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Antigens last (0).ppt
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- 2. The ‘traditional’definition of antigen is a substance that may stimulate B and/or T cells and react with the products of that response, including immunoglobulin antibodies, and/or specific receptors on T cells. Immunogenicity Is the ability to induce a humoral and/or cell mediated (specific) immune response. All immunogens are antigens, but not all Antigens are immunogens.
- 3. Alloantigen isan antigen present in some members or strains of a species, but not in others. Alloantigen include blood group substances on erythrocytes and histocompatibility antigens present in grafted tissues
- 4. Haptens Haptens, smallorganic molecules that are antigenic but not immunogenic. Carrier: is Chemical coupling of a hapten to a large protein yield an immunogenic hapten-carrier conjugate. It is the basis of allergic responses to drugs such as penicillin.
- 5. Antigenic determinant Epitopesare the immunologically active regions of an immunogens that bind to antigen-specific membrane receptors on lymphocytes or to secreted antibodies.
- 6. ANTIGENIC DETERMINANTS: A. Determinantsrecognized by B cells are small and are limited to approximately 4-8 residues. (amino acids and or sugars). are either: primary sequence residues))Linear Conformational(secondary, tertiary or quaternary) B. Determinants recognized by T cells: are limited to approximately 8-15 residues Only primary sequence residues
- 7. Ab1 Ab2 hidden/revealed determinant denaturation new/neoantigen determinant conformational determinant cleveage conformational/linear determinant TYPES (STRUCTURE) OFANTIGEN DETERMINANTS surface/accessible determinants linear determinant conformational determinant (TCR, BCR, Ig) (BCR, Ig)
- 8. Epitopes • In proteinantigens epitopes can be defined in terms of: – Amino acid composition – Protein location – Length (5-15 amino acids) • epitopes: • Immunodominant – Epitopes bound by a greater proportion of antibodies than others in a normal in vivo immune response – Also known as Major Antigenic Sites • Sequestered • Epitopes can be divided into 2 classes: – Discontinuous epitopes – Continuous (linear) epitopes
- 9. Antigenic valence: Total numberof determinant which can be combined with Ab.
- 10. Types of PeptideEpitope LinearB cell Epitope Antibody or “B cell” Epitope Conformational Non-Conformational Class II MHCs Professional Antigen Presenting cells Foreign proteins 8-20 amino acids Class I MHCs all cells Foreign and self proteins 8-10 amino acids T cell Epitope Epitope
- 11. B cells canrecognize linear or conformational epitopes on cell surfaces, of proteins, of carbohydrates or of lipids. The B cell antigen receptor is a form of membrane Ig. T cells recognize linear peptide fragments bound to MHC class I or class II molecules. T cells and B cells use Distinct Antigen Receptors to Recognize Fundamentally Different Forms of Antigen
- 12. Properties of Epitopes •They occur on the surface of the protein and are more flexible than the rest of the protein. • They have high degree of exposure to the solvent. • The amino acids making the epitope are usually charged and hydrophilic.
- 13. Antigen-specific membrane receptors Membrane molecules or receptors that responsible for antigen recognition by the immune system are: 1. Membrane-bound antibodies on B cells 2. T-cell receptors 3. Class I MHC molecules 4. Class II MHC molecules
- 14. T cell vs.B cell Epitopes
- 15. Types of Antigens •T-cell independent antigens-Does not require T cell involvement; polysaccharides • T-cell dependent antigens-Requires T cell involvement; proteins
- 16. Types of Antigens T-independent •Polysaccharides • Properties – Polymeric structure – Polyclonal B cell activation • Yes -Type 1 (TI-1) • No - Type 2 (TI-2) – Resistance to degradation • Examples – Pneumococcal polysaccharide, lipopolysaccharide – Flagella
- 17. Types of Antigens T-dependent •Proteins • Structure • Examples – Microbial proteins – Non-self or Altered- self proteins
- 18. Chemical nature oAntigens Lipids Proteins Carbohydrates Nucleic Acids
- 19. Substances that actas antigens: Microbial structures: Such as bacterial and fungal cell walls, protozoan cell membranes, bacterial and fungal capsules, microbial flagella, bacterial pili, viral capsids, viral envelope- associated glycoproteins , etc. microbial toxins. Allergens The body's own cells that the body fails to recognize as "normal self” such as cancer cells, infected cells, cells involved in autoimmune diseases.
- 20. Factors influencing immuneresponse of Ag Antigen Properties 1.Foreigness: The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. 2.Chemical properties of Ag Chemical nature Proteins>Polysaccharides >Nucleic Acids >Lipids 0
- 21. Factors influencing immuneresponse of Ag Antigen Properties 3.Molecule weight (size) reasonable large molecule( >10.0 kd) has good immuogenecity. – more stationary – more surface structure for lymphocyte to recognize
- 22. Factors influencing immuneresponse of Ag Antigen Properties 4. Complexity of Ag structure ring > linear aromatic ring
- 23. 5. Conformation andaccessibility 6. Physical states : Polymer > monomer Particulate > Soluble Denatured > Native 7.Degradability Antigens that are easily phagocytosed are generally more immunogenic. Factors influencing immune response of Ag Antigen Properties
- 24. Factors influencing immuneresponse of Ag Body Factors Genetics, Species: Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non responders). MHC Individual :Age, health, etc. Age can also influence immunogenicity, usually the very young and the very old have a diminished ability to mount and immune response in response to an immunogen.
- 25. Factors influencing immuneresponse of Ag Method of Administration 1. Genotype Influences, MHC, T and B cell receptors, etc… 2.Immunogen dosage – Too small – no response – Too large – tolerance – Boosters – repeated dosages • 3. Routes of dministration
- 26. Biological Influences onImmunogenicity • Adjuvants-Enhance immunogenicity – Potential mechanism • Ag persistence • Cell signaling or cytokine effect • Induction of inflammation • Lymphocyte stimulation • Change the chemical and physical charactes of Ag • Improves the Ag process and presentation ability of macrophages • stimulates proliferation of lymphocytes Types • Biological adjuvant:BCG,LPS • Synthesized adjuvant Freund’s incomplete adjuvant Freund’s complete adjuvant • Chemical adjuvant : Alum
- 27. 1. Binding anduptake of antigen – depends on the physical state of the antigen and the cell type involved. 2. Antigen processing – MHC class I processing pathway – MHC class II processing pathway 3. Antigen presentation Susceptibility to Antigen Processing & Presentation
- 28. Cross reaction • Reactionbetween the same Ab and different Ag with same similar determinants. • Mechanism of cross reaction: - Common Ag determinant - Similar structure of Ag determinant • Significance: Because there are some common antigen determinants between different microbes, so the antiserum against one kind of Ag can also react with another Ag and couse a cross reaction .
- 29. Antigen Presenting Cells(APCs) A group of immune cells, whose role is to take up, process and present antigenic peptides to T cells. First internalize antigen, either by Phagocytosis or by endocytosis, and then display a part of that antigen on their membrane bound to a class II MHC molecule. Except for the B cell, APCs are non specific
- 30. • Professional APC –Macrophages, dendritic cells, and B cells, which can express MHC class II molecules. • Non-professional APC – Other cell type capable of expressing MHC class II molecules eg. Endothelial cells, EC Fibroblasts Activated T cell
- 31. Dendritic cell，DC • highlybranched morphology • can active naive T cells • markers
- 32. 1) Markers – CD1a,CD11c, CD83 – Pathogen receptor, FcR – MHC II – co-stimulating factors (CD80,CD86) – Adhesion molecular CD40 – CD54 (ICAM-1), etc. • secreting cytokines – IL1, IL-6, IL-12, TNF-a, IFN-a, chemokines
- 33. 2) Source, distributionand classification • Source DC are bone marrow-derived – Myeloid DC – Lymphoid DC
- 34. • Distribution andclassification DCs are found in many organs throughout the body – DC in lymphoid tissue • Interdigitating cell, IDC • Follicular DC, FDC • thymic dendritic cell, TDC – DC not in lymphoid tissue • Langerhans cells • Interstitial DC – DC in body fluid • Veiled cells • Peripheral blood DC
- 35. Markers of Bcells
- 36. Antigen-presenting cells APC Macrophage Tcell via MHC antigen Dendritic cells T cell via MHC antigen B cells T cell via antigen captrue by surface antibody and MHC antigen Activated T cells T cell via MHC antigen
- 37. EXOGENOUS ANTIGENS Antigenthat enters the body of the organism from the outside, e.g. through inhalation, ingestion, or injection. The immune system's response to exogenous antigens is often subclinical. By endocytosis or phagocytosis, Endocytosis is a process by which cells absorb molecules (such as proteins) by engulfing them.
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- 41. Two antigen-processing pathways MHCclass I MHC class II Major antigen sources endogenous antigen exogenous antigen Processing machinery proteasome lysosomal enzymes Cell type where active all nucleated cells professional APCs Site of antigen- MHC binding endoplasmic reticulum lysosome and endosome MHC utilized MHC class I MHC class II Presents to CD8+ T cell (Tc) CD4+ T cells (Th)
- 42. Endogenous Antigen • Antigenthat is produced from within the cell as part of normal cell metabolism or when the cell is infected by bacteria or viruses. • Endogenous antigens include xenogenic (heterologous), autologous and idiotypic or allogenic (homologous) antigens.
- 43.
- 44. Autoantigen An autoantigenis usually a normal protein or complex of proteins (and sometimes DNA or RNA) . Is an endogenous antigen that stimulates the production of autoantibodies.
- 45. Tumor antigens Tumorantigen is an antigenic substance produced in tumor cells. Classification of tumor antigens: Tumor-Specific Antigens (TSA), which are present only on tumor cells and not on any other cell . Tumor-Associated Antigens (TAA), which are present on some tumor cells and also some normal cells.
- 46. Superantigens Superantigens (SAgs)are a substance (as an enterotoxin) that acts as an antigen capable of stimulating much larger numbers of T cells than an ordinary antigen. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune syste Example: Staphylococcal enterotoxins (food poisoning), Staphylococcal toxic shock toxin (toxic shock syndrome), Staphylococcal exfoliating toxins (scalded skin syndrome) and Streptococcal pyrogenic exotoxins (shock).
- 47. Superantigens Conventional Antigen Monoclonal/ OligoclonalT cell response 1:104 - 1:105 Superantigen Polyclonal T cell response 1:4 - 1:10 Definition