Immune System

Nonspecific and Specific Immunity

The first line of defense prevents pathogens from entering the body, the second line of defense attacks pathogens indiscriminately once they do enter the body, and the third line of defense attacks and remembers pathogens.

The immune system is the body's system of defense against pathogens, such as viruses, bacteria, fungi, parasites, and other microorganisms that could cause harm to the body. It also serves to help get rid of abnormal cells that cause harm, such as cancer cells, and old cells that need to be eliminated from the body. To protect the body, the immune system makes use of a layered system of defense. The first line of defense includes physical barriers such as the skin and mucous membranes that prevent pathogens from entering the body. The first line of defense also includes chemical barriers, such as highly acidic stomach acids, that destroy microorganisms or inhibit their growth.

If a pathogen manages to get through this first line of defense, the second line of defense provides an immediate, nonspecific response, attacking pathogens indiscriminately. Three major immune responses are activated as part of the body's second line of defense. When an infection first enters the body, the first line of defense includes phagocytic cells, which ingest and destroy any foreign microorganisms that enter the body. If the phagocytic cells fail, the second line of defense against in invading organism includes inflammation, which is a localized tissue response that helps recruit more white blood cells to the site of injury or place where microorganisms have invaded the body. Lastly, the third type of response includes a fever that functions to stop microbial growth and reduce the effects from an infection by increasing the body's core temperature, which creates an internal environment where the microbes are unable to survive.

Both the first and second lines of defense are nonspecific. These immediate responses do not target any particular pathogen or microorganism; the body responds in the same general way to all foreign microorganisms. This nonspecific immunity is also described as innate immunity, which is a nonspecific, immune response, including chemical and physical barriers and internal cellular and chemical defenses. In contrast to the innate immune system, the third line of defense is specific and adaptive. This specific immunity is also described as adaptive immunity, which is the immune system's ability to destroy specific targets and "remember" those targets. The third line of defense is specific because it differentiates, or divides, into certain immune cells that specifically respond to and target a microorganism for removal from the body. This line of defense is also adaptive because it generates immunological memory, which means this type of immunity can "remember" the type of pathogen that originally entered the body and elicit a heightened response if reexposure happens.

The Immune System's Lines of Defense

The first line of defense of the immune system consists of the skin, mucus membranes, and other physical barriers and chemical barriers that prevent the pathogens from entering the body. The second line of defense involves the actions of phagocytic cells, which are white blood cells that kill pathogens. The third line of defense activates antibodies in the blood that can act on specific targets and remove them.

Leukocytes and Phagocytic Cells

There are five types of leukocytes, also called white blood cells—neutrophils, monocytes, eosinophils, basophils, and lymphocytes—with each having a specialized mechanism to fight foreign invaders.
A leukocyte is also called a white blood cell (WBC) and is one of several specialized immune cells that circulate in various places such as the bloodstream and the body's tissues. These cells originate from hematopoietic stem cells found in the red bone marrow that are able to differentiate into many different types of cells, including leukocytes. There are five main types of leukocytes—neutrophils, monocytes, eosinophils, basophils, and lymphocytes—all of which play an important role in the body's immune response. Each neutrophil, eosinophil, and basophil is called a granulocyte because it has granules, or small particles, in its cytoplasm.

Origin of Immune Cells

Hematopoietic stem cells are blood cells that originate in the red bone marrow and divide, or differentiate, into a wide variety of specialized cells, including myeloid or lymphoid stem cells. These stem cells can continue dividing into cells like neutrophils, T cells, B cells, and dendritic cells.
A neutrophil is the most common type of leukocyte in the body. Neutrophils are phagocytic cells because they carry out phagocytosis, which is a process by which cells such as macrophages engulf and digest pathogens or other material. Roughly 40–75 percent of the leukocytes in blood are neutrophils. The granules in neutrophils stain to a light pink color that can be used to identify them from other immune cells under a microscope. They are normally found in the bloodstream, but during an inflammatory response neutrophils follow chemical signals and quickly migrate to the site of inflammation. This process is referred to as chemotaxis, which involves the movement of a cell in response to a chemical stimulus. There, neutrophils engulf and destroy pathogens, leading to the formation of pus, which is white/yellow in color.

Like a neutrophil, a monocyte is also phagocytic. Recognized as the largest type of leukocyte in the body, a monocyte circulates in the bloodstream until chemical signals attract it into tissues, at which point it differentiates into a phagocytic cell that patrols tissues in search of pathogens. In addition to engulfing and destroying pathogens in a nonspecific manner, macrophages, which are a type of phagocytic cell that monocytes differentiate into, also play a role in adaptive immunity. After engulfing a pathogen, macrophages present a portion of that pathogen to special leukocytes called T cells. This activates the specific immune response.

An eosinophil is a leukocyte (white blood cell) from the myeloid lineage that contains granules, releases cytotoxic chemicals to kill large parasites, and plays a role in allergies and asthma. Making up just 1–3% of the body's leukocytes, these cells are not phagocytic. They perform their immune function by releasing toxic chemicals to kill large parasites such as worms that are too big for a single leukocyte to engulf. Eosinophils play a role in allergies and asthma just like a mast cell, which is an immune cell derived from the myeloid lineage that lives for a long time in the body's tissues and releases chemicals, triggering allergic-mediated responses from the immune system. Symptoms associated with this type of response range from a runny nose to itchy eyes.

A basophil is a leukocyte (white blood cell) from the myeloid lineage that releases histamine and heparin to promote inflammation. Recognized as the rarest type of leukocyte, a basophil's release of histamine, which is a type of protein molecule also released from mast cells, triggers allergic responses following the invasion of a foreign pathogen into the body. Both histamine and heparin promote inflammation and also play a role in asthma and allergies. Histamine promotes inflammation by dilating blood vessels and thereby increasing the blood flow to injured or infected tissues. Heparin is an anticoagulant, which basophils release to make it easier for leukocytes to enter the area of the injury.

A lymphocyte is a specific type of leukocyte that includes several different types of specialized immune cells, all of which are primarily found in lymph (interstitial fluid that has entered the lymphatic system).The three types of lymphocytes most important to the immune system are B cells, T cells, and natural killer (NK) cells. Of these lymphocytes, B cells and T cells work together to carry out specific, adaptive immunity. When a B cell, a lymphocyte that originates and matures in the red bone marrow and produces antibodies, which bond to pathogens and neutralize them, recognize an invader, it produces large quantities of antibodies, the large proteins used by the adaptive immune system to target pathogens for destruction. Some B cells also differentiate to become memory B cells. Memory B cells are long-lived cells that play a key role in adaptive immunity. When memory B cells detect the presence of a pathogen they have encountered before, these cells quickly replicate to produce large numbers of new cells targeted toward the familiar pathogen.

A T cell is a leukocyte produced by red bone marrow that migrates to the thymus gland, where it matures. They play a role in eliciting the adaptive immune response. There are several types of T cells. These include the following:

  • Helper T cells: They produce cytokines, which are secreted by the cell to alter the effect on a neighboring cell. For example, certain cytokines such as interleukin 4 (IL-4) activate B cells to produce antibodies as a mounting immune defense.
  • Killer T cells or cytotoxic T cells: These release cytotoxic granules that kill infected cells.
  • Memory T cells: These are similar to memory B cells in that they are long-lived cells, playing a key role in adaptive immunity.
Unlike B and T cells, NK cells are lymphocytes that are part of the nonspecific, innate immune response. These cells recognize infected cells or tumors by detecting changes in cell-surface proteins. Once activated, NK cells release cytotoxic granules to kill the infected or diseased cell.

Types of Leukocytes

Leukocytes, or white blood cells (WBCs), are specialized immune cells. Each leukocyte plays an important role in the body's immune response. There are five main types of leukocytes: neutrophils, monocytes, eosinophils, basophils, and lymphocytes, which include NK cells, B cells, and T cells.

First Line of Defense

As a first line of defense, the skin and mucous membranes provide a physical barrier to pathogens and also secrete chemicals that can destroy or inhibit pathogens.

The first line of defense is a form of nonspecific immunity, part of the innate immune response, that includes both physical and chemical barriers necessary for preventing pathogens from entering the body. The surface of the skin contains a thick layer of dead cells. This layer provides a physical barrier that prevents most pathogens from entering the body. The body continually sheds these dead cells, which further removes pathogens that are found on the surface of the skin. Mucous membranes do not have a thick layer of dead cells. Instead, these exposed regions of the body trap pathogens and debris in viscous mucous. In some parts of the body, such as the nose or ears, hair provides a barrier that filters debris and pathogens. In the upper respiratory tract, specialized hairlike cellular projections called cilia sweep away particles including pathogens and pollutants.

The body can also expel or flush away pathogens. Vomiting, coughing, and sneezing are all mechanisms the body uses to actively expel foreign particles, irritants, or pathogens. Fluids such as tears, saliva, and urine all help wash pathogens away when they are shed or excreted. Chemical barriers also help prevent pathogens from entering the body. Lysozyme, an enzyme present in tears, saliva, and sweat, is an antibacterial agent that can digest bacterial cell walls. On the surface of the skin, sweat and sebum, which is an oily substance, combine to form the body's acidic mantle, which also helps protect the body from pathogens. Finally, the highly acidic gastric juice in the stomach destroys pathogens and toxins that enter the digestive system.

Second Line of Defense

Inflammation is a secondary line of defense feedback mechanism to injured tissue that is activated after phagocytic cells, the body’s first line of immune defense, has responded, resulting in increased blood flow to the site and mobilizing the defensive cells.

The body's second line of defense consists of the mobilization of various kinds of phagocytic cells, specifically macrophages, which attack pathogens and help initiate an inflammatory response in the body. As inflammation occurs at the localized area of tissue injury or an infection, a fever can also begin, causing the body's core temperature to rise in an attempt to kill the foreign pathogens. Derived from monocytes, a macrophage is a phagocytic cell that patrols tissues in search of pathogens. Inflammatory signals attract macrophages and other leukocytes to the area of infection or injury. When a macrophage encounters a pathogen that needs to be removed from the body, it wraps its plasma membrane around the offending microbe, cell, or particle and creates a vesicle around the particle called a phagosome. This phagosome then merges with lysosomes, which are cellular organelles filled with digestive enzymes. These digestive enzymes break down and destroy the pathogen.

When phagocytic cells such as macrophages encounter foreign particles or pathogens, they can release chemical messengers, each called a cytokine, which is a member of a family of chemical messengers that regulates several different immune functions. Cytokines regulate immune responses in several different ways. For example, macrophages release a specific cytokine called interleukin that attracts leukocytes to the site of the infection. An interferon is another type of cytokine that is released from viral-infected cells that causes a series of protective changes in neighboring cells. By sending a signal to neighboring cells, this cytokine decreases protein synthesis, thereby limiting viral proliferation and reducing the spread of a viral infection. Interferon also activates the immune system to clear away the infected cells.

Another type of immune defense initiated by proteins is the complement system, which is activated by antibodies. The complement system is made up of cell membrane proteins that are normally activated by pathogen-bound antibodies. When triggered by an antibody bound to a pathogen, however, these complement proteins form a pore that kills the cell through cytolysis, the rupture of the cell membrane that causes the cell to burst apart. The cascade of events that is initiated as a result of the complement system involves the rupturing, or bursting, of the pathogen and infected cells, ingestion of this cellular debris following rupturing with the help of phagocytic cells, and activation of an inflammatory response at the site of the tissues where these infected cells reside. Hallmark symptoms related to an inflammatory response include redness, heat, swelling, and pain.

Inflammation and fever are important parts of the second line of defense. Inflammation is described as a local response to injured tissue that results in an increased blood flow to the affected site and triggers a cell-mediated immune response if the second line of defense fails. When tissues are injured by some foreign pathogen, trauma, or microorganism, the cells in the tissues are damaged and begin releasing chemicals such as histamine that stimulate blood vessels to leak fluid into the tissue site, causing swelling. Because of this response to the tissue injury, cytokines rapidly attract leukocytes, including neutrophils and macrophages. These leukocytes exit the bloodstream through intact capillary walls and migrate to the affected tissue. This chemically directed migration, or chemotaxis, of leukocytes from the bloodstream, through capillary walls, and into surrounding tissue is called diapedesis. Diapedesis is a key feature of the body's inflammatory response. Protein signals, such as histamines and prostaglandins, are also important for inflammation. These signals are released from basophils, eosinophils, and mast cells, and they trigger vasodilation, or the expansion of blood vessels, which increases blood flow to the infected or injured area. Prostaglandins also produce fever, which is a systemic response to pathogens that inhibits bacterial growth and aids in the overall immune response by increasing leukocyte mobility and T cell proliferation.

Inflammation

Following an injury, macrophages and mast cells release chemical signals that initiate inflammation. Histamines released from mast cells cause capillaries to dilate, which increases the blood flow into the area and fluid in the injured tissue. Cytokines released by macrophages attract phagocytic cells to the site of injury, a process called diapedesis, which includes the passage of cells through capillary walls. There, phagocytic cells engulf and destroy pathogens.
Natural killer (NK) cells are lymphocytes from the lymphoid lineage that are another part of the immune system's second line of defense. These cells recognize cells infected by viruses as well as cells that have become cancerous. The NK cell identifies the infected cell or pathogen through cell membrane protein interactions. The NK cell also has inhibitory membrane proteins that prevent the release of cytotoxic granules when the NK cell identifies other lymphocytes. When activated, NK cells release cytotoxic granules that destroy the target cell.
NK cells use cytotoxic granules to destroy infected cells that the NK cell does not recognize. Macrophages envelop pathogens in a phagosome, which merges with lysosomes to break down and destroy the pathogen. Indigestible debris is expelled through exocytosis.