Antigens. Definitions Immunogen Immunogen Antigen (Ag) Antigen (Ag) Hapten Hapten Epitope or Antigenic Determinant Epitope or Antigenic Determinant Antibody.

AntigensAntigens

DefinitionsDefinitions

ImmunogenImmunogen Antigen (Ag)Antigen (Ag) HaptenHapten Epitope or Antigenic DeterminantEpitope or Antigenic Determinant Antibody (Ab) Antibody (Ab)

Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityContribution of the ImmunogenContribution of the Immunogen

ForeignnessForeignnessSizeSize

Conformational determinants

Sequence determinants

• Chemical Composition– Primary Structure– Secondary Structure– Tertiary Structure– Quarternary Structure

Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityContribution of the ImmunogenContribution of the Immunogen

ForeignessForeigness SizeSize Chemical CompositionChemical Composition Physical FormPhysical Form

Particulate > SolubleParticulate > Soluble Denatured > NativeDenatured > Native

Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityContribution of the ImmunogenContribution of the Immunogen

ForeignessForeigness SizeSize Chemical CompositionChemical Composition Physical FormPhysical Form DegradabilityDegradability

Ag processing by Ag Presenting Cells (APC)Ag processing by Ag Presenting Cells (APC)

Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityContribution of the Biological SystemContribution of the Biological System

GeneticsGenetics SpeciesSpecies IndividualIndividual

Responders vs Non-respondersResponders vs Non-responders

AgeAge

Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityMethod of AdministrationMethod of Administration

DoseDose RouteRoute

Subcutaneous > Intravenous > IntragastricSubcutaneous > Intravenous > Intragastric AdjuvantAdjuvant

Substances that enhance an immune response to an Substances that enhance an immune response to an AgAg

Chemical Nature of ImmunogensChemical Nature of Immunogens

ProteinsProteins PolysaccharidesPolysaccharides Nucleic AcidsNucleic Acids LipidsLipids

Some glycolipids and phospholipids can be Some glycolipids and phospholipids can be immunogenic for T cells and ellicit a cell mediated immunogenic for T cells and ellicit a cell mediated immune responseimmune response

Types of AntigensTypes of AntigensT-independentT-independent

PolysaccharidesPolysaccharides• Properties

– Polymeric structure

– Polyclonal B cell activation

Resistance to degradation

• Examples– Pneumococcal polysaccharide, lipopolysaccharide

Types of AntigensTypes of AntigensT-dependentT-dependent

ProteinsProteins

• Structure• Examples

– Microbial proteins

– Non-self or Altered-self proteins

Hapten-carrier conjugatesHapten-carrier conjugates

DefinitionDefinition

Native determinants

Haptenic determinants• Structure

– native determinants

– haptenic determinants

Antigenic DeterminantsAntigenic Determinants Recognized by B cells and Ab Recognized by B cells and Ab

CompositionComposition Proteins, polysaccharides, nucleic acids, Proteins, polysaccharides, nucleic acids,

haptenshaptens Sequence (linear) determinantsSequence (linear) determinants Conformational determinantsConformational determinants

SizeSize

Antigenic DeterminantsAntigenic Determinants Recognized by B cells and Ab Recognized by B cells and Ab

CompositionComposition SizeSize NumberNumber

Limited Limited (immunodominant (immunodominant epitopes)epitopes)

Located on the Located on the external surfaces of external surfaces of the Agthe Ag

Fe

Antigenic DeterminantsAntigenic DeterminantsRecognized by T cellsRecognized by T cells

CompositionComposition Proteins (some lipids)Proteins (some lipids) Sequence determinantsSequence determinants

ProcessedProcessed MHC presentation (lipid presentation by MHC-like MHC presentation (lipid presentation by MHC-like

CD1)CD1)

SizeSize 8 -15 residues8 -15 residues

NumberNumber Limited to those that can bind to MHCLimited to those that can bind to MHC

EpitopesEpitopes

اپی توپ های خطیاپی توپ های خطی Linear Linear determinantsdeterminants

اپی توپ های فضایی یا نا اپی توپ های فضایی یا نا

conformationalconformational پیوستهپیوسته

Direct effectsDirect effects SAg stimulation of antigen presenting cells and T-cells elicits SAg stimulation of antigen presenting cells and T-cells elicits

a response that is mainly inflammatory, focused on the action a response that is mainly inflammatory, focused on the action of Th1 of Th1 T-helper cells. Some of the major products are cells. Some of the major products are IL-1, , IL-2, , IL-6, , TNF-α, gamma interferon (IFN-γ), , gamma interferon (IFN-γ),

Deletion or Deletion or anergy of activated T-cells follows infection. This of activated T-cells follows infection. This results from production of results from production of IL-10 from prolonged exposure to from prolonged exposure to the toxin. IL-10 downregulates production of IL-2, MHC the toxin. IL-10 downregulates production of IL-2, MHC Class II, and costimulatory molecules on the surface of APCsClass II, and costimulatory molecules on the surface of APCs

IFN-α is another product of prolong SAg exposure. This IFN-α is another product of prolong SAg exposure. This cytokine is closely linked with induction of autoimmunitycytokine is closely linked with induction of autoimmunity

Indirect effectsIndirect effects

*their mitogenic activity*their mitogenic activity* SAgs are able to cause symptoms that are * SAgs are able to cause symptoms that are

characteristic of infectioncharacteristic of infectionOne such effect is One such effect is emesis *SAgs are able to stimulate recruitment of *SAgs are able to stimulate recruitment of

neutrophils to the site of infection to the site of infection *ability of SAgs to augment the effects of *ability of SAgs to augment the effects of

endotoxins in the body in the body

treatmenttreatment

eliminate the microbeliminate the microbantibodies

Synthetic antibodiesSynthetic antibodies ImmunosuppressantsImmunosuppressants

Diseases associated with superantigen productionDiseases associated with superantigen production Toxic Shock Syndrome Toxic Shock Syndrome Kawasaki Disease Kawasaki Disease Eczema Eczema Guttate psoriasis Guttate psoriasis Rheumatoid arthritis Rheumatoid arthritis Diabetes mellitus Diabetes mellitus Scarlet feverScarlet fever

Endogenous SAgsEndogenous SAgs

rabies,rabies, cytomegaloviruscytomegalovirus HIVHIV Epstein-Barr virusEpstein-Barr virus

SuperantigensSuperantigens

Conventional Antigen

Monoclonal/Oligoclonal T cell response

1:104 - 1:105

Superantigen

Polyclonal T cell response

1:4 - 1:10

• Definition

Protein electrophoresisProtein electrophoresis

Ab structureAb structure

Ab structureAb structure

AntibodyAntibody

Ab structureAb structure

Ab IsotypesAb Isotypes

IgAIgA

immunotoxinimmunotoxin

Humanized AbHumanized Ab

Humanized AbHumanized Ab

Half-life of AntibodiesHalf-life of Antibodies

IgE(2 days)IgE(2 days) IgA(3days)IgA(3days) IgM(4days)IgM(4days) IgG(21-28)IgG(21-28)

Monoclonal antibodies Monoclonal antibodies applicationapplication

Identification of phenotypic markersIdentification of phenotypic markers ImmunodiagnosisImmunodiagnosis Tumor detectionTumor detection TherapyTherapy

all autoimmune conditions all autoimmune conditions

Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation

Infectious diseasesInfectious diseases

Neutralization of animal toxinsNeutralization of animal toxins