Immunogenecity and antigenecity

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About This Presentation

Immunogen, antigen, adjuvents, immunosuppresents,immunostimulants


Slide Content

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 humoraland cell
mediated immune response. All Immunogensare antigen.
B cell+ Antigen→EffectorB Cell +Memory B cell
T cell+ Antigen→EffectorT Cell+ Memory T cell
Ability to combine specifically the product of humoralor cell
mediated immune response.Allantigen are not immunogen.
Antigenecityis the ability to combine specifically with secreated
antibodies and surface receptor of T cell
All the molecule which have the properties of immunogenecityalso
have the properitiesof 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 immunogenfrom self-structures of the host):
Upon entry of the immunogeninto 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 immunogenhappen 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 immunogenshould have peptides
different from the peptides of the animal, which is referred to as foreignness of the
immunogen.

Chemical Composition and chemical
complexity
Usuallyproteinsarepotentimmunogens.Polysaccharidesand
somesyntheticorganicpolymers(Forexample,polyvinyl
pyrrolidone)canalsobeimmunogenic.Usuallylipidsarenot
immunogenic.Butfewlipids,(likethemycolicacidof
mycobacteria)areknowntobeimmunogenic.
Moleculeswithcomplexnaturearemoreimmunogenicwhen
comparedtosimplemolecules.Moleculeswithmorethantwoor
threedifferentaminoacidresiduesaremoreimmunogenic
whencomparedtomoleculesmadeofhomopolymersofasingle
aminoacid.Aromaticaminoacidsaremoreimmunogenicthan
nonaromaticaminoacids.Polypeptideswithaminoacid
tyrosinearebetterimmunogens thanpolypeptideswithout
tyrosine.

Molecular size
The most potent immunogensare 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
Theminimumquantityoftheimmunogenrequiredtoinduceimmuneresponsesin
animalsvarieswithrespecttotheanimalandtheimmunogen.Iftinyamountof
immunogenisused,verypoorimmuneresponsesmaybeinduced.Ontheother
hand,iftoolargeamountofimmunogenisused,theanimalmayfailtodevelopany
immuneresponseatall;aconditioncalledtolerance(orspecificunresponsiveness).
Thisphenomenonisalsoreferredtoashigh-dosetolerance.

Genetic Constitution of the Host
Theimmuneresponseofananimaltoaparticular
substancealsodependsonthegeneticconstitutionof
theanimal.Aparticularsubstancemayinduce
immuneresponseinrabbits.Whereas,thesame
substancemaynotinduceimmuneresponseinguinea
pigs.Evenwithinthesamespecies,onestrainmay
respondtoaparticularsubstancewhereasotherstrain
maynotrespondtothatsubstance.

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
Immunesystem=cells,tissues,
andmoleculesthatmediate
resistancetoinfections
Immunology=studyofstructure
andfunctionoftheimmune
system
Immunity=resistanceofahostto
pathogensandtheirtoxiceffects
Immuneresponse=collectiveand
coordinatedresponsetothe
introductionofforeignsubstances
inanindividualmediatedbythe
cellsandmoleculesoftheimmune
system

Functionsof
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
bacterialantigen.
Endogenous adjuvants include histamine, IL-1, tuftsin, transfer factor,
andinterferon.
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
Proposedmechanismsofactionofadjuvants.
Someadjuvantspresumablyformadepotatthesiteofinjection,whichis
associatedwithslowreleaseofantigen.
Otheradjutantsareassociatedwithtransientsecretionofcytokinesand
chemokines.Secretedcytokinesandchemokinesareinvolvedinrecruitmentof
variousimmunecellstotheinjectionsite.Theserecruitedcellssecretecytokines
andchemokines,inturnattractotherimmunecells.Alltheseeventsleadto
formationofalocalimmuno-competentenvironmentattheinjectionsite.
TherecruitedAPCsexpressvariousPRRsbothonthesurface(TLRs,CLRs)and
intracellularly(NLRsandRLRs),whicharerecognizedand/orareactivatedbythe
adjuvants.
ThisleadstomaturationandactivationofrecruitedAPCs.MatureAPCsup-
regulatetheexpressionofMHCandco-stimulatorymolecules.
Theyarealsocharacterizedbyincreasedcapacityforantigenprocessingand
presentation.
MatureAPCsthenmigratetothedraininglymphnodestointeractwithantigen-
specificBorTcellto(8)activatepotentantibodysecretingBcellsand/oreffector
CD8
+
Tcellresponses.

Mode of action of Immunoadjuvents

Immunostimulants
These agents also stimulate or boost either cellular or humoralimmune responses.
Some of them are specific immunostimulants, such as vaccines, which stimulate an
immune responseagainst 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
immunostimulantslike 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, immunosupressionis of two types-
deliberate induced
◼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). Tacrolimusand sirolimus
antibiotics are also used in transplantation and graft rejection.
Nondeliberateimmune suppression.
◼Nondeliberateimmunosuppressioncan 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(Abbasetal.,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