Structural Biochemistry/Genetic code/Immune System

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The immune system destroys foreign invaders to the body. It also destroys some non-foreign cells that are no longer performing their functions, such as cancer cells.

Introduction[edit]

The immune system is a biological system inside an organism which is supposed to fight against diseases. In vertebrates, the immune system is considered the last line of defense against foreign invaders.It fights by destroying pathogens and tumor cells using mechanisms that constantly adapt to recognize and rid these disease causing cells. This mechanism is needed so that the immune system does not attack itself or the organisms healthy cells. Unfortunately, pathogens can evolve rapidly which would allow it to avoid the immune system and attack the host.

There are many mechanisms that have evolved that allow for the immune system to recognize and even neutralize pathogens. Every living organism even the most basic unicellular organisms, bacteria, contain some enzyme systems that are used to protect from viral infections. Similarly, there are many ancient eukaryotes in which basic immune mechanisms that been evolved and have been passed down to their modern descendants. Some of these evolved mechanisms are the complement system, phagocytosis, and defensins which are antimicrobial peptides. The immune system of vertebrates, like humans, is an elaborate network that consists of many types of tissues, cells, organs, and proteins. Due to this advanced immune system, it can more efficiently recognize specific pathogens over time. This adaptation is known as “acquired immunity” and results in an immunological memory that can be compared to a textbook full of information. This immunological memory, formed from direct encounter to a specific pathogen, results in a well-prepared response to the same specific pathogen the second time around. A vaccination serves this purpose.

However, a disease can result in the immune system when it begins to properly operate. One such disease is called immunodeficiency in which the immune system performs at a much lower level than its suppose to and thus results in infections that are constantly recurring and may be life-threatening. This disease can be a result of either genetic disease or an infection such as AIDS which is caused by HIV. On the other extreme end is the disease known as autoimmune disease in which the immune system is so active that is begins to attack its own tissues as if they were foreign invaders.

The immune system has many layers of defenses, to protect against infections, each with increasing specificity. The most basic defense is physical barriers that prevent pathogens from being able to enter the organism. However, if the pathogen is able to get through these physical barriers, the innate immune system takes over and provides a non-specific immediate response. Second line of the defense is the internal defense in the innate immunity. Internal defenses in innate immunity include phyagocytic cells, antimicrobial proteins, inflammatory response, natural killer cells. If the pathogens are able to get through this second line of defense, then the third layer of defense is the adaptive immune system. In order to improve its ability to recognize the pathogen during an infection, the immune system will adapt its response. After the pathogen has been nullified, the improved response is retained forming an immunological memory allowing the adaptive immune system to attack the same pathogen faster and stronger the next time it is encountered.

Both the adaptive and innate immunity require that the immune system is able to differentiate between which molecules are self and non-self. Self molecules are parts of the organism’s body that are distinct and distinguished from outside foreign substances while non-self molecules are often known as antigens that specific immune receptors bind to.

Organisms protect themselves through various barriers. The first line of defense against infection are surface barriers including membranes and exoskeletons. Other bodily systems also protect the body by naturally repelling foreign agents. Tears, urine, mucus, coughing and sneezing are all examples of ways the body expels foreign agents. Another barrier to fight against infection is the chemical barrier which uses enzymes, also known as antibacterials, to kill pathogens.

Innate Immunity[edit]

Cellular Barriers[edit]

Certain cells of the mucous membranes produce mucus, a viscous fluid that enhances defenses by trapping microbes and other particles. Saliva, tears, and mucous secretions that bathe various exposed epithelia provide a washing action that also inhibits colonization by microbes. Pathogens that make their way into the body are subject to detection by leukocytes. These cells recognize microbes using Toll-like receptor. Toll-Like Receptor recognizes fragments of molecules characteristic of a set of pathogens. Similarly, on the inner surface of vesicles formed by endocytosis, is the sensor for double-stranded RNA a form of nucleic acid characteristic of certain viruses.

There are four types of internal defenses in the innate immunity:

Phagocytosis[edit]

Phagocytosis is the ingestion and digestion of bacteria and other foreign substances. It is triggered by hemocytes that circulate within the hemolymph. Six steps of ingestion and destruction of a microbe by a typical phagocytic cell are shown below.
(1) Pseudopodia surround microbes.
(2) Microbes are engulfed into cell.
(3) Vacuole containing microbes forms inside the cell.
(4) Vacuole and lysosome fuse.
(5) Toxic compounds and lysosomal enzymes destroy microbes.
(6) Microbial debris is released by exocytosis

There are four types of phagocytic leukocytes that play a different role in the innate immune system.
(1) Neutrophils are the most abundant phagocytic cells in the mammalian body. neutrophils represent 50-60% of the total leukocytes that circulate in the bloodstream.Signals from infected tissues attract neutrophils, which then engulf and destroy microbes.
(2) Macrophages provide a more effective phagocytic defense than neutrophiles. Some of macrophages migrate throughout the body, while others reside permanently in various organs and tissues. Macrophages in the spleen, lymph nodes, and other tissues of the lymphatic system are particularly well positioned to combat pathoogens. Microbes in the blood become trapped in the spleen, whereas microbes in the interstitial fluid flow into lymph and are trapped in lymph nodes.
(3) Eosinohpis have low phagocytic activity but are important in defending against multicellular invaders such as parsitic worms. Rather than engulfing such parasites, eosinophils position themselves against the parasite's body and then discharge destructive enzymes that damage the invaders.
(4) Dendritic cells populate tissues that are in contact with the environment. They mainly stimulate development of adapative immunity against microbes they encounter. Dendritic cells are also phagocytes in the tissue but have contact with the external environment and thus exiss mainly in the intestines, stomach, nose, lungs, and skin. They are similar to neuronal dendrites as both have spine-like projections. Dendritic cells link both the bodily tissues and the adaptive and innate immune systems as they present antigens to T-cells.

Antimicrobial Proteins[edit]

Interferons are proteins that provide innate defense against viral infections. Virus-infected body cells secrete interferons, inducing neraby uninfected cells to produce substances that inhibit viral reproduction. Interferons limit the cell-to-cell spread of viruses in the body, helping control viral infections such as colds and influenza. Some white blood cells secrete a different type of interferon that helps activate macrophages, enhacing their phagocytic ability.
Complement System consists of roughly 30 proteins in blood plasma that function together to fight infections. These proteins circulate in an inactive state and are activated in a cascade of biochemical reactions leading to bursting of invading cells.

Inflammatory Response[edit]

Inflmmatory response is the pain and swelling that alert you to a splinter under your skin. One important inflammatory signaling molecule is histamine, which is stored in the mast cells. Mast cells, which exist in both mucous membranes and connective tissues, regulate the inflammatory response. They secrete chemical mediators that are often found in the defense against parasites and sometimes also are found in allergic reactions like asthma. Natural killer cells are a type of leukocyte that attack tumor cells and cells that have been virus-infected. Histamine released by mast cells at sites of tissue damage triggers nearby blood vessels to dilate and beomce more permeable.
Steps of major events in a local inflammatory response are shown below.
(1) Activated macrophages and mast cells at the injury site release signaling molecules that act on nearby capillaries.
(2) The capillaries widen and become more permeable, allowing fluid containing antimicrobial peptides to enter the tissue. Signaling molecules released by immune cells attract additional phagocytic cells.
(3) Phagocytic cells digest pathogens and cell debris at the site, and the tissue heals.

Natural Killer Cells[edit]

Natural Killer (NK) cells help recognize and eliminate certain diseased cells in vertebrates. With the exception of red blood cells, all cels in the body normally have on their surface a protein called class I MHC molecule. Following viral infection or conversion to a cancerous state, cells sometimes stop expressing this protein. The NK cells that patrol the body attach to such stricken cells and release chemicals that lead to a cell death, inhibiting further spread of the virus or cancer.

Adaptive Immunity[edit]

There are two types of immunity in the adaptive immunity:

Cellular immunity[edit]

Cellular immunity is also known as cell-mediated immunity (CMI). This type of immunity act as the second arm of the immune responses. There are different functions of immune cells. For example, this type of cell-mediated immunity includes the killing of intracellular pathogens and direct cell killing by cytotoxic T cells, natural killer cells, and killer cells (T-cells work by scanning the surface of a cell for anything that appears foreign.) In CMI, the T cells or the lymphocytes would attach to the surface of other cells, then it would display an antigen and trigger a response. This type of immune response may also include white blood cells (leukocytes).

Humoral immunity[edit]

This type of immunity guards against infections caused by bacteria and extracellular phases of viral infections. The immunity is mediated by a big, diverse collection of proteins which are related termed antibodies or immunoglobins; in mammals, these are produced by the B cells in bone marrow. B cells play a major role in humoral immunity. B cells like T cells also have surface receptors, which allows them to recognize certain antigen. The variable portion in the B cells accepts specific antigens. Once a B cell recognizes this antigen it has the ability to perform two functions. One is to generate plasma B cells that can reproduce more cells with the specific binding site. The other is to form memory B cells, which acts as an immunity to the antibody whenever it is encountered again.

In the immune system inflammation is often one of the first responses. This can be typically seen through swelling and redness which are a result of increased blood flow to a tissue. The injured or infected cells release cytokines and eicosanoids which results in inflammation. The dilation of the blood vessels and the fever are produced by the prostaglandins while the white blood cells are attracted by leukotrienes both of which are part of the eicosanoids. The common cytokines are interferons which can shut down protein synthesis and interleukins which communicate between white blood cells. Cytokines as well as other chemicals, attract immune cells to where the infection is and remove the pathogens followed by healing of the damaged tissue.

Histamine is an important chemical in immunity system

Immune Response Chem114A.jpg

Adaptive Immune System[edit]

The adaptive immune system allows for a strong immune response and is the basis of the immunological memory as each pathogen the body encounters is now remembered by a specific antigen. The adaptive immune response requires that the body recognizes specific non-self antigens during antigen presentation. This antigen specificity allows the body to generate responses that are meant to fight that specific pathogen and the pathogen-infected cells. The ability to generate the correct responses specific to that pathogen is maintained by memory cells in the body. If a pathogen infects the body more than one time, the specific memory cells will quickly eliminate the pathogen.

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.

Immunological Memory[edit]

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.

Passive Memory[edit]

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.

Active Memory and Immunization[edit]

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[edit]

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[edit]

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[edit]

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.

Immunology of Tumors[edit]

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.

Pathogen’s Evade the Immune System[edit]

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.

Medicine Manipulation[edit]

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.

Mechanism[edit]

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.

The complement system attacks the surface of pathogens. Containing over 20 proteins, the complement system is the biggest humoral component of the innate immune response. This response is triggered by complement binding to antibodies attached to carbohydrates on the surface of microbes triggering the rapid killing response. The complement proteins are initially bound to microbes and activate their protease activity which activates other complement proteases producing a catalytic cascade that amplifies the inial signal using positive feedback. This results in the production of peptides attracting immune cells and increasing the cascular permeability while marking the surface of the pathogen for destruction.

Another quick response to infection is inflammation. Usually marked by redness and swelling caused by increased blood flow to the tissue, inflammation is produce by eicosanoids and cytokins that are released by attacked cells. Eicosanoids induce fever and dilation of blood vessels while leukotrienes attract white blood cells. Cytokins recruit immune cells to the infection site to promote healing of damaged tissue after removing the pathogens.

The adaptive immune system proves to eliminate and prevent pathogens by recognizing and remembering specific pathogens and creating stronger attacks for each encounter of the pathogen. This adaptive property helps prepare the body for future challenges.

When an antigen binds to this immunoglobin, the B cell engulfs the anibody-antigen complex and degrades it. Following this process, the T cells stimulate the B cells to proliferate and the process is repeated for additional antigens. B cells may live for several days; some B cells live for years and are called memory B cells. These can stimulate a more rapid response to an antigen they have encountered in the past.

Image:newImmuneSystemOverview.gif

Structure[edit]

Antibody structures form a related and big group of proteins. All immunoglobins contain four subunits at the least: 2 identical heavy chains (weighing 53-75 kD) and 2 identical light chains (weighing approximately 23 kD). The subunits are attached by disulfide bonds as well as non-covalent interactions to form a Y shaped structure which is symmetric. There are five different classes of immunoglobins (IgA, IgD, IgE, IgG, IgM) differing mostly in the type of heavy chain they contain and sometimes in their subunit structure. As a result, different immunoglobins have different functions. For example, IgE bids to allergens and protects against parasitic worms while IgA is found in mucus and prevents colonization. The most common of th immunoglobins by far is IgG.

An antibody has 2 heavy chains and 2 light chains used to recognize the cooresponding antigen.

An immunoglobin consists of homology units which all have the same characteristic fold. This fold, which is in the light chain, consists of a 'sandwich'-like structure composed of three and four stranded anti-parallel beta-sheets that are linked by a disulfide bond. This structure can accommodate an enormous variety of antigens. The light chain recognizes antigens through three loops in its variable domain (which is an area part of the light chain). This domain includes the most amino acid variation among antibodies in the whole immunoglobin; these are called hybervariable sequences.

The forces and bonding involved between an antibody and antigen include van der waals, hydrogen bonding, hydrophobic, and ionic interactions. The two are structurally complementary to each other; therefore, strong bonds are formed. Dissociation constants between an antigen and an antibody range from 10^-4 - 10^-10, which is greater than or equal to the dissociation constant associated with an enzyme and its substrate.

For the most part, immunoglobins are divalent molecules capable of binding to two different antigens at the same time. A foreign organism or substance usually has many antigens on its surface. Thus, a typical immune response consists of a mixture of antibodies with different specificities divalently binding to the antigens. This binding allows the cross-linking of the antigens to form an extended lattice formation, which assists and decreases the time in which it takes to remove the antigen. This also triggers further B cell formation and proliferation. [[Media:Media:Example.ogg]]

Antibody generation[edit]

An antigen does not influence a B cell to produce new immunoglobin to bind to. Instead, an antigen stimulates the proliferation of a pre-existing B cell antibodies that recognize the antigen. Thus, the immune system has the ability to generate a plethora of different antibodies. Most of these are sufficient for a person to respond through his or her immune system to respond to almost any antigen he or she may encounter. The diversity in antibody sequences arises from genetic changes during B lymphocyte development not only from the number of immunoglobin genes.

The immune system is unique in that it only responds to foreign substances and not to the high and diverse amount of endogenous molecules.Because most macromolecules are virtually antigenic, transferring tissues, organs, or blood samples among individuals and within species presents great challenges and is being researched continuously.

The immune system may lose tolerance to some of its self-antigens, causing an autoimmune disease, which at its worst, could be deadly. Autoimmune diseases include: Addison's disease, Crohn's disease, Multiple sclerosis, Psoriasis, and Graves' disease.

Addison's disease is caused when the adrenal glands do not produce enough steroid hormones known as cortisol. This rare genetic disease may develop in children, adults, and even some species of animals. The treatment involves the replacement of hormones.

Crohn's disease is the autoimmune, inflammatory disease of the intestines. The body's immune system attacks the gastrointestinal tract causing inflammation. Commonly believed to be a primary T cell autoimmune disorder, new studies believe it to be an impaired innate immunity due to impaired cytokine secretion by macrophages causing microbial-induced inflammatory response.

Multiple sclerosis is when the body's immune system attacks the central nervous system leading to demyelination. Affecting the communication between the spinal cord and the brain, nerve cells communicate by sending electrical signals (action potentials) down axons which are wrapped in myelin. Myelin is attacked and is damaged resulting in MS.

Psoriasis is a chronic, mostly hereditary, non-contagious auntoimmune disease affecting the skin and joins as it becomes red and scaly patches appear on the skin. These areas of inflammation and excess skin production have a silvery-white appearance. In this special case, inflammation isn't caused by pathogens as T cells move from the dermis to the epidermis.

Graves' disease is an autoimmune disease affecting the thyroid causing it to enlarge its size twice and become overactive. This also affects the eyes and other systems of the body. The body produces antibodies to the receptor for the thyroid-stimulating hormone (TSH) causing hyperthyroidism as the TSH receptor and antibodies bind. There becomes an abnormally high production of T3 and T4 which causes hyperthyroidism and enlargement of the thyroid gland.