Understanding How the Immune System Works

2. What are the two groups of the defense mechanisms of the body against foreign or harmful agents? What is the difference between them?

The body has many defense mechanisms against foreign pathogenic agents. These mechanisms are divided into two groups: specific mechanisms and the nonspecific mechanisms. Specific mechanisms are part of the immune system and consist of the humoral immune response and the cellular immune response that produce antibodies and defense cells against specific antigens, respectively. Nonspecific mechanisms fight in a general manner against any type of antigen (they are not specific) and, in them, a series of defense mechanisms are included, such as the skin barrier against foreign agents, the mucous and ciliated epithelium of the airway, inflammation (the inflammatory response) and the action of nonspecific proteins and defense cells (such as interferons and macrophages).

3. What is inflammation?

Inflammation is the initial response of the nonspecific defense system against attacks on the body (the attacks may be caused by infectious parasites, chemical contamination, trauma, physical agents such as heat and fire, autoimmunity, etc.). During inflammation, a series of nonspecific leukocytes present in circulation are attracted to the injury site in an attempt to destroy the harmful agents and to isolate the affected region of the tissue.

4. How does the inflammation mechanism work?

When a tissue injury occurs, histamine and other vasoactive substances (called mediators of inflammation) are released, causing vasodilation and increasing blood flow to the affected site. Granulocyte leukocytes present in the blood are attracted to the site of the injury by substances known as chemotactic factors, which are released by the injured tissue and by the active granulocytes in the area. The granulocytes exit the capillaries via diapedesis, that is, using pseudopods. Macrophages present in the region are also activated. These cells flood the extracellular space of the affected area in an attempt to kill or eliminate the harmful agents, to prevent tissue necrosis and to isolate the damaged tissue.

• The Immune System Review - Image Diversity: the inflammation mechanism

5. What is pus?

Pus is a residue of the inflammatory reaction. It contains a mixture of fragments of dead leukocytes, infectious agents (generally bacteria) and tissues.

6. What is the association between inflammation and fever?

In the tissue region where inflammation occurs, bacterial toxins, cytokines, prostaglandins, interleukins and endothelins are released. These substances enter into circulation and reach the central nervous system, which then commands an increase in the body temperature.

7. Which type of defense cell do bacteria attract and cause to multiply during the inflammation process? What is the name given to the waste material produced by the inflammation triggered by bacterial infection?

The main leukocytes that multiply and participate in the inflammatory reaction against bacterial infections are neutrophils. In this type of inflammation, the blood level of these cells are increased, a clinical condition known as neutrophilia.

In bacterial inflammation, fragments of dead bacteria, dead neutrophils and tissue form pus.

8. What type of defense cell does worm infection stimulate to multiply?

The main leukocytes that multiply and participate in the defense against worm infections are eosinophils. In this type of inflammation, the level of these cells in the blood is increased, a clinical condition known as eosinophilia.

Eosinophils are also increased in allergic conditions.

9. What type of defense cell do viral infections stimulate to multiply?

The main leukocytes that multiply and participate in the defense against viral infections are lymphocytes. In this type of inflammation, the level of these cells in the blood is increased, a clinical condition known as lymphocytosis.

The Immune System Review - Image Diversity: lymphocytes

10. What defense mechanism begins to work when inflammation fails to stop an infection?

If the inflammatory attack is not enough to halt the infectious process, the body relies on a specific defense, the immune response (humoral and cellular), which is carried out by the lymphocytes.

11. What is the difference between a humoral specific immune response and cellular specific immune response?

Humoral specific immune response is the defense system made up by of antibodies, defense proteins secreted by lymphocytes that attack foreign agents with a high degree of specificity. Cellular specific immune response is the defense system in which specific lymphocytes (cells) directly attack other foreign cells and agents.

12. What is an antigen?

An antigen is any substance, particle or infectious agent recognized as foreign to the body. The contact of the antigen with the body triggers a defense reaction against the antigen (nonspecific, specific or both).

13. What cells are responsible for the production of antibodies?

The cells that produce antibodies, or rather, the cells of the humoral immune system, are B lymphocytes (B cells).

• The Immune System Review - Image Diversity: B cells

14. What are immunoglobulins?

Immunoglobulin is the alternate name for antibody. Immunoglobulins are complex proteins which contain an invariable portion and a variable portion and which are made of four polypeptide chains. The variable portion of each immunoglobulin is responsible for the high specificity of the antigen-antibody bond.

• The Immune System Review - Image Diversity: immunoglobulin molecule

15. How do antibodies work to neutralize antigens?

Antibodies, or immunoglobulins, act to facilitate the destruction of antigens. They attract phagocytic leukocytes, trigger the attack of specific defense molecules (activation of the complement system) and directly neutralize the toxicity of some antigens.

16. How can a body that previously came into contact with an antigen be immunized against future infections by the same agent?

This phenomenon is called immune memory. When an antigen comes into contact with cells of the humoral immune system for the first time, B lymphocytes that are producers of specific immunoglobulins against that antigen multiply and, in days, synthesize their antibodies. This is called primary response. Some of these specific B lymphocytes remain in circulation for a long time, sometimes during the entire life of the individual, and become the memory cells of the immune system. When the body is exposed to the same antigen in the future, the production of antibodies will be faster and more intense, since the immune system is already prepared to react against that antigen. This is called the secondary response.

17. How can immune memory be involved in both the effectiveness of vaccines and allergic reactions?

Vaccines are controlled inoculations of fragments of infectious agents or inactive infectious agents to induce the primary immune response, the formation of specific memory B lymphocytes against the antigen. Therefore, the body produces immunoglobulins and is prepared to destroy antigens when exposed to new infections by those agents.

In allergies, the humoral immune system is sensitized (makes antibodies and specific memory B lymphocytes) against common environmental substances wrongly recognized as antigens. For example, pollen-derived substances, dust particles, compounds present in foods or in medicines, etc. may be recognized as antigens, thus triggering the primary response and creating an immune memory against them that then becomes the cause of the allergy. The more the individual is exposed to those substances, the more intense the immune reaction is.

The IgE antibodies that cause the allergy bind to the receptors of leukocytes called mastocytes, whose cytoplasm is full of histamine granules. The antibody-mastocyte bond causes these cells to release a large amount of histamine into circulation, stimulating inflammation and generating allergic symptoms and signs. For this reason, allergies are treated with antihistamines, drugs that block the histamine reaction. Exacerbated allergic reactions, such as the hypersensitivity to some medicines like penicillin and sulfas, may cause anaphylactic shock, a severe clinical condition that sometimes results in death.

18. How different are the actions of antibodies against bacteria and viruses? Why is the cellular immune response activated in the case of chronic viral infection?

The antibodies of the humoral immune system act against extracellular agents, such as toxins or bacteria, but are not active in the intracellular space and cannot fight viruses efficiently.

In case of viral infection (and also of cancerous or precancerous cells), the immune attack is carried out by the cellular immune system, through which T and NK (natural killers) lymphocytes destroy specific cells and viruses.

19. How does the cellular immune response take place?

The lymphocytes that participate in the cellular immune response are T lymphocytes. T lymphocytes can be divided into three main types: cytotoxic T lymphocytes (cytotoxic T cell), helper T lymphocytes (helper cell) and suppressor T lymphocytes. Cytotoxic cells are the effectors of the system, meaning that they directly attack other cells recognized as foreign (for example, fungi cells, cells infected by viruses, neoplastic cells, graft cells, etc.). Helper cells and suppressor T lymphocytes act as regulators of the system by releasing substances that respectively stimulate and inhibit the immune action of T and B lymphocytes. After the primary immune response, memory T lymphocytes also remain in circulation to provide a faster and more effective reaction in the case of future infections.

• The Immune System Review - Image Diversity: T cells

20. What are the antigen-presenting cells of the immune system?

The antigen-presenting cells of the immune system, also known as APC cells, are cells that carry out phagocytosis and the digestion of foreign (to the body) microorganisms, later exposing the antigens derived from these microorganisms on the outer side of their plasma membrane. These processed antigens are then recognized by lymphocytes, which activate the immune response. Several types of cells, such as macrophages, can act as antigen-presenting cells.

• The Immune System Review - Image Diversity: antigen-presenting cells

21. What are passive and active immunization? What is the difference between these types of immunization in terms of the duration of their protection? 

Active immunization is that in when an antigen penetrates the body, triggering the primary immune response and the production of memory lymphocytes and antibodies, which then provide a faster and more effective immune defense during future infections by the same antigen. Passive immunization is when immunoglobulins against an antigen are injected into the body to provide protection in the event that the body becomes infected by the antigen.

Active immunization tends to be longer lasting than passive immunization, since in the active type,  in addition to antibodies, specific memory lymphocytes remain in the circulation. In passive immunization, the duration of the protection is the same as the duration of the antibodies in circulation.

22. Why is maternal milk important for the immune protection of a baby?

Besides being nutritionally important, maternal milk is involved in the defense of the baby against infectious agents. Shortly after delivery, the mother produces more fluid milk called colostrum, which is rich in immunoglobulins (antibodies). These antibodies are not absorbed by the baby’s circulation but rather cover the internal surface of the baby’s bowels, attacking possible antigens and making it more difficult for pathogenic bacteria to proliferate within the organ.

23. How are antivenoms produced? Why are antivenoms an example of passive immunization?

Antivenoms are obtained by the following process: the venom (antigen) is injected into other mammals, such as in horses; these animals make specific antibodies against the antigen; blood from the animals is collected and purified to obtain the antibodies; and this antibody-containing material is the antivenom. When a human being is infected by the antigen, the specific antivenom is given to him/her and the action against the antigen occurs.

Antivenoms may also be administered as a preventive measure and, since they basically consist of specific immunoglobulins against some antigen, the process is an example of passive immunization.

24. What is the difference between homologous and heterologous immunoglobulins?

Homologous immunoglobulins are human (from the same species) immunoglobulins. In the case of inoculation in animals, such as in veterinary procedures, homologous immunoglobulins from the blood of animals of the same species of the animal undergoing treatment are treated. Heterologous immunoglobulins are obtained from animals of different species from the one into which they will be injected.

Homologous immunoglobulins are safer, since it is collected from individuals of the same species of the individual into which they will be injected and therefore the risk of the antibodies being recognized as foreign and triggering an immune response is lower. Heterologous immunoglobulins are more prone to being destroyed by the antibodies of the individual.

25. What are natural active immunization and artificial active immunization?

Natural active immunization is when a prior natural infection induces the primary immune response, specific memory cells are produced and the individual becomes immune to new infections from the antigen. This is what happens in diseases that affect people only once in life, such as the mumps and chickenpox.

Artificial active immunization is when the primary immune response is caused by the inoculation of specially prepared antigens into an individual. This is the case with vaccines.

26. Why are vaccines made of the disease agent or fragments of it?

The goal of vaccines is to artificially induce a specific primary immune response (and the resulting formation of antibodies and memory cells) for a given infection or disease, in order to immunize the individual against infections by the pathogenic agent in the future.

Since each antibody does not act against a variety of antigens but rather acts only against its specific antigen, it is necessary for the immune system to come into contact with the antigen against which the immunization is intended. The recognition of specific molecular portions of each antigen causes the immune system to produce the specific variable portion of the immunoglobulins to attack that antigen. Therefore, to induce active immunization, it is necessary to inoculate the body with small parts of the infectious agent or the entire agent (dead or inactivated).

27. What types of antigenic agents may constitute vaccines?

Vaccines can be composed of dead agents of the disease, inactivated agents of the disease, inactivated toxins or fragments of the infectious agent.

Examples of some vaccines and their type of antigenic agents are: BCG, inactivated tuberculosis bacilli; the tetanus vaccine, inactivated toxin; the anti-diphtheria, inactivated toxin; antipolio Salk vaccine, dead poliovirus; antipolio Sabin vaccine, attenuated (inactivated) poliovirus.

28. Why doesn't a long lasting vaccine against the common cold yet exist?

Viruses that have a high mutation rate, such as the virus that causes the common cold, easily circumvent the action of vaccines against them. After a primary immune response (natural or artificially induced) against the virus, during the next season of infection, new mutant resistant strains appear and the protection obtained by the immune response of the last season is lost. (It can be said that this high mutation rate is a form of “immunization” discovered by these viruses.)

29. Why are vaccines used in the prevention but not in the treatment of infections? Why can antivenom serums be used in prevention and treatment?

Vaccines are not used in the treatment of infections because they depend on the primary immune response, which takes about a week to occur and is not so intense and effective. On the other hand, antivenom serums are inoculated into circulation and are used as an immediate treatment because they are made of a large amount of immunoglobulin (antibodies) which are potent against their respective specific venom.

30. What is a DNA vaccine?

A DNA vaccine, or DNA vaccination, is a vaccination technology based on genetic engineering. In DNA vaccination, a recombinant plasmid (vector) containing the gene of a specific antigen that is part of a given pathogenic agent is inserted into the cells of the individual to be immunized. These cells then begin to produce the antigen that triggers the primary immune response and, theoretically, the individual becomes immunized against that antigen.

31. What is the name given to conditions in which the immune system of an individual is the agent of diseases? What are some examples of these conditions?

Diseases caused by the action of an individual's own immune system are called autoimmune diseases.

Autoimmune diseases appear when the immune system produces antibodies or defense cells that attack cells, tissues and organs of its own body. The attacked cells or tissues are wrongly recognized as antigens by the immune system. Rheumatoid arthritis, lupus, scleroderma, vitiligo, pemphigus, type I diabetes mellitus, Crohn's disease (chronic inflammation of the gut), myasthenia gravis, Graves' disease, Hashimoto's disease, etc., are all examples of autoimmune diseases.