The adaptive immune system cells are called lymphocytes which are a special type of leukocyte. Major types of lymphocytes include B cells and T cells derived from bone hematopoietic stem cells found in the bone marrow. While T cells are involved in cell-mediated immune response, B cells are involved in the humoral immune response.
Both T cells and B cells contain receptor molecules that are used to recognize specific targets. T cells can recognize a non-self target like a pathogen only after antigens (small part of the pathogen) has been processed together in combination with a self receptor referred to as a major histomcompatbility complex (MHC) molecule. There includes two major types of T cells which are the helper T cells and the killer T cells. While Killer T cells can only recognize antigens coupled with a Class I MHC molecule, helper T cells only can recognize antigens that are coupled with Class II MHC molecules.
On the other hand, B cell antigen-specific receptors are an antibody molecule that exists on the surface of the B cell and recognize pathogens without needing any antigen processing. Different B cells express a different antibody, thus the complete set of B cell antigen receptors is the representation of all the antibodies that the body can make.
Killer T cells kill cells that are infected with viruses and/or other pathogens or cells that are damaged or dysfunctional. Similar to B cells, the different types of T cells recognize a different antigen. Killer T cells are then activated when their respective T cell receptor (TCR) binds to the specific antigen which is in a MHC Class I complex receptor of another cell. CD8, a co-receptor on the T cell helps recognition of this MHC antigen complex. T cells travel throughout the body searching for cells in which the MHC I receptors contain this antigen. When an activated T cell comes in contacts with these cells, it releases cytotoxins which results in the formation of pores in the target cell’s plasma membrane which allows water, toxins, and ions to enter. The entry of granulysin which is another toxin causes the target cell to undergo apoptosis which is basically the self-destruction of the cell. The T cells that kill hosts cells are extremely important in preventing viruses from replicating. T cell activation is controlled extremely tightly and usually requires a really strong MHC/antigen activation signal provided by helper T cells.
When B and T cells begin to replicate, some of the offspring that they produce will end up becoming long-lived memory cells. These memory cells will remember all specific pathogens encountered during the animal’s lifetime and can thus call forth a strong response if the pathogen ever invades the body again. This is called “adaptive immune system” since it is a result of an adaptation to an infection with the pathogen during the individual’s lifetime and continues to prepare the immune system for potential future pathogens. Immunological memory can either be in active long-term memory or passive short-term memory.
Newborn infants are particularly vulnerable to infections since they have no prior exposure to pathogens. Thus, the mother protects the infant through several layers of passive protection. During pregnancy, TgG, which is a certain type of antibody, is transported to the baby from the mother through the placenta so even babies have high levels of antibodies that have similar antigen specificities as the mother. Even breast milk contains antibodies that are transferred to the infant’s gut and protect against bacterial infections until the baby is capable of making its own antibodies. Since the fetus isn’t making any memory cells or antibodies, it is called passive immunity. The passive immunity is short-lived, ranging from a couple days to a couple months.
Following an infection, long-term active memory is acquired by activation of B and T cells. Vaccinations take advantage of this by artificially generating active immunity. During a vaccination, the antigen of a pathogen is introduced into the body and stimulates the immune system to develop a specific immunity against that pathogen without actually causing the disease that the pathogen brings. This deliberate introduction of the pathogen is successful since it exploits the immune system’s natural specificity and its inducibility. Vaccination is an extremely effective manipulation of the immune system that helps fight diseases.
Many bacterial vaccinations are the acellular components of the microorganisms while viral vaccinations are the live attenuated viruses as well as harmless toxin components. Since bacterial vaccines derived from acellular components do not induce a strongly adaptive response, most of the bacterial vaccines are thus provided in addition with adjuvants that activate the antigen-presenting cells that are existent in the innate immune system to maximize the immunogenicity.
Immunodeficiencies occurs in a human when parts of the immune system are inactive. Since a component is inactive, its ability to respond to pathogens is reduced . Common causes of poor immune function are obesity, drugs, and alcohol. The most common cause of immunodeficiency is malnutrition in developing countries. The lack of sufficient proteins often result in impaired complement activity, cell-mediated immunity, cytokine production, and phagocyte function. Deficiency of single nutrients also reduces the immune responses. Also the loss of the thymus either through a genetic mutation of removal through surgery also results in severe immunodeficiency as the animal becomes high susceptible to infection.
Immunodeficiency can also be acquired or inherited. An example of inherited immunodeficiency is the chronic granulomatous disease in which the phagocytes’ ability to destroy pathogens have been reduced. An example of an acquired immunodeficiency is AIDS and some types of cancer.
Autoimmunity occurs when there is an overactive immune response resulting in autoimmune disorders. In these disorders, the immune system is unable to properly distinguish between itself and non-self and as a result, attacks its own body. Usually, the antibodies and T cells react with self peptides. To prevent autoimmunity, one of the functions of specialized cells, often found in the thymus and bone marrow, is to have young lymphocytes that have self antigens produced throughout the body and to get rid of the cells that recognize self-antigens.
Hypersensitivity happens when the immune response damages the body’s own tissues. There are four classes of hypersensitivity (Type I-IV). Type I hypersensitivity is an anaphylactice reaction often associated with allergies. The symptoms have a huge range anywhere from just mild discomfort to death. Type I hypersensitivity is often mediated by IgE which is released from basophils and mast cells. Type II hypersensitivity occurs when the antibodies bind to the antigens on the animal’s own cells marking them for destruction often referred to as antibody-dependent hypersensitivity. Type III hypersensitivity reactions are often triggered by immune complexes that are deposited in various tissues. Delayed type hypersensitivity or Type IV hypersensitivity, involve many autoimmune and infectious diseases and often take two to three days to develop. These are often mediated by macrophages, monocytes, and T cells.
An important role that the immune system serves is to identify and eliminate tumors. The tumor’s transformed cells express antigens that aren’t normally found on normal cells. These antigens appear foreign to the immune system and when near tumors, the immune cells attack the transformed tumor cells. The antigens that are expressed by the tumors come from various sources including papillomavirus which is derived from an oncogenic virus which often results in cervical cancer while other sources are the organism’s own proteins that normally only have low levels in normal cells but reach unusually high levels in tumor cells. An example of this is the enzyme tyrosinase that can transform certain skin cells into tumor cells called melanomas when expressed at really high levels. Another source of tumor antigens are the mutation of proteins that are normally important for survival regulating cell growth into cancer inducing molecules.
The main response that the immune system uses for tumors is to use killer T cells to with the assistance of helper T cells to destroy the abnormal cells. The tumor antigens that are present on MHC class I molecules are really similar to viral antigens. This similarity allows the killer T cells to recognize tumor cells as abnormal. NK cells kill tumor cells as well in similar ways especially if on their surface, there are fewer than normal MHC class I molecules; this is a common trait with tumors. Sometimes there are antibodies that are generated against tumor cells to destroy them.
However, some tumors evade the immune system and end up causing cancer. Since the tumor cells often have only a reduced MHC class I molecule count on their surface, they often avoid detection by the killer T cells. Some of the tumor cells release products that inhibit the immune response as well like when they secrete the cytokine TGF-B which is known to suppress the activity of lymphocytes and macrophages. Also sometimes the immune system doesn’t attack the tumor cells anymore when immunological tolerance is developed against tumor antigens.
Macrophages can promote the growth of tumors and thus tumor cells release cytokines that can attract macrophages that release cytokines and growth factors that end up nurturing the tumors for development. Both the combination of hypoxia in the tumor and the cytokines that are released by the macrophages induce tumor cells that decrease the production of a protein that often blocks metastasis that help the spread of cancer cells.
The pathogen’s success is depends on its ability to evade the host’s immune responses. Thus, pathogens have evolved several methods allowing them to infect a host successfully by evading detection and destruction by the immune system. Bacteria usually overcome the physical barriers by secreting enzymes to digest the barrier like type II secretion system. They also use a type III secretion system that allows them to insert a hallow tube providing a direct route for the proteins to enter the host cell. These proteins often shutdown the defenses of the host.
Some pathogens avoid the innate immune system by hiding within the cells of the host also referred to as intracellular pathogenesis. The pathogen hides inside the host cell where it is protected from direct contact with the complement, antibodies, and immune cells. A lot of pathogens release compounds that misdirect of diminish the host’s immune response. Some bacteria even form biofilms which protects them from the proteins and cells of the immune system. Many successful infections often involve biofilms. Some bacteria create surface proteins that will bind to antibodies making them ineffective such as Streptococcus.
Other pathogens invade the body by changing the non-eseential epitopes on their surface rapidly while keeping the essential epitopes hidden. This is referred to as antigenic variation. HIV rapidly mutates so the proteins that are on its viral envelope which are essential for its entry into the host’s target cell are consistently changing. Since these antigens are changing so much, this is why vaccines have not been invented. Another common strategy that is used is asking the antigens with host molecules thus evading detection by the immune system. With HIV, the envelope covering the viron is created from the host cell’s outmost membrane making it hard for the immune system to identify it as a non-self structure.
The immune response system can be manipulated so that the unwanted responses that occur from allergy and autoimmunity can be suppressed. It can also be manipulated to heighten the protective responses against pathogens that evade the immune system. Autoimmune disorders, inflammation due to excessive tissue damage, and prevention of transplant rejection after donation of an organ transplant are controlled by immunosuppressive drugs. Anti-inflammatory drugs are used to control effects of inflammation, however with undesirable side effects such as osteoporosis. Thus anti-inflammatory drugs are often used with immunosuppressive drugs. Cytotoxic drugs can inhibit the immune system by destroying dividing cells like activated T cells. However, the negative part is that it is indiscriminate killing and other constantly dividing cells are also affected resulting in toxic side effects.
Larger drugs can promote a neutralizing immune response especially if it is repeatedly administered or in large doses. This thus limits its effectiveness based on larger proteins and peptides. Methods have been made to predict the immunogenicity of proteins and peptides which is particular useful when designing therapeutic antibodies. Earlier techniques often relied on the observation that hydrophilic amino acids are often more represented in epitope regions than hydrophobic amino acids.
An immune response is triggered by the presence of a foreign macromolecule, often a protein or carbohydrate; these are known as an antigen. For example, immunoglobins exist on the surface of B cells.
An innate immune system response is usually triggered by microbes identified by pattern recognition receptors. These defenses are non-specific and does not have long-lasting immunity against a foreign agent, but it is the most dynamic way a defense system responds in most organisms.The innate immune system functions to recruit immune cells to the infection site by producing cytokines, activate complement cascade to identify pathogen, assist white blood cells in identification, and activation of the adaptive immune system through antigen presentation.