Chap 1

• Immunology


  The study of the immune system and its responses to the invading pathogens

  
• Immune system


  The collection of cells, tissues and molecules that mediate resistance to infections

  
• Immune response


  The coordinated reaction of these cells and molecules to the infectious molecules

  
• Immunity


  State of protection against foreign organisms or substances (antigens) (innate & adaptive)

  
• Serology


  The science of antigen-antibody reactions of the body using a serum specimen

  
• Purpose of serology


  • To diagnose infectious diseases by observing the presence of an immune antibody in the patient, resulted from infection or entry by the pathogen into the body

  
• Applications of immunology


  • Diagnosis of diseases
  • Understanding of diseases process (pathogenesis of infections, autoimmune)
  • Prevention and treatment of diseases (active & passive immunisation)
  • Blood transfusion serology (blood grouping, typing, crossmatching)
  • Tissue typing and histocompatibility testing (organ transplantation)
  • Forensic medicine (paternity testing, stain identification)
• Types of immunity


  • Innate immunity (first & second line of defense; include barriers, phagocytic cells & molecules)
  • Adaptive immunity (more effective & defense against infections) - cell-mediated, humoral

  
• Innate immunity


  • Also called non-specific, natural, native immunity
  • Present in an individual from birth
  • Appeared in all multicell organisms
  • The first and second line of defense (induction of specific immune response)
  • Always present in healthy individuals (prepared to block the entry of microbes)
  • The response is fast (takes few hours) which rapidly eliminate microbes that do succeed in entering host tissue

  
• Adaptive immunity


  • Also called specific, acquired immunity
  • Appeared in vertebrates
  • Adaptive immunity is the third line of defense after innate immunity

  
• Antigen


  Any agent that binds to components of the immune response: lymphocytes and their receptors (antibodies and the T cell receptor)

  
• Immunogen


  Any substance that induces a specific immune response mediated by either T cell or B cell or both

  
• Criteria for immunogenicity


  • Foreignness
  • Chemical complexity
  • High molecular weight
  • Dosage and route of administration
  • Genetic constitution of the host

  
• Foreignness


  Molecules that are recognised as "self" by the immune system are not immunogenic. Normally the body is tolerant to its own component and does not show any immune responses against these (exceptional case - autoimmunity)

  
• High molecular weight


  Must have certain minimal MW to become immunogenic. High MW substances - usually good immunogens. In general, compounds with MW <100 Dalton are not immunogenic. Optimum MW for immunogenicity - 5000 Dalton. Exceptions: Silk fibre (MW 600-100 Dalton) - immunogenic, Dextrin (MW 100 000 Dalton) - not immunogenic.
• Effectiveness of immunogens to activate immune responses


  • Foreignness
  • Chemical complexity
  • High molecular weight
  • Dosage and route of administration
  • Genetic constitution of the host

  
• Foreignness


  Molecules that are recognised as "self" by the immune system are not immunogenic. Normally the body is tolerant to its own component and does not show any immune responses against these (exceptional case – autoimmunity)

  
• High molecular weight


  Must have certain minimal MW to become immunogenic. High MW substances – usually good immunogens. In general, compounds with MW <100 Dalton are not immunogenic. Optimum MW for immunogenicity – 5000 Dalton. Exceptions: Silk fibre (MW 600 - 100 Dalton) – immunogenic, Dextrin (MW 100 000 Dalton) – not immunogenic
• Chemical complexity


  Increase in chemical complexity of a compound is associated with an increase in immunogenicity. Eg. Amino acid homopolymers are less immunogenic than the heteropolymers containing 2 or 3 different amino acids
• Dosage and route of administration


  Any quantity of antigen, which is ineffective when injected intravenously, may evoke antibody response when injected subcutaneously. In general, a minimum quantity of antigen is required to attain a threshold level and once that level is exceeded, increase dose does not lead to increase in proportionate immune response, rather blocking effect occurs
• Genetic constitution of the host

  Determines whether a molecule is immunogenic to that host or not. Different strains of the same species may respond differently to the same antigen

  
• Classification of Antigens (by Chemical Nature)


  • Proteins
  • Polysaccharides (e.g. ABO blood group antigens)
  • Lipids
  • Nucleic acids (poor immunogens)

  
• Classification of Antigens (by Mode of Action)


  • Thymus dependent antigen (Immunogens require help from T-lymphocytes for the induction of immune response, e.g. proteins)
  • Thymus independent antigen (Immunogens which can induce antibody production without the help of T-cells, e.g. polysaccharide component of bacteria cell wall)

  
• Classification of Antigens (by Epitope or Antigenic Determinant)


  • Unideterminant univalent (Single epitope of a given specificity, e.g. hapten)
  • Unideterminant multivalent (Two or more determinants of the same kind, e.g. many polysaccharides)
  • Multideterminant multivalent (Multiple determinants and different kinds, e.g. proteins)

  
• Superantigens


  A class of immunostimulatory molecules produced by bacteria and viruses. E.g. exotoxins secreted by staphylococcus and streptococcus. This class of antigens that result in excessive activation of the immune system. Polyclonal T-cell activation, Massive cytokine release

  
• Antigenic Determinant or Epitope


  Specific portion of macromolecule antigen which antibody or T cells bind. Immune system does not recognize foreign molecule as a whole but reacts specifically with structurally distinct areas (epitopes). Epitopes determine the specificity of Ag-Ab reaction. Size: 5-10 amino acids (protein Ag), 3-6 sugar molecules (polysaccharide)

  
• Polyvalent antigen


  A polyvalent antigen with two or more epitopes can bind to two or more antibodies

  
• Non-overlapping epitopes


  Sometimes when two epitopes are too close to one another, binding of one epitope to antibody can cause structural change in the nearby epitope

  
• Types of Epitopes


  • Linear epitope (single or sequential segment of primary sequence forms it, recognized by antibodies by its linear sequence of amino acids, or primary structure, able to bind antibody after denaturation)
  • Conformational epitope (Assembled from residues far apart from primary sequence but brought together on the surface by the folding of the molecule into its native conformation, Composed of specific region of protein chain, Epitope lost once the structure lost (denatured), T cells recognize sequential epitopes, B cells recognize conformational epitopes)

  
• Hapten


  Low molecular weight compounds that are antigenic but not immunogenic by themselves. Become immunogenic when they are conjugated to high molecular weight proteins known as carriers. E.g. drugs, antibiotics (penicillin), cosmetics and many small synthetic peptides