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29 Cards in this Set
- Front
- Back
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where are immunoglobulins typically expressed
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on the surface of B cells where they serve as bcell pathogen recognition receptors
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Plasma cells are the
terminal cell of the B cell series and thus effector B-cells secrete immunoglobulins called |
antibodies
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human serum contains how many serum proteins
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25-30
in this group is the globulin fraction, which is further subdivided into various fractions one of which is the immunoglobulin fraction |
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what are the four compartments fo serum proteins
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albumen, alpha-globulins, beta-globulins, and gammaglobulins
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Substances found in the body fluids or humors mediate ____ immunity
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humoral
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Substances found in the body fluids or humors mediate humoral immunity. These are protein molecules called antibodies, which are synthesized by B-lymphocytes. B-lymphocytes and their progeny (plasma cells) are responsible for the function of humoral immunity. This is expressed through the production of circulating plasma proteins, which we refer to as:
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(i) Immunoglobulins: a family of serum proteins some of which function as antibodies
(ii) Antibodies: serum proteins formed in response to immunologic stimulation, combines with inducing agent |
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talk about antibodies in terms of vaccines and other stuff
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The function of an antibody molecule is to specifically bind an antigen and inactivate of remove it from the body. If you are immunized with tetanus toxoid, your body responds with antibodies specific for the tetanus toxoid. Your body will produce a host of antibodies, which will recognize different antigenic determinants on the tetanus toxoid molecule. These antibodies will be different than the antibodies that your immune system will use to respond to E. coli, poliovirus or to a transplanted kidney. The humoral or antibody response is highly specific for specific antigens.
Antibodies are found either on the surface of the B-lymphocytes which made them, or in body fluids (humors). These include the blood, lymph, fluid between the tissues, and secretions. The antibody molecules are found in the gamma globulin fraction, and were called immune-globulins or immunoglobulins. The words antibody and immunoglobulin are used interchangeably in this lecture. |
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talk about the structure of the antibody
heavy/light chains types of bonds |
Antibodies function in binding antigens as well as in inactivating and removing the antigens from the body. An antibody is a protein consisting of four polypeptide chains. There are two identical heavy chains and two identical light chains. The amino terminal of both the light and heavy chains is at the top. The chains are linked to each other through cysteine bridges (disulfide bonds). There is a disulfide bridge between each light chain and its corresponding heavy chain, and there are two cysteine bridges between the two heavy chains. The antibody is a glycoprotein with carbohydrate attached at various positions, mostly at the heavy chain constant region.
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talk about the Fab and Fc fragments of antibodies
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Reducing agents break the disulfide bonds and separate antibodies into heavy and light chains. Proteases chop the molecule into pieces. Papain cuts right above the disulfide bonds, which hold the two heavy chains together, and yields three pieces. There are two identical pieces, which contain the entire light chain, disulfide bonded to the amino terminus of the heavy chain. The two pieces are exactly identical to one another. The pieces at the top are able to bind antigen. They therefore called them Fab fragments (fraction with antigen-binding capability). This means that the intact antibody molecule has two regions, which bind Ag. It is bivalent. Because the regions are identical, each Ab binds two identical antigenic determinants. The third fragment produced with papain crystallized in the refrigerator and is called the Fc fragment. It consists of the carboxy-terminal region of the two heavy chains disulfide bonded to one another. If you use the enzyme pepsin, under limited conditions, it cleaves right below the same disulfide bonds, which hold the heavy chains together. You therefore get one large fragment and a lot of little fragments. The large fragment consists of the two Fab fragments disulfide bonded together.
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are variants, which are present in all members of a species. For example, in the different antibody classes and subclasses there are distinct genes for each variant lying within the immunoglobulin heavy chain gene cluster. Thus if I were to inject human Ig into a rabbit, the rabbit would see the broadest difference class, subclass, and types and would mount an immune response.
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Isotypes:
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are variants due to the large amount of structural heterogeneity in the immunoglobulin variable region (V), related to the great variability of V domains required to bind diverse antigens. The array of amino acids (AA) that define antigen-combining site is different from one ab to the next since each plasma cell produces an antibody molecule unique unto itself. All offspring’s or clones of that plasma cell will produce the same ab. Within an individual other plasma cells' ab molecules will be structurally similar except at this idiotypic site. When antibodies are directed against this idiotypic site they are called "anti-idiotypic antibodies.
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Idiotypes:
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are variants due to the intraspecies differences. Each individual has a particular variant at each Ig gene locus, which will often differ from those of other individuals. This would be seen as ab made by a member of one species against the Ig of the same species. This will define allelic substitution or variation between antibodies. For example, in kappa chain could substitute Leucine for Valine at a specific site on the chain.
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Allotypes:
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what are the different class of light chains
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kappa and lambda
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what are the different classes of heavy chains
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mu, gamma, allpha, delta, epsilon
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talk about IgG
it makes up what % of serum immunoglobulin how many subclasses how are they different different molecular weights which ones activate complement do they cross the placenta |
Immunoglobulins (IgGs) all have gamma heavy chains, and kappa or lambda light chains. This is the most predominant immunoglobulin in serum, comprising 70-75% of serum immunoglobulin. It is 7S (refers to Svedberg coefficient which is a measure of sedimentation rate). There are four subclasses of IgG called IgG l-4. They have different gamma constant regions. The predominant difference is in the hinge region. The differences give each subclass slightly different effector functions and probably different abilities in Ag binding. The molecular weights vary slightly, but the ballpark molecular weights are about the same. Another effector function is that IgG's activate the classical complement pathway. If the organism is for example an E. coli to which the antibodies are bound, complement protein Cl is bound to the two IgGs. After this, a series of other proteins bind, resulting in lyses of the bacterial cell. The three important things we need to know about this are that the complement pathway is activated by IgG, that Cl binds to the CH2 domain of the constant region of IgG, and that it must bind to two different CH2 regions on two different antibodies for the cascade to start. The various subclasses of IgG have different abilities to activate the complement cascade. IgG 3 > 1 > 2 > 4. These antibodies also cross the placenta. This is good in that the maternal Ab's protect the fetus. This can be bad in that some Ab's can damage the fetus. This is the case when the child is Rh+ and the mother is Rh-, but has anti-Rh Ab's. If these are IgG antibodies, they will cross the placenta and lyse the fetus' red blood cells.
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talk about IgM
where does it appear what is it how are they held together how much is there in the serum what is agglutination how well does it fix complement |
IgM appears on the surface of a virgin B cell. IgM is a monomer; it is secreted as a pentamer (19S). The five antibodies are held together by disulfide bonds, and they also have a J (joining) chain, which allows them to hook up to one another. There is about 5-10% IgM in serum. It has 10 Ag binding sites, and is therefore good at forming large ab/ag clusters. This is called agglutination. IgM is good at binding antigens with repeating subunits, like viruses and red blood cells. It is very primitive and is the first Ab produced in our initial humoral immune response to an antigen! It fixes complement very efficiently and is the main antibody component of the response of T-independent antigens. It is also the first to develop in the phylogenetic scale, and is the first in human ontogeny! As B cells mature, they go from stem cells to pre B cells, and then IgM is the first antibody produced by mature B cells. It is put on the cells' surface, and then the B cell waits to encounter Ag. IgM is the first antibody made in the initial immune response to a given antigen (i.e. 1st encounter). In addition, IgM activates the classical (as opposed to the alternate) complement pathway very effectively
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talk about IgA
when does it develop how much is there in serum what are the two forms of IgA which pathway can it activate complement thru |
This is the second most abundant Ig (10%), and is the third class of Ig to develop. It comes in a monomeric form (7S) and a dimeric form (11S). The dimeric form is secretory IgA and has an extra polypeptide unit called the "secretory component" which affords the molecule resistance to proteolytic enzymes produced by invading organisms. The secretory piece is produced in the subepithelial tissue of exocrine glands. It also has a J chain derived from the plasma cell, which binds the Ig together. The monomeric form is found in the serum; the dimer form in secretions primarily on surfaces. IgA can activate the complement pathway via the alternative pathway.
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talk about IgD
how much is there in serum how well does it fix complement where is it found what does it do when is it elevated |
This is 7-8S, and has been found to be difficult to study in that it is present in very low concentrations with a short half-life and rapid degradation. It does not fix complement. It appears to be on the surface of "virgin" B cells with IgM where it influences the differentiation process of the B cell. It has been found to be elevated in chronic infections, autoimmune diseases, and in some allergic states (penicillin).
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talk about IgE
how much of it is in serum what is special about it what can it fix what cant it fix |
This was previously called "reagin". It is 8 S, has high carbohydrate content, and is very susceptible to degradation by heat, reducing agents, and enzymes; thus it has a very short half-life. It is present in trace amounts in the serum. It is homocytotropic i.e. it is the only Ig capable of fixing to homologous tissue. IgE fixes mast cells basophils, and platelets (all of which can release vasoactive amines). IgE does not fix complement. It is responsible for the reaction seen in anaphylaxis and other allergic states (asthma, allergic rhinitis, etc). It has a most important function against parasites, especially worms. It is abundant in respiratory mucosa and is found in secretions. It is the immunoglobulin of the allergic reaction
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talk about B cell differentiation with the different types of immunoglobulins
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All B cells start out as stem cells in the bone marrow. The maturation of the B cell involves the production of IgM and IgD antibodies. IgM is expressed on the membrane before IgD. The mature B cell has both IgD and IgM membrane bound. Since it hasn't encountered any antigen at this point it is said to be naive. It is important to note that the antigen specificity of membrane bound IgD and IgM is identical. Once the B cell binds to antigen it begins to secrete IgM. Some time later there may be a class or isotype switch to IgG, IgA, or IgE.
There is an antigen-independent phase from the progenitor cell to the mature B cell having IgM and IgD on the surface, and an antigen-dependent phase, which goes from the activated B cells to the memory cell and the plasma cell, which is the secretory cell. |
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the part of the antigen to which an antibody binds is called an antigenic determinant or epitope
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Epitope:
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a single antigenic determinant of the variable region of an antibody or T-cell receptor related to the antigen-binding site
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Idiotope:
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a set of antigenic determinants in immunoglobulin or T-cell receptor variable regions that are in or near the antigen-binding site. It is a unique antigenic determinant present on homogeneous antibody or myeloma protein. The idiotype appears to represent the antigenicity of the antigen-binding site of an antibody and is therefore located in the V region. (E.g. specific to one tree pollen)
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Idiotype:
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Antigenic characteristics of given class or subclass of immunoglobulin H and L chains (e.g. IgM, IgE, IgAl, IgA2, kappa, lambda)
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Isotype:
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The genetically determined antigenic difference in serum proteins, varying in different members of the same species (e.g. variations in CH/CL; at times VH/VL such as Can variation in different humans)
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Allotype:
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A substance that reacts with antibodies or T-cell receptors evoked by immunogens
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Antigen:
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substances capable of eliciting an immune response
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Immunogens:
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A substance that non-specifically induces DNA synthesis and cell division
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Mitogen:
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A small molecule that can act as an epitope but is incapable of eliciting an antibody response unless coupled to an immunogenic carrier molecule
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hapten
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