The age-related decline in immune function

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 Such biofilms are present in many successful infections, e.g., the chronic Pseudomonas aeruginosaand Burkholderia cenocepacia infections characteristic of cystic fibrosis.^[124] Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include Streptococcus (protein G), Staphylococcus aureus (protein A), and Peptostreptococcus magnus (protein L).^[125] DELL Vostro 1018 Series CPU FAN The mechanisms used to evade the adaptive immune system are more complicated. The simplest approach is to rapidly change non-essential epitopes (amino acidsand/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed. This is called antigenic variation. DELL Vostro 1088 Series CPU FAN An example is HIV, which mutates rapidly, so the proteins on its viral envelope that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of vaccines directed at this virus.^[126] The parasite Trypanosoma brucei uses a similar strategy, constantly switching one type of surface protein for another, DELL Vostro 1310 CPU FAN allowing it to stay one step ahead of the antibody response.^[127] Masking antigens with host molecules is another common strategy for avoiding detection by the immune system. In HIV, the envelope that covers 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. DELL Vostro 1400 Series CPU FAN The innate immune system, also known as non-specific immune system and first line of defense,^[1] comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. DELL Vostro 1510 CPU FAN This means that the cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system (which is only found in vertebrates), it does not confer long-lasting or protective immunity to the host.^[2] Innate immune systems provide immediate defense against infection, and are found in all classes of plant and animal life. DELL Vostro 2510 CPU FAN The innate immune system is an evolutionarily older defense strategy, and is the dominant immune system found in plants,fungi, insects, and in primitive multicellular organisms.^[3]The major functions of the vertebrate innate immune system include:Recruiting immune cells to sites of infection, through the production of chemical factors, including specialized chemical mediators, called cytokines. DELL Vostro 3300 CPU FAN Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells orantibody complexes. The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialised white blood cells. DELL Vostro 3350 CPU FAN Activation of the adaptive immune system through a process known as antigen presentation.

Acting as a physical and chemical barrier to infectious agents.

The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents, acting as the first line of defense against invading organisms.^[4] DELL Vostro 3400 CPU FAN Desquamation of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces.^[4] In the gastrointestinal and respiratory tract, movement due to peristalsis or cilia, respectively, helps remove infectious agents.^[4]Also, mucus traps infectious agents.^[4] DELL Vostro 3450 CPU FAN

 The gut flora can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces.^[4] The flushing action of tears and saliva helps prevent infection of the eyes and mouth.

Inflammation is one of the first responses of the immune system to infection or irritation. DELL Vostro 3500 CPU FAN Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.^[5] The process of acute inflammation is initiated by cells already present in all tissues, DELL Vostro 3700 CPU FAN mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. These cells present receptors, contained on the surface or within the cell, named pattern recognition receptors (PRRs), which recognise molecules that are broadly shared by pathogens but distinguishable from host molecules, DELL Vostro 3700 Series CPU FAN collectively referred to as pathogen-associated molecular patterns(PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRR recognize a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation. DELL Vostro 3750 CPU FAN Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause vasodilationof the blood vessels at the scene, and attract phagocytes, especially neutrophils.^[5] Neutrophils then trigger other parts of the immune system by releasing factors that summon other leukocytes and lymphocytes. DELL Vostro A840 CPU FAN Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1.^[6] The inflammatory response is characterized by the following symptoms: redness, heat, swelling, pain, and possible dysfunction of the organs or tissues involved. DELL Vostro A860 CPU FAN