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ANTIGENECITY AND
IMMUNOGENECITY
Dr.Sujit Ghosh
Antigen Vs Immunogen
Antigen Immunogen
A substance specifically binds to antibodies or
a cell surface receptor of B cell and T cell
An antigen capable of immunogenic response
Can either be immunogenic or
nonimmunogenic
Always immunogenic
Chemically protein, nucleic acid,
polysaccharides,lipids
Chemically protein, polysaccharides
Haptens can bind with antibodies but not
immunogenic
Haptens with attached protein is
immunogenic
Immunogenecity and Antigenecity
 Immunogenecity : ability to induce humoral and cell
mediated immune response. All Immunogens are antigen.
 B cell+ Antigen→Effector B Cell +Memory B cell
 T cell+ Antigen→ Effector T Cell+ Memory T cell
 Ability to combine specifically the product of humoral or cell
mediated immune response.All antigen are not immunogen.
 Antigenecity is the ability to combine specifically with secreated
antibodies and surface receptor of T cell
All the molecule which have the properties of immunogenecity also
have the properities of antigenicity
Characteristics
of immunogen
Foreignness
from self
structure of
host
Chemical
Composition
Chemical
Complexity
Molecular
Size
Dose of
Immunogen
Genetic
Constitution
of the Host
Features of Immunogen
1. Foreignness of the Immunogen (relative degree of difference
of the immunogen from self-structures of the host):
 Upon entry of the immunogen into the animal body, immune responses are usually induced
against short peptide structures of the immunogen. But animal cells are also made up of
many peptides. If the peptides of the immunogen happen to be similar to the peptides of the
animal cell, the animal’s immune system will not develop immune responses against the
immunogen.
 [For example, isolate albumin from the serum of rabbit and inject the albumin back into the
same rabbit. There is no immune response against the injected albumin, because the injected
albumin is not recognized as foreign (“non- self”) by the rabbit. Whereas, if albumin from a
rabbit is injected into a guinea pig, the guinea pigs immune system recognizes the injected
albumin as foreign (“non- self”) and mount immune responses against the injected albumin.
 Therefore for the induction of immune responses, the immunogen should have peptides
different from the peptides of the animal, which is referred to as foreignness of the
immunogen.
Chemical Composition and chemical
complexity
 Usually proteins are potent immunogens. Polysaccharides and
some synthetic organic polymers (For example, polyvinyl
pyrrolidone) can also be immunogenic. Usually lipids are not
immunogenic. But few lipids, (like the mycolic acid of
mycobacteria) are known to be immunogenic.
 Molecules with complex nature are more immunogenic when
compared to simple molecules. Molecules with more than two or
three different amino acid residues are more immunogenic
when compared to molecules made of homopolymers of a single
amino acid. Aromatic amino acids are more immunogenic than
nonaromatic amino acids. Polypeptides with amino acid
tyrosine are better immunogens than polypeptides without
tyrosine.
Molecular size
ď‚— The most potent immunogens are proteins with a molecular size greater
than 100,000. Substances smaller than MW 10,000 are not usually
immunogenic. Yet, molecular size is not an absolute criterion with
respect to the immunogenicity of a substance because few peptides with
molecular weights below 1,100 also induce strong immune responses.
Dose of Immunogen
The minimum quantity of the immunogen required to induce immune responses in
animals varies with respect to the animal and the immunogen. If tiny amount of
immunogen is used, very poor immune responses may be induced. On the other
hand, if too large amount of immunogen is used, the animal may fail to develop any
immune response at all; a condition called tolerance (or specific unresponsiveness).
This phenomenon is also referred to as high-dose tolerance.
Genetic Constitution of the Host
The immune response of an animal to a particular
substance also depends on the genetic constitution of
the animal. A particular substance may induce
immune response in rabbits. Whereas, the same
substance may not induce immune response in guinea
pigs. Even within the same species, one strain may
respond to a particular substance whereas other strain
may not respond to that substance.
Route of entry of Immunogen
 The route of entry of the immunogen into the body of an animal
greatly influences the type and intensity of the immune responses.
[For example, the entry of the microbe through gut mucosa (oral
route) leads to IgA type of antibody production, whereas if the
same microbe enters through the skin it leads to IgG type of
antibody production].
Oral route: Subcutaneous
route:
Intramuscular
route:
Intravenous
route
Respiratory
route
Genitourinary
route
Enter through
mouth
Enter the tissues
just below the
skin (by injury or
injection)
Injected into the
muscles
Injected directly
into the veins
Inhaled through
respiratory
system
Enter through
the genital or
urinary tract.
Definitions
 Immune system = cells, tissues,
and molecules that mediate
resistance to infections
 Immunology = study of structure
and function of the immune
system
 Immunity = resistance of a host to
pathogens and their toxic effects
 Immune response = collective and
coordinated response to the
introduction of foreign substances
in an individual mediated by the
cells and molecules of the immune
system
Functions of
the immune
system
 Defense against microbes
 Defense against the growth
of tumor cells
kills the growth of tumor
cells
 Homeostasis
destruction of abnormal or
dead cells
(e.g. dead red or white blood
cells, antigen-antibody
complex)
Immunoadjuvents
 These agents are generally used in the vaccine development for the
generation of greater immune response.
 They act as an immune enhancer of antigenic component of vaccine.
Adjuvants augment, stimulate, potentiate, enhance, activate, or modulate
the immune response at either cellular or humoral level.
 Exogenous best known examples include Freund’s adjuvant, Bacillus
Calmette–Guérin (BCG), Corynebacterium parvum; all of which contain
bacterial antigen.
 Endogenous adjuvants include histamine, IL-1, tuftsin, transfer factor,
and interferon.
 Although, their mode of action may be nonspecific but it results in
increased immune responsiveness to a variety of antigens or group of
antigens.
Mechanism of action of Immunoadjuvents
Proposed mechanisms of action of adjuvants.
 Some adjuvants presumably form a depot at the site of injection, which is
associated with slow release of antigen.
 Other adjutants are associated with transient secretion of cytokines and
chemokines. Secreted cytokines and chemokines are involved in recruitment of
various immune cells to the injection site. These recruited cells secrete cytokines
and chemokines, in turn attract other immune cells. All these events lead to
formation of a local immuno-competent environment at the injection site.
 The recruited APCs express various PRRs both on the surface (TLRs, CLRs) and
intracellularly (NLRs and RLRs), which are recognized and/or are activated by the
adjuvants.
 This leads to maturation and activation of recruited APCs. Mature APCs up-
regulate the expression of MHC and co-stimulatory molecules.
 They are also characterized by increased capacity for antigen processing and
presentation.
 Mature APCs then migrate to the draining lymph nodes to interact with antigen-
specific B or T cell to (8) activate potent antibody secreting B cells and/or effector
CD8+ T cell responses.
Mode of action of Immunoadjuvents
Immunostimulants
 These agents also stimulate or boost either cellular or humoral immune responses.
 Some of them are specific immunostimulants, such as vaccines, which stimulate an
immune response against specific antigens contrary to nonspecific stimulants.
 These types of stimulants are being used widely in the cases of autoimmunity, allergy,
immunodeficiency, and cancer.
 In healthy individuals, stimulants act as a prophylactic agent, that is, they potentiate the
basal levels of immune system. When an individual is exposed to pathogen, it elicits the
heightened immune response that allows the rapid clearance of pathogen and its products
that eventually prevent disease. In individuals with impaired immune response, stimulants
act as immunotherapeutic agents.
 Immunocompromised condition includes patients with primary and secondary
immunodeficiency.
 A condition resulting from a genetic or developmental defect in immune system is called
as primary immunodeficiency. For example, severe combined immunodeficiency (SCID),
Wiskott–Aldrich syndrome (WAS), and X-linked agammaglobulinemia.
 Secondary immunodeficiency is the loss of immune function, which results from
exposure to various agents, for example, AIDS, malignancy, different types of
immunostimulants like cytokines (IL-2, interferons, G-CSF), microbial toxins/fragments,
herb, venom and so on.
Immunosuppressants
 These agents weaken or suppress the activation of the immune
system.
 In general, immunosupression is of two types-
 deliberate induced
â—Ľ In deliberately induced immunosuppression, there is a need for the same
because it is performed mainly to prevent body from rejecting an organ
transplant, treating graft-versus-host disease after a bone marrow transplant,
or the treatment of autoimmune diseases like rheumatoid arthritis, Grave’s
disease, and myasthenia gravis. Cortisone was the first immunosuppressant
identified but its use is limited because of side effects, but discovery of
cyclosporine led to the remarkable choice and is being used in various
transplantations (including kidney, liver, and heart). Tacrolimus and sirolimus
antibiotics are also used in transplantation and graft rejection.
 Nondeliberate immune suppression.
â—Ľ Nondeliberate immunosuppression can occur in aging, malnutrition, cancer,
and chronic infections like HIV. In this case, unwanted immunosuppression
leads to the increase in susceptibility to various pathogens, such as bacteria,
fungi, viruses, or protozoans (Abbas et al., 2012).
Immune
System
Organs Cells .Molecules
Thymus
Lymph nodes
Spleen
Payer’s patches
Appendix
Lymphatic vessels
Bone marrow
Tonsils and adenoids
Lymphocytes
•T-lymphocytes
•B-Lymphocytes, plasma
cells
•natural killer
lymphocytes
•Monocytes, Macrophage
•Granulocytes
•neutrophils
•eosinophils
•basophils
•Antibodies
•Complement
•Cytokines
•Interleukines
•Interferons
Types of immunity
Innate (non-
adaptive)
First line of immune
response
Relies on mechanisms
that exist before
infection
.Acquired (adaptive)
Second line of
response (if innate
fails)
Relies on mechanisms
that adapt after
infection
Handled by T- and
B- lymphocytes
One cell determines
one antigenic
determinant

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ANTIGENECITY AND IMMUNOGENICITY

  • 2. Antigen Vs Immunogen Antigen Immunogen A substance specifically binds to antibodies or a cell surface receptor of B cell and T cell An antigen capable of immunogenic response Can either be immunogenic or nonimmunogenic Always immunogenic Chemically protein, nucleic acid, polysaccharides,lipids Chemically protein, polysaccharides Haptens can bind with antibodies but not immunogenic Haptens with attached protein is immunogenic
  • 3. Immunogenecity and Antigenecity  Immunogenecity : ability to induce humoral and cell mediated immune response. All Immunogens are antigen.  B cell+ Antigen→Effector B Cell +Memory B cell  T cell+ Antigen→ Effector T Cell+ Memory T cell  Ability to combine specifically the product of humoral or cell mediated immune response.All antigen are not immunogen.  Antigenecity is the ability to combine specifically with secreated antibodies and surface receptor of T cell All the molecule which have the properties of immunogenecity also have the properities of antigenicity
  • 4. Characteristics of immunogen Foreignness from self structure of host Chemical Composition Chemical Complexity Molecular Size Dose of Immunogen Genetic Constitution of the Host
  • 5. Features of Immunogen 1. Foreignness of the Immunogen (relative degree of difference of the immunogen from self-structures of the host):  Upon entry of the immunogen into the animal body, immune responses are usually induced against short peptide structures of the immunogen. But animal cells are also made up of many peptides. If the peptides of the immunogen happen to be similar to the peptides of the animal cell, the animal’s immune system will not develop immune responses against the immunogen.  [For example, isolate albumin from the serum of rabbit and inject the albumin back into the same rabbit. There is no immune response against the injected albumin, because the injected albumin is not recognized as foreign (“non- self”) by the rabbit. Whereas, if albumin from a rabbit is injected into a guinea pig, the guinea pigs immune system recognizes the injected albumin as foreign (“non- self”) and mount immune responses against the injected albumin.  Therefore for the induction of immune responses, the immunogen should have peptides different from the peptides of the animal, which is referred to as foreignness of the immunogen.
  • 6. Chemical Composition and chemical complexity  Usually proteins are potent immunogens. Polysaccharides and some synthetic organic polymers (For example, polyvinyl pyrrolidone) can also be immunogenic. Usually lipids are not immunogenic. But few lipids, (like the mycolic acid of mycobacteria) are known to be immunogenic.  Molecules with complex nature are more immunogenic when compared to simple molecules. Molecules with more than two or three different amino acid residues are more immunogenic when compared to molecules made of homopolymers of a single amino acid. Aromatic amino acids are more immunogenic than nonaromatic amino acids. Polypeptides with amino acid tyrosine are better immunogens than polypeptides without tyrosine.
  • 7. Molecular size ď‚— The most potent immunogens are proteins with a molecular size greater than 100,000. Substances smaller than MW 10,000 are not usually immunogenic. Yet, molecular size is not an absolute criterion with respect to the immunogenicity of a substance because few peptides with molecular weights below 1,100 also induce strong immune responses. Dose of Immunogen The minimum quantity of the immunogen required to induce immune responses in animals varies with respect to the animal and the immunogen. If tiny amount of immunogen is used, very poor immune responses may be induced. On the other hand, if too large amount of immunogen is used, the animal may fail to develop any immune response at all; a condition called tolerance (or specific unresponsiveness). This phenomenon is also referred to as high-dose tolerance.
  • 8. Genetic Constitution of the Host The immune response of an animal to a particular substance also depends on the genetic constitution of the animal. A particular substance may induce immune response in rabbits. Whereas, the same substance may not induce immune response in guinea pigs. Even within the same species, one strain may respond to a particular substance whereas other strain may not respond to that substance.
  • 9. Route of entry of Immunogen  The route of entry of the immunogen into the body of an animal greatly influences the type and intensity of the immune responses. [For example, the entry of the microbe through gut mucosa (oral route) leads to IgA type of antibody production, whereas if the same microbe enters through the skin it leads to IgG type of antibody production]. Oral route: Subcutaneous route: Intramuscular route: Intravenous route Respiratory route Genitourinary route Enter through mouth Enter the tissues just below the skin (by injury or injection) Injected into the muscles Injected directly into the veins Inhaled through respiratory system Enter through the genital or urinary tract.
  • 10. Definitions  Immune system = cells, tissues, and molecules that mediate resistance to infections  Immunology = study of structure and function of the immune system  Immunity = resistance of a host to pathogens and their toxic effects  Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system
  • 11. Functions of the immune system  Defense against microbes  Defense against the growth of tumor cells kills the growth of tumor cells  Homeostasis destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigen-antibody complex)
  • 12. Immunoadjuvents  These agents are generally used in the vaccine development for the generation of greater immune response.  They act as an immune enhancer of antigenic component of vaccine. Adjuvants augment, stimulate, potentiate, enhance, activate, or modulate the immune response at either cellular or humoral level.  Exogenous best known examples include Freund’s adjuvant, Bacillus Calmette–GuĂ©rin (BCG), Corynebacterium parvum; all of which contain bacterial antigen.  Endogenous adjuvants include histamine, IL-1, tuftsin, transfer factor, and interferon.  Although, their mode of action may be nonspecific but it results in increased immune responsiveness to a variety of antigens or group of antigens.
  • 13. Mechanism of action of Immunoadjuvents Proposed mechanisms of action of adjuvants.  Some adjuvants presumably form a depot at the site of injection, which is associated with slow release of antigen.  Other adjutants are associated with transient secretion of cytokines and chemokines. Secreted cytokines and chemokines are involved in recruitment of various immune cells to the injection site. These recruited cells secrete cytokines and chemokines, in turn attract other immune cells. All these events lead to formation of a local immuno-competent environment at the injection site.  The recruited APCs express various PRRs both on the surface (TLRs, CLRs) and intracellularly (NLRs and RLRs), which are recognized and/or are activated by the adjuvants.  This leads to maturation and activation of recruited APCs. Mature APCs up- regulate the expression of MHC and co-stimulatory molecules.  They are also characterized by increased capacity for antigen processing and presentation.  Mature APCs then migrate to the draining lymph nodes to interact with antigen- specific B or T cell to (8) activate potent antibody secreting B cells and/or effector CD8+ T cell responses.
  • 14. Mode of action of Immunoadjuvents
  • 15. Immunostimulants  These agents also stimulate or boost either cellular or humoral immune responses.  Some of them are specific immunostimulants, such as vaccines, which stimulate an immune response against specific antigens contrary to nonspecific stimulants.  These types of stimulants are being used widely in the cases of autoimmunity, allergy, immunodeficiency, and cancer.  In healthy individuals, stimulants act as a prophylactic agent, that is, they potentiate the basal levels of immune system. When an individual is exposed to pathogen, it elicits the heightened immune response that allows the rapid clearance of pathogen and its products that eventually prevent disease. In individuals with impaired immune response, stimulants act as immunotherapeutic agents.  Immunocompromised condition includes patients with primary and secondary immunodeficiency.  A condition resulting from a genetic or developmental defect in immune system is called as primary immunodeficiency. For example, severe combined immunodeficiency (SCID), Wiskott–Aldrich syndrome (WAS), and X-linked agammaglobulinemia.  Secondary immunodeficiency is the loss of immune function, which results from exposure to various agents, for example, AIDS, malignancy, different types of immunostimulants like cytokines (IL-2, interferons, G-CSF), microbial toxins/fragments, herb, venom and so on.
  • 16. Immunosuppressants  These agents weaken or suppress the activation of the immune system.  In general, immunosupression is of two types-  deliberate induced â—Ľ In deliberately induced immunosuppression, there is a need for the same because it is performed mainly to prevent body from rejecting an organ transplant, treating graft-versus-host disease after a bone marrow transplant, or the treatment of autoimmune diseases like rheumatoid arthritis, Grave’s disease, and myasthenia gravis. Cortisone was the first immunosuppressant identified but its use is limited because of side effects, but discovery of cyclosporine led to the remarkable choice and is being used in various transplantations (including kidney, liver, and heart). Tacrolimus and sirolimus antibiotics are also used in transplantation and graft rejection.  Nondeliberate immune suppression. â—Ľ Nondeliberate immunosuppression can occur in aging, malnutrition, cancer, and chronic infections like HIV. In this case, unwanted immunosuppression leads to the increase in susceptibility to various pathogens, such as bacteria, fungi, viruses, or protozoans (Abbas et al., 2012).
  • 17. Immune System Organs Cells .Molecules Thymus Lymph nodes Spleen Payer’s patches Appendix Lymphatic vessels Bone marrow Tonsils and adenoids Lymphocytes •T-lymphocytes •B-Lymphocytes, plasma cells •natural killer lymphocytes •Monocytes, Macrophage •Granulocytes •neutrophils •eosinophils •basophils •Antibodies •Complement •Cytokines •Interleukines •Interferons
  • 18. Types of immunity Innate (non- adaptive) First line of immune response Relies on mechanisms that exist before infection .Acquired (adaptive) Second line of response (if innate fails) Relies on mechanisms that adapt after infection Handled by T- and B- lymphocytes One cell determines one antigenic determinant