Third Line of Defence


The third line of defence against pathogenic invasion is the adaptive immune response, which has two key qualities:

  • It is specific (it can differentiate between specific microorganisms and respond accordingly)
  • It is adaptive (it can produce a heightened response upon re-exposure - in other words, it has memory)


Antigen Presentation

  • An antigen is a substance that the body recognises as foreign and can evoke an immune response
  • The immune system can differentiate between foreign ('non-self') and native ('self') cells due to the presence of identification markers (MHC molecules)
  • All body cells (excluding red blood cells) possess MHC class I markers on their cell surface, identifying them as part of the organism
  • Certain immune cells (e.g. macrophages) possess MHC class II markers, which present foreign substances to the adaptive immune system
  • The body is initially capable of recognising invaders as they do not possess the molecular markers that designated them as 'self' (MHC class I)
  • When non-specific macrophages engulf a pathogen and destroy it (via the lysosome), they present antigenic fragments on their surface, complexed with MHC class II molecules ('non-self')
  • This allows cells of the adaptive immune system (i.e. lymphocytes) to generate a specific response against that particular antigenic determinant
  • Infected body cells (e.g. viruses and tumors) may present antigenic fragments on MHC class I molecules, denoting that the cell is now compromised and needs to be destroyed


Comparison of Class I and Class II Major Histocompatability Complex (MHC) Molecules


Antibody Production

  • The adaptive immune response functions by producing proteins called antibodies (or immunoglobulins) which are each specific to a particular antigen
  • Antibodies are made up of 4 polypeptide chains (2 light and 2 heavy chains) joined together by disulphide bonds to form a Y-shaped molecule
  • The ends of the arms are where the antigens bind and these areas are called the variable regions, as these will differ between antibodies
  • Each type of antibody will recognise a unique antigenic fragment, making this interaction specific (like enzyme-substrate interactions) 


Structure of a Generalised Antibody


Humoral Immunity

  • Humoral immunity describes the production of antibodies by B lymphocytes (B cells)
  • B cells are antibody-producing cells that develop in the bone marrow to produce a highly specific antibody that recognises one type of antigen
  • Each B lymphocyte has a specific antibody on its surface that is capable of recognising a specific antigen
  • When antigens are presented to B cells (and TH cells) by macrophages, only the B cell with the appropriate antibody will become activated and clone
  • The majority of B cell clones will differentiate into antibody-producing plasma cells, a minority will become memory B cells (BM cells)
  • Plasma cells produce massive quantities of specific antibody for a limited time (~2,000 molecules per second for ~4 - 5 days)
  • Because pathogens may contain several antigenic determinants, several B cell clones may become activated (polyclonal activation)


Clonal Selection


Cell-Mediated Immunity

  • Cell-mediated immunity describes the activation of humoral immunity by T helper cells and the targeted destruction of infected cells by cytotoxic T cells
  • It is important to recognise that humoral immunity will not occur without activation by cell-mediated immunity


Helper T Lymphocytes (TH cells)

  • When a pathogen invades the body, it is engulfed by wandering macrophages which present the antigenic fragments on its surface
  • This macrophage becomes an antigen-presenting cell, and presents the antigen to helper T cells (TH cells)
  • The TH cells bind to the antigen and become activated, and in turn activate the B cell with the specific antibody for the antigen
  • This B cell clones and differentiates into plasma cells and memory cells


Antibody Production via the Activation of Helper T cells


Cytotoxic T Lymphocytes (TC cells)

  • Cytotoxic T cells recognise antigenic fragments on infected cells (bound to MHC-I markers) and kill these cells before the virus has time to replicate
  • Some TC cells can even destroy certain types of cancer cells
  • Cytotoxic T cells destroy infected cells by releasing lymphotoxins, which cause cell lysis
  • Once the infected cells have been destroyed, suppressor T cells inhibit the TC cells, to ensure that normal cells are not subsequently attacked
  • TC cells (adaptive immunity) differ from natural killer cells (innate immunity) in their ability to form memory cells for subsequent reinfections


Immunological Memory

  • Because the adaptive immune response is dependent on clonal expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies
  • When B and T cells divide and differentiate in order to produce antibodies, a small proportion of clones will differentiate into memory cells
  • Memory cells remain in the body for years (or even a lifetime)
  • If a second infection with the same antigen occurs, the memory cells react faster and more vigorously than the initial immune response, such that the symptoms of the infection do not normally appear
  • Because the individual no longer presents with the symptoms of infection upon exposure, the individual is thus said to be immune


Overview of the Adaptive Immune Response