Antigens.pdf

Antigens George Nadăș,Professor of Immunology, [email protected] Antigens Antigens: Triggers of adaptive immunity The antigen (Ag) is any chemical non-self complex, which after invading the body triggers an immune response. An antigen (from antibody generator) - originally defined as any molecule...

Antigens George Nadăș,Professor of Immunology, [email protected] Antigens Antigens: Triggers of adaptive immunity The antigen (Ag) is any chemical non-self complex, which after invading the body triggers an immune response. An antigen (from antibody generator) - originally defined as any molecule that binds specifically to an antibody. immunogenicity - all molecules – the ability to stimulate immune responses antigenicity – the ability to form complexes with the products of the immune system Antigens according to their localization respect to the body cells: JehiiaCellsDendritic macrophages mastcells - outside the body cells - exogenous - inside the body’s own cells - endogenous 2 APC Antigenpresentingcell What makes a good antigen? MHCI Allnucleatedcells Antigens HighlydenceonAPCs 1. Foreignness The immune system normally discriminates between self and non-self such that only foreign are molecules are immunogenic 2. Size There is not absolute size above which a substance will be immunogenic. However, in general, the larger the molecule is, the more immunogenic it is likely to be – in order to stimulate the immune system, the size should exced 1000 Da 3. Chemical composition the more complex the substance is chemically, the more immunogenic it will be 3 Antigens What makes a good antigen? 4. Physical form particulate antigens are more immunogenic than soluble ones and denatured antigens are more immunogenic than the native form Particulate soluble Denatured native 5. Degradability Antigens that are easily phagocytosed are generally more immunogenic 4 Antigens The conditions for a good antigen chemical important most erements saccharides ii.ieii iijipi ijinpens Ñay Pitkin's A. 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. B. Polysaccharides Pure polysaccharides and lipopolysaccharides are good immunogens. C. Nucleic Acids Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins. D. Lipids In general lipids are non-immunogenic, although they may be haptens incomplete a ntigens 5 Antigens The conditions for a good antigen not all foreign molecules can stimulate an immune response stainless steel bone pins and plastic heart valves are implanted without triggering an immune response, because they cannot be degraded and processed by the cells the immunogenicity of a molecule also depends on the degree of foreignness. The greater the difference in structure between a foreign antigen and an animal’s own antigen, the greater will be the intensity of the immune response 6 Antigens Structure of the antigen molecule Schematically, an immunogenic substance consists of a carrier group, conferring the size, and one or more determinant or epitopes, responsible for Example Eigena the specificity a b Carrier Determinants (epitopes) 7 Antigens Structure of the antigen molecule Carrier - usually represented by a macromolecular protein acting as a colloidal support with no specific activity – confers the size, making it detectable by the immune cells Determinants (epitopes) - the distinct molecular surface features of an antigen capable of being bound specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope 8 Antigens The complexity of the antigen molecule Complete antigens are those antigens that have both the colloidal support (carrier) and specific groups (epitopes)Detectable abletostimulateresponses This type determine the formation of antibodies and react specifically with them in vitro Most of the natural antigens are complete antigens Carrier Epitopes 9 Antigens Haptens – incomplete antigens substances that are non-immunogenic but which can react with the products of a specific immune response Haptens (in Greek haptein = to fasten) are small molecules which could never induce an immune response when administered by themselves but which can when bind to a carrier molecule Haptens have the property of antigenicity but lack immunogenicity unlessattached tolargecarrier Many drug allergies occur because drug molecules, although small, can bind to normal body proteins and so act as haptens 10 Antigens Haptens – incomplete antigens Haptens Carrier 11 Antigens Types of antigens 1. Natural antigens – are represented by various natural constituents seen in animals, plants and microorganisms. May be soluble substances (proteins, polysaccharides, nucleic acids) or other insoluble particles, corpuscular (cells, bacteria, viruses, parasites) 2. Artificial antigens consist of natural macromolecules acting as a carrier, which binds various haptens in artificial conditions 3. Synthetic antigens are produced in laboratory conditions by different methods of synthesis. Are the artificially synthesized polypeptides by polymerization of derivatives of L or D amino acids 12 Antigens Types of antigens A. T-independent antigens T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help In general, polysaccharides are T-independent antigens The responses to these antigens differ from the responses to other antigens 13 Antigens Types of antigens Properties of T-independent antigens: 1. Polymeric structure These antigens are characterized by the same antigenic determinant repeated many times 2. Polyclonal activation of B cells Many of these antigens can activate B cell clones specific for other antigens (polyclonal activation) 3. Resistance to degradation T-independent antigens are generally more resistant to degradation and thus they persist for longer periods of time and continue to stimulate the immune system 14 Diversity of epitopesfoundonsurface Antigens Types of antigens B. T-dependent Antigens T-dependent antigens are characterized by a few copies of many different antigenic determinants T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells Proteins are T-dependent antigens Structurally these antigens are characterized by a few copies of many different antigenic determinants 15 Antigens Microbial antigens – bacterial antigens Somatic antigens “O“ - extracted from the bacteria cell wall The cell wall of Gram-positive organisms is largely composed of peptidoglycan (chains of alternating N-acetyl glucosamine and N-acetyl muramic acid cross-linked by short peptide side chains) Gram-positive cell walls also contain lipoteichoic acids that are involved in the transport of ions across the cell wall 16 Antigens Microbial antigens – bacterial antigens Somatic antigens “O“ - extracted from the bacteria cell wall The cell wall in Gram-negative organisms, in contrast, consists of a thin layer of peptidoglycan covered by an outer membrane consisting of a lipopolysaccharide Most of the antigenicity of Gram-negative bacteria is associated with the lipopolysaccharide (LPS) This consists of an oligosaccharide attached to a lipid (lipid A) and to a series of repeating trisaccharides The structure of these trisaccharides determines the antigenicity of the organism 17 Antigens Microbial antigens – bacterial antigens Flagellar antigens “H“ - extracted from the bacterial flagella The chemical nature is pure protein – flagellin H antigens have been well studied in bacteria from the family Enterobacteriaceae, especially those of the genus Salmonella and Escherichia having an important role in serological identification (typing) of these bacteria 18 Antigens Microbial antigens – bacterial antigens Fimbrial antigens “F“ - extracted from the bacterial fimbriae and pili The chemical nature is pure protein – pillin used toattaton tosurfaces F antigens are short projections that cover the surfaces of some Gram-negative bacteria used toremain attained during mating Pili (sex pili) bind bacteria together – important in conjugation and movement Fimbriae bind bacteria to cell surfaces - E. coli antigens -F4 (K88) in piglets and F5 (K99) in calves 19 Antigens Microbial antigens – bacterial antigens Capsular antigens “K“ - extracted from the bacterial capsules The chemical nature is pure protein – Bacillus anthracis, while for all the other encapsulated bacteria is polysaccharidic The capsules protect bacteria against phagocytosis and intracellular destruction, whwreas anticapsular antibodies can overcome the effects of the capsule and protect an infected animal They are also important to prevent desiccation 20 Antigens Microbial antigens – viral antigens Viruses are very small structures that grow only inside living cell as “obligate” intracellular parasites Structure – nucleic acid core covered by a protein layer = capsid (good antigens) – immunogenic Some viruses – surrounded by an envelope containing lipoproteins and glycoproteins Endogenous antigens - presented at the surface by MHC I 21 Antigens Nonmicrobial antigens Invading microorganisms are not the only source of foreign material entering the body Food may contain foreign molecules which under some circumstances may trigger an immune response and cause an allergic reactions The cytoplasmic membrane of every mammalian cell consists of a mosaic of protein molecules – reactions to organ grafts or therapeutic procedures Red blood cells and leucocytes possess hundreds of different protein molecules on their cytoplasmic membrane. These proteins are good antigens and cause the elimination of transfused red blood cells 22 Antigens Autoantigens In some situations an animal may mount immune responses against normal body components = autoimmune responses – induced by autoantigens Hormones – tyroglobulin Structural components – basement membranes Complex lipids – myelin Intracellular components – mitochondrial proteins, nucleic acids or nucleoproteins Cell surface proteins – hormone receptors 23 Antigens Superantigens is once Superantigens activate a large fraction of T cells in contrast to conventional T-dependent antigens 24 Antigens Superantigens When the immune system encounters a conventional T-dependent antigen, only a small fraction (1 in 104 -105) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response) However, there are some antigens which polyclonally activate a large fraction of the T cells (up to 25%) = superantigens – induce a cytokine storm Examples of superantigens include: Staphylococcal enterotoxins (food poisoning) Staphylococcal toxic shock toxin (toxic shock syndrome) Staphylococcal exfoliating toxins (scalded skin syndrome) and superantigens associated with viruses and other microorganisms 25 Antigens ©2024 Ross University School of Veterinary Medicine. 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