaped on T/B lymphocytes? what are they composed of?
Definition
an antigenic determinant, the part of an antigen that directly interacts with the antigen receptor, (hypervariable region), on lymphocytes. epitopes are usually linear for T cells, (due to processing that degrades protein), and confrontational or linear for B cells. they are usually 5-7 AAs for antibody, longer for T cell epitopes.
Term
how can B cells recognize linear as well as conformational/discontinous epitopes?
Definition
the two variable regions of the immunoglobulin can catch all the AAs of an epitope at once in a line or if the protein is folded, (coformational), it can touch them all if all the AAs stick out at the right angle
Term
what are immunoglobins? what proportion of blood+lymph plasma do they consist? what are they called when secreted? what are they called when on the surface of B cells?
Definition
immunoglobulins are variable, antigen-specific glycoproteins made by B cells. they are a major component of blood+lymph plasma. when secreted, they are called antibodies and when bound to the surface of B cells, they serve as the cell receptor for antigen
Term
why is it better for an antigen to be protein?
Definition
they can elict a B and T cell response
Term
what is the difference between immunoglobin and antibody, term-wise?
Definition
"immunoglobin" refers to the chemical structure, "antibody" is a response term
Term
what three things need to happen to get a B cell to start making antibodies?
Definition
B cells need to be stimulated by a relevant antigen, get "help" from T cells, (cytokine release and surface to surface interactions between B+T cells), and differentiate into plasma cells to start making antibodies
Term
what is the basic structure of an immunoglobulin?
Definition
two heavy chains composed of 3-4 globular constant, (C), domains, and 1 variable, (V), domain. the heavy chains can be one of 5 classes, (M.A.D.G.E.). there are two light chains that have one V and C domain each and can be kappa (85%) and lamba (15%)
Term
what are the 2 functional fragments of immunoglobulins? what do they do?
Definition
Fab, (antigen binding portion) and Fc, (crystallizable, "business end")
Term
what fragments can you cleave an immunoglobulin into if you use the enzyme papain? what determines this?
Definition
2 Fab and 1 Fc. this is because papain cuts above the hinge region.
Term
what fragments can you cleave an immunoglobulin into if you use the enzyme pepsin? what determines this?
Definition
1 F(ab)2 and one degraded Fc. this is because pepsin cuts below the hinge region.
Term
what is the hinge region?
Definition
the hinge region functions to link the Fc and Fab portions of the immunoglobulin molecule as a molecular ball and socket joint, allowing for more flexibility
Term
are variable regions found in both heavy and light chains? what do they do? do they contain subregions?
Definition
variable regions are found in heavy and light chains. they are antigen binding and contain highly variable hypervariable regions and less variable framework regions
Term
what are the 5 classes of immunoglobulin? which have 3 globular constant, (C), regions? 4 C?
Definition
IgG, IgD, IgA have 3 C, IgM and IgE have 4 C
Term
what do IgA and IgM have the propensity to do?
Definition
polymerize
Term
Can IgA exist as a dimer or trimer? what facilitates this? where is IgA found? how does it get there?
Definition
the "J chain" polymerizes IgA into dimers or trimers. IgA is mainly secretory, (breast milk, tears, nasal secretions, vaginal discharge, saliva), and it has to pass through a secretory component to get out of the bloodstream and into the extracellular lumen, (it is the only immunoglobulin that requires a secretory component)
Term
how does IgM exist? when is it produced? what holds it together?
Definition
as a pentamer, it is the first class of immunoglobin to respond, so it is highly efficient, (held together by J chain)
Term
what class(es) of immunoglobins are responsible for opsonization? why is this?
Definition
IgG, IgA, (to a lesser degree). this is because neutrophils and macrophages have receptors on their surface for the Fc region of IgG.
Term
what class(es) of immunoglobins are responsible for neutralization? why is this?
Definition
IgG, IgA, (major). this works b/c IgA is mucosal, and the GI tract's mucosal layer is constantly exposed to foreign protiens
Term
what class(es) of immunoglobins are responsible for sensitization for killing by NK cells? why is this?
Definition
IgG, NK cells also have a receptor for the Fc region of IgG
Term
what class of immunoglobins are responsible for sensitization of mast cells?
Definition
IgE
Term
what class(es) of immunoglobins are responsible for activation of the classical complement pathway?
Definition
IgM, IgG via the classical pathway, (IgA can do it via alternate pathway when aggregated)
Term
what class of immunoglobins are responsible for transport across the epithelium?
Definition
IgA
Term
what class of immunoglobins are responsible for transport across the placenta?
Definition
IgG
Term
what class of immunoglobins are responsible for diffusion into extravascular sites?
Definition
IgG, IgA
Term
what immunoglobulin is highest in himan serum? why?
Definition
IgG, immunologic memory from a humoral standpoint is a function of IgG, (has the longest half-life)
Term
why is IgD almost never secreted?
Definition
it is cell-associated
Term
why are IgM serum levels usually low?
Definition
b/c you are not normally mounting a primary response
Term
why are IgE serum levels usually low?
Definition
you are not normally mounting an allergic response
Term
why are IgA serum levels usually low?
Definition
b/c it doesn't usually stay in the serum, it is secreted into extravascular sites
Term
how are there immunoglobulins already present in the body that match incoming pathogens never seen by the body before?
Definition
there are only 3 genes for the immunoglobulin V domains, (2 light chain/1 heavy chain), but each gene can recombine many many times.
Term
are genes encoding the kappa, lambda and the single locus containing the heavy chain genes found on the same chromosome?
Definition
no
Term
what are the three separately encoded sections within each heavy chain V region? how are they combined?
Definition
V, (variable), D, (diversity), J, (joining). they are brought together amidst recombination and deletion of other Vs,Ds, and Js
Term
what are the two separately encoded sections within each light chain V region? how are they combined?
Definition
V, (variable) and J, (joining). they are brought together amidst recombination and deletion of other Vs and Js
Term
are all classes of immunoglobin made from the same gene? how are the genes for the C regions for each class lined up after the V as been chosen?
Definition
yes, this allows the different Ig classes to all have the same variable region to fight off a specific attack, but still play different parts in the immune response. the genes for each C region are lined up on the gene after the V has been chosen in order of what will be needed first, (thus IgM is first, then IgG or A depending on B+T cell interaction)
Term
what are some important biologic properties of IgG?
Definition
opsonization, agglutination/formation of precipitates, passage through placenta, immobilization of bacteria, and neutralization of viruses
Term
how does opsonization by IgG work?
Definition
IgG binds microbes' epitopes via Fab/binds phagocytic cells via Fc.
Term
how does agglutination/formation of precipitates by IgG work? what does it looke like?
Definition
particulate antigens, (bacteria), can agglutinate with IgG, soluble multivalent antigens can precipitate, and phagocytosis is enhanced. positive tests are clumped, while negative tests are smooth. the test for syphilis and mono are ex.
Term
what does passage through placenta by IgG entail?
Definition
the transfer of immunity from mother to fetus
Term
how does bacterial immobilization by IgG work?
Definition
IgG antibodies cling to cilia or flagella, causing clumping
Term
how does viral neutralization by IgG work?
Definition
antibodies coat the virus, preventing it from attaching
Term
what biologic role does IgA play? where is it found?
Definition
IgA plays a prominent role in mucosal immunity, antibacterial/viral, it is found in tears, saliva, colostrum, sweat, and mucus
Term
what biologic roles does IgM play?
Definition
the best agglutinator, due to pentamer shape. it activates the complement system and the IgM type contains isohemaglutinin, a naturally occuring antibody against the ABO blood group antigens
Term
what biologic roles does IgD play?
Definition
unknown, but involved with B cell maturation
Term
what biologic roles does IgE play?
Definition
this type included the reaginic antibody, (allergies), and helps produce immunity against parasitic infection
Term
what is the ELISA test?
Definition
enzyme-linked immunosorbent assay, also called ELISA, is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample.
Term
how does an ELISA test work?
Definition
the antigen for various diseases are placed in wells of an assay. the pt's blood is introduced, if they have antibodies for any of the antigens then the antibodies will stay. another antibody is introduced, (that has been conjugated with an enzyme that changes color w/addition of a substrate), and has an affinity for human antibodies is then added, and the dyed spots show what the pt has produced antibodies for. the pt's blood is also serially diluted so that it will show concentration of antibody.
Term
what is an antibody titer?
Definition
a term used to denote the relative amount of specific antibody in an ELISA preparation, (like serum). the serum is usually diluted usually in 2x increments until the antibody is undetectable. the titer is usually expressed as a reciprocal of the last dilution where the effect was seen
Term
what is an acute vs convalescent titer?
Definition
acute: serum taken while illness is symptomatic, convalescent: serum taken after symptoms subside, (~4 weeks). you are looking for a 4-fold increase in titer, (convalescent to acute), or you can look for more IgG than IgM
Term
what does the appearance of IgG tell you?
Definition
there is an immunity already developed, could be a late phase immunity of a first time infection or a memory response
Term
what does the appearance of IgM tell you?
Definition
that it is a first time infection
Term
what does a western blot tell you? how is it used?
Definition
what component you are actually responding to, (ELISA just tells you how much antibody is being made). a western blot consists of dissociating all the virus's proteins and laying them out according to molecular weight, then adding the pt's blood and seeing if there are antibodies that bind to any of those proteins, (same dye process as ELISA is uses to make this visible. this is usually done to check against ELISA false positives.
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