How Drugs Work

Defense and Resistance

The body's ability to fight pathogens, or disease-producing organisms, is called resistance. The human body has different mechanisms to defend itself against microbial agents that may or may not have the potential to cause disease. The first line of defense is external. The skin, mucous membranes, and secretions of the skin provide a non-specific defense line. Since the skin is the largest organ of the human body, it is effective physical barrier and chemical barrier against microbes. Secretions of the skin increase the acidity of the surface making it uninhabitable for certain microbes. Other secretions like tears, saliva, mucosal secretions have antimicrobial enzymes like lysozymes that break down bacterial cell walls. ²⁸ (See the cell wall in Figure 1.)

A second line of defense is achieved through non-specific phagocytosis, antimicrobial proteins, and inflammatory responses. If microbes like bacteria are able to pass the skin's defense lines then phagocytic cells (neutrophils and monocytes) ingest the microorganism. Phagocytosis means cell-eating. Phagocytic cells make up 60-70% of white blood cells and are responsible for identifying, engulfing, and destroying infected or damaged cells. ²⁹ Other cells helpful against viral attacks are Natural Killer Cells (NK), which can kill viral infected cells by causing them to burst or lyse. Beside phagocytic cells, an inflammatory response occurs at a site of injury and is responsible for calling phagocytic cells to the site. The response begins with edema (swelling) and an increase in blood flow. An increase in blood flow not only raises the number of blood clotting elements but also promotes the migration of phagocytic cells to the area.

The third line is specific immune defense, which is selective for specific foreign organisms: they function by selective action on invaders and exhibit memory of invading organisms for quicker defense during a second assault or infection. Specific defense mechanisms that possess memory are often called "immunity," which is dependent upon the action of lymphocytes and macrophages. Immunity works through the differentiation of self vs. non-self. A key part of immunity is the ability of cells of the immune system to recognize molecules that do not belong in the body: those "not-belonging" protein or carbohydrate molecules are called foreign antigens. ³⁰ Macrophages, and other antigen-presenting cells, have mechanisms for alerting other immune cells to the presence of foreign antigens, by displaying them on the macrophage surface in ways that stimulate the rest of the immune system.

More specifically, macrophages recognize the difference between infected cells and healthy cells because infected cells present a piece of the infecting microbial protein (antigen) on its surface glycoproteins. These surface glycoproteins are known as major histocompatibility complex (MHC), which are found on almost every nucleated cell of the human body and make us uniquely different from one another. An antigen presentation on the MHC signals lymphocytes to an infection.

Types of Immunity

There are several types of immunity. Cell-mediated immunity is dependent upon T lymphocytes (T-cells) recognizing antigens presented on the MHC. This type of immune response is effective against viruses and bacteria inside infected body cells. When T-cells recognize an antigen, the immune responds by stimulating T-helper cells to create clones or copies with specific tasks. T-helper clones may help to activate other T-cells like cytotoxic T-cells, or B-cells. Other clones may differentiate to become memory T-helper cells which will aide in the recognition of antigens during a second immune response. In cell-mediated immunity, cytotoxic T-cells will lyse infected cells, or produce more memory T-helper cells for an antigen.

Humoral Immunity or Antibody-Mediated Immunity is dependent upon B-cells, which recognize a specific antigen and differentiate into cells that produce antibodies, which are proteins that can neutralize that antigen. Initially T-cells and B-cells function similarly. However, B-cells do not directly attack antigens, instead they proliferate and differentiate into both plasma cells and memory B-cells. Plasma cells secrete antibodies that disrupt the function of the antigen and form complexes with antigen, making them more easily removable by macrophages. Memory B-cells make the recognition of invading pathogens easier during a secondary attack. Finally, acquired immunity includes two subgroups: natural and artificial immunity. Natural immunity depends upon natural exposure to a pathogen and slow building immunity, whereas artificial immunity occurs when someone is deliberately exposed to a pathogen. For example, getting a vaccination for measles or smallpox is a type of artificial acquired immunity. ³¹