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

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Presentation on theme: "Antigens. Definitions Immunogen Immunogen Antigen (Ag) Antigen (Ag) Hapten Hapten Epitope or Antigenic Determinant Epitope or Antigenic Determinant Antibody."— Presentation transcript:

1 Antigens

2 Definitions Immunogen Immunogen Antigen (Ag) Antigen (Ag) Hapten Hapten Epitope or Antigenic Determinant Epitope or Antigenic Determinant Antibody (Ab) Antibody (Ab)

3 Factors Influencing Immunogenicity Contribution of the Immunogen Foreignness Foreignness Size Size Conformational determinants Sequence determinants Chemical Composition –Primary Structure –Secondary Structure –Tertiary Structure –Quarternary Structure

4 Factors Influencing Immunogenicity Contribution of the Immunogen Foreigness Foreigness Size Size Chemical Composition Chemical Composition Physical Form Physical Form Particulate > Soluble Particulate > Soluble Denatured > Native Denatured > Native

5 Factors Influencing Immunogenicity Contribution of the Immunogen Foreigness Foreigness Size Size Chemical Composition Chemical Composition Physical Form Physical Form Degradability Degradability Ag processing by Ag Presenting Cells (APC) Ag processing by Ag Presenting Cells (APC)

6 Factors Influencing Immunogenicity Contribution of the Biological System Genetics Genetics Species Species Individual Individual Responders vs Non-responders Responders vs Non-responders Age Age

7 Factors Influencing Immunogenicity Method of Administration Dose Dose Route Route Subcutaneous > Intravenous > Intragastric Subcutaneous > Intravenous > Intragastric Adjuvant Adjuvant Substances that enhance an immune response to an Ag Substances that enhance an immune response to an Ag

8 Chemical Nature of Immunogens Proteins Proteins Polysaccharides Polysaccharides Nucleic Acids Nucleic Acids Lipids Lipids Some glycolipids and phospholipids can be immunogenic for T cells and ellicit a cell mediated immune response Some glycolipids and phospholipids can be immunogenic for T cells and ellicit a cell mediated immune response

9 Types of Antigens T-independent Polysaccharides Polysaccharides Properties –Polymeric structure –Polyclonal B cell activation Resistance to degradation Examples –Pneumococcal polysaccharide, lipopolysaccharide

10 Types of Antigens T-dependent Proteins Proteins Structure Examples –Microbial proteins –Non-self or Altered-self proteins

11 Hapten-carrier conjugates Definition Definition Native determinants Haptenic determinants Structure –native determinants –haptenic determinants

12 Antigenic Determinants Recognized by B cells and Ab Composition Composition Proteins, polysaccharides, nucleic acids, haptens Proteins, polysaccharides, nucleic acids, haptens Sequence (linear) determinants Sequence (linear) determinants Conformational determinants Conformational determinants Size Size

13 Antigenic Determinants Recognized by B cells and Ab Composition Composition Size Size Number Number Limited (immunodominant epitopes) Limited (immunodominant epitopes) Located on the external surfaces of the Ag Located on the external surfaces of the Ag Fe

14 Antigenic Determinants Recognized by T cells Composition Composition Proteins (some lipids) Proteins (some lipids) Sequence determinants Sequence determinants Processed Processed MHC presentation (lipid presentation by MHC-like CD1) MHC presentation (lipid presentation by MHC-like CD1) Size Size 8 -15 residues 8 -15 residues Number Number Limited to those that can bind to MHC Limited to those that can bind to MHC

15 Epitopes اپی توپ های خطی Linear determinants اپی توپ های خطی Linear determinants اپی توپ های فضایی یا نا پیوسته conformational اپی توپ های فضایی یا نا پیوسته conformational

16 Direct effects SAg stimulation of antigen presenting cells and T-cells elicits a response that is mainly inflammatory, focused on the action of Th1 T-helper cells. Some of the major products are IL-1, IL-2, IL-6, TNF-α, gamma interferon (IFN-γ), SAg stimulation of antigen presenting cells and T-cells elicits a response that is mainly inflammatory, focused on the action of Th1 T-helper cells. Some of the major products are IL-1, IL-2, IL-6, TNF-α, gamma interferon (IFN-γ),T-helperIL-1 IL-2IL-6TNF-αT-helperIL-1 IL-2IL-6TNF-α Deletion or anergy of activated T-cells follows infection. This results from production of IL-10 from prolonged exposure to the toxin. IL-10 downregulates production of IL-2, MHC Class II, and costimulatory molecules on the surface of APCs Deletion or anergy of activated T-cells follows infection. This results from production of IL-10 from prolonged exposure to the toxin. IL-10 downregulates production of IL-2, MHC Class II, and costimulatory molecules on the surface of APCsanergyIL-10anergyIL-10 IFN-α is another product of prolong SAg exposure. This cytokine is closely linked with induction of autoimmunity IFN-α is another product of prolong SAg exposure. This cytokine is closely linked with induction of autoimmunity

17 Indirect effects *their mitogenic activity * SAgs are able to cause symptoms that are characteristic of infection One such effect is emesis emesis *SAgs are able to stimulate recruitment of neutrophils to the site of infection neutrophils *ability of SAgs to augment the effects of endotoxins in the body endotoxins

18 treatment eliminate the microb eliminate the microb antibodies antibodies antibodies Synthetic antibodies Synthetic antibodies Immunosuppressants Immunosuppressants Immunosuppressants

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

20 Endogenous SAgs rabies, rabies, rabies cytomegalovirus cytomegaloviruscytomegalovirus HIV HIV HIV Epstein-Barr virus Epstein-Barr virus Epstein-Barr virus Epstein-Barr virus

21 Superantigens Conventional Antigen Monoclonal/Oligoclonal T cell response 1:10 4 - 1:10 5 Superantigen Polyclonal T cell response 1:4 - 1:10 Definition

22 Protein electrophoresis

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25 Ab structure

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27 Antibody

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32 Ab Isotypes

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35 IgA

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38 immunotoxin

39 Humanized Ab

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41 Half-life of Antibodies IgE(2 days) IgE(2 days) IgA(3days) IgA(3days) IgM(4days) IgM(4days) IgG(21-28) IgG(21-28)

42 Monoclonal antibodies application Identification of phenotypic markers Identification of phenotypic markers Immunodiagnosis Immunodiagnosis Tumor detection Tumor detection Therapy Therapy all autoimmune conditions Hematopoietic stem cell transplantation Infectious diseases Neutralization of animal toxins


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