Immune System: Defenses, Responses, and Immunopathology
Concept of Immunity
Immunity is a set of mechanisms that an individual possesses to counter the invasion of any foreign body or to deal with tumors. This property is acquired before birth and matures and consolidates in the first years of life. In vertebrates, it implies that different agencies distinguish self from outside, i.e., recognize all cell types. The immune system is responsible for conferring immunity. This system, present even in invertebrates, reaches its greatest complexity in primates and humans. The science charged with studying these processes is called immunology.
Body Defenses Against Infection
Unspecific Defense
These are present in the body naturally and are defined as the set of mechanisms that tend to prevent the invasion of microorganisms. They are of two types: some prevent the entrance of the invading agent, and others fight it once it has penetrated.
External Innate Mechanisms
a) Physical Barriers: The skin in animals, thanks to the keratin layer, which undergoes continuous desquamation, prevents microorganisms from entering or proliferating. Thus, only its effect allows spirilla to pass through membranes.
b) Chemical Barriers: Natural orifices are lined by mucous membranes secreting mucus to cover and remove foreign particles. The mucus also has substances that deceive certain viruses, making them “believe” that they have already penetrated into the cell. The virus releases its nucleic acid, which is lost on the outside of cells that it could infect. Also, the presence of fluids in certain areas, for example, tears in the eyes or saliva in the mouth, washes away and carries microorganisms, preventing them from installing or entering. In addition, these fluids contain antimicrobial substances, e.g., saliva contains lysozyme, semen contains spermine, and so on. As a curiosity, eye infections are more common in men than in women.
c) Flora: Microorganisms present naturally in certain parts of our body, for example, bacteria that form the intestinal flora, prevent other substances secreted from installing or setting up competition for nutrients.
Internal Innate Mechanisms
If the foreign agent succeeds in bypassing the previous obstacles, both cellular and acellular responses are involved.
a) Natural Killer Cells (NK): These cells resemble lymphoid cells and kill microorganisms, infected cells, tumor cells, or foreign cells. It is not known how they are recognized. Upon joining, they destroy them by making “perforin,” a protein that creates holes in the cell membrane, attacking and killing them. They are killer cells.
b) Interferon: Proteinaceous molecules are secreted by cells infected with viruses that are picked up by adjacent cells. These are stimulated to synthesize antiviral enzymes, preventing viral proliferation by inhibiting viral genome replication, inhibiting protein synthesis, or activating NK cells to destroy infected cells.
c) The Complement: A macromolecular complex consisting of proteins that are synthesized in the liver and circulate in the blood. When any of them are activated by various substances, such as polysaccharides or antibodies, a series of chain reactions is triggered, which can have different defensive actions. For example, some of these substances can cause lysis of the cells paired with holes in their membranes, causing cell death by emptying. Other complement proteins can bind to bacterial surface proteins and thereby induce the binding of other complement molecules that attract phagocytes, which digest microorganisms coated with complement.
d) The Inflammatory Response: This is part of innate immunity and occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. Chemicals, including histamine, bradykinin, serotonin, and others, are released by damaged tissue and cause blood vessels to leak fluid into the tissues, resulting in localized inflammation. This helps to identify and isolate the foreign substance from further contact with body tissues.
Specific Defenses
Throughout the process of evolution, many organisms have become parasites of cells, including cells that defend us from them: macrophages. In these circumstances, the innate response is not effective. This is why we have developed specific defenses against them. These defenses are conducted by the immune system and, unlike non-specific mechanisms, which are always present, only develop in response to invasion by a specific foreign agent. These are cellular responses: cell-mediated and humoral (antibodies). The characteristic of this system is that it specifically targets parasites, organ transplants, cancer cells, microorganisms, and toxic substances produced by them. Individuals are born with an immune system capable of responding to self and others. During the early stages of development, this system “learns” what is proper, and this capability is called immune tolerance. This tolerance is lost when autoimmune diseases appear.
Occasionally, hypersensitivity reactions may occur: allergies, which are responses of the immune system to substances that are harmless in principle (e.g., pollen). The cells and substances that behave as foreign to the body and against which it develops a specific immune response are called antigens. Almost any macromolecule (proteins or polysaccharides, in particular) can trigger the immune response, especially if it is strange to the receiver. The lymph nodes serve as filters in the movement of microbes, foreign particles, tissue debris, and dead cells. They contain lymphocytes and macrophages, and it is inside them where interactions between immune responders occur.
The Immune Response
The agencies that develop acquired immunity will react by unleashing two responses:
The Humoral Immune Response: The purpose of this response is the production of antibodies by plasma cells. These will attach to organisms and foreign molecules with antigenic capacity, causing a series of reactions that lead to the destruction of foreign agents, which are primarily phagocytosed by macrophages. This response is directed mainly to foreign agents, such as viruses emerging from infected cells to infect new cells.
The Cellular Immune Response: The humoral response is ineffective if the foreign agents are inside the body’s own cells. The cellular response is directed to destroy these infected cells and prevent foreign agents from continuing to replicate in them.
Both act in a coordinated response against circulating pathogens, those inside the cells, and the toxins produced by them.
Immunostimulation: Vaccines and Sera
Vaccines
Vaccines are antigenic preparations made of non-virulent organisms, dead organisms, or non-toxic molecules derived from them. They are obtained from microorganisms or other infectious agents and induce in the individual active acquired immunity against these agents with minimal risk and local and general reactions. Vaccines must have two properties:
- Efficiency: They must trigger the proper immune response.
- Safety: The vaccine should be devoid of pathogenicity, achieving this goal without interfering with the immune response.
Sera
With sera, immediate immunity is achieved because inoculated biological preparations contain antibodies specific to the urgency required. It is a rapid response but less severe and lasting than that caused by vaccination. The patient does not participate in the elaboration of molecules; therefore, it is a passive acquired immunity. There are two types of sera:
- Homologous Sera: They are obtained from human sera that have antibodies to a given antigen.
- Heterologous Sera: They come from other species but contain antibodies to human pathogens.
Immunopathology
Description of Autoimmune Diseases
Immune system cells (lymphocytes, macrophages, and others) have to learn to tolerate each cell and each protein in the body so as not to attack the invaders. However, it may be the case that some immature cells respond to elements of the body itself. Normally, if an immune cell reacts to a product of the body itself while being formed in the thymus or bone marrow, it is usually destroyed or, at least, inactivated by the body itself. However, despite this security mechanism, some cells may escape inactivation or destruction and trigger an immune response against molecules or cells from the body itself, producing autoimmune diseases. Autoimmune diseases can affect any organ, although some are affected more often than others.
Transplant Rejection
For some time, the technique of transplantation has been used to solve situations that endanger the health of an individual. In a transplant, damaged tissue or organ is removed, and another is introduced that is suitable for the survival of the recipient. In an autograft, the transplant comes from the same body, and the tissue is simply moved from one position to another. This always succeeds if appropriate aseptic surgical techniques are used. Transplants also succeed when the donor and recipient are genetically identical twins.
Another possibility is between individuals of the same species but genetically different. Also, sometimes transplants are performed between individuals of different species, xenografts, as between man and pig. In the latter two cases, the transplanted tissue will generate, by the receiver, a destructive immune response called rejection. It originates from the existence of surface proteins in the membranes (MHC molecules) that are recognized as foreign, triggering a specific immune response. To avoid these problems, transplant immunologists perform preliminary tests of histocompatibility.