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The "immune system" comprises many biological structures and biological process within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, from viruses to parasitic worm, and distinguish them from the organism's own healthy biological tissue. The innate immune system is the first line of defense to recognize a set of a pattern-/damage-associated molecular pattern by using pattern recognition receptors. The adaptive immune system creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen. This process of acquired immunity is the basis of vaccination. Disorders of the immune system can result in immunodeficiency, allergy disease, autoimmune diseases, and cancer. While we are still studying the mechanisms of these diseases, some treatments have been available such us immunotherapy for cancer and monoclonal antibody-based drug for autoimmune disease.

Introduction[edit | edit source]

The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system.

Pathogens can rapidly evolve and adapt, thereby avoiding detection and neutralization by the immune system; however, multiple defense mechanisms have also evolved to recognize and neutralize pathogens. Human and other jawed vertebrates have sophisticated defense mechanisms, including the ability to adapt over time to recognize specific pathogens more efficiently. Adaptive immunity creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen. This process of acquired immunity is the basis of vaccination.

Disorders of the immune system can result in autoimmune diseases, inflammatory diseases, and cancer.[1] Immunodeficiency occurs when the immune system is less active than normal, resulting in recurring and life-threatening infections. In humans, immunodeficiency can either be the result of a genetic disease such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS, or the use of immunosuppressive medication. In contrast, autoimmunity results from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimoto's thyroiditis, rheumatoid arthritis, diabetes mellitus type 1, and systemic lupus erythematosus.

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Figure 1 |  Image caption text goes here
name of image creator, CC-BY 3.0

Innate immune system[edit | edit source]

Microorganisms or toxins that successfully enter an organism encounter the cells and mechanisms of the innate immune system. Innate immune cells express pattern recognition receptors (PRRs) which recognize components that are conserved among broad groups of microorganisms called as pathogen-associated molecular patterns (PAMPs),[2] or substances released by damaged and dying cells called as damage-associated molecular patterns (DAMPs).[3]

Pattern recognition by cells[edit | edit source]

Toll-like receptors[edit | edit source]

Inflammasomes[edit | edit source]

Cytosolic receptors[edit | edit source]

Epithelial barriers[edit | edit source]

The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins.[4]

Mucosal immunity[edit | edit source]

Cellular components[edit | edit source]

The innate leukocytes include the phagocytes (macrophages, neutrophils), dendritic cells, innate lymphoid cells (including natural killer cells), mast cells, eosinophils, basophils. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms.[5]

Phagocytosis is an important feature of cellular innate immunity performed by cells called phagocytes that engulf, or eat, pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines.[6] Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome, which subsequently fuses with another vesicle called a lysosome to form a phagolysosome. The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome.[7][8]

Phagocytes[edit | edit source]

Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens.[9] Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, normally representing 50% to 60% of the total circulating leukocytes.[10] During the acute phase of inflammation, particularly as a result of bacterial infection, neutrophils migrate toward the site of inflammation in a process called chemotaxis, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce a wide array of chemicals including enzymes, complement proteins, and cytokines, while they can also act as scavengers that rid the body of worn-out cells and other debris, and as antigen-presenting cells that activate the adaptive immune system.[11]

Dendritic cells[edit | edit source]

Dendritic cells are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines. Dendritic cells serve as a link between the bodily tissues and the innate and adaptive immune systems, as they present antigens to T cells, one of the key cell types of the adaptive immune system.[12]

Granulocytes[edit | edit source]

Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response.[13] They are most often associated with allergy and anaphylaxis.[10] Basophils and eosinophils are related to neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma.[14]

Innate lymphoid cells[edit | edit source]

Innate cells are important mediators in lymphoid organ development and the activation of the adaptive immune system.[15]

Natural killer cells, or NK cells, are lymphocytes and a component of the innate immune system which does not directly attack invading microbes.[16] Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a condition known as "missing self." This term describes cells with low levels of a cell-surface marker called MHC I (major histocompatibility complex)—a situation that can arise in viral infections of host cells. They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self." For many years it was unclear how NK cells recognize tumor cells and infected cells. It is now known that the MHC makeup on the surface of those cells is altered and the NK cells become activated through recognition of "missing self". Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) which essentially put the brakes on NK cells.[17]

Complement system[edit | edit source]

The complement system is a biochemical cascade that attacks the surfaces of foreign cells. It contains over 20 different proteins and is named for its ability to "complement" the killing of pathogens by antibodies. Complement is the major humoral component of the innate immune response.[18][19]

In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding of complement proteins to carbohydrates on the surfaces of microbes. This recognition signal triggers a rapid killing response.[20] The speed of the response is a result of signal amplification that occurs after sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback.[21] The cascade results in the production of peptides that attract immune cells, increase vascular permeability, and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane.[22]

Inflammatory response[edit | edit source]

Inflammation is one of the first responses of the immune system to infection.[23] The symptoms of inflammation are redness, swelling, heat, and pain, which are caused by increased blood flow into tissue. Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes).[24][25] Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell.[26] Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.[27]

Antiviral response[edit | edit source]

Adaptive immune system[edit | edit source]

The recognition of antigen[edit | edit source]

Antigen presentation to T lymphocytes[edit | edit source]

T-cell mediated immunity[edit | edit source]

The humoral immune response[edit | edit source]

A B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigen.[28] This antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides. The B cell then displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell.[29] As the activated B cell then begins to divide, its offspring (plasma cells) secrete millions of copies of the antibody that recognizes this antigen. These antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytes. Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells.[30]

Disorders of human immunity[edit | edit source]

Immunodeficiency diseases[edit | edit source]

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 diminished in both the young and the elderly, with immune responses beginning to decline at around 50 years of age due to immunosenescence.[31] In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function.[32] Additionally, the loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection.[33]

Immunodeficiencies can also be inherited or acquired.[6] Chronic granulomatous disease, in which phagocytes have a reduced ability to destroy pathogens, is an example of an inherited or congenital immunodeficiency. AIDS and some types of cancer cause acquired immunodeficiency.[34][35]

Allergy diseases[edit | edit source]

Autoimmunity[edit | edit source]

Overactive immune responses comprise the other end of immune dysfunction, particularly the autoimmune disorders. Here, the immune system fails to properly distinguish between self and non-self, and attacks part of the body. One of the functions of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self antigens produced throughout the body and to eliminate those cells that recognize self-antigens, preventing autoimmunity.[28]

Manipulation in medicine[edit | edit source]

Immunosupression[edit | edit source]

Immunosuppressive drugs are used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent transplant rejection after an organ transplant.[36]

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 undesirable adverse effect effects, such as central obesity, hyperglycemia, osteoporosis, and their use must be tightly controlled.[37] Lower 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 dividing cells such as activated T cells. However, the killing is indiscriminate and other constantly dividing cells and their organs are affected, which causes toxic side effects.[36] Immunosuppressive drugs such as cyclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.[38]

Vaccination[edit | edit source]

Long-term active memory is acquired following infection by activation of B and T cells. Active immunity can also be generated artificially, through vaccination. The principle behind vaccination is to introduce an antigen from a pathogen in order to stimulate the immune system and develop adaptive immune response against that particular pathogen without causing disease associated with that organism.[6] This deliberate induction of an immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility. With infectious disease remaining one of the leading causes of death in the human population, vaccination represents the most effective manipulation of the immune system mankind has developed.[39]

Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are based on acellular components of micro-organisms, including harmless toxin components.[6] Since many antigens derived from acellular vaccines do not strongly induce the adaptive response, most bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells and maximize immunogenicity.[40]

Tumor immunology[edit | edit source]

Concluding remarks[edit | edit source]

Additional information[edit | edit source]

Acknowledgements[edit | edit source]

Any people, organisations, or funding sources that you would like to thank.

Competing interests[edit | edit source]

Any conflicts of interest that you would like to declare. Otherwise, a statement that the authors have no competing interest.

Ethics statement[edit | edit source]

An ethics statement, if appropriate, on any animal or human research performed should be included here or in the methods section.

References[edit | edit source]

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