221 Immune System

Our immune systems offer us protection against a world full of pathogens. Our immune systems work by providing two types of immunity. In non-specific immunity our bodies present the same kinds of defense systems regardless of the type of pathogens. Non-specific immunity works much like a fence around your property. The fence does not differentiate between friend or foe. It keeps everyone out. The other type of immunity is known as specific immunity (defense). Specific defense produces an attack against a specific pathogen. This is much like having an attendant at the gate of the fence around your house. The attendant can identify potential foes and keep them out.

Before birth the body inventories all of the cells and tissues of the body and classifies them as “self” cells. The presentation of non-self cells can then trigger the immune system.

Non-Specific Defense

Non-specific defense (innate immunity) consists of mechanisms that either keep pathogens out or destroy them regardless of their type. Non-specific defense includes mechanical barriers, chemical substances, cells and inflammation.

Mechanical barriers include the skin and mucous membranes. Besides presenting a physical barrier that stops pathogens they also work to remove substances from the surface of membranes. Examples include the movement of mucous moving substances toward the digestive tract and tears washing substances from the eyes.

Chemical substances work to destroy pathogens. These include enzymes, cytokines, and the complement system. For example, mucous from the respiratory tract moves toward the pharynx and esophagus where it is swallowed. Upon reaching the digestive tract pathogens are destroyed by powerful digestive enzymes.

Cytokines are a series of protein substances secreted by cells that work to destroy pathogens. Interferons are cytokines that bind to cells causing them to produce substances that inhibit viral replication. One type of interferon can affect many types of viruses. Interferons can also activate other immune cells such as macrophages and natural killer cells. Some cytokines produce fever. Interleukin I (endogenous pyrogen) is a cytokine that acts as a pyrogen (raises body temperature). This cytokine is released in response to toxins or pathogens and causes an increase in body temperature.

The compliment system is a series of about 20 plasma proteins. They include proteins that are named C1-C9 and factors B, D, P. They act much like the clotting cascade in that activation of the first compliment protein causes the others to activate. Complement system responses include inflammation, phagocytosis from white blood cells attracted to the area, and attacking non-self cells.

Inflammation is characterized by swelling, redness, heat and pain (tumor, rubor, calor, dolor). Inflammation is produced by tissue destruction from trauma, cuts, temperature and chemicals. Inflammation causes an increased blood flow to the damaged area. Blood brings substances for repair and the stasis of blood in the area prevents further spread of pathogens. Inflammation is primarily caused by the release of histamine and heparin from mast cells (similar to basophils). Histamine promotes local vasodilation and capillary permeability while heparin inhibits clotting. Phagocytes are also attracted to the area and remove debris. Neutrophils release substances that activate fibroblasts to begin to repair the area. Substances released by cells stimulate pain receptors in the tissue causing the sensation of pain.

Specific Defense

Specific defense (sometimes called adaptive immunity) recognizes and coordinates attacks against specific pathogens. The system can also remember pathogens and produce a powerful response the next time a pathogen enters the body.

There are two types of specific defense. These include cell-mediated immunity and antibody-mediated immunity. Cell-mediated immunity occurs when T-lymphocytes (T-cells) become activated by exposure to pathogens. Activated T-cells then attack pathogens directly.

T-cells become activated when exposed to antigens on pathogens. T-cells react with portions of antigens called antigenic determinants (epitopes). T-cells contain antigen receptors on their surface that combine with antigenic determinants on pathogens. The antigen receptors are polypeptide chains that contain variable and constant regions. The variable region binds to the antigenic determinant. This is known as direct activation of T-cells.

Major Histocompatibility Complexes

Specific glycoproteins can activate T-cells. These glycoproteins are called major histocompatibility complex molecules (MHC molecules). MHC molecules reside on cell membranes and contain a variable region. The variable region is the portion of the molecule that allows for binding to antigens.

MHC class I molecules display antigens on the surface of cells. The antigens are produced inside cells. One example is a cell infected with a virus. The virus replicates inside the cell producing proteins. These proteins combine with MHC class I molecules that move to the outer cell membrane for display. Once displayed on the surface of the cell the immune system can attack and destroy the cell.

MHC class II molecules are found on cells that present antigens. Antigens enter cells via endocytosis and combine with MHC class II molecules in vesicles. The antigen-MHC complex combination is then transported to the cell membrane and displayed on the surface. The response to MHC class II complexes differs from MHC class I in that the MHC class II presenting cells are not directly attacked. The MHC II complex acts more like a signal to other immune system cells to mobilize against the antigen.