Non-specific defenses are the body’s first line of defense against diseases. They are not directed against a particular pathogen. Non-specific defenses guard against all infections, regardless of their cause. It is also called as innate immunity (Fig. 2).
Plants and many lower animals rely only on innate immunity and do not possess the second category of specific defense mechanisms. Nonspecific defense mechanisms work against a wide variety of invaders. Innate immunity consists of various types of barriers that prevent entry of pathogens into the body.
Barriers in Human Body:
i. Anatomic Barriers:
Anatomic barriers or physical barriers are barriers that prevent the entry of pathogens into the body.
a. The body’s most important anatomic barrier is the skin. The skin is a passive barrier to infectious agents such as bacteria and viruses. The organisms living on the skin surface are unable to penetrate the layers of dead skin at the surface.
Skin glands like the oil and sweat glands secrete acids that retard the growth of bacteria at the surface of the skin. The acidic environment can kill bacteria and other microorganisms. Sweat, saliva and tears also contain lysozyme that can attack the cell wall of bacteria.
b. Pathogens can also enter the body through the mouth and nose. However, non-specific defenses protect these openings. Mucous membranes lining the respiratory, digestive, urinary, and reproductive tracts secrete mucus that forms an effective barrier. Mucous, which is a sticky fluid traps pathogens. The mucous, cilia and hairs in the nose and throat trap viruses and bacteria.
ii. Physiological Barriers:
A number of physiological barriers protect the body against pathogens.
a. Acid secretion, i.e. HCI in the stomach destroys organisms that may enter the digestive system.
b. Lysozyme, an enzyme found in tears, saliva, sweat and tissue fluid attacks bacteria by dissolving the cell walls of many bacteria.
c. Ear wax or cerumen traps dust particles and kills bacteria and insects.
d. Complement complex is a group of 20 proteins which destroys bacteria in various ways.
e. Basic polypeptides in the blood can inactivate certain specific types of gram +ve bacteria.
f. Certain cells when infected with a virus release interferons, a class of glycoproteins. The interferons protect the surrounding uninfected cells. This is also referred to as cytokine barrier.
g. Fever occurs in the body as a response to an infection. It is not a disease and serves to inhibit the growth of disease causing microorganisms; since microorganisms can only survive within a narrow range of temperature. Therefore fever often slows down or stops growth of microorganisms.
Antipyretic drugs such as paracetamol help in lowering the set point of the thermostat and provide relief from symptoms of fever. It is advisable to take the drug only in case of extremely high temperature to avoid irreversible damage to the brain.
iii. Phagocytic or Cellular Barriers:
Phagocytosis means ‘cellular ingestion of the invading agent’. Phagocytic cells include macrophages and neutrophil granulocytes that are capable of attacking and engulfing bacteria, viruses and other invading agents that enter the blood and tissues. These cells are formed in the bone marrow and are released into the blood as need arises. These cells can move through the pores of the blood vessels by diapedesis. The macrophages together with the neutrophils form the body’s reticulo endothelial system.
Neutrophils are mature cells that can attack and destroy bacteria in circulating blood while the macrophages are formed from monocytes. The macrophages are capable of destroying intra-tissue disease agents. Macrophages are found distributed throughout the body.
Inflammatory Response:
Despite the various barriers of the human body, pathogens sometimes enter the body and cause tissue injury. Chemicals, heat, trauma etc. may also cause tissue injury. The injured cells release chemicals like histamine, serotonin, prostaglandin, reaction products of complement system, bradykinin and lymphokines (released by a type of special cell T-cells). These chemicals starts a series of changes called the inflammatory response. The inflammatory response is a non-specific defense reaction of the body to tissue damage.
Inflammation is characterised by the following changes:
a. The local blood vessels dilate considerably and cause increase in capillary blood flow into the affected area and raises the temperature locally. The heat makes the environment unfavourable for microbes, promotes healing, raises mobility of white blood cells, and increases the metabolic rate of nearby cells.
b. The permeability of the capillary wall increases. This increases the leakage of fluid into the interstitial spaces.
c. The increased leakage causes the infected/ injured area to swell. This is called Oedema.
d. Clotting factors trigger formation of many small blood clots due to excessive amount of fibrinogen and other proteins. Interferons are also released by the macrophages and other white blood cells when viral infection occurs. The interferons make the uninfected cells resistant to infection.
e. Large number of granulocytes and monocytes migrate into the tissues. These cells clean up dead microbes, cells and debris. After the onset of severe inflammation, the number of neutrophils increases from a normal 4000-5000 to about 15000-25000 per microlitre. This increase in neutrophils is called neutrophilia.
f. The macrophages and the neutrophils destroys the pathogens by phagocytosis. The inflammatory response is often strong enough to stop the spread of disease-causing agents such as viruses, bacteria and fungi to the adjoining areas. The response begins with the release of chemical signals and ends with cleanup by monocytes. If this is not enough to stop the invaders, the complement system and the specific defense mechanisms act.
After several days of inflammation in the injured tissues, varying portions of dead neutrophils and macrophages, necrotic tissue and tissue fluid accumulate. This is called pus.
Complement System:
The complement system includes a group of about 20 protective proteins that are produced in the liver. Many of them are enzyme precursors. They are found in the plasma as well as the tissue spaces. They are designated C1 through C9, B and D protein. These are normally inactive and can be activated when the need arises.
Complement proteins become active in a sequence. This is referred to as cascade mechanism, i.e. C1 activates C2, etc. The final five proteins form a membrane attack complex (MAC) that embeds itself into the plasma membrane of the attacker.
Salts enter the invader, facilitating water to cross the membrane, swelling and bursting the microbe. Complement proteins also work along with the immune response by tagging to the outer surface of invaders for attack by phagocytes and complements the actions of the immune system.
Interferons and Natural Killer Cells – Defense Against Viruses:
Two components of the immune system fight only viruses, interferons and natural killer cells. Since these components attack many types of viruses, they are considered as non-specific defenses.
a. Interferon is a protein that interferes with the replication of viruses. Interferons are species-specific chemicals produced by cells that are attacked by virus. It alerts the neighbouring uninfected cells to resist attack by the virus (Fig. 3). It slows down the progress of infection and often gives the specific defenses of the immune system time to respond. Interferon and natural killer cells also help to fight against cancer cells.
b. Natural Killer cells or NK cells are large white blood cells that, unlike phagocytes, attack cells that have been infected by pathogens, not the pathogen themselves. These cells attack body cells that have been infected by viruses. Since viruses can only replicate in a host cell, killing the host cell also destroys the virus.
Natural killer cells are particularly effective in killing cancer cells and cells infected with viruses. A natural killer cell punctures the cell membrane of its target cell, allowing water to rush into the cell, causing the cell to burst. This is called cytolysis. The NK cells also secrete cytokines that are antiviral and inflammatory in nature.