The Immune System

Physical Barriers

The human skin has a thick outer layer composed of dead cells that bacteria and viruses usually cannot penetrate on their own. As well, acids in sweat and oil secreted by the epidermis inhibit the progress of bacteria, while saliva, tears, and sweat contain lysozyme, an enzyme which destroys the cell membrane of some bacteria.

Even the two organ systems that are vulnerable to infection because they are open to the outside environment, the respiratory and digestive systems, have their own methods of protection; the respiratory system is lined with mucus that traps bacteria and dust, while the digestive system has hydrochloric acid that protects it.

Physical barriers defeat most pathogens, since they make it harder for pathogens to enter the body.

The Innate Immune Response

The innate immune response is an immediate, non-specific defence mechanism executed by the body to defend against pathogens that have gotten past the physical barriers of the body.

This non-specific defence is executed by non-specific defence cells, which are certain types of leukocytes including neutrophils, some monocytes, eosinophils, and basophils. Lymphocytes and macrophages are not often a part of this response, and instead take part in the Adaptive Immune Response.

Any bacteria that do get past the physical barriers of the body are confronted almost immediately by the phagocytic neutrophils and monocytes found in the interstitial fluid and blood vessels. These leukocytes engage in phagocytosis to engulf any pathogens they encounter in large amounts. See Figure 1.G to view the picture of a macrophage engulfing several bacteria.

Figure 1.G – A macrophage engaging in phagocytosis of multiple bacteria.

Proteins: Interferons

Interferons are proteins that are produced when a cell is infected by a virus. These proteins allow other cells around the infected cell protection against the virus and against other viruses. The interferons do not confer invulnerability to one specific virus; interferons released for a specific virus will protect the cell against other unrelated viruses.

Figure 1.H – The Interferon mechanism against viruses.

In Figure 1.H, the steps are:

1. Viral Nucleic Acid enters cell.
2. Interferon genes of the cell's DNA are turned on.
3. Interferon molecules are produced and released by the cell.
4. The first host cell is killed by the virus.
5. The interferons are recieved by another cell. In response, the second cell makes antiviral proteins, which block viral reproduction.

The resistance imparted by the interferons is short-termed, however, and does not last forever. Interferons are also not the only important proteins in pathogen inhibition.

Proteins: Complement Proteins

Complement proteins are so called for their cooperation with the immune system to help rid the body of pathogens. Prior to activation, they float in the bloodstream, but are actually released by the liver. After being activated by either the immune system or pathogens such as microbes, they coat the surface of the microbes, making it far easier for macrophages to identify and engulf the microbe. Furthermore, when six of the complement proteins gather to destroy one microbe, they can form a hole in the microbe’s cell membrane, causing the death of the microbe because of cellular fluids exiting the body due to the rupture in the membrane (ie. cell lysis). See Figure 1.I for a picture of this complement protein arrangement.

Figure 1.I - The way a complement protein can help the immune response.

Complement proteins also augment the inflammatory response of the innate immune response.

The Inflammatory Response

The inflammatory response is a major part of the non-specific defence system, and is activated by any damage caused to the tissues of the body, whether caused by a pathogen (such as damage caused by an infectious microorganism) or even physical injury such as that caused by a scratch or an insect bite. The affected area becomes red and swollen, or inflamed.

Figure 1.J shows the steps of the inflammatory response. In the example shown, a pin pierces through the skin surface, and infects the tissue with bacteria. The steps shown are:

1. As soon as the tissue is ruptured, the damaged cells release chemicals such as histamine, which serve as alarm signals.
2. The chemicals released activate numerous defence mechanisms in the body. For example, histamine forces nearby blood vessels to dilate and to allow more diffusion by becoming leakier. Due to this, blood flow to the affected area increases, and the plasma of the blood seeps into the interstitial fluid of the damaged tissues. Other chemicals that are released attract phagocytes and other leukocytes to the affected area. These leukocytes squeeze out of the blood vessels into the interstitial fluid and tissue spaces. This increase in blood flow, blood plasma, and white blood cells causes the redness, heat, and swelling that are normally found in inflammation.
3. The leukocytes that have been attracted to the area engulf the bacteria, and any dead body cells damaged by the pathogens or by the injury. This may result in the death of the leukocytes, as well, and their remains are also digested. Pus found at the site of infection consists mainly of white blood cells and blood plasma.

Figure 1.J – The Inflammatory Response against pathogens.

The inflammatory response has two major purposes: to disinfect and to clean injured tissues. In addition to this, the inflammatory system also helps halt the spread of pathogens to tissues not already infected. Clotting proteins that are present in the blood plasma also leak into the interstitial fluid when the blood vessels dilate and become leakier. With platelets, thromboplastin, prothrombin, fibrinogen, and calcium ions, localized clots can be formed, and healing can be underway, while the pathogens are also restricted to one area, making it easier for them to be engulfed by phagocytes.

Although the inflammatory response may be localized, as shown, it may also be widespread and in effect throughout the body. If there are numerous pathogens, or pathogens have travelled through the bloodstream and come to reside all over the body, the body will react with a widespread inflammatory response that has other effects in addition to the ones experienced in localized responses. The number of leukocytes in the blood may increase. The body may also experience abnormally high body temperatures, or fever, which may be caused by either toxins released by pathogens, or due to compounds released by specific leukocytes. Although an extremely high fever is dangerous to the body, a less extreme temperature may aid the body by stimulating phagocytosis and inhibiting the reproduction and growth of pathogens.

The Adaptive Immune System

The adaptive immune response is the only component of the immune system that confers any immunity against pathogens. It also enhances some effects of the innate immune system, such as inflammation and complement protein responses. The adaptive immune system protects the body from invading pathogens and even infected or cancerous cells, which are usually identified to be foreign.

In an adaptive immune response, a macrophage (a specific type of monocyte) engulfs a pathogen and presents the pathogen’s foreign proteins (called antigens – which are anything that triggers an immune response) on its own cell membrane. The macrophage then releases chemicals, which are responded to by two different types of lymphocytes.

When B-lymphocytes receive these chemicals, they divide and specialize to become immunocompetent B-lymphocytes. These B-lymphocytes take part in plasma-mediated immunity, whereby they produce antibodies that attach to the antigens and make the pathogen harmless. The antibodies may force many pathogens to clump together, in which case they cannot function and become an easy target for macrophages, or by the antibodies blocking vital active sites on the pathogen, whereby the pathogen is unable to function. After the pathogen has been fought off, most immunocompetent B-lymphocytes die. However, some will specialize and become memory B-cells, which contain all the information about the specific antibody-antigen combination. If that particular pathogen is encountered again in the future, the body will be able to respond to that pathogen more efficiently by rapidly cloning the memory B-cells from the previous infection.

T-lymphocytes also respond to the chemicals released by the macrophages. In their case, they divide and specialize into Cytotoxic T-cells, Helper T-cells, Memory T-cells, and Suppressor T-cells. T-cells deal primarily with cells found in the body, such as cancerous cells or cells harbouring viruses. Cytotoxic T-cells puncture any cells in the body that are infected with viruses or are cancerous. Helper T-cells connect to macrophages via a Major Histocompatibility Complex, and greatly increase the rate of cell division of all lymphocytes, helping the defence system cope with more pathogens. Memory T-cells store the chemical composition of pathogens and the attacks against them. Suppressor T-cells shut down the immune response in case the attack is against the body itself (an autoimmune response), or when the immune response is over.

The adaptive immune response can remember the antigens (and hence, the pathogens) it has encountered before, and attack them more vigorously than it did previously. Thus, exposure to a certain pathogen or foreign molecule improves future responses to that pathogen or molecule.

It is failure of part of the adaptive immune system combined with the over-zealousness of another that results in an autoimmune disease. Immune cells attacking the body are part of the T-lymphocytes’ jurisdiction – particularly the Suppressor T-cells, which normally contain any out-of-control responses where the body is attacking itself.