Antigens and immunogens immunogenecity

Antigens immunogens immunogenicity

1. Immunogens & Antigens HAFIZ M WASEEM UE LAHORE

2. Immunogenicity & Antigenicity Immunogenicity Ability to induce humoral and/or cell-mediated immune response Immunogen is substance that induces response Antigenicity Ability to combine specifically with Abs or T-cell receptor/MHC Not all antigens are immunogenic Haptens

3. Immunogenicity & Antigenicity

4. Immunogenicity & Antigenicity

5. Properties of an Immunogen Foreignness Molecular size Chemical composition and complexity Ability to be processed and presented on MHC

6. Foreignness Ability to tolerate self antigens arises during lymphocyte development, during which immature lymphocytes are exposed to self-components Lymphocytes that do not bind to self antigens are allowed to further develop Therefore they will later only recognize non-self antigens Bovine serum albumin (BSA) is not immunogenic when injected into cow but is immunogenic when injected into chicken Some macromolecules are highly conserved throughout evolution and display little immunogenicity ( Cytochrome c, collagen)

7. Molecular Size Active (good) immunogens > 100,000 Daltons Poor immunogens < 5,000-10,000 Daltons

8. Chemical composition & complexity Synthetic homopolymers (polymers composed of a single amino acid or sugar) tend to lack immunogenicity regardless of their size Copolymers composed of different amino acids or sugars are usually more immunogenic Protein organization—primary, secondary, tertiary, and quaternary all contribute to the structural complexity of a protein and hence affect its immunogenicity Lipids are haptens and need to be conjugated with carrier to produce antibodies Important for assays for detection of some steroids, vitamins

9. Antigen processing Large, insoluble macromolecules generally are more immunogenic than small, soluble ones because the larger molecules are more readily phagocytosed and processed Macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens . Degradative enzymes within antigen-presenting cells can degrade only proteins containing L-amino acids, polymers of D-amino acids cannot be processed and thus are poor immunogens .

10. Antigen presenting cells (APC’S) Internalize antigens by phagocytosis or pinocytosis and process the antigens Display part of the antigens on their membrane along with MHC complex to T cells Types of APC’S (Dentritc cells, Macrophages and B cells)

11. The Biological system & Immunogenecity Host Genetic make-up Immunogen dosage & route of administration Use of agents ( adjuvants ) to enhance immunogenicity

12. Host Genotype Genetic variability in all of these genes affects the immunogenicity of a given macromolecule in different animals Genes of MHC Genes coding for specific antibodies Genes for BCR & TCR Immunoregulatory genes

13. Immunogen dosage and route of administration Too low or high of dosage can induce tolerance Single dose is often not enough – booster is needed Route Intravenous (iv) Intradermal (id) Subcutaneous (sc) Intramuscular ( im ) Intraperitoneal ( ip ) Antigen administered iv would travel to spleen; administered sc would travel to lymph nodes

14. Adjuvants Antigen persistence is prolonged Co-stimulatory signals are enhanced Local inflammation is increased The nonspecific proliferation of lymphocytes is stimulated Aluminum potassium sulfate (alum) prolongs the persistence of antigen

15. Antigens Antigen  is a substances usually protein in nature and sometimes polysaccharide, that generates a specific immune response and induces the formation of a specific antibody or specially sensitized T cells or both. Epitope  is immunologically active regions of an antigen that binds to antigen-specific membrane receptors on lymphocytes or to secreted antibodies. It is also called  antigenic determinants.

16. Chemical nature of Antigens Proteins The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens . Polysaccharides   Pure polysaccharides and lipopolysaccharides are good immunogens . Nucleic Acids Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins. Lipids In general lipids are non-immunogenic, although they may be haptens .

17. Types of Antigens Exogenous antigens These antigens enters the body or system and start circulating in the body fluids and trapped by the APCs (Antigen processing cells such as macrophages, dendritic cells, etc.) The uptakes of these exogenous antigens by APCs are mainly mediated by the phagocytosis Examples: bacteria, viruses, fungi etc Some antigens start out as exogenontigens , and later become endogenous (for example, intracellular viruses)

18. Endogenous antigens These are body’s own cells or sub fragments or compounds or the antigenic products that are produced. The endogenous antigens are processed by the macrophages which are later accepted by the cytotoxic T – cells. Endogenous antigens include xenogenic ( heterologous ), autologous and idiotypic or allogenic (homologous) antigens. Examples: Blood group antigens, HLA ( Histocompatibility Leukocyte antigens), etc.

19. Autoantigens An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease These antigens should not be, under normal conditions, the target of the immune system, but, due mainly to genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost in these patients. Examples: Nucleoproteins, Nucleic acids, etc.

20. Complete Antigen or Immunogen Posses antigenic properties denovo , i.e. these are able to generate an immune response by themselves. High molecular weight (more than 10,000) May be proteins or polysaccharides

21. Incomplete Antigen or Hapten These are the foreign substance, usually non-protein substances Unable to induce an immune response by itself, they require carrier molecule to act as a complete antigen. The carrier molecule is a non-antigenic component and helps in provoking the immune response. Example: Serum Protein such as Albumin or Globulin. Low Molecular Weight (Less than 10,000) Haptens can react specifically with its corresponding antibody. Examples: Capsular polysaccharide of pneumococcus , polysaccharide “C” of beta haemolytic streptococci, cardiolipin antigens, etc.