The Brain and Host Defense: 9 (NeuroImmune Biology)


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Particular emphasis is placed on inflammation, a critical host defense reaction that serves as an effector response for both the adaptive and innate immune systems. Mechanisms implicated in brain defense, as well as in more general host defense, are discussed. Gender-related differences in immune responsiveness, circadian modulator of immune responses, and evidence that behavioral conditioning e. Key historical findings are presented, and the reciprocal interactions These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms.

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. The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome. Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens.

Immune system - Wikipedia

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.

Dendritic cells DC 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. Mast cells reside in connective tissues and mucous membranes , and regulate the inflammatory response.

They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma. Natural killer cells , or NK cells, are lymphocytes and a component of the innate immune system which does not directly attack invading microbes. 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.

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The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.

The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens small fragments of the pathogen have been processed and presented in combination with a "self" receptor called a major histocompatibility complex MHC molecule.

There are two major subtypes of T cells: In addition there are regulatory T cells which have a role in modulating immune response. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole pathogens without any need for antigen processing. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.

Killer T cells are a sub-group of T cells that kill cells that are infected with viruses and other pathogens , or are otherwise damaged or dysfunctional. Recognition of this MHC: The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such 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 a protease induces the target cell to undergo apoptosis. Helper T cells regulate both the innate and adaptive immune responses and help determine which immune responses the body makes to a particular pathogen. They instead control the immune response by directing other cells to perform these tasks.

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Helper T cells have a weaker association with the MHC: Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as pattern recognition receptors. A B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigen.

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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. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms. It has been firmly established already that the Nervous, Endocrine and Immune systems form a regulatory network, a Super-System, which governs all events from conception till death in higher animals and in man, including physiological and pathophysiological processes. The immune system, particularly the innate component, plays a decisive role in tissue repair after an insult. No, cancel Yes, report it Thanks! Clinical Pharmacology of Cerebral Ischemia.

This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell. 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.

How the brain processes immune derived signals - Harald Engler, University of Duisburg-Essen

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. Evolution of the adaptive immune system occurred in an ancestor of the jawed vertebrates.

The Brain and Host Defense

It is now well recognized that the brain, and especially the hypothalamus, plays an important role in the regulation of immune reactions and inflammation. Purchase The Brain and Host Defense, Volume 9 - 1st Edition. Print Book & E- Book. Page Count: View all volumes in this series: NeuroImmune Biology.

Many of the classical molecules of the adaptive immune system e. However, a distinct lymphocyte -derived molecule has been discovered in primitive jawless vertebrates , such as the lamprey and hagfish. These animals possess a large array of molecules called Variable lymphocyte receptors VLRs that, like the antigen receptors of jawed vertebrates, are produced from only a small number one or two of genes.

These molecules are believed to bind pathogenic antigens in a similar way to antibodies, and with the same degree of specificity. 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.

The Brain and Host Defense, Volume 9 (NeuroImmune Biology)

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. 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 through the placenta , so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother.

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-rich serum.

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 also called immunization 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.

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. 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.

The immune system is a remarkably effective structure that incorporates specificity, inducibility and adaptation.

Section I Introduction

Failures of host defense do occur, however, and fall into three broad categories: 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. 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.

Immunodeficiencies can also be inherited or ' acquired'. AIDS and some types of cancer cause acquired immunodeficiency. 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. Hypersensitivity is an immune response that damages the body's own tissues. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. 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.

This is also called antibody-dependent or cytotoxic hypersensitivity, and is mediated by IgG and IgM antibodies. 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.

Inflammation is one of the first responses of the immune system to infection, [28] but it can appear without known cause. 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.

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. 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 systemic immunity.

Ribonucleases and the RNA interference pathway are conserved across all eukaryotes , and are thought to play a role in the immune response to viruses. Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals that are sent through a plant. Systemic acquired resistance SAR is a type of defensive response used by plants that renders the entire plant resistant to a particular infectious agent.

Another important role of the immune system is to identify and eliminate tumors. This is called immune surveillance. The transformed cells of tumors express antigens that are not found on normal cells.

Immune system

To the immune system, these antigens appear foreign, and their presence causes immune cells to attack the transformed tumor cells. The antigens expressed by tumors have several sources; [90] some are derived from oncogenic viruses like human papillomavirus , which causes cervical cancer , [91] while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells.

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One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells e. 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. This allows killer T cells to recognize the tumor cell as abnormal. Clearly, some tumors evade the immune system and go on to become cancers. Paradoxically, macrophages can promote tumor growth [] when tumor cells send out cytokines that attract macrophages, which then generate cytokines and growth factors such as tumor-necrosis factor alpha that nurture tumor development or promote stem-cell-like plasticity.

The immune system is involved in many aspects of physiological regulation in the body. The immune system interacts intimately with other systems, such as the endocrine [] [] and the nervous [] [] [] systems. The immune system also plays a crucial role in embryogenesis development of the embryo , as well as in tissue repair and regeneration.

Hormones can act as immunomodulators , altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive [] and innate immune responses. By contrast, male sex hormones such as testosterone seem to be immunosuppressive. When a T-cell encounters a foreign pathogen , it extends a vitamin D receptor. 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 , which is the gene responsible for converting the pre-hormone version of vitamin D, calcidiol into the steroid hormone version, calcitriol.