Second Line of Defence


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

  • It is non-specific (cannot differentiate between specific microorganisms)
  • It is non-adaptive (produces the same response every time - in other words, it does not possess memory)


Blood and Lymph Systems

Two inter-related fluid systems support the body's immune response - the blood system and the lymphatic system

These two systems provide a transportation network for the cellular defenses that comprise the second and third lines of defence against infection


Blood System

  • The blood system produces the body's leukocytes (white blood cells) and transports these immune cells to the sites of infection
  • All blood cells (erythrocytes, leukocytes and platelets) are produced by multipotent stem cells in the bone marrow (via haematopoiesis)
  • These cells circulate in the blood and are moved between arteries, capillaries and veins by the pumping of the heart


Lymphatic System

  • The lymph system is a secondary transport system that serves to protect and maintain the internal fluid environment by producing and filtering lymph
  • Lymph is a clear fluid that contains white blood cells and arises from the drainage of fluid from the bloodstream and surrounding tissue
  • The fluid is filtered at points called lymph nodes - where pathogens are removed - before returning to venous circulation
  • In addition to its key immune function, the lymphatic system also absorbs fats from the small intestine and absorbs excess tissue fluid
  • Major lymphatic organs include the spleen, thymus, tonsils and adenoids


Cellular Defenses

The cellular defenses of the innat immune system describe the types of cells employed along with the processes initiated by these cells

These defenses include inflammation (by mast cells), phagocytosis, fever and clotting (by platelets)


Inflammation

  • The inflammatory response is the way in which the body reacts when pathogens damage cells
  • When tissue damage occurs, mast cells release a chemical called histamine, which causes local vasodilation and increased capillary permeability
  • It also releases chemotactic factors which recruit wandering macrophages (phagocytes) to the site of damage to fight the infection
  • While inflammation is necessary to allow immune cells to access infected tissue, side effects include redness, swelling, heat and pain
  • Inflammation can be either short-term (acute) or long-term (chronic)


Histamine Release by Mast Cells Leading to Inflammation


Overview of the Inflammatory Response


Phagocytosis

  • Phagocytic leucocytes (macrophages) circulate in the blood but may move into body tissue (extravasation) in response to infection
  • They concentrate at sites of infection due to the release of chemicals (such as histamine) from damaged body cells
  • Pathogens are engulfed when cellular extensions (pseudopodia) surround the pathogen and then fuse, sequestering it in an internal vesicle
  • The vesicle may then fuse with the lysosome to digest the pathogen
  • Some of the pathogens antigenic fragments may be presented on the surface of the macrophage, in order to help stimulate antibody production
  • This mechanism of endocytosis is called phagocytosis ('cell-eating')


Overview of Phagocytosis by a Leucocyte


Fever

  • A fever is an abnormally high body temperature associated with infection and is triggered by the release of prostaglandins
  • Fever may help to combat infection by reducing the growth rate of pathogens (via the inactivation of enzymes and toxins required by the invader)
  • It may also increase metabolic activity of body cells and activate heat shock proteins in order to strengthen the overall immune response
  • Up to a certain point fever may be beneficial, but beyond a tolerable limit it can cause damage to a body's own enzymes


Blood Clotting

  • Clotting (haemostasis) is a mechanism that prevents the loss of blood from broken vessels
  • Damaged cells and platelets release chemical signals called clotting factors which trigger a coagulation cascade:
    • Clotting factors convert the inactive zymogen prothrombin into the activated enzyme thrombin
    • Thrombin catalyses the conversion of the soluble plasma protein fibrinogen into an insoluble form (fibrin)
    • Fibrin forms an insoluble mesh of fibres that trap blood cells at the site of damage
  • Clotting factors also cause platelets to become sticky, which then adhere to the damaged region to form a solid plug called a clot
  • The clot prevents further blood loss and blocks entry to foreign pathogens


Molecular Defenses

Molecular defenses involves a number of proteins that either attack invading microbes directly or hinder their ability to reproduce

These defenses include complement proteins, cytokines and interferons


Complement Proteins

  • Complement proteins are produced by macrophages, monocytes and other body cells (particularly liver cells)
  • These proteins are normally inactive in the blood, but in response to immune activation initiate a cascade of reactions that help protect the body
  • Activation of the complement system may provide protection in the following ways:
    • Assist in the destruction of pathogenic organisms by destroying cell membranes
    • Recruiting phagocytes to the site of infection (chemotaxis)
    • Aid in identification of pathogens (opsonization)
    • Intensifying the inflammatory response


Cytokines

  • Cytokines are proteins produced in response to antigens and function as chemical messengers in the immune response
  • They may facilitate immunity in three main ways:
    • They may regulate the innate immune response (via chemotaxis and activation of the inflammatory response)
    • They may regulate the adaptive immune response (via activation of lymphocytes)
    • They may activate haematopoiesis (production and differentiation of new white blood cells)


Interferons

  • Interferons are a specific type of cytokine that provide protection against viruses and tumor cells
  • Infected cells release interferons which alert surrounding cells to reduce their susceptibility to infection (e.g. by activating antiviral agents)
  • Interferons will also recruit natural killer cells (NK cells) which target and destroy infected cells