This page is "borrowed" from Dr. John Stevenson at the University of Miami.  

Human Host Defense against Infectious Disease

Nonspecific Host Defense (Resistance)

Resistance factors are present before infection and nonspecific - i.e., they work all the time and effective against many different kinds of microbes

External resistance factors - those which act on body surfaces

• physical
  • barriers - skin, mucus, nasal hair
  • environmental conditions - dryness
  • flushing action - blinking of eyelid, peristalsis, urination
• chemical - activities carried out by molecules
  • salts - secreted by sweat glands in skin
  • acids - low pH (HCl in stomach; lactic and other skin acids produced by normal microbiota)
  • lipids - fatty acids secreted by sebaceous glands and by gall bladder
  • enzymes - lysozyme (secretions), digestive enzymes (stomach, small intestine)
• cellular - activities carried out by cells
  • normal microbiota compete with pathogens for attachment sites and nutrients as well as producing factors toxic to pathogens
  • phagocytes (macrophages; polymorphonuclear leukocytes [PMN]) are cells that engulf and destroy particles on mucous membranes by a process known as phagocytosis

Internal resistance factors - those which act within tissues

• physical - barriers such as connective tissue, blood-brain barrier
• chemical - activities carried out by molecules
  • enzymes - lysozyme and other enzymes in blood and tissue fluids
  • complement - can be nonspecifically activated by bacterial and fungal polysaccharides or lipopolysaccharides
    • triggers inflammation and enhances phagocytosis (opsonization) by enhancing binding of particles to phagocytes via receptors
    • membrane attack complex (MAC) disrupts (lyses) enveloped viruses and some bacteria
• cellular - activities carried out by cells
  • inflammation - "early-warning" system
    • histamine released from mast cells at sites of tissue damage
    • increases permeability of capillaries at these sites
    • capillaries become "leaky" causing accumulation of complement, enzymes and phagocytes at sites of infection
    • pathogens eliminated (phagocytosis, etc.) and healing initiated
    • cardinal signs of inflammation - erythema (redness); edema (swelling); fever (heat); pain (soreness)
  • phagocytes (macrophages; polymorphonuclear leukocytes [PMN]) are cells that engulf and destroy particles, including pathogens, by a process known as phagocytosis:
    • adhesion (attachment) - phagocyte and pathogen bind to each other
    • ingestion (engulfment) - pseudopodia surround the pathogen, then fuse to form a vacuole called a phagosome
    • digestion/killing - inside phagolysosomes, which are formed by fusion of lysosomes with phagosomes:
      • hydrogen peroxide and related compounds kill microbes
      • enzymes digest microbes
    • egestion - residual (non-digestable) particles are released from the cell by a process that is essentially the reverse of ingestion

Specific Host Defense (Immunity)

Immune factors are triggered during infection by antigens, substances produced by microbes, and is specific for only those pathogens to which one is exposed

Antibody-Mediated Immunity (AMI)

• antibody responses - antibody is produced by B cells (B lymphocytes) stimulated by T cells (T lymphocytes) in response to antigens made by infectious agents
  • antigen presenting cells (APCs) engulf, process and present fragments of exogenous antigen molecules on their surfaces
  • Th cells recognize (using antigen receptors on their surfaces) antigen fragments, then proliferate and differentiate to form a large population of cytokine-producing Th cells
  • B cells bind exogenous antigen (using antigen receptors on their surfaces) and bind cytokines (using cytokine receptors on their surfaces), then proliferate and differentiate to form a large population of antibody-producing plasma cells
• mechanisms of action (ways in which AMI functions) - antibody binds specifically to the antigen that induced its formation to carry out these AMI mechanisms:
  • neutralization - inhibition of toxin function, viral infectivity, microbe attachment due to antibody binding to surface antigens of pathogens
  • antibody/complement-mediated lysis - complement is activated by binding to antibody molecules that have bound to antigens, and causes lysis of microbes via formation of a membrane attack complex (MAC)
  • opsonization - antibody and complement both enhance attachment of pathogens to phagocytes via receptors that bind them

Cell-Mediated Immunity (CMI)

• cellular responses
  • cytotoxic T lymphocytes (CTLs) are activated by T helper cells in the presence of viral antigens on virus-infected cells
    • APCs engulf, process and present fragments of exogenous antigen molecules on their surfaces
    • Th cells recognize (using antigen receptors on their surfaces) antigen fragments, then proliferate and differentiate to form a large population of cytokine-producing Th cells
    • Tc cells (CTL precursor cells) bind exogenous antigen (using antigen receptors on their surfaces) and bind Th cell-produced cytokines (using cytokine receptors on their surfaces), then proliferate and differentiate to form a large population of CTLs
  • macrophages are also activated by T helper cells
    • APCs engulf, process and present fragments of exogenous antigen molecules on their surfaces
    • Th cells recognize (using antigen receptors on their surfaces) antigen fragments, then proliferate and differentiate to form a large population of cytokine-producing Th cells
    • macrophages bind Th cell-produced cytokines (using cytokine receptors on their surfaces), then differentiate to form activated macrophages
• mechanisms of action (ways in which CMI functions)
  • CTLs kill "target" cells by destroying their membranes (necrosis) or inducing them to destroy themselves (apoptosis)
  • activated macrophages engulf, kill and digest intracellular bacteria and fungi much more efficiently than normal macrophages do, partially because they starve these microbes (by destroying nutrients the microbes need to grow)

Immunocompromised people are more susceptible to infectious diseases than normal people, and this increased susceptibility can be due to one or more of these:

• genetics - inheritance of defective genes that block normal development or expression of immune response elements (cells or molecules)
• immaturity - newborns are highly susceptible because their immune systems have not yet had a chance to mature and become fully functional
• infectious diseases - lowered resistance caused by diseases such as AIDS
• disease treatment - weakened resistance caused by drug therapy for cancer, etc.
• stress - decreases resistance and immune response development