The immune system is a host defense system consisting of many biological structures and processes within an organism that protects against disease. In order to function properly, the immune system must detect a variety of agents, known as pathogens, from viruses to parasitic worms, and differentiate them from the healthy tissues of the organism itself. In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system, or humoral immunity versus cellular immunity. In humans, the blood-brain barrier, cerebrospinal blood-barrier, and similar fluid-like barrier separate the peripheral immune system from the neuroimmune system, which protects the brain.
Pathogens can quickly evolve and adapt, thereby avoiding detection and neutralization by the immune system; However, various defense mechanisms have also evolved to recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria have an imperfect immune system in the form of enzymes that protect against bacteriophage infections. Other basic immune mechanisms evolved in ancient eukaryotes and remained in their modern descendants, such as plants and invertebrates. These mechanisms include phagocytosis, an antimicrobial peptide called defensins, and complement system. Jumped vertebrates, including humans, have more sophisticated defense mechanisms, including adaptability over time to identify specific pathogens more efficiently. Adaptive (or acquired) immunity creates immunological memory after an initial response to a particular pathogen, leading to an improved response for subsequent encounters with the same pathogen. This acquired immune process is the basis of vaccination.
Immune system disorders can cause autoimmune diseases, inflammatory diseases and cancer. Immunodeficiency occurs when the immune system is less active than usual, resulting in recurrent and life-threatening infections. In humans, immunodeficiency can be the result of genetic diseases such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS, or immunosuppressive drug use. In contrast, autoimmunity results from hyperactive immune systems attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimoto's thyroiditis, rheumatoid arthritis, type 1 diabetes mellitus, and systemic lupus erythematosus. Immunology includes the study of all aspects of the immune system.
Video Immune system
Sejarah imunologi
Immunology is the study of the structure and function of the immune system. It comes from drugs and early studies on the causes of immunity to disease. The earliest known reference to immunity was during the outbreak of Athens in 430 BC. Thucydides notes that people who have recovered from previous disease attacks can treat the sick without having the disease a second time. In the 18th century, Pierre-Louis Moreau de Maupertuis made experiments with scorpion poison and observed that certain dogs and rats are immune to this poison. These observations and other observations about acquired immunity were later exploited by Louis Pasteur in the development of vaccinations and the proposed germ disease theory. Pasteur's theory goes against the contemporary theory of disease, such as the theory of miasma. It was not until Robert Koch's 1891 proof, that he was awarded the Nobel Prize in 1905, that microorganisms were confirmed as the cause of infectious diseases. The virus was confirmed as a human pathogen in 1901, with the discovery of a yellow fever virus by Walter Reed.
Immunology made great progress toward the end of the nineteenth century, through rapid development, in the study of humoral immunity and cellular immunity. Most important is the work of Paul Ehrlich, who proposed a side-chain theory to explain the specificity of antigen-antibody reactions; his contribution to the understanding of humoral immunity was recognized by the Nobel Prize in 1908, jointly given to the founder of cellular immunology, Elie Metchnikoff.
Maps Immune system
Layered defense
The immune system protects the organism from infection with a layered defensive enhancing specificity. In simple terms, physical barriers prevent pathogens such as bacteria and viruses entering the organism. If a pathogen breaks through this barrier, the innate immune system responds directly, but is not specific. The innate immune system is found in all plants and animals. If the pathogen successfully avoids the innate response, the vertebrates have a second layer of protection, the adaptive immune system, which is activated by a congenital response. Here, the immune system adjusts its response during infection to increase its recognition of pathogens. This enhanced response is then maintained after the pathogen is removed, in immunological memory, and allows the adaptive immune system to perform faster and stronger attacks each time the pathogen is encountered.
Innate and adaptive immunity depends on the ability of the immune system to distinguish between self molecules and non-self. In immunology, the self molecule is a body component of an organism that can be distinguished from foreign substances by the immune system. In contrast, the non-self molecule is a molecule known as a foreign molecule. A class of non-self molecules is called an antigen (the abbreviation of anti body gene erators) and is defined as a substance that binds to specific immune receptors and obtains an immune response.
The innate immune system
Microorganisms or toxins that successfully enter the organism meet the cells and mechanisms of the innate immune system. The innate response is usually triggered when the microbe is identified by the pattern recognition receptor, which recognizes components that are conserved among large groups of microorganisms, or when damaged cells, injuries or stress send alarm signals, many of which (but not all) are recognized. by the same receptor as the receptor that recognizes the pathogen. The innate immune defenses are not specific, meaning they respond to pathogens in a generic way. This system does not provide long-term immunity to pathogens. The innate immune system is the dominant host defense system in most organisms.
Surface barriers
Some barriers protect the organism from infection, including mechanical, chemical, and biological barriers. The wax cuticle of most leaves, exoskeleton insects, shells and eggs are stored externally, and the skin is an example of the mechanical barrier that is the first line of defense against infection. However, since organisms can not be completely sealed from their environment, other systems act to protect body openings such as the lungs, intestines, and genitourinary tracts. In the lungs, coughing and sneezing mechanically secrete pathogens and other irritants from the respiratory tract. The act of flushing the tears and urine also mechanically expels the pathogens, while the mucus secreted by the respiratory tract and gastrointestinal tract serves to trap and involve microorganisms.
Chemical barriers also protect against infection. Skin and respiratory tracts secrete antimicrobial peptides such as -defensin. Enzymes such as lysozyme and A2 phospholipase in saliva, tears, and breast milk are also antibacterial. Vaginal secretions serve as a chemical barrier after menarche, when they become slightly acidic, while semen contains defensin and zinc to kill pathogens. In the stomach, gastric acid and proteases serve as a strong chemical resistance against the pathogen that is digested.
In the genitourinary and gastrointestinal tract, commensal flora serves as a biological barrier by competing with pathogenic bacteria for food and space and, in some cases, by changing conditions in their environment, such as pH or iron available. As a result of the symbiotic relationship between the komensal and the immune system, the probability that the pathogen will reach an amount sufficient to cause the disease is reduced. However, since most antibiotics do not specifically target the bacteria and do not affect the fungus, oral antibiotics may cause "overgrowth" of the fungus and cause conditions such as vaginal candidiasis (yeast infection). There is good evidence that the introduction of probiotic flora, such as pure lactobacilli cultures commonly found in unpasteurized yoghurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encourage preliminary data in studies of bacterial gastroenteritis, inflammatory bowel. disease, urinary tract infections and post-surgical infections.
Inflammation
Inflammation is one of the first responses of the immune system to infection. The symptoms of inflammation are redness, swelling, heat, and pain, caused by increased blood flow to the tissues. Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes). Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines promoting chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in host cells. Growth factors and cytotoxic factors can also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of damaged tissue after the removal of pathogens.
Complementary system
The complement system is a biochemical cascade that attacks the surface of foreign cells. It contains more than 20 different proteins and is named for its ability to "complement" the killing of pathogens by antibodies. Complement is the main humoral component of the innate immune response. Many species have complementary systems, including non-mammals such as plants, fish, and some invertebrates.
In humans, this response is activated by a complement that binds to antibodies attached to these microbes or the binding of a complementary protein to carbohydrates on the microbial surface. This recognition signal triggers a quick killing response. The speed of response is the result of signal strengthening that occurs after sequential proteolytic sequencing of complementary molecules, which is also a protease. After supplementing proteins that initially bind to microbes, they activate their protease activity, which in turn activates other complementary proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlling the positive feedback. The cascade produces peptide production that attracts immune cells, increases vascular permeability, and opsonizes the surface of the pathogen, marking it for destruction. These complementary deposits can also kill cells directly by disrupting their plasma membranes.
Mobile restraint
Leukocytes (white blood cells) act like single-celled independent organisms and are the second group of innate immune systems. Congenital leukocytes include phagocytes (macrophages, neutrophils, and dendritic cells), congenital lymphoid cells, mast cells, eosinophils, basophils, and natural killer cells. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by swallowing and then killing microorganisms. Innate cells are also an important mediator in the development of lymphoid organs and activation of the adaptive immune system.
Phagocytosis is an important feature of cellular innate immunity performed by cells called phagocytes that ingest, or eat, pathogens or particles. Phagocytes generally patrol the body looking for pathogens, but can be called to specific locations by cytokines. Once the pathogen is engulfed by the phagocytes, it is trapped in an intracellular vesicle called the phagosome, which then joins the other vesicle called lysosomes to form phagolisosomes. The pathogen is killed by the activity of the digestive enzyme or after a respiratory outburst that releases free radicals into the phagolysosome. Phagocytosis evolves as a means of obtaining nutrients, but this role is extended in phagocytes to include pathogen buildup as a defense mechanism. Phagocytosis may be the oldest form of host defense, because phagocytes have been identified in vertebrate and invertebrate animals.
Neutrophils and macrophages are phagocytes that travel throughout the body in an attempt to invade pathogens. Neutrophils are commonly found in the bloodstream and are the most abundant type of phagocytes, typically representing 50% to 60% of the total leukocyte circulation, and consist of neutrophil-killer and neutrophil-cager sub-populations. During the acute phase of inflammation, mainly as a result of bacterial infection, neutrophils migrate toward inflammation in a process called chemotaxis, and usually the first cell arrives at the scene of the infection. Macrophages are multi-purpose cells that reside within the tissues and produce a variety of chemicals including enzymes, complement proteins, and cytokines, while they can also act as carcasses that cleanse the body of obsolete cells and other debris, and as presenting antigen. which activates the adaptive immune system.
Dendritic cells (DCs) are phagocytes in tissues that are in contact with the external environment; therefore, they are primarily in the skin, nose, lungs, stomach, and intestines. They are named for their resemblance to neuronal dendrites, because they have many spinal projections, but dendritic cells are not at all connected to the nervous system. Dendritic cells act as a link between body tissue and the innate and adaptive immune system, as they present antigens to T cells, one of the key cell types of the adaptive immune system.
Mast cells are in connective tissue and mucous membranes, and regulate the inflammatory response. They are most commonly associated with allergies and anaphylaxis. Basophils and eosinophils are associated with neutrophils. They secrete chemical mediators involved in defense against parasites and play a role in allergic reactions, such as asthma. Natural killer cells (NK cells) are leukocytes that attack and destroy tumor cells, or cells that have been infected by the virus.
Natural killer cell
Natural killer cells, or NK cells, are lymphocytes and components of the innate immune system that do not attack directly to attack microbes. Instead, NK cells destroy host cells that are compromised, such as tumor cells or virus-infected cells, recognizing these cells with a condition known as "missing self". This term describes cells with low-level surface cell markers called MHC I (major histocompatibility complex) - situations that can appear in host cell virus infection. They were named "natural killers" because of the initial idea that they did not require activation to kill cells that "lost themselves." For years it was not clear how NK cells recognize tumor cells and infected cells. It is now known that MHC makeup on the surface of cells is altered and NK cells become activated through the recognition of "lost self". Normal body cells are not recognized and attacked by NK cells because they express the full MHC antigen. The MHC antigen is acknowledged by the killer cell immunoglobulin receptor (KIR) which basically brakes on the NK cell.
Adaptive immune system
The adaptive immune system evolved in the early vertebrates and enabled a stronger immune response and immunological memory, in which each pathogen was "remembered" by the signature antigen. The adaptive immune response is antigen-specific and requires the introduction of certain "non-self" antigens during a process called antigen presentation. The antigen specificity makes it possible to produce responses tailored to specific pathogens or pathogen-infected cells. The ability to install this customized response is maintained in the body by "memory cells". If a pathogen infects the body more than once, these specific memory cells are used to remove it rapidly.
Lymphocyte
Adaptive immune system cells are a special type of leukocytes, called lymphocytes. B cells and T cells are the main types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are involved in the cell-mediated immune response.
Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize "non-self" targets, such as pathogens, only after antigens (small fragments of pathogens) have been processed and presented in combination with self-receptors called major histocompatibility complex (MHC) molecules. There are two major subtypes of T cells: killer T cells and helper T cells. In addition there are regulatory T cells that have a role in modulation of the immune response. Killer T cells only recognize antigens combined with Class I MHC molecules, while helper T cells and regulatory T cells only recognize antigens that are coupled to Class II MHC molecules. These two mechanisms of representation of these antigens reflect the different roles of the two T cell types. The third third subtype is? T cells that recognize intact antigens that are not bound to MHC receptors. Double-positive T cells are exposed to various self-antigens in the thymus, where iodine is necessary for the development and activity of the thymus.
In contrast, the B cell-specific antigen receptor is an antibody molecule on the surface of cell B, and recognizes all pathogens without the need for antigen processing. Each line of cell B expresses different antibodies, so the complete set of B cell antigen receptors represents all the antibodies that the body can produce.
Killer T cells
Killer T cells are sub-groups of T cells that kill infected cells (and other pathogens), or are otherwise damaged or dysfunctional. Like cell B, each type of T cell recognizes a different antigen. Killer T cells are activated when T-cell receptors (TCRs) bind to this specific antigen in complexes with Class I MHC receptors from other cells. The introduction of this MHC: antigen complex is assisted by a co-receptor on T cells, called CD8. T cells then travel throughout the body to search for cells in which the MHC receptor I bore this antigen. When an activated T-cell contacts these cells, it releases cytotoxins, such as perforin, which form pores in the target cell's plasma membrane, allowing ions, water and toxins to enter. The entry of another toxin called granulysin (protease) induces target cells to undergo apoptosis. Assassination of host cell T cells is very important in preventing viral replication. T cell activation is tightly controlled and generally requires very strong MHC/antigen activation signals, or additional activation signals provided by the helper T cells (see below).
Helper T helper
Helper T cells regulate both the innate and adaptive immune response and help determine the body's immune response to a particular pathogen. These cells have no cytotoxic activity and do not kill infected cells or clean pathogens directly. They instead control the immune response by directing other cells to perform these tasks.
Rescue T cells express T cell receptors (TCRs) that recognize antigens bound to Class II MHC molecules. MHC: antigen complexes are also recognized by CD4 cell receptor auxiliaries, which recruit molecules in T cells (eg, Lck) responsible for T cell activation. Helper T cells have a weaker relationship with MHC: antigen complex observed for T cells killer, meaning many receptors (about 200-300) in helper T cells should be bound by MHC: antigen to activate helper cells, while killer T cells can be activated by the involvement of one MHC: antigen molecule. Activation of a helper T-cell also requires a longer duration of involvement with cells presenting antigens. Activation of resting T helper cells causes it to release cytokines that affect the activity of many cell types. Signal cytokines produced by helper T cells enhance the microbicide function of macrophages and killer T cell activity. In addition, activation of helper T cells leads to an increase in the regulation of molecules expressed on the surface of T cells, such as the CD40 ligand (also called CD154), which provides extra stimulatory signals normally required to activate B cells that produce antibodies.
Gamma delta T cells
Gamma delta T cells have alternative T cell receptor (TCR) as opposed to CD4 and CD8 (??) T cells and share the characteristics of helper T cells, cytotoxic T cells and NK cells. Conditions that generate responses from ?? T cells are not fully understood. Like an unconventional T cell subset containing invariant TCR, such as CD1d-T cell membrane Natural Killer, ?? T cells straddle the border between innate and adaptive immunity. On one side, ?? T cells are adaptive immune components because they rearrange the TCR gene to produce receptor diversity and can also develop a memory phenotype. On the other hand, various subsets are also part of the innate immune system, since TCR or NK receptors are limited to use as a pattern recognition receptor. For example, a large number of human V cells? 9/V? 2 T reacts within hours to the common molecules produced by microbes, and the very limited T cells in the epithelium respond to the emphasized epithelial cells.
B lymphocytes and antibodies
B cells identify pathogens when antibodies on their surfaces bind to certain foreign antigens. This antigen/antibody complex is taken up by B cells and processed by proteolysis into a peptide. B cells then display these antigenic peptides on their class II MHC molecules. This combination of MHC and antigen attracts suitable helper T cells, which release lymphokines and activate B cells. When activated B cells then begin to divide, their offspring (plasma cells) secrete millions of copies of antibodies that recognize this antigen. These antibodies circulate in blood and lymph plasma, bind to pathogens expressing antigens and marking them to be destroyed by complement activation or for phagocytic uptake and damage. Antibodies can also neutralize the challenge directly, by binding to bacterial toxins or by disrupting the receptors that viruses and bacteria use to infect cells.
Alternative adaptive immune system
Evolution of the adaptive immune system occurs in ancestral jawed vertebrates. Many classic molecules of the adaptive immune system (eg, immunoglobulins and T-cell receptors) exist only in jawed vertebrates. However, a different lymphocyte derivative molecule has been found in primitive primitive jaws, such as lampreys and hagfish. These animals have a large array of molecules called Variable lymphocyte receptors (VLRs) which, like the antigen receptors of jawed vertebrates, are produced only from a small number (one or two) genes. These molecules are believed to bind pathogenic antigens in a manner similar to antibodies, and with the same degree of specificity.
Immunological memory
When B cells and T cells are activated and begin to replicate, some of their descendants become long-lived memory cells. Throughout the lifetime of animals, these memory cells remember any specific pathogens encountered and can put up a strong response if pathogens are detected again. It is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with pathogens and prepares the immune system for future challenges. Immunological memory may be either passive short-term memory or long-term active memory.
Passive memory
Newborns have no exposure to microbes and are particularly susceptible to infection. Several layers of passive protection are provided by the mother. During pregnancy, certain types of antibodies, called IgG, are transported from mother to baby directly through the placenta, so that human infants have high levels of antibodies even at birth, with the same range of antigen specificity as their mother. Breast milk or colostrum also contains antibodies that are transferred to the baby's intestine and protect against bacterial infections until newborns can synthesize their own antibodies. This is passive immunity because the fetus does not actually make memory cells or antibodies - just borrow it. Passive immunity is usually short-term, which lasts from a few days to several months. In medicine, protective passive immunity can also be transferred artificially from one person to another through serum-rich antibodies.
Active memory and immunization
Long-term active memory is acquired after infection with B and T cell activation. Active immunity may also be artificially generated, by vaccination. The principle behind vaccination (also called immunization) is to introduce antigens from pathogens to stimulate the immune system and develop special immunity against certain pathogens without causing disease associated with the organism. The induction of a deliberate immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility. With the remaining contagious diseases one of the leading causes of death in the human population, vaccination is the most effective manipulation of the immune system that humans have developed.
Most viral vaccines are based on directly attenuated viruses, while many bacterial vaccines are based on the cellular components of micro-organisms, including harmless toxin components. Because many antigens from acellular vaccine do not induce adaptive responses, most bacterial vaccines are given with adjuvants that activate the antigen-presenting cells of the innate immune system and maximize immunogenicity.
Human Immune Disorders
The immune system is a very effective structure that combines specificity, induction and adaptation. Host defense failures do occur, however, and fall into three broad categories: immunodeficiency, autoimmunity, and hypersensitivity.
Immunodeficiencies
Immunodeficiencies occur when one or more of the components of the immune system are inactive. The ability of the immune system to respond to pathogens is reduced both in young people and the elderly, with immune responses beginning to decline in about 50 years due to immunosenescence. In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function. However, malnutrition is the most common cause of immunodeficiency in developing countries. Diets with adequate protein deficiency are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgA antibody concentration, and cytokine production. In addition, the loss of thymus at an early age through genetic mutations or surgical removal results in severe immunodeficiency and high susceptibility to infection.
Immunodeficiencies can also be inherited or 'obtained'. Chronic granulomatous disease, in which phagocytes have a reduced ability to destroy pathogens, is an example of inherited, or innate immunodeficiency. AIDS and some cancers cause immunodeficiency.
Autoimmunity
An excessive immune response consists of other immune dysfunctions, especially autoimmune disorders. Here, the immune system fails to distinguish between self and non-self, and attacks the body parts. Under normal circumstances, many T cells and antibodies react with the "self" peptide. One function of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self-antigens produced throughout the body and to remove cells that recognize self-antigens, preventing autoimmunity.
Hypersensitivity
Hypersensitivity is an immune response that damages the body's own tissues. They are divided into four classes (Type I - IV) based on the mechanisms involved and the timing of a hypersensitive reaction. Type I hypersensitivity is a direct reaction or anaphylaxis, often associated with allergies. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE, which triggers degranulation of mast cells and basophils when cross linked by antigen. Type II Hypersensitivity occurs when antibodies bind to the antigen in the patient's own cells, marking them for destruction. It is also called hypersensitivity that depends on antibodies (or cytotoxic), and is mediated by IgG and IgM antibodies. Immune complexes (antigen aggregation, complement proteins, and IgG and IgM antibodies) stored in various tissues trigger type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed cell type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve Idiopathic inflammation
Inflammation is one of the first responses of the immune system to infection, but it can appear without any known cause.
Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes). Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines promoting chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in host cells. Growth factors and cytotoxic factors can also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of damaged tissue after the removal of pathogens.
Other mechanisms and evolutions
It is likely that a multicomponent, adaptive immune system appears with the first vertebrates, since invertebrates do not produce lymphocytes or humoral-based antibody responses. Many species, however, use mechanisms that seem to be precursors of these aspects of vertebrate immunity. The immune system emerges even in the simplest of structural life forms, with bacteria using a unique defense mechanism, called a limiting modification system to protect themselves from viral pathogens, called bacteriophages. Prokaryotes also have acquired immunity, through systems that use CRISPR sequences to retain fragments of the phag genome they have been in contact with in the past, allowing them to block viral replication through forms of RNA interference. Prokaryotes also have other defense mechanisms. The offensive elements of the immune system are also present in the unicellular eukaryotes, but studies of their role in defense are few.
The pattern recognition receptor is a protein used by almost all organisms to identify molecules associated with pathogens. An antimicrobial peptide called defensin is a preserved evolutionary component of the innate immune response found in all animals and plants, and represents a major form of invertebrate systemic immunity. The complement and cell phagocytic systems are also used by most invertebrate life forms. Ribonucleases and RNA interference pathways are preserved in all eukaryotes, and are thought to play a role in the immune response to the virus.
Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals sent through plants. Each plant cell responds to molecules associated with pathogens known as molecular patterns associated with pathogens or PAMP. When parts of the plant become infected, the plant produces a local hypersensitive response, in which cells at the site of infection undergo rapid apoptosis to prevent the spread of the disease to other parts of the plant. Systemic Resistance (SAR) is a type of defensive response used by plants that make whole plants resistant to certain infectious agents. The mechanism of silencing RNA is very important in this systemic response because they can block viral replication.
Immunity of tumor
Another important role of the immune system is to identify and remove tumors. This is called immune control . Cells cell-changed from tumors express antigens not found in normal cells. For the immune system, these antigens appear alien, and their presence causes the immune cells to attack tumor cells that change. The antigen expressed by the tumor has several sources; some derived from oncogenic viruses such as human papillomavirus, which causes cervical cancer, while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. One example is an enzyme called tyrosinase which, when expressed at high levels, converts certain skin cells (eg melanocytes) into tumors called melanomas. A possible third source of tumor antigens is a protein that is usually important for regulating cell growth and survival, which generally mutates into cancer-induced molecules called oncogenes.
The main response of the immune system to tumors is to destroy abnormal cells using killer T cells, sometimes with the help of a helper T cell. Tumor antigens are presented in class I MHC molecules in a way that is similar to the virus antigen. This allows cell killer T to recognize tumor cells as abnormal. NK cells also kill tumor cells in the same way, especially if the tumor cells have fewer MHC molecules on the surface than normal; This is a common phenomenon with tumors. Sometimes antibodies generated against tumor cells allow for their destruction by complementary systems.
Obviously, some tumors avoid the immune system and continue to become cancerous. Tumor cells often have a reduced number of MHC class I molecules on their surface, thus avoiding detection by killer T cells. Some tumor cells also secrete products that inhibit the immune response; eg by secreting the TGF-cytokine, which suppresses macrophage and lymphocyte activity. In addition, immunological tolerance can develop against tumor antigens, so the immune system no longer attacks tumor cells.
Paradoxically, macrophages can increase tumor growth when tumor cells transmit cytokines that attract macrophages, which then produce cytokines and growth factors such as tumor-necrosis factor alpha that nourish tumor development or promote stem cell plasticity. In addition, the combination of hypoxia in tumors and cytokines produced by macrophages induces tumor cells to reduce the production of proteins that inhibit metastasis and thus help the spread of cancer cells.
Physiological settings
The immune system is involved in many aspects of physiological regulation in the body. The immune system interacts closely with other systems, such as the endocrine and nervous system. The immune system also plays an important role in embryogenesis (embryonic development), as well as tissue repair and regeneration.
Hormones
Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, female sex hormones are known as immunostimulators of adaptive and innate immune responses. Some autoimmune diseases such as lupus erythematosus affects women in a special way, and their onset often coincides with puberty. In contrast, male sex hormones such as testosterone appear to be immunosuppressive. Other hormones seem to regulate the immune system as well, especially prolactin, growth hormone and vitamin D.
Vitamin D
When a T-cell encounters a foreign pathogen, it extends the vitamin D receptor. It is essentially a signaling device that allows T cells to bind to the active form of vitamin D, the steroid calcitriol hormone. T-cells have a symbiotic relationship with vitamin D. Not only do T-cells prolong the vitamin D receptor, essentially asking to bind to the steroid hormone version of vitamin D, calcitriol, but T-cells express the CYP27B1 gene, which is the gene responsible for change the pre-hormone version of vitamin D, calcidiol into the steroid hormone version, calcitriol. Only after binding to calcitriol, T cells can perform the desired function. Other immune system cells known to express CYP27B1 and thus activate vitamin D calcidiol, are dendritic cells, keratinocytes and macrophages.
It is thought that a progressive decline in hormone levels by age is partly responsible for a weakened immune response in an aging individual. Conversely, some hormones are regulated by the immune system, especially the activity of the thyroid hormone. Decreased age-related immune function is also associated with lower vitamin D levels in older people. As we get older, two things happen that have a negative impact on their vitamin D levels. First, they stay indoors more because the activity level decreases. This means they get less sunlight and therefore produce less cholecalciferol via UVB radiation. Secondly, as people of skin age become less proficient produce vitamin D.
Sleep and break
The immune system is affected by sleep and rest, and lack of sleep impairs immune function. Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-? produced in response to infection, also appears to play a role in non-rapid eye movement (REM) sleep regulation. Thus an immune response to infection may result in changes in the sleep cycle, including an increase in slow-wave sleep relative to REM sleep.
When suffering from lack of sleep, active immunization may have a reduced effect and may result in lower antibody production, and lower immune responses, than would be noted in well-rested individuals. In addition, proteins such as NFIL3, which has been shown to be closely related to T-cell differentiation and our circadian rhythms, can be affected through natural light disturbances and dark cycles through sleep deprivation instances, shift work, etc. consequently, this disorder can lead to an increase in chronic conditions such as heart disease, chronic pain, and asthma.
In addition to the negative consequences of sleep deprivation, sleep and circadian systems intertwined has been shown to have a strong regulatory effect on immunological functions that affect both innate and adaptive immunity. First, during the early stages of slow-wave sleep, decreased levels of cortisol, epinephrine and norepinephrine abruptly lead to elevated levels of leptin blood hormone, pituitary growth hormone, and prolactin. These signals induce a pro-inflammatory state through the production of pro-inflammatory cytokines interleukin-1, interleukin-12, TNF-alpha and IFN-gamma. These cytokines then stimulate immune function such as immune cell activation, proliferation, and differentiation. During this time that is indistinguishable, or less differentiated, such as na ¯ve and central memory T cells, the peak (ie during the adaptive immune response time is slowly evolving). In addition to this effect, the currently produced hormone environment (leptin, pituitary growth hormone, and prolactin) supports the interaction between APC and T cells, shifting T h 1/T h 2 balance of cytokines against one that supports T h 1, overall increase of cell proliferation T h , and nave T cell migration. lymph gland. This environment is also considered to support the formation of long-term immune memory through initiation of Th1 immune responses.
In contrast, during the wake period the effector cells are differentiated, such as cytotoxic natural killer cells and CTL (cytotoxic T lymphocytes), their peak to obtain an effective response to any disturbing pathogens. Likewise when active wake, anti-inflammatory molecules, such as cortisol and catecholamines, peaks. There are two theories why a pro-inflammatory state is reserved for sleep. First, inflammation will cause serious cognitive and physical impairment if it occurs during waking hours. Second, inflammation can occur during bedtime because of the presence of melatonin. Inflammation causes a lot of oxidative stress and the presence of melatonin during bedtime can actively counteract the production of free radicals during this time.
Nutrition and diet
Overnutrition is associated with diseases such as diabetes and obesity, which are known to affect immune function. More moderate malnutrition, as well as mineral minerals and certain mineral deficiencies, can also disrupt the immune response.
Foods rich in certain fatty acids can help a healthy immune system. Likewise, fetal deficiency can lead to a lifetime decline in the immune system.
Repair and regeneration
The immune system, especially the innate component, plays a decisive role in tissue repair after humiliation. The main actors include macrophages and neutrophils, but other mobile actors, including ?? T cells, innate lymphoid cells (ILC), and T regulator cells (Tregs), are also important. Immune cell plasticity and a balance between pro-inflammatory and anti-inflammatory signals are important aspects of efficient tissue repair. Immune components and pathways are also involved in regeneration, for example in amphibians. According to one hypothesis, the regenerating organisms can be less immunocompetent than non-regenerative organisms.
Manipulation in medicine
Immune responses can be manipulated to suppress unwanted responses resulting from autoimmunity, allergies, and transplant rejection, and to stimulate protective responses to pathogens that largely avoid the immune system (see immunization) or cancer.
Immunosuppression
Immunosuppressive drugs are used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent transplant rejection after organ transplantation.
Anti-inflammatory drugs are often used to control the effects of inflammation. Glucocorticoids are the most powerful of these drugs; However, these drugs can have many unwanted side effects, such as central obesity, hyperglycemia, osteoporosis, and their use should be strictly controlled. Low doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs such as methotrexate or azathioprine. Cytotoxic drugs inhibit the immune response by killing the dividing cell as activated T cells. However, murder does not discriminate and other cells continue to divide and their organs are affected, which causes toxic side effects. Immunosuppressive drugs such as cyclosporine prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.
Immunostimulation
Cancer immunotherapy includes medical ways to stimulate the immune system to attack cancerous tumors.
Theoretical approach to the immune system
Immunology is highly experimental in everyday practice but is also characterized by a sustained theoretical attitude. Many theories have been suggested in immunology from the late nineteenth century to the present. The late nineteenth and early twentieth centuries saw a battle between the theory of "cell" and "humoral" immunities. According to the theory of cellular immunity, which is represented specifically by Elie Metchnikoff, it is a cell - more precisely, phagocytes - that are responsible for the immune response. In contrast, humoral immunity theory, held by, among others, by Robert Koch and Emil von Behring, states that the active immune agent is a soluble component (molecule) found in the "humors" of the organism rather than its cells.
In the mid-1950s, Frank Burnet, inspired by suggestions made by Niels Jerne, formulated the theory of clonal selection (CST) immunity. On the basis of CST, Burnet developed a theory of how immune responses are triggered according to self/non-self differences: the "self" constituents do not trigger destructive immune responses, while the "non-self" entities (pathogens, allogaft) trigger an immune response which is damaging. This theory was later modified to reflect new discoveries about histocompatibility or "two signaling" activation of T cell complexes. Self-immunity theory and self-null and self-vocabulary have been criticized, but remain highly influential.
Recently, several theoretical frameworks have been proposed in immunology, including the "autopoietic" view, the view of "cognitive immunity", "hazard model" (or "hazard theory"), and the theory of "discontinuity". The hazard model, suggested by Polly Matzinger and colleagues, is very influential, raises many comments and discussions.
Predicting immunogenicity
Larger drugs (& gt; 500 Da) may provoke a neutralizing immune response, especially if the drug is given repeatedly, or in larger doses. This limits the effectiveness of drugs based on larger peptides and proteins (which are usually greater than 6000 Da). In some cases, the drug itself is not immunogenic, but may be administered along with immunogenic compounds, as sometimes occurring with Taxol. Computational methods have been developed to predict the immunogenicity of peptides and proteins, which are particularly useful in designing therapeutic antibodies, assessing the possible virulence of mutations in viral mantle particles, and validation of proposed peptide-based drug treatments. The initial technique depends mainly on the observation that hydrophilic amino acids are represented in the epitope area rather than hydrophobic amino acids; However, recent developments depend on machine learning techniques using a database of known epitopes, usually on well-studied viral proteins, as training devices. A publicly accessible database has been established for the epitope cataloging of pathogens known to be recognized by B cells. The emerging field of immunogeneity-based bioinformatics studies is referred to as immunoinformatics . Immunoproteomics is the study of a large set of proteins (proteomics) involved in the immune response.
Manipulation by pathogen
The success of any pathogen depends on its ability to avoid the host immune response. Therefore, pathogens develop several methods that enable them to successfully infect hosts, while avoiding detection or destruction by the immune system. Bacteria often overcome physical obstacles by removing enzymes that digest barriers, for example, using a system of type II secretions. Or, using a type III secretion system, they can insert a vacuum tube into the host cell, providing a direct route for proteins to move from pathogen to host. This protein is often used to kill host defenses.
The avoidance strategy used by some pathogens to avoid the innate immune system is to hide inside its host cell (also called intracellular pathogenesis). Here, the pathogen spends most of its life cycle inside the host cell, where it is protected from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, food poisoning bacteria Salmonella and eukaryotic parasites that cause malaria (Plasmodium falciparum ) and leishmaniasis ( Leishmania spp. ). Other bacteria, such as Mycobacterium tuberculosis , live inside a protective capsule that prevents lysis by complement. Many pathogens emit compounds that reduce or mislead host immune responses. Some bacteria form biofilms to protect themselves from cells and proteins from the immune system. Such biofilms are present in many successful infections, for example, chronic infections of Pseudomonas aeruginosa and Burkholderia cenocepacia characteristic of cystic fibrosis. Other bacteria produce surface proteins that bind antibodies, making them ineffective; examples include Streptococcus (G protein), Staphylococcus aureus (protein A), and Peptostreptococcus magnus (L).
The mechanisms used to avoid adaptive immune systems are more complicated. The simplest approach is to quickly transform non-essential epitopes (amino acids and/or sugars) on the surface of the pathogen, while keeping the essential epitope hidden. This is called antigenic variation. An example is HIV, which mutates rapidly, so the proteins in its viral envelope that are essential to enter the target host cell are constantly changing. The frequent changes in these antigens can explain the failure of vaccines directed against this virus. The parasite Trypanosoma brucei uses the same strategy, constantly diverting one type of surface protein to another, enabling it to stay one step ahead of the antibody response. Masking antigen with host molecules is another common strategy to avoid detection by the immune system. In HIV, the envelope covering the virion is formed from the outermost membrane of the host cell; Such "self-cloaked" viruses make it difficult for the immune system to identify them as "non-self" structures.
See also
References
External links
- Immune System - from Hartford University (school/undergraduate level)
- Microbiology and Immunology On-Line Textbook - from University of South Carolina School of Medicine (undergraduate)
- Immunobiology; Fifth Edition - An online version of a textbook by Charles Janeway (Advanced undergraduate/postgraduate level)
- Stanley Falkow's talk: "Host-Pathogen Interactions and Human Illness"
Source of the article : Wikipedia
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