Weather changes. Many of us react to them and get a cold. The flu abounds during the winter. We’ve all become sick before. The question is, how does our body fight sickness? Let us explore another incredible aspect of the human body, the immune system.
What is the immune system? The immune system is the functional system of the human body which provides resistance against disease, or immunity. This system is astonishing in its ability to maintain our health, and it works 24/7. There are two systems in our bodies which fight against disease: the innate (nonspecific) defense system and the adaptive (specific) defense system. An overview of the two systems can be seen in the following diagram:
Let us delve into each separately.
What is the innate defense system? The innate defense system is the rapid response to foreign invaders, and is activated in just minutes. It is always ready to go. This system has two lines of defense. The first line of defense is the external body membranes, the intact skin and mucosae. As long as the epidermis (see Onesies) remains unbroken, the skin presents a formidable barrier to most microorganisms which want to invade our body. There are microorganisms everywhere, even in the air. Just ask anyone who has ever studied microbiology. The tough keratin layer, which is what we see, is resistant to most weak acids and bases (which can be very harmful to the body) and bacterial enzymes and toxins. Mucous membranes provide similar barriers. The skin also provides other protective chemicals. The acidity of the skin is low, which stops bacterial growth. Lipids (a class of macromolecules) in sebum (the secretion of sebaceous glands) and dermicidin are toxic to bacteria. The mucous membranes which line our stomachs secrete a concentrated hydrochloric acid solution and protein-digesting enzymes, which kill bacteria. Sticky mucus traps microorganisms which enter the digestive and respiratory passageways. Saliva and lacrimal fluid (see Picture Frames and Hanging Accessories) contain lysozyme, which destroys bacteria. Here is a summary:
The second line of defense is a bit more complicated. The body uses an enormous number of nonspecific cellular and chemical devices to destroy foreign invaders. These include phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever. Let’s go one by one:
Phagocytes– Phagocytes are literally cellular “eaters”. They actually chew up the foreign pathogen (a disease-causing substance). The chief phagocytes are macrophages, which come from monocytes, a type of white blood cell. Free macrophages, like those in the alveoli of the lungs (the alveoli are the cluster shaped bunches in the lungs where gas exchange takes place. This is a discussion for a different time), wander throughout the tissue in search of foreign invaders. Fixed macrophages like those is the liver and brain permanently reside in that organ. So how does phagocystosis (cellular eating) work? The phagocyte engulfs the foreign material and ingests it. The result is a phagosome, which combines with a lysosome to form a phagolysosome. The critical step in ingestion is adherence. The phagocyte must attach itself to the invader. This is made possible by recognizing the pathogen’s carbohydrate “signature” structure. Some types of microbes (microorganisms) can evade detection by phagocytes because their structures are not recognized by the phagocytes. Lysosomal enzymes then digest the invader, leaving residue. The residue is then ejected out of the cell as non-harmful material. However, sometimes certain bacteria or parasites are resistant to lysosomal enzymes. These require special treatment. When the macrophage is stimulated by helper T cells (see later in the adaptive defense system part), additional enzymes are activated, which produces a “respiratory burst”. This unleashes free radicals, such as nitric oxide and superoxide, which are very potent cell-killers. If a phagocyte cannot ingest a material for some reason, like size, it can release its toxic chemicals into the extracellular fluid. Here is a diagram of phagocytosis:
Natural Killer (NK) Cells- These specialized police cells scan the body for foreign substances, especially for abnormal invaders which may not be picked up by the adaptive immune system. They lyse (cause to burst) and kill cancerous cells and infected cells by direct contact, which induces the cell to undergo apoptosis (cell programmed death). NK cells also secrete potent chemicals which enhance the inflammatory response.
Inflammation- Inflammation is triggered whenever the body encounters physical trauma, intense heat, irritating chemicals, or infection. This response has several beneficial effects: it prevents the spread of damaging materials to nearby tissues, disposes of cell debris and pathogens, and sets the stage for repair. There are four cardinal signs of inflammation: redness, heat, swelling, and pain.
Inflammation begins with a chemial “alarm” as the area is flooded with inflammatory chemicals. Macrophages have surface membrane proteins, called Toll-Like Receptors (TLRs) which recognize a specific class of microbe. Once activated, the TLR triggers the release of cytokines, which promotes inflammation and attracts white blood cells. Mast cells release histamine, a potent inflammatory chemical. Also, injured tissue, phagocytes, lymphocytes (a type of WBC), basophils (another type of WBC), and blood proteins release histamine, cytoknes, kinins, prostaglandins, leukotrines, and complement proteins. These cause arterioles to dilate. As more blood flows to the area, local hyperemia (congestion with blood) occurs, which explains redness and heat in the inflamed area. The chemicals also increase the permeability (ability for other substances to pass through) of the capillaries in the area, which allows exudate (fluid containing clotting factors and antibodies) to seep into the tissue space from the blood. This causes swelling, or edema, which presses on nerve endings, contributes to the pain sensation. Pain also results from bacterial toxins, and also the sensitizing affects of kinins and prostaglandins. The surge of protein-rich fluids sweeps foreign materials into the lymph for processing. It also delivers important proteins such as complement and clotting factors; clotting factors form a gel-like mesh that forms a scaffold for permanent repair. This isolates the area, which is very important.
Soon after the start of inflammation, the damaged area is flooded by phagocytes. Neutrophils are followed by macrophages. The process of phagocyte mobilization consists of four steps: 1. Leukocytosis- neutrophils enter the blood from red bone marrow in response to certain factors released by damaged tissue. Within a few hours, the amount of neutrophils in the blood increases by 4x or 5x, which is called leukocytosis. 2. Marigination- the neutrophils cling to the cell walls of the capillaries. They cling in response to inflamed endothelial cells which produce signals called cell adhesion molecules (CAM). 3. Diapedesis- the neutrophils squeeze through the capillary walls to get to the injured site. 4. Chemotaxis- inflammatory chemicals act as homing devices, attracting neutrophils and other WBCs to the site of injury. Monocytes (a type of WBC) are late arrivers to the scene, and are poor phagocytes, but within 12 hours of being released from the blood they swell into monstrous macrophages with huge appetites. Macrophages are the central players in the final disposal of cell debris.
Here is a diagram of phagocyte mobilization:
In severely infected areas, a creamy-yellow pus can accumulate in the wound. Pus is a mixture of dead or dying neutrophils, broken-down tissue cells, and living and dead pathogens.
Here is a summary of inflammation:
Antimicrobial Proteins- Antimicrobial proteins attack microbes directly or disrupt their ability to reproduce. The two most important are interferons and complement proteins. Viruses do their work by taking over the cells of the host’s body. This is why there are very few antiviral drugs, because we don’t want to attack our own cells. Infected cells can do little to save themselves, but some can secrete interferons to protect nearby cells. The interferons diffuse to nearby cells where they stimulate the synthesis of proteins which “interfere” with viral replication by blocking protein synthesis and degrading viral RNA. There are different kinds of interferons. The complement protein system is a group of at least 20 proteins in the plasma which circulate in inactive form. Complement activation unleashes chemicals which amplifies virtually all aspects of the inflammatory response. Certain bacteria and other cells types are killed by cell lysis. Our own cells are equipped with inactivating proteins. There are three pathways to complement activation, which are illustrated in the following diagram. Notice the cascade action of all three:
Fever- Fever, as we all know, is when body temperature is abnormally high. The body’s “thermostat’ is located in the hypothalamus of the brain. The thermostat is reset in response to chemicals called pyrogens, which are secreted by leukocytes and macrophages when exposed to foreign material. Very high fevers are dangerous because it destroys body enzymes. But low to mid-grade fever is a response which benefits the body. Fever increases the metabolic rate of tissue cells, speeding up the repair process. In additon, during a fever, the liver and spleen sequester zinc and iron, which are required for bacterial multiplication.
All of the above are part of the nonspecific immune system because the response is always the same regardless of what the foreign invader is. However, the adaptive immune system is species-specific, and is a topic for a different time.
All information is via the following source: Marieb, Elaine N. and Hoehn, Katja, Human Anatomy and Physiology, 8th ed., San Francisco, Pearson Education Inc., 2010. Print