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When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells. Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. DELL Latitude D400 Series CPU FAN
This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can be in the form of either passive short-term memory or active long-term memory.

Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. DELL Latitude D410 Series CPU FAN
Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called IgG, is transported from mother to baby directly across the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother.[64] DELL Latitude D420 CPU FAN

 Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies.[65] This is passive immunitybecause the fetus does not actually make any memory cells or antibodies—it only borrows them. DELL Latitude D430 CPU FAN
This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be transferred artificially from one individual to another via antibody-richserum.

Long-term active memory is acquired following infection by activation of B and T cells. DELL Latitude D500 Series CPU FAN
Active immunity can also be generated artificially, through vaccination. The principle behind vaccination (also calledimmunization) is to introduce an antigen from a pathogen in order to stimulate the immune system and develop specific immunity against that particular pathogen without causing disease associated with that organism.[14] DELL Latitude D505 Series CPU FAN
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.[35][67]DELL Latitude D510 Series CPU FAN

Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are based onacellular components of micro-organisms, including harmless toxin components.[14] Since many antigens derived from acellular vaccines do not strongly induce the adaptive response, DELL Latitude D531 CPU FAN
most bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells of the innate immune systemand maximize immunogenicity.

The immune system is a remarkably effective structure that incorporates specificity, inducibility and adaptation. DELL Latitude D600 Series CPU FAN
Failures of host defense do occur, however, and fall into three broad categories: immunodeficiencies, autoimmunity, and hypersensitivities.

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, DELL Latitude D610 Series CPU FAN
with immune responses beginning to decline at around 50 years of age due to immunosenescence.[69][70] In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function.[70] However, malnutrition is the most common cause of immunodeficiency indeveloping countries.[70] DELL Latitude D620 CPU FAN 

Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgAantibody concentrations, and cytokine production. 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.[71]DELL Latitude D630 CPU FAN

Immunodeficiencies can also be inherited or 'acquired'.[14] Chronic granulomatous disease, where 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. DELL Latitude D800 Series CPU FAN
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. Under normal circumstances, many T cells and antibodies react with "self" peptides.[74] DELL Latitude D810 Series CPU FAN
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.

Hypersensitivity is an immune response that damages the body's own tissues. DELL Latitude D820 CPU FAN
They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. DELL Latitude D830 CPU FAN
Type I hypersensitivity is mediated by IgE, which triggers degranulation of mast cells and basophils when cross-linked by antigen.[75] Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies.[75] DELL Latitude E4200 Series CPU FAN
Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions.[75] Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. DELL Latitude E4300 Series CPU FAN
Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy). These reactions are mediated by T cells, monocytes, and macrophages.

It is likely that a multicomponent, adaptive immune system arose with the first vertebrates, as invertebrates do not generate lymphocytes or an antibody-based humoral response.[1] DELL LATITUDE E4310 Series CPU FAN
Many species, however, utilize mechanisms that appear to be precursors of these aspects of vertebrate immunity. Immune systems appear even in the structurally most simple forms of life, with bacteria using a unique defense mechanism, called the restriction modification system to protect themselves from viral pathogens, called bacteriophages.[76] DELL Latitude E5400 CPU FAN Prokaryotes also possess acquired immunity, through a system that uses CRISPR sequences to retain fragments of the genomes of phage that they have come into contact with in the past, which allows them to block virus replication through a form of RNA interference.[77][78] DELL Latitude E5500 CPU FAN
Pattern recognition receptors are proteins used by nearly all organisms to identify molecules associated with pathogens. Antimicrobial peptides called defensins are an evolutionarily conserved component of the innate immune response found in all animals and plants, and represent the main form of invertebrate systemicimmunity.[1] DELL Latitude E6400 Series CPU FAN
The complement system and phagocytic cells are also used by most forms of invertebrate life. Ribonucleases and the RNA interference pathway are conserved across all eukaryotes, and are thought to play a role in the immune response to viruses.[79]

Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals that are sent through a plant.[80] DELL Latitude E6410 CPU FAN
Individual plant cells respond to molecules associated with pathogens known as Pathogen-associated molecular patterns or PAMPs.[81] When a part of a plant becomes infected, the plant produces a localized hypersensitive response, whereby cells at the site of infection undergo rapid apoptosis to prevent the spread of the disease to other parts of the plant. DELL Latitude E6410 Series CPU FAN
Systemic acquired resistance (SAR) is a type of defensive response used by plants that renders the entire plant resistant to a particular infectious agent.[80] RNA silencing mechanisms are particularly important in this systemic response as they can block virus replication. DELL Latitude E6420 CPU FAN
Another important role of the immune system is to identify and eliminate tumors. The transformed cells of tumors expressantigens that are not found on normal cells. To the immune system, these antigens appear foreign, and their presence causes immune cells to attack the transformed tumor cells. DELL Latitude E6500 CPU FAN
The antigens expressed by tumors have several sources;[84]some are derived from oncogenic viruses like human papillomavirus, which causes cervical cancer,[85] while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. DELL Latitude E6500 Series CPU FAN
One example is anenzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (e.g. melanocytes) into tumors called melanomas.[86][87] A third possible source of tumor antigens are proteins normally important for regulatingcell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes.[84][88][89] DELL Latitude E6510 CPU FAN
The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells.[87][90] Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to recognize the tumor cell as abnormal.[91] DELL Latitude E6510 Series CPU FAN

 NK cells also kill tumorous cells in a similar way, especially if the tumor cells have fewer MHC class I molecules on their surface than normal; this is a common phenomenon with tumors.[92] Sometimes antibodies are generated against tumor cells allowing for their destruction by the complement system.[88] DELL Precision M4400 Series CPU FAN
Clearly, some tumors evade the immune system and go on to become cancers.[93] Tumor cells often have a reduced number of MHC class I molecules on their surface, thus avoiding detection by killer T cells.[91] Some tumor cells also release products that inhibit the immune response; DELL Precision M4500 CPU FAN
for example by secreting the cytokine TGF-β, which suppresses the activity ofmacrophages and lymphocytes.[94] In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.[93] DELL Precision M6400 Series CPU FAN
Paradoxically, macrophages can promote tumor growth [95] when tumor cells send out cytokines that attract macrophages, which then generate cytokines and growth factors that nurture tumor development. In addition, a combination of hypoxia in the tumor and a cytokine produced by DELL Precision M65 CPU FAN
macrophages induces tumor cells to decrease production of a protein that blocks metastasis and thereby assists spread of cancer cells.

Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, DELL Precision M70 Series CPU FAN
female sex hormones are known immunostimulators of both adaptive[96] and innate immune responses.[97] Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty. By contrast, male sex hormones such as testosterone seem to be immunosuppressive.[98] DELL Precision M90 CPU FAN
Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.[99][100]

When a T-cell encounters a foreign pathogen, it extends a vitamin D receptor. DELL Pricision M6300 CPU FAN
This is essentially a signaling device that allows the T-cell to bind to the active form of vitamin D, the steroid hormone calcitriol. T-cells have a symbiotic relationship with vitamin D. Not only does the T-cell extend a vitamin D receptor, in essence asking to bind to the steroid hormone version of vitamin D, calcitriol, but the T-cell expresses the gene CYP27B1, DELL Studio 1435 CPU FAN
which is the gene responsible for converting the pre-hormone version of vitamin D, calcidiol into the steroid hormone version, calcitriol. Only after binding to calcitriol can T-cells perform their intended function. Other immune system cells that are known to express CYP27B1 and thus activate vitamin D calcidiol, are dendritic cells,keratinocytes and macrophages.[101][102] DELL Studio 1450 CPU FAN
It is conjectured that a progressive decline in hormone levels with age is partially responsible for weakened immune responses in aging individuals.[103]Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity.[104] DELL Studio 1457 CPU FAN
The age-related decline in immune function is also related to dropping vitamin D levels in the elderly. As people age, two things happen that negatively affect their vitamin D levels. First, they stay indoors more due to decreased activity levels. This means that they get less sun and therefore produce less cholecalciferol via UVB radiation. DELL Studio 1458 CPU FAN
Second, as a person ages the skin becomes less adept at producing vitamin D.[105]

The immune system is affected by sleep and rest,[106] and sleep deprivation is detrimental to immune function.[107] Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-α produced in response to infection, DELL Studio 1535 Series CPU FAN
appear to also play a role in the regulation of non-rapid eye movement (REM) sleep.[108] Thus the immune response to infection may result in changes to the sleep cycle, including an increase in slow-wave sleep relative to REM sleep.

Overnutrition is associated with diseases such as diabetes and obesity, which are known to affect immune function.DELL Studio 1536 Series CPU FAN

More moderate malnutrition, as well as certain specific trace mineral and nutrient deficiencies, can also compromise the immune response.[ Foods rich in certain fatty acids may foster a healthy immune system.[111] Likewise, fetal undernourishment can cause a lifelong impairment of the immune system. DELL Studio 1537 Series CPU FAN
The immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy, and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system (see immunization).Immunosuppressive drugs are used to control autoimmune disorders or inflammation when excessive tissue damage occurs, DELL Studio 1555 Series CPU FAN
and to prevent transplant rejection after an organ transplant.[35][113]

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 side effects, such as central obesity, hyperglycemia, osteoporosis, DELL Studio 17 CPU FAN

 and their use must be tightly controlled.[114] Lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxicor immunosuppressive drugs such as methotrexate or azathioprine. Cytotoxic drugs inhibit the immune response by killing dividing cells such as activated T cells. DELL Studio 1735 CPU FAN

However, the killing is indiscriminate and other constantly dividing cells and their organs are affected, which causes toxic side effects.[113] Immunosuppressive drugs such as cyclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.[115]

Larger drugs (>500 Da) can provoke a neutralizing immune response, particularly if the drugs are administered repeatedly, or in larger doses. DELL Studio 1736 CPU FAN

This limits the effectiveness of drugs based on larger peptides and proteins (which are typically larger than 6000 Da). In some cases, the drug itself is not immunogenic, but may be co-administered with an immunogenic compound, as is sometimes the case for Taxol. Computational methods have been developed to predict the immunogenicity of peptides and proteins, DELL Studio 1737 CPU FAN

which are particularly useful in designing therapeutic antibodies, assessing likely virulence of mutations in viral coat particles, and validation of proposed peptide-based drug treatments. Early techniques relied mainly on the observation thathydrophilic amino acids are overrepresented in epitope regions than hydrophobic amino acids;[116] DELL Studio XPS 1340 CPU FAN

however, more recent developments rely on machine learningtechniques using databases of existing known epitopes, usually on well-studied virus proteins, as a training set.[117] A publicly accessible database has been established for the cataloguing of epitopes from pathogens known to be recognizable by B cells.[118] DELL Studio XPS 1640 CPU FAN

The emerging field of bioinformatics-based studies of immunogenicity is referred to as immunoinformatics.[119] Immunoproteomics is the study of large sets of proteins (proteomics) involved in the immune response.

The success of any pathogen depends on its ability to elude host immune responses. DELL Studio XPS 1645 CPU FAN

Therefore, pathogens evolved several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system.[120] Bacteria often overcome physical barriers by secreting enzymes that digest the barrier, for example, by using a type II secretion system.[121] DELL Studio XPS 1647 CPU FAN

Alternatively, using a type III secretion system, they may insert a hollow tube into the host cell, providing a direct route for proteins to move from the pathogen to the host. These proteins are often used to shut down host defenses.[122]

An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called intracellularpathogenesis). DELL Vostro 1000 Series CPU FAN

Here, a pathogen spends most of its life-cycle inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, the food poisoning bacterium Salmonella and the eukaryotic parasites that cause malaria(Plasmodium falciparum) and leishmaniasis (Leishmania spp.). DELL Vostro 1014 Series CPU FAN

Other bacteria, such as Mycobacterium tuberculosis, live inside a protective capsule that preventslysis by complement.[123] Many pathogens secrete compounds that diminish or misdirect the host's immune response.[120] Some bacteria form biofilms to protect themselves from the cells and proteins of the immune system. DELL Vostro 1015 Series CPU FAN


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