1. Instructive and selective theories in generation of the immune effectors;
Instructive theory
-an antibody molecule is synthesized in the presence of the antigen that acts as a
template
Selective theory
-the combination of an antigen with an Ab, will trigger the cell to make and secrete
more of those receptors
2. Immunogenicity and antigenicity; factors dependent of antigen that influence
immunogenicity;
-an immunogen is any substance that elicits adaptive immune response
-an antigen is any substance that is specifically recognized and bound by the
antigen receptors of T and B lymphocytes
Factors dependent of antigen that influences immunogenicity:
a. Foreignness- an antigen must be perceived as a foreign structure; the more
deviated from self-structures, the more it is recognized as a non-self-structure and
the stronger the immune response; if the molecules is similar enough to self-
structures, self-tolerance will be induced
b. Molecular complexity- molecular size, subunit composition, conformation, charge
and processing potential
- they must be at least 40kDa, the best immunogen has its mass close to 100kDa-> the
larger the molecule the higher the probability it has epitopes recognized by both B and
T cells;
- regarding structural subunits, hetero polymers are better than homo polymers;
-conformation affects immunogenicity: conformational epitopes are far apart amino
acids that come together in natural or native shape of protein and they are recognized
by BCRs, whereas linear epitopes are formed by consecutive amino acids that can be
buried in the 3D structure of protein so it will be accessible when the protein is
denatured and recognized by TCR
, 3. Immunogenicity and antigenicity; factors dependent of the immune system of the
host and of the administration conditions;
Role of the biological system in immunogenicity and their factors:
-genetic constitution of the individual: the children below 3 and adults above 70 years
old have a weaker immune response;
-MHC gene products that are involved in antigenic presentation to T cells influence the
degree of immune system response to a certain antigen; each person inherits a certain
collection of MHC proteins and those are involved in presentation of certain non-self-
peptides to T cells; as long as these do not find the proper MHC among those belonging
to the host, the peptide will not be detected by the immune host cells
-physiological and pathological conditions of individual-pregnancy causes immune
suppression due to presence of fetus; also there are congenital or acquired
immunodeficiencies
4. Epitopes, haptens, carriers, adjuvants; cross reactivity; practical applications;
Epitopes
-also called antigenic determinants
-are regions in the (hyper)variable regions of antibodies of B cells that bind to the
antigen; they bind to paratopes (on antigens)
-also present on the T cells, bound to MHC molecules (MHC class II presented by
APCs, whereas MHC class I presented by most nucleated cells)
Haptens
-molecules too small to be immunogenic (cannot induce formation of antibodies) by
themselves but they can interact with antibodies once they are formed
-also called partial antigens
-they induce formation of antibodies by making complexes with most often proteins,
which are immunogenic by themselves and that are called carriers
-examples include antibiotics, analgesics, polysaccharides
,Carriers
-molecules, mostly proteins that are immunogenic and that bind haptens to cause an
immune response
-examples include globulins, albumins, synthetic polypeptides
=> the complex hapten-carrier will act as an epitope
Adjuvants
-substances able to increase the immunogenicity of an antigen (if this antigen is dead
or purified, lacking the ability to replicate, which usually results in a poor immune
response)
-adjuvants used in vaccination are:
a. Freund’s complete adjuvant- contains antigens in aqueous phase and a suspension
of killed bacteria in oily phase
b. Freund’s incomplete adjuvant-similar to the previous one, except that in the oily
phase there is no bacilli
c. Aluminum based compounds-such as phosphates and hydroxides
-their function is to provide long lived antigen reservoir in extracellular environment
or within APCs, to activate macrophages and lymphocytes
Cross reactivity
-if an antibody binds to an antigen's epitope, the paratope could become the epitope for
another antibody that will then bind to it. If this second antibody is of IgM class, its
binding can upregulate the immune response; if the second antibody is of IgG class, its
binding can downregulate the immune response
Practical applications
-haptens are important in immunological research; helpful in evaluating specificity,
affinity and cross reactivity of antibodies, also can explain the adverse reactions of
some drugs in vivo due to their hapten-like behaviour as well as in explaining the
pathological basis of autoimmune diseases such as systemic lupus erythemathosus (in
which self-DNA molecules form hapten-carrier complexes that induce formation of
auto antibodies against self-DNA
, -similarly, it demonstrated that both the hapten and carrier are needed to generate the
immune response and they have to be linked together
-hapten carrier complexes artificially created are very important in generating
antibodies against small molecules such as drugs or hormones that are not
themselves immunogenic but whose identification and level assessment using
antibodies is important in diagnostic and therapy
5. Epitopes recognized by B lymphocytes versus epitopes recognized by T
lymphocytes;
-T dependent immunogens (TdAg) are immunogens that are recognized by B cells, but
they do not induce the activation of B cells unless they are interacting with primed Th
cells (Th cells previously activated through contact with a different epitope of the same
antigen)
-T independent antigens antigens (TiAg) on the contrary are not requiring Th cell
intervention for B cell activation.
-The B cells response against Ti antigens is fast and does not associate memory
component, being predominantly mediated by IgM. The B cell response against Td
antigen is slower, induces class switch from IgM to IgG and also a memory component
-Ti are inducing B cell activation in the absence of Th cells because they are able to
cross-link the BCR copies present on the surface of B cell due to the fact that they
present identical (repetitive) epitopes. Td antigens contain different epitopes, therefore
they are not able to crosslink BCR copies and the cross linking signal is replaced by
the cytokinic signal supplied by the Th cells
-The conformation can also affect immunogenicity. T dependent antigens offer both
conformational and linear epitopes
-Conformational epitopes are formed by aminoacids that are located far apart in the
linear structure but become adjacent in the natural folded or native shape of the
protein. These epitopes disappear when the protein is denatured or when is unfolded
(that is when the intramolecular bonds are destroyed) and they are the ones
recognized by BCR
-The linear epitopes are formed by consecutive aminoacids. They are found on the
surface but more often they are buried inside the tridimensional structure of the
protein, so they become accessible when the protein is denatured and they are
recognized by TCR when they form complexes with the MHC after protein processing
Instructive theory
-an antibody molecule is synthesized in the presence of the antigen that acts as a
template
Selective theory
-the combination of an antigen with an Ab, will trigger the cell to make and secrete
more of those receptors
2. Immunogenicity and antigenicity; factors dependent of antigen that influence
immunogenicity;
-an immunogen is any substance that elicits adaptive immune response
-an antigen is any substance that is specifically recognized and bound by the
antigen receptors of T and B lymphocytes
Factors dependent of antigen that influences immunogenicity:
a. Foreignness- an antigen must be perceived as a foreign structure; the more
deviated from self-structures, the more it is recognized as a non-self-structure and
the stronger the immune response; if the molecules is similar enough to self-
structures, self-tolerance will be induced
b. Molecular complexity- molecular size, subunit composition, conformation, charge
and processing potential
- they must be at least 40kDa, the best immunogen has its mass close to 100kDa-> the
larger the molecule the higher the probability it has epitopes recognized by both B and
T cells;
- regarding structural subunits, hetero polymers are better than homo polymers;
-conformation affects immunogenicity: conformational epitopes are far apart amino
acids that come together in natural or native shape of protein and they are recognized
by BCRs, whereas linear epitopes are formed by consecutive amino acids that can be
buried in the 3D structure of protein so it will be accessible when the protein is
denatured and recognized by TCR
, 3. Immunogenicity and antigenicity; factors dependent of the immune system of the
host and of the administration conditions;
Role of the biological system in immunogenicity and their factors:
-genetic constitution of the individual: the children below 3 and adults above 70 years
old have a weaker immune response;
-MHC gene products that are involved in antigenic presentation to T cells influence the
degree of immune system response to a certain antigen; each person inherits a certain
collection of MHC proteins and those are involved in presentation of certain non-self-
peptides to T cells; as long as these do not find the proper MHC among those belonging
to the host, the peptide will not be detected by the immune host cells
-physiological and pathological conditions of individual-pregnancy causes immune
suppression due to presence of fetus; also there are congenital or acquired
immunodeficiencies
4. Epitopes, haptens, carriers, adjuvants; cross reactivity; practical applications;
Epitopes
-also called antigenic determinants
-are regions in the (hyper)variable regions of antibodies of B cells that bind to the
antigen; they bind to paratopes (on antigens)
-also present on the T cells, bound to MHC molecules (MHC class II presented by
APCs, whereas MHC class I presented by most nucleated cells)
Haptens
-molecules too small to be immunogenic (cannot induce formation of antibodies) by
themselves but they can interact with antibodies once they are formed
-also called partial antigens
-they induce formation of antibodies by making complexes with most often proteins,
which are immunogenic by themselves and that are called carriers
-examples include antibiotics, analgesics, polysaccharides
,Carriers
-molecules, mostly proteins that are immunogenic and that bind haptens to cause an
immune response
-examples include globulins, albumins, synthetic polypeptides
=> the complex hapten-carrier will act as an epitope
Adjuvants
-substances able to increase the immunogenicity of an antigen (if this antigen is dead
or purified, lacking the ability to replicate, which usually results in a poor immune
response)
-adjuvants used in vaccination are:
a. Freund’s complete adjuvant- contains antigens in aqueous phase and a suspension
of killed bacteria in oily phase
b. Freund’s incomplete adjuvant-similar to the previous one, except that in the oily
phase there is no bacilli
c. Aluminum based compounds-such as phosphates and hydroxides
-their function is to provide long lived antigen reservoir in extracellular environment
or within APCs, to activate macrophages and lymphocytes
Cross reactivity
-if an antibody binds to an antigen's epitope, the paratope could become the epitope for
another antibody that will then bind to it. If this second antibody is of IgM class, its
binding can upregulate the immune response; if the second antibody is of IgG class, its
binding can downregulate the immune response
Practical applications
-haptens are important in immunological research; helpful in evaluating specificity,
affinity and cross reactivity of antibodies, also can explain the adverse reactions of
some drugs in vivo due to their hapten-like behaviour as well as in explaining the
pathological basis of autoimmune diseases such as systemic lupus erythemathosus (in
which self-DNA molecules form hapten-carrier complexes that induce formation of
auto antibodies against self-DNA
, -similarly, it demonstrated that both the hapten and carrier are needed to generate the
immune response and they have to be linked together
-hapten carrier complexes artificially created are very important in generating
antibodies against small molecules such as drugs or hormones that are not
themselves immunogenic but whose identification and level assessment using
antibodies is important in diagnostic and therapy
5. Epitopes recognized by B lymphocytes versus epitopes recognized by T
lymphocytes;
-T dependent immunogens (TdAg) are immunogens that are recognized by B cells, but
they do not induce the activation of B cells unless they are interacting with primed Th
cells (Th cells previously activated through contact with a different epitope of the same
antigen)
-T independent antigens antigens (TiAg) on the contrary are not requiring Th cell
intervention for B cell activation.
-The B cells response against Ti antigens is fast and does not associate memory
component, being predominantly mediated by IgM. The B cell response against Td
antigen is slower, induces class switch from IgM to IgG and also a memory component
-Ti are inducing B cell activation in the absence of Th cells because they are able to
cross-link the BCR copies present on the surface of B cell due to the fact that they
present identical (repetitive) epitopes. Td antigens contain different epitopes, therefore
they are not able to crosslink BCR copies and the cross linking signal is replaced by
the cytokinic signal supplied by the Th cells
-The conformation can also affect immunogenicity. T dependent antigens offer both
conformational and linear epitopes
-Conformational epitopes are formed by aminoacids that are located far apart in the
linear structure but become adjacent in the natural folded or native shape of the
protein. These epitopes disappear when the protein is denatured or when is unfolded
(that is when the intramolecular bonds are destroyed) and they are the ones
recognized by BCR
-The linear epitopes are formed by consecutive aminoacids. They are found on the
surface but more often they are buried inside the tridimensional structure of the
protein, so they become accessible when the protein is denatured and they are
recognized by TCR when they form complexes with the MHC after protein processing
