antigens. definitions immunogen immunogen antigen (ag) antigen (ag) hapten hapten epitope or...
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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
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
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