| Understand the Immune Defense System
1. What is the function of the immune system?
The immune system performs specific defense against agents, the antigens, that are foreign or harmful to the body.
Exogenous antigens are often in contact with the skin or entering the airway, the digestive tube and the genital orifices and mucosae. They can also penetrate the circulation directly through wounds.
2. What are the two groups of 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: the specific mechanisms and the unspecific mechanisms. The specific mechanisms are part of the immune system and comprehend the humoral immune response and the cellular immune response that respectively produce antibodies and defense cells against specific antigens. The unspecific mechanisms fight in a general manner any type of antigen (they do not have specificity) and in them a series of defense means are included, like the skin barrier against foreign agents, the mucous and ciliated epithelium of the airway, inflammation (the inflammatory response) and the action of unspecific proteins and defense cells (e.g., interferons and macrophages).
3. What is inflammation?
Inflammation is the initial response of the unspecific defense system versus aggressions against the body (the aggressions may be caused by infectious parasites, chemical contamination, trauma, physical agents like heat and fire, autoimmunity, etc.). During inflammation a series of unspecific leukocytes present in the circulation are attracted to the injury site in an attempt to destroy harmful agents and to isolate the affected region of the tissue.
4. How does the inflammation mechanism work?
When some tissue injury occurs histamine and other vasoactive substances (called mediators of inflammation) are released, they cause vasodilation and the blood flow to the affected site increases. Granulocyte leukocytes present in the blood are attracted to the site of the injury by substances known as chemotactic factors also released by the injured tissue and by the active granulocytes in the area. The granulocytes exit the capillaries by diapedesis, i.e., using pseudopods. Macrophages present in the region are activated too. These cells flood the extracellular space of the affected area trying to kill or eliminate harmful agents, to prevent tissue necrosis and to isolate the damaged tissue.
The Immune System - Image Diversity: inflammation mechanism
5. What is pus?
Pus is a residual 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 gain the circulation and reach the central nervous system which then commands the increase of 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 generally multiply and participate in the inflammation reaction against bacterial infections are the neutrophils. In this type of inflammation the blood level of these cells are increased, a clinical condition known as neutrophilia.
In the bacterial inflammation fragments of dead bacteria, dead neutrophils and tissues form the pus.
8. Of which type of defense cell do worm infections stimulate the multiplication?
The main leukocytes that generally multiply and participate in the defense against worm infections are the eosinophils. In this type of inflammation the blood level of these cells are increased, a clinical condition known as eosinophilia.
Eosinophils are also increased in allergic conditions.
9. Of which type of defense cell do viral infections stimulate the multiplication?
The main leukocytes that generally multiply and participate in the defense against viral infections are the lymphocytes. In this type of inflammation the blood level of these cells are increased, a clinical condition known as lymphocytosis.
The Immune System - Image Diversity: lymphocytes
10. What is the defense mechanism that begins to work when inflammation fails to stop an infection?
If the inflammatory attack is not enough to halt the infectious process the body still relies on a specific defense, the immune response proper (humoral and cellular) performed by the lymphocytes.
11. What is the difference between humoral specific immune response and cellular specific immune response?
Humoral specific immune response is the defense system by means of antibodies, defense proteins secreted by lymphocytes that attack foreign agents with high specificity. Cellular specific immune response is the defense system by means of specific lymphocytes (cells) that directly attack other foreign cells and agents.
12. What is an antigen?
Antigen is any substance, particle or infectious agent recognized as foreign to the body. The contact of the antigen with the body promotes a defense reaction against the antigen (unspecific, specific or both).
13. What are the cells responsible for the production of antibodies?
The cells that produce antibodies, i.e., the cells of the humoral immune system, are the B lymphocytes (B cells).
The Immune System - Image Diversity: B cells
14. What are immunoglobulins?
Immunoglobulin is the alternate name given to antibody. Immunoglobulins are complex proteins containing an invariable portion and a variable portion and 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 - Image Diversity: immunoglobulin molecule
15. How do antibodies work to neutralize antigens?
The antibodies, or immunoglobulins, act to facilitate the destruction of antigens: they attract phagocytic leukocytes, they trigger the attack of specific defense molecules (activation of the complement system) and they directly neutralize the toxicity of some antigens.
16. How can an organism that once underwent contact with an antigen be immunized against future infections by the same agent?
This phenomenon is called immune memory. When an antigen makes contact for the first time with cells of the humoral immune system, 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 the circulation for a long time, sometimes during the entire life of the individual, and they become the memory cells of the immune system. When the body is exposed in the future to the same antigen 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 the immune memory lead to the efficacy of vaccines and also produce allergies?
Vaccines are controlled inoculations of fragments of infectious agents or of inactive infectious agents to induce the primary immune response, the formation of specific memory B lymphocytes against the antigen. Therefore the organism produces immunoglobulins and becomes 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 some 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 triggering the primary response and creating an immune memory against them that then become causes of allergy. The more the individual is exposed to those substances the more intense is the immune reaction.
The IgE antibodies that cause allergy bind to receptors of leukocytes called mastocytes whose cytoplasm is full of histamine granules. The antibody-mastocyte bond causes these cells to release a great amount of histamine in the circulation, stimulating inflammation and generating the allergic symptoms and signs. For this reason allergy is treated with antihistamines, drugs that block the histaminic reaction. Exacerbated allergic reactions, for example, in hypersensitivity to some medicines like penicillin and sulfas, may cause anaphylactic shock, a severe clinical condition that sometimes leads to death.
18. How different are the actions of antibodies against bacteria and against virus? Why is the cellular immune response activated in case of chronic viral infection?
The antibodies of the humoral immune system act against extracellular agents, like toxins or bacteria, but they are not active in the intracellular space and they cannot fight virus efficiently.
In case of viral infection (and also of cancerous or precancerous cells) the immune attack is made by the cellular immune system, mediated by T and NK (natural killers) lymphocytes that destroy specific cells and virus.
19. How does the cellular immune response take place?
The lymphocytes that participate in the cellular immune response are the T lymphocytes. T lymphocytes differentiate into three main types: cytotoxic T lymphocytes (cytotoxic T cell), helper T lymphocytes (helper cell) and suppressor T lymphocytes. The cytotoxic cells are the effectors of the system, i.e., they directly attack other cells recognized as foreign (for example, fungi cells, cells infected by virus, neoplastic cells, graft cells, etc.). The helper cells and the suppressor T lymphocytes act as regulators of the system 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 the circulation to provide faster and more effective reaction in case of future infections.
The Immune System - 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 do phagocytosis and digestion of foreign (to the body) microorganisms and later expose antigens derived from these microorganisms in the outer side of their plasma membrane. These processed antigens are then recognized by lymphocytes that activate the immune response. Several types of cells, like the macrophages, can act as antigen-presenting cells.
The Immune System - Image Diversity: antigen-presenting cells
21. What are passive and active immunization? According to the duration of the protection how do these types of immunization differ?
Active immunization is that in which an antigen penetrates the body triggering the primary immune response and the production of memory lymphocytes and antibodies that provide faster and more effective immune defense in future infections by the same antigen. Passive immunization is that in which immunoglobulins against an antigen are inoculated in the body to provide protection in case the body becomes infected by the antigen.
Active immunization tends to be longer lasting than passive immunization since in the active type as well as antibodies, specific memory lymphocytes remain in the circulation. In the passive immunization the duration of the protection is that of the duration of the antibodies in the circulation.
22. Why is maternal milk important for the immune protection of the baby?
Besides being nutritionally important, maternal milk participates in the defense of the baby against infectious agents. Soon after delivery the mother produces a more fluid milk called colostrum that is rich in immunoglobulins (antibodies). These antibodies are not absorbed by the baby’s circulation but they cover the internal surface of the baby’s bowels thus attacking possible antigens and making more difficult the proliferation of pathogenic bacteria 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 inoculated into other mammals, e.g., in horses; these animals make specific antibodies against the antigen; blood from the animals is collected and purified to get the antibodies; 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 it is basically made 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 immunoglobulin is the human (from the same species) immunoglobulin. In case of inoculation in animals as in veterinary procedures homologous immunoglobulin is that from the blood of animals of the same species of the animal undergoing treatment. Heterologous immunoglobulin is that obtained from animals of different species from the individual into which it will be inoculated.
The homologous immunoglobulin is safer since it is collected from beings of the same species of the individual in which it will be inoculated and thus the risk of the antibodies to be recognized as foreign and to trigger an immune response is lower. Heterologous immunoglobulins are more prone to being destroyed by the own antibodies of the individual.
25. What are natural active immunization and artificial active immunization?
Natural active immunization is that in which a previous natural infection induces the primary immune response, specific memory cells are produced and the individual becomes immune to new infections with the antigen. This is what happens in diseases that affect people only once in life, like mumps and chickenpox.
Artificial active immunization is that in which the primary immune response is caused by the inoculation into an individual of specially prepared antigens. This is the case with vaccines.
26. Why are vaccines made of the own disease agent or of fragments of it?
The goal of vaccines is to artificially induce a specific primary immune response (and the consequent formation of antibodies and memory cells) concerning 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 instead it acts only against its specific antigen, it is necessary for the immune system to make contact in some way with the antigen against which the immunization is wanted. The reconnaissance 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 the active immunization it is necessary to inoculate into the body small parts of the infectious agent or the agent entirely (dead or inactivated).
27. What are the types of antigenic agents that may constitute vaccines?
Vaccines can be constituted of dead agents of disease, of inactivated agents of disease, of inactivated toxins or of fragments of the infectious agent.
Examples of some vaccines and their type of antigenic agents are: BCG, inactivated tuberculosis bacilli; antitetanic vaccine, inactivated toxin; antidiphtheric, inactivated toxin; antipolio Salk, dead poliovirus; antipolio Sabin, attenuated (inactivated) poliovirus.
28. Why doesn't a long lasting vaccine against common cold exist yet?
Viruses that present a high mutation rate like the virus that causes the common cold escape easily from the action of vaccines against them. After a primary immune response (natural or artificially induced) against the virus in the next season of infection new mutant resistant strains appear and the protection obtained with the immune response of the last season is lost. (One could say that the high mutation rate is a form of “immunization” found 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 that takes about a week to occur and is not so intense and effective. Antivenom serums however are inoculated into the circulation and used as an immediate treatment because they are made of a great amount of immunoglobulin (antibodies) which is potent against their respective specific venom.
30. What is the DNA vaccine?
The 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 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 own immune system of the individual is the agent of diseases? What are some examples of these conditions?
Diseases caused by the action of the own immune system of the individual are called autoimmune diseases.
The autoimmune diseases appear when the immune system makes 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.
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