The Immune System

There are physical, chemical, and cellular defenses against invasion by viruses, bacteria, and other agents of disease.

During the early stages of an infection, there is an inflammatory response

• Non-specific attack
• Phagocytes active ("eat" pathogen)

During later stages, leucocytes produce immune responses

• Antigen - a foreign substance which triggers an immune response
• Some WBC's produce antibodies in huge amounts
  • Antibodies - substances which bind to specific antigens and tag them for destruction
  • Other WBC's (executioner cells) directly destroy body cells

Surface coverage - the first line of defense

• The body is protected from pathogens by the skin and mucous membranes
  • Skin - dead cellular layer - dry, low pH
  • Mucous membranes contain lysozymes (enzymes which break down bacteria)
  • Other cells contain cilia which filter pathogens and particulates
• Breaks in the protective barrier
  • Digestive openings
  • Reproductive openings
  • Respiratory openings
  • Sensory Organs

Non-specific responses - the second line of defense

• Non-specific responses are generalized responses to pathogen infection - they do not target a specific cell type
• The non-specific response consist of some WBC's and plasma proteins
• Phagocytes - cells which "eat" foreign material to destroy them
  • Phagocytes are formed from stem cells in bone marrow (stem cells are undifferentiated WBC's)
    • Neutrophil - phagocytize bacteria
    • Eosinophils - secrete enzymes to kill parasitic worms among other pathogins
• Macrophage - "big eaters" phagocytize just about anything

• Non-phagocytic leucocytes - 
  • Basophil - contain granules of toxic chemicals that can digest foreign microorganisms.  These are cells involved in an allergic response
  • Mast Cells - similar to basophils, mast cells contain a variety of inflammatory chemicals including histamine and seratonin.  Cause blood vessels near wound to constrict.
• Complement proteins - plasma proteins which have a role in nonspecific and specific defenses

• Form a cascade effect - if only a few are activated, they will trigger others to become active in great numbers
  • Some punch holes in bacterial walls (forms holes where cellular components leak out)
  • Some promote inflammation
    • Concentration gradients attract phagocytes to irritated or damaged tissue
    • Encourage phagocytosis in phagocytes (promotes "eating")
  • Some bind to the surface of invading organisms
• Chemokines - create a chemical gradient to attract neutrophils and other leucocytes to the wound site
• Inflammation

• Causes localized redness, swelling, heat, and pain
• Changes in capillary wall structure allow interstitial fluid and WBC's to leak out in tissue
• Promotes macrophage (phagocytic WBC's) activity
• Macrophages secrete Interleukins (communication proteins among WBC's)
  • Interleukin-1: increases body temperature (i.e. causes a fever)
    • This enhances the WBC's ability to protect the body
    • Causes drowsiness - reduces the body's energy usage and stress

The Immune System (Specific Responses) - the third line of defense

• Called into action when nonspecific methods are not enough and infection becomes widespread

Types of cells involved in the immune system:

• Macrophages - engulf foreign objects
  • Inform T lymphocytes at a specific antigen is present
• Helper T cells - produce and secrete chemicals which promote large numbers of effector and memory cells
• Cytotoxic T cells - T lymphocytes that eliminate infected body cells and tumor cells
• B cells - produce antibodies (secrete them in the blood or position them on their cell surfaces)

Each type of virus, bacteria, or other foreign body has molecular markers which make it unique

• Host lymphocytes (i.e. those in your body) can recognize self proteins (i.e. those which are not foreign)
• When a nonself (foreign) body is detected, mitotic activity in B and T lymphocytes is stimulated
  • While mitosis is occurring, the daughter populations become subdivided
    • Effector cells - when fully differentiated, they will seek and destroy foreign
    • Memory cells - become dormant, but can be triggered to rapid mitosis if pathogen encountered again

Thus, immunological specificity and memory involve three events:

(1) Recognition of a specific invader

(2) Repeated cell divisions that form huge lymphocyte populations

(3) Differentiation into subpopulations of effector and memory cells

• Antigen - a nonself marker that triggers the formation of lymphocyte armies
• Antibodies - molecules which bind to antigens and are recognized by lymphocytes

Antigen-presenting cell - a macrophage which digests a foreign cell, but leaves the antigens intact. It then binds these antigens to MHC molecules on its cell membrane. The antigen-MHC complexes are noticed by certain lymphocytes (recognition) which promotes cell division (repeated cell divisions)

T cells (Helper T cells and Cytotoxic T cells)

• T cells arise from stem cells in the bone marrow - they then travel to the thymus where the differentiate and mature. At maturity, they acquire receptors for self markers (MHC molecules) and for antigen-specific receptors. They are then released into the blood as "virgin" T cells.
• T cells ignore other cells with MHC molecules and they ignore free-floating antigens. However, they will bind with a antigen-presenting macrophage (a macrophage possessing a MHC-antigen complex). This binding promotes rapid cell division and differentiation into effector and memory cells (all with receptors for the antigen)
• Effector helper T cells secrete interlukins (stimulate both T and B cells to divide and differentiate)
• Effector cytotoxic T cells recognize infected cells with the MHC-antigen complex. They then destroy the cell with perforans (enzymes which perforate the cell membrane, allowing cytoplasm to leak out) and other toxins which attack organelles and DNA

B cells and Antibodies

• B cells also arise from stem cells in the bone marrow. As they develop and mature, they start synthesizing a single type of antibody
• Antibodies are proteins which recognize antigens
• The virgin B cell produces antibodies which move to the cell surface and stick out
• The B cell floats in the blood - when it encounters the specific antigen it becomes primed for replication
• The B cell must receive an interleukin signal from a helper T cell which has already become activated by a macrophage with a MHC-antigen complex. This promotes rapid cell division.
• The B cell population then differentiates into effector and memory B cells
• The effector B cells then produce a staggering amount of free-floating antibodies
  • When these free-floating antibodies encounter an antigen, they tag it for destruction by phagocytes and complementary proteins
  • These types of responses are only good for extracellular toxins and pathogens - they cannot detect pathogens or toxins located inside of a cell

Where do all of these interactions take place? - in the lymph nodes.