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Study of MicroRNA Helps NIH Scientists Unlock Secrets of Immune Cells With the rapid and continuous advances advan ces in biotechnology, scientists are better able to see inside the nucleus of a cell to unlock the secrets of its genetic material. However, what happens outside of the nucleus has, in many ways, remained a mystery. Now, researchers with the National Institutes of Health are closer to understanding how activity outside of the nucleus determines a cell's behavior. They looked at mouse immune cells and examined the types, amount, and activity of microRNAs, genetic components that help regulate the production of proteins. Their  study provides a map to the variety of microRNAs contained within mouse immune cells and reveals the complexity of cellular protein regulation. The study appears online in the journal Immunity. An organism is made up of cells containing genetic material in the form of deox yribonucleic acid (DNA) residing within the nucleus. An organism’s entire collection of DNA is called its genome and consists of genes, short segments of DNA that code for proteins, and many long segments of  DNA that do not contain genes. While each cell contains the entire genome, not all of a cell’s genes are making proteins all of the time. Which genes are turned on and which are turned off, and when, determine the behavior of a cell, such as the type of cell it becomes, where it goes, and what it does. "A plethora of cellular functions, ranging from development, differentiation, metabolism, and host defense, are impacted by protein levels," said Rafael Casellas, Ph.D., the study’s principal investigator from the Genomics and Immunity Group of the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). " We were interested in discovering how microRNAs contribute to the regulation of these functions."

A cell makes proteins through a process called transcription, in which genes are cop ied from DNA into messenger ribonucleic acid (RNA), which travels from the nucleus into the body of  the cell. Not all RNA transcribed from DNA are messenger RNA, however. There are many other forms of RNA that do not code for proteins. MicroRNAs (miRNAs), for example, are small strands of RNA that modulate the production of proteins from messenger RNA, thereby helping to regulate protein levels in the cell. Previous studies have shown that cells are very sensitive to fluctuations in miRNA levels, which require tight control in order to regulate protein activity effectively. In the current study, the NIH scientists used a new microsequencing technology to comprehensively identify all of the different miRNAs existing in mouse immune cells. In addition to increasing the number of known k nown miRNAs, the scientists also discovered several cellular mechanisms that regulate miRNA abundance. The study found that some miRNA constructs exist in a dormant state within the nucleus un til they receive signals from the epigenome to become active. The epigenome regulates transcription and comprises all of the non-genetic material in the nucleus. Other miRNAs, the researchers determined, are not hampered by these epigenetic mechanisms and are controlled simply through transcription. However, for some of these miRNAs, abundance depends upon the amount of target messenger  RNA available in the cell. According to NIAMS Director Stephen I. Katz, M.D., Ph.D., "The data generated from this study represent a useful tool for immunologists and cell biologists to use for future studies o n functional aspects of the immune system and basic miRNA biology." More information about the NIAMS Genomics and Immunity section can be found at http://www.niams.nih.gov/Research/Ongoing_Research/Branch_Lab/Laboratory_Molecular_Im munogenetics/gis.asp.. munogenetics/gis.asp The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services' National Institutes of  Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research p rogress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22 NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov http://www.niams.nih.gov.. The National Institutes of Health (NIH) — The — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs

http://www.nih.gov/news/health/jun2010/niams-03.htm

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Components of the human immune system. Source: NIAID. The immune system is a network of special cells cells,, proteins  proteins,, tissues, and organs that prevents the infection and growth of  bacteria,  bacteria, viruses viruses,, and parasites in the body. bo dy. It also prevents the uncontrolled growth of rogue cells or cancerous or cancerous cells. cells. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and problems. At certain times, the immune system does not  perform its functions adequately and infections occur. In other situations, the immune system is overactive and attacks normal cells of the body, leading to autoimmune disorders. In addition, the immune system may react to seemingly harmless particles or antigens such as p ollen, causing allergies.

Contents [hide hide]] •

1 De Descr script iption ion ○

1.1 Video description descriptio n of the immune system



2 Role of Immune System in the Body



3 How It Works Work s





3.1 Self and nonnon-self  self 



3.2 Passi Passive ve immun immunity ity



3.3 Inna Innate te Immun Immunity ity



3.4 Adap Adaptive tive immun immunity ity

4 Components of the Immune System ○

4.1 4. 1 Or Orga gans ns 

4.1.1 4.1. 1 Bone marrow





4.1.2 4.1. 2 Lymph nodes



4.1.3 4.1 .3 Thy Thymus mus



4.1.4 4.1 .4 Spl Splee een n



4.1.5 4.1. 5 Othe Otherr lymph lymphoid oid tissu tissue e

4.2 Immune cel cells ls 



4.2.1 4.2. 1 Leuk Leukocyte ocytes s 

4.2.1.1 4.2. 1.1 Phag Phagocyte ocytes s



4.2.1.2 4.2. 1.2 Lympho Lymphocyte cytes s



4.3 4. 3 Ant Antibo ibodie dies s



4.4 4. 4 Com Compl pleme ement nt



4.5 4. 5 Vac Vaccin cines es

5 Disorders of the Immune System ○

5.1 Auto Autoimmun immune e disor disorders ders



5.2 5. 2 All Aller ergy gy



5.3 Immun Immune e defi deficien ciencies cies



6 Rela Related ted Prof Professi essions ons



7 Clin Clinical ical Trials



8 Immun Immune e System and Canc Cancer er



9 Re Rese sear arch ch ○

9.1 Gene Ther Therapy apy



10 Ref Refere erence nces s



11 Exte External rnal Links

Description The immune system is a network of cells, tissues, and organs that work together to defend the  body against infection by bacteria, parasites, fungi and viruses. It also helps to prevent the development and growth of cancer cells. Normally, the immune system works in harmony with other systems in the body. There are times, however, when the immune system can "overreact" to an immune stimulus which can result in damage to normal, healthy tissues. Such is thought to  be the case with diseases such as arthritis arthritis,, lupus lupus,, and diabetes diabetes.. The immune system can also be weakened, either by infections such as HIV/AIDS or by cancer , or because of the use of o f drugs that suppress the immune system. Such drugs are used to stop the rejection of an organ transplant or to treat cancer. If the immune system is weakened, the condition is called immunosuppression or immune or immune deficiency. deficiency. In its weakened state, the immune system cannot defend the body and the result can be the development of opportunistic of opportunistic infections (infections that occur only with a weakened immune system) or cancer.

Video description of the immune system

Role of Immune System in the Body The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade our body and cause disease. The immune system also monitors the body for cells that become damaged or that grow uncontrollably, such as cancer cells. It destroys these cells and removes them from the body. bod y. The immune system is made up of a network of cells, tissues, and organs that work together to protect the body.

How It Works

 The immune system protects the body against bacteria, parasites, viruses, and fungi.  Adapted from: NCI.  The immune system has two components: the innate system and the adaptive system. The innate component, though not specific for a particular microbe, is the first line of defense against infections. An example of innate immunity is the action of cilia in the lungs and respiratory tract; these are the fine "hairs" that sweep foreign material out of the lungs. The adaptive immune system is microbe-specific and is able to respond to almost any invader. It is amazingly complex. The adaptive immune system can recognize and remember millions of different invaders or antigens.. It can produce antibody antigens antibody,, other secretions (release of fluids), and cells to remove these invaders from the body. The innate and adaptive systems work together to provide complete immunity. They share many components, such as cells and molecules that activate both parts of the immune system. system. Self and non-self 

The key to a healthy immune system is its remarkable ability to distinguish between the body’s own cells, recognized as “self,” and foreign cells, or “non-self.” The body’s immune defenses normally coexist peacefully with cells that carry distinctive “self” marker molecules. But when immune defenders encounter foreign cells or organisms carrying markers that say “non-self,” they quickly launch an attack.

Anything that can trigger this immune response is called a n antigen. An antigen can be almost anything that the body doesn't recognize: a microbe such as a virus virus,, or a part of a microbe such as a protein molecule. Tissues or cells from another person (except an identical twin) also carry non-self markers and act as foreign antigens. This explains why tissue transplants may be rejected. Antigens carry marker molecules that identify them as foreign. In abnormal situations, the immune system can mistake self for nonself and launch an attack against the body’s own cells c ells or  tissues. The result is called an autoimmune disease. Some forms of arthritis of arthritis and diabetes are autoimmune diseases. In other cases, the immune system responds to a seemingly harmless foreign substance such as ragweed pollen. p ollen. The result is allergy allergy,, and this kind of antigen is called an allergen. Passive immunity

Passive immunity is "borrowed" from another source and lasts for a short time. For exa mple, antibodies in a mother's breast milk provide an infant with temporary immunity to diseases to which the mother has been exposed. This can help protect the infant against infection during the early years of childhood. Passive immunity can also be administered in the healthcare setting by giving immunoglobulins immunoglobulins.. For example, pregnant women who have a certain blood certain blood type (Rh (Rh negative) negative) are sometimes given Rhogam,, which is an immunoglobulin that protects the unborn child from attack by the mother's Rhogam immune system should the child have an incompatible blood type. Similarly, many types of  autoimmune diseases are also treated with different types of immunoglobulins. Innate Immunity

Innate, or nonspecific, immunity is a type of general protection that humans and other animals are born with. Innate immunity protects the body against all antigens, and involved barriers that keep foreign materials from entering the body. These barriers form the first line of defense in the  body's immune response. Examples of innate immunity include the following: •

Skin



Mucous membranes (which trap bacteria and small particles)



Cough reflex



Enzymes in tears, saliva and skin oils



Stomach acid



Acidity and low ionic concentration of tears, saliva, and urine



Defensins (which are anti-microbial anti-microbial peptides secreted from epithelial surfaces)

Innate immunity also includes proteins includes proteins released by the body, called innate humoral immunity. Examples include: the body's complement system and substances called interferon and interleukin-1 (which causes fever ). ). If an antigen is able to get g et through these natural barriers, it is attacked and destroyed by other   parts of the immune system.

Adaptive immunity

A second kind of protection is called adaptive (or active) immunity. This type of immunity develops throughout our lives. Adaptive immunity involves lymphocytes called B cells and T cells and develops as children and adults are exposed to diseases or immunized against them through vaccination.

Components of the Immune System

Colorized electron photomicrograph photomicrograph of a white blood cell (yellow) and a lymphocyte lymphocyte (blue), cells that are part of the immune system. Adapted from: NIH.  The immune system is made up of the following components: Organs

The organs of the immune system include the following: Bone marrow

Bone marrow is the soft tissue in the hollow center of  bones.  bones. It is where all blood cells, including the immune cells, grow.

Lymph nodes

Lymph nodes or glands, organized collections of lymphoid tissue where immune cells are found and where they interact with antigens. Thymus

The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just T cells, mature there. Spleen

The spleen is a flattened organ in the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells g ather and confront antigens. Other lymphoid tissue

In addition to these organs, clumps of lymphoid tissue are found in many parts of the bo dy, especially in the linings of the digestive tract and the airways and lungs—gateways to the body. These tissues include the tonsils, adenoids, and appendix. Immune cells Leukocytes

The cells that are part of this defense system are white blood cells, or leukocytes. Leukocytes are  produced or stored in many locations throughout the body, including the thymus thymus,, spleen spleen,, and  bone marrow. marrow. These organs are called the lymphoid organs. organs. There are also clumps of lymphoid tissue throughout the body, primarily in the form of lymph nodes, that house the leukocytes. Leukocytes circulate through the body between the organs and nodes by means of thelymphatic the lymphatic vessels.. Leukocytes can also circulate through blood vessels. In this way, the immune system vessels works in a coordinated manner to monitor the body for germs or substances that might cause  problems. The two basic types of leukocytes are:

Phagocytes These are cells that engulf (phago means "to eat") and chew up invading microbes and foreigh  particles. The different types of phagocytes include the following: Monocytes are phagocytes that circulate in the blood. When monocytes migrate into tissues, they develop into macrophages. Specialized types of macrophages can be found in many organs, including the lungs lungs,, kidneys kidneys,, brain  brain,, and liver . Macrophages play many roles. As scavengers, they rid the body of worn-out cells and other  debris. They also sweep up foreign particles like bac teria and viruses and display small bits of  antigen. This display activates matching lymphocytes which help rid the body of  them as foreign as foreign antigen. unwanted invaders. Macrophages also produce a variety of powerful chemical signals, known as monokines, which are central to the immune response. Granulocytes are another type of phagocyte, and consist of neutrophils, of neutrophils, basophils, and eosinophils. Neutrophils eosinophils. Neutrophils use prepackaged chemicals to break down the microbes they ingest.  Eosinophils and basophils are related types of white blood cells that contain material that appears

like granules under the microscope. These types of white bloods cells “degranulate” by spraying their chemicals onto harmful cells or microbes nearby. Mast cells function much like basophils, except they are not found in the blood. Instead, they are found in the lungs, skin, tongue, and linings of the nose and intestinal tract, where they play a role in allergic reactions.

Related structures, called blood platelets blood platelets,, are actually cell fragments. Platelets also contain granules. In addition to promoting blood clotting and wound repair, platelets activate some immune defenses.  Dendritic cells are found in parts of lymphoid organs where T cells also exist. Like macrophages, dendritic cells in lymphoid tissues display antigens to T cells and help "turn on" T cells during an immune response. Dendritic cells get this name because they have branchlike extensions that can interlace to form a network.

Lymphocytes Lymphocytes are small white blood cells that are part of the adaptive immune system. There are two kinds of lymphocytes: the B lymphocytes (B cells) and the T lymphocytes (T cells) . Lymphocytes start out in the bone marrow and either stay there and mature into B cells, or they head to the thymus gland, where they mature into T cells. When an antigen is detected, several types of cells, including antigen-presenting cells, work  together to recognize and respond to it. These cells trigger the B lymphocytes to produce antibodies, antibodies, specialized proteins that bind specific antigens. Antibodies and antigens fit together  like a hand in glove. Once the B lymphocytes have produced antibodies, they become memory cells. A few remain circulating in the blood, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. That's why if someone gets sick with a certain disease, like chickenpox chickenpox,, that person typically doesn't get sick from it again—afterwards they are immune. This is also why we use vaccinations or immunizations to prevent getting considered immune. certain diseases. The immunization introduces the body to the antigen in a way that doesn't d oesn't make a person sick, but it does allow the body to produce antibodies an tibodies that then protect that person from future attack by the disease-causing organism.

Antibodies

A drawing of an IgG antibody molecule. IgG has two light chains and two heavy chains of proteins. The variable region is the antigen binding site. Source: Wikimedia Commons . An antibody is made up of two heavy chains and two light chains, which together are called immunoglobulins. Antibodies also have a variable region, which differs from one antibody to the next, and allows an antibody to recognize its matching antigen. There are five types of  immunoglobulin, (abbreviated as Ig): •









IgG is a kind of antibody that works efficiently to coat microbes, speeding their uptake by other cells in the immune system. IgM is very effective at killing bacteria. IgA concentrates in body fluids—tears, fluids—tears, saliva, and the secretions of the respiratory and digestive tracts—guarding the entrances to the body. IgE protects against parasitic infections, and is also responsible for the symptoms of allergy. IgD remains attached to B cells and plays a key role in initiating early B cell responses.

Antibodies can neutralize toxins (poisonous or damaging substances) produced by different organisms. They can also activate a group g roup of proteins called complement that complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells. Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That is the job of o f the T cells which contribute to immune defenses in two major  ways: some direct and regulate immune responses, whereas others directly attack infected or 

cancerous cells. There are actually T cells c ells that are called "killer T cells." The T cells are part of  the system that destroys antigens that have been tagged by antibodies, or cells that have been infected or somehow changed. T cells are also involved in helping signal other cells (like  phagocytes) to do their jobs. Unlike B cells, T cells do not no t recognize free-floating antigens. Rather, their surfaces contain specialized antibody-like receptors that see fragments of antigens on the surfaces of infected or  cancerous cells. Helper T cells, or Th cells, coordinate immune responses by communicating with other cells. Some stimulate nearby B cells to produce antibodies, o thers call in phagocytes, and still others activate other T cells. Cytotoxic T lymphocytes (CTLs)—also called killer T cells—perform a different function. These cells directly attack other cells carrying certain foreign or abnormal molecules on their surfaces. CTLs are especially useful for attacking viruses because viruses often h ide from other parts of  the immune system while they grow inside infected cells. CTLs recognize small fragments of  these viruses peeking out from the cell membrane and launch an attack to kill the infected cell. Cells of the immune system communicate with one ano ther by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to coordinate appropriate immune responses. Cytokines include a diverse assortment of compounds called interleukins, interferons, and growth factors. Complement

The complement system is made up of about 25 proteins that work together to assist, or  “complement,” the action of antibodies in destroying d estroying invaders. Complement also helps to rid the  body of antibody-coated antigens (antigen-antibody complexes). Complement proteins, which cause blood vessels to become dilated and then leaky, contribute to the redness, warmth, swelling, pain, and loss of function that characterize an inflammatory response. Complement proteins circulate in the blood in an inactive form. When the first protein in the complement series is activated—typically by antibody that has locked onto an antigen—it sets in motion a domino effect. Each component takes its turn in a precise chain of steps known as the complement cascade. The end products are molecular cylinders that are inserted into—and that  punch holes in—the cell walls that surround the invading bacteria. This causes certain fluids and molecules to flow into the bacterium and others to flow out. The end result is that the bacterial cell swells, bursts, and dies. Other components of the complement system make bacteria more susceptible to being eaten by phagocytes, or beckon other immune cells to the area. Vaccines

An immune response can be sparked not only by infection but also by immunization with vaccines.. Some vaccines contain microorganisms, or parts of microorganisms, that have been vaccines treated so they can provoke an immune response but not full-blown disease. Vaccines consist of  killed or modified microbes, components of microbes, or microbial DNA that trick the body into thinking an infection has occurred. A vaccinated person’s immune system attacks the harmless vaccine, which prepares the body for  future invasions against the kind of microbe the vaccine contained. In this way, the person  becomes immunized against the microbe. Vaccination remains one of the best ways to prevent infectious diseases, and vaccines have an excellent safety record. Previously devastating diseases

such as smallpox smallpox,, polio  polio,, and whooping cough have been greatly controlled or eliminated through worldwide vaccination programs. Some vaccines contain a weakened form of a live virus. The yellow fever vaccine fever vaccine and the oral  polio vaccine are examples of this type of vaccine. As a general rule, people who have a weakened immune system should not receive a vaccine that contains live virus. Vaccines Va ccines containing killed virus can be used instead. There are other conditions where a doctor may decide not to give a vaccine. vaccine.[1]

Disorders of the Immune System Disorders of the immune system can be broken down into four main categories: •







Immunodeficiency disorders (primary or acquired) Autoimmune disorders (in which the body's own immune system attacks its own tissue as foreign matter) Allergic disorders (in which the immune system overreacts in response to an antigen) Cancers of the immune system

Autoimmune disorders

Autoimmunity is a condition where the immune system mistakenly recognizes host tissue or  cells as foreign. Because of this false recognition, the immune system reacts against the host components. There are a variety of autoimmune disorders. An autoimmune disease can be very specific, involving a single organ. Three examples are Crohn's disease (where the intestinal tract is the target), multiple sclerosis (where tissues of the brain the brain are the target), and diabetes mellitus Type I (where the insulin insulin-producing -producing cells of the pancreas are the target). Other autoimmune disorders are more general, and involve multiple sites in the body. One example is rheumatoid arthritis. arthritis. Allergy

These types of disorders result when the immune system overreacts or reacts inappropriately (eg., allergies, systemic lupus erythematosus) erythematosus) Immune deficiencies

These types of disorders are the result of diminished immune function [eg.,AIDS [eg.,AIDS,, severe combined immunodeficiency (SCID)] (SCID)]

Related Professions An immunologist is typically a medical professional who has received an MD or PhD with special emphasis and.training in the immune system and immune disorders.

Clinical Trials A list of open clinical research trials studying the immune system is available here here..

Immune System and Cancer When normal cells turn into cancer cells, c ells, some of the antigens on their surface chan ge. These cells, like many body cells, constantly shed bits of protein from their surface into the circulatory system.. Often, tumor antigens are among the shed proteins. system These shed antigens prompt action from immune defenders, including cytotoxic T cells, natural killer cells, and macrophages. According to one theory theory,, patrolling cells of the immune system  provide continuous body-wide surveillance, catching and eliminating cells that undergo malignant transformation. Tumors develop when this immune surveillance breaks down or is overwhelmed.

Research Scientists are now able to mass-produce immune cell secretions, both antibodies and lymphokines, as well as specialized immune cells. The ready supply of these materials not only has revolutionized the study of the immune system itself but also has had an enormous impact on medicine, agriculture, and industry. Monoclonal antibodies are identical antibodies made by the many clones of a single B cell. Monoclonal antibody technology makes it possible to mass produce specific antibodies to order. Because of their unique specificity for different antigens, monoclonal antibodies are promising treatments for a range of diseases. Researchers make monoclonal antibodies by injecting a mouse with a target antigen and then fusing B cells from the mouse with other long-lived cells. The resulting hybrid cell becomes a type of antibody factory, turning ou t identical copies of antibody molecules specific for the target antigen. Mouse antibodies are “foreign” to people, however, and might trigger an immune response when injected into a human. Therefore, researchers have developed “humanized” monoclonal antibodies. To construct these molecules, scientists take the antigen-binding portion of a mouse antibody and attach it to a human antibody scaffolding, greatly reducing the foreign portion of  the molecule. Because they recognize very specific molecules, mono clonal antibodies are used in diagnostic tests to identify invading pathogens or changes in the body’s proteins. In medicine, monoclonal antibodies can attach to cancer cells, blocking the chemical growth signals that cause the cells to divide out of control. In other cases, ca ses, monoclonal antibodies can carry potent toxins into certain cells, killing the dangerous cells while leaving their neighbors untouched. Gene Therapy 

Genetic engineering also holds promise for gene therapy—replacing altered or missing genes or  adding helpful genes. One disease in which gene therapy has been b een successful is SCID, or severe combined immune deficiency disease. SCID is a rare genetic disease that disables a person’s immune system and leaves the person unable to fight off infections. It is caused by mutations in one of several genes that code for  important components of the immune system. Until recently, the most effective treatment for  SCID was transplantation of blood-forming stem cells from the bone marrow of a healthy person who is closely related to the patient. However, doctors have also been able ab le to treat SCID by giving the patient a genetically engineered version of the missing gene. Using gene therapy to treat SCID is generally accomplished by taking blood-forming cells from a person’s own bone marrow, introducing into the cells a genetically changed virus that carries

the corrective gene, and growing the modified cells outside the person’s body. After the genetically changed bone marrow cells begin to produce the enzyme or other protein that was missing, the modified blood-forming marrow cells can be injected back into the person. Once  back inside the body, the genetically modified cells can produce the missing immune system component and begin to restore the person’s ability to fight off infections. Cancer is another target for gene therapy. In pioneering experiments, scientists are removing cancer-fighting lymphocytes from the cancer patient’s tumor, inserting a gene that boosts the lymphocytes’ ability to make quantities of a natural anticancer product, then growing the restructured cells in quantity in the laboratory. These cells are injected ba ck into the person, where they can seek out the tumor and deliver large doses of the anticancer chemical. Although scientists have learned much about abou t the immune system, they continue to study how the  body launches attacks that destroy invading microbes, infected cells, and tumors while ignoring healthy tissues. New technologies for identifying individual immune cells are now allowing scientists to determine quickly which targets are triggering an immune response. Improvements in microscopy are permitting the first-ever observations of living B cells, T cells, and other cells as they interact within lymph nodes and other body tissues. In addition, scientists are rapidly unraveling the genetic blueprints that d irect the human immune response, as well as those that dictate the biology of bacteria, viruses, and parasites. The combination of new technology and expanded genetic information will no doubt reveal even more about how the body bo dy protects itself from disease.

See Also •



Immune System Tolerance  The Immune System and HIV



Nutrients keeps immune system in balance



Immunosuppressive



Flt3L

References 1. ↑ Centers for Disease Control and Prevention. Who Should Not Get Vaccinated.

External Links  National Cancer Institute: The Immune System  National Institute of Allergy and Infectious Diseases: Immune System  National Institute of Child Health and Human Dev elopment: Primary Immunodeficiency Medline Plus: Immune System and Disorders Jeffrey Modell Foundation: Ten Warning Signs of Primary Immunodeficiency Immune Deficiency Foundation: About Primary Immunodeficiencies American Academy of Allergy, Asthma Asthma,, and Immunology: Patients & Consumers Center 

What is Halotherapy: Salt Room Therapy? Adjust font-size: + –

Published June 29, 2010 by:  Jolynne M Hudnell View Profile | Follow | Add to Favorites More: Alternative Therapy Salt Salt Water Respiratory Diseases

Can Salt Be Good for You? Halotherapy is deemed an alternative therapy for many respiratory issues and skin conditions. What is halotherapy and is it safe?

What Is Halotherapy? Halotherapy is also known as speleotherapy and salt room therapy.

It is an alternative therapy widely used in Europe for respiratory and skin ailments. Salt rooms are created in an attempt to mimic

the environment found in a natural salt cave.

What Conditions Does Salt Room Therapy Claim to Treat? Halotherapy is believed to

help reduce symptoms of respiratory ailments such as asthma, colds, bronchitis, allergies and even cystic fibrosis. Skin conditions such as eczema, psoriasis and acne are said to improve after salt room therapy treatments.

How Does Halotherapy Work? Salt is believed to have antibacterial and anti-

inflammatory properties. You can find saline nasal sprays at the store to relieve congestion. Often, doctors will recommend gargling with salt water for sore throats. With halotherapy, very small particles of salt are inhaled as you sit in specially constructed salt rooms.

Does Salt Room Therapy Really Work? While researching this topic, most of the

information found was from companies who own salt rooms. There were also many personal testimonials. However, very few research studies have been made into the effectiveness of  salt room therapy.

Research on Halotherapy. There are several research studies published by Russian

doctor A.V. Chervinskaya. Abstracts in English can be found. However, salt rooms were not used for many of the studies. Rather, special inhalers that delivered concentrated doses of  salt particles were used and showed some effectiveness for the conditions mentioned above.

Salt Rooms in the United States. Many entrepreneurs are creating salt rooms in the

United States, especially in the major cities. Be careful of companies that claim using their salt room is an actual cure for conditions, as these claims have not been proven or thoroughly researched.

Page: 12Nex Nextt Page P age » PrintFlag Print Flag Close Published by Jolynne by Jolynne M Hudnell - Featured Health & Wellness, Dieting & Weight Loss and Parenting Contributor I am a Featured Contributor in Health & Wellness, Dieting & Weight Loss and Parenting. Health & Wellness: I have considerable experience with many medical disorders both common and rare. I began my colleg... View profile

Structure of the Respiratory System The respiratory system is represented by the following structures, shown in Figure 1 :

Figur A view of the entire respiratory system and the upper respiratory tract. e1



The nose consists of the visible external nose n ose and the internal nasal cavity. The nasal septum divides the nasal cavity into right and left sides. Air enters two openings, the external nares (nostrils; singular, naris), and passes into the vestibule and through  passages called meatuses. The bony walls of the meatuses, called concha, are formed by facial bones (the inferior nasal concha and an d the ethmoid bone). From the meatuses, air  then funnels into two (left and right) internal nares. Hair, mucus, blood capillaries, and cilia that line the nasal cavity filter, moisten, warm, and eliminate debris from the passing air.





The pharynx (throat) consists of the following three regions, listed in order through which incoming air passes: ○

The nasopharynx receives the incoming air from the two internal nares. The two auditory (Eustachian) tubes that equalize air pressure in the middle ear also enter  here. The pharyngeal tonsil (adenoid) lies at the back of the nasopharynx.



The oropharyrnx receives air from the nasopharynx nasoph arynx and food from the oral cavity. The palatine and lingual tonsils are located here.



The laryngopharynx passes food to the esophagus e sophagus and air to the larynx.

The larynx receives air from the laryngopharynx. It consists of the following nine pieces of cartilage that are joined by membranes and ligaments, shown in Figure 2 .

Figur Anterior and sagittal section of the larynx and the trachea. e2



The epiglottis, the first piece of cartilage of the larynx, is a flexible flap that covers the glottis, the upper region of o f the larynx, during swallowing to prevent the entrance of food.



The thyroid cartilage protects the front of the larynx. A forward projection of this cartilage appears as the Adam's apple.



The paired arytenoids cartilages in the rear are horizontally attached to the thyroid cartilage in the front by folds of mucous membranes. The upper vestibular folds (false vocal cords) contain muscle fibers that bring the folds together and allow the breath to be held during periods of muscular pressure on the thoracic cavity

(straining while defecating or lifting a heavy object, for example). The lower  vocal folds (true vocal cords) contain elastic ligaments that vibrate when skeletal muscles move them into the path of outgoing air. Various sounds, including speech, are produced in this manner. ○



The cricoid cartilage, the paired cuneiform cartilages, and the paired corniculate cartilages are the remaining cartilages supporting the larynx.

The trachea (windpipe) is a flexible tube, 10 to 12 cm (4 inches) long and 2.5 cm (1 inch) in diameter, whose wall consists of four layers, as shown in Figure 2 : ○

The mucosa is the inner layer of the trachea. It contains mucusproducing goblet cells and pseudostratified ciliated epithelium. The movement o f the cilia sweep debris away from the lungs toward the pharynx.



The submucosa is a layer of areolar a reolar connective tissue that surrounds the mucosa.



Hyaline cartilage forms 16 to 20 C-shaped rings that wrap around the submucosa. The rigid rings prevent the trachea from collapsing during inspiration.



The adventitia is the outermost layer of the trachea. It consists of areolar  connective tissue.



The primary bronchi are two tubes that branch b ranch from the trachea to the left and right lungs.



Inside the lungs, each primary bronchus divides repeatedly into branches of smaller  diameters, forming secondary (lobar) bronchi, tertiary (segmental) bronchi, and numerous orders of bronchioles (1 mm or less in diameter), including terminal bronchioles (0.5 mm in diameter) and microscopic respiratory bronchioles. The wall of the primary bronchi are constructed like the trachea, but as the branches of the tree get g et smaller, the cartilaginous rings and the mucosa are replaced by smooth muscle.



Alveolar ducts are the final branches of the bronchial tree. Each alveolar duct has enlarged, bubblelike swellings along its length. Each swelling is called an alveolus, and a cluster of adjoining alveolar is called an alveolar sac. Some adjacent alveoli are connected by alveolar pores.



The respiratory membrane consists of the alveolar and capillary walls. Gas ex change occurs across this membrane. Characteristics of this membrane follow: ○

Type I cells are thin, squamous epithelial cells that constitute the primary cell type of the alveolar wall. Oxygen diffusion occurs across these cells.



Type II cells are cuboidal epithelial cells that are interspersed among the type I cells. Type II cells secrete pulmonary surfactant (a phospholipid bound to a  protein) that reduces the surface tension of the moisture that covers the alveolar  walls. A reduction in surface tension permits oxygen to diffuse more easily into the moisture. A lower surface tension also prevents the moisture on opposite walls of an alveolus or alveolar duct from cohering and causing the minute airway to collapse.



Alveolar macrophage (dust cells) wander among the other cells of the alveolar  wall removing debris and microorganisms.



A thin epithelial basement membrane forms the ou ter layer of the alveolar wall.



A dense network of capillaries surrounds each alveolus. The capillary walls consist of endothelial cells surrounded by a thin basement membrane. The  basement membranes of the alveolus and the capillary are often so close that they fuse.

Read more: http://www.cliffsnotes.com/WileyCDA/CliffsReviewTopic/Structure-ofthe-Respiratory-Syst the-Respira tory-System.topicArtic em.topicArticleId-22032,artic leId-22032,articleId-21997.html leId-21997.html#ixzz0t3uq3 #ixzz0t3uq3iRx iRx http://www.cliffsnotes.com/WileyC http://www.cliffsnotes.c om/WileyCDA/CliffsRev DA/CliffsReviewTopic/Str iewTopic/Structure-of-theucture-of-theRespiratory-System.to Respirator y-System.topicArticleId-22 picArticleId-22032,articleId-2 032,articleId-21997.html 1997.html

External Respiration The subsystem that removes carbon dioxide from the lungs in moves in fresh air from outside is made up of the nasal cavity ( nose ), the pharynx the pharynx , the larynx , the trachea , the bronchi the bronchi (and all the smaller branches of the bronchi), and the air sacs, or alveoli, to which the entire external respiration subsystem leads to. The respiration zone consists of the bronchioles (not the large  bronchi), the alveolar ducts, and the alveoli, all of which basically make up the lungs. This is where the oxygen and carbon dioxide are exchanged. All other organs in the external respiration subsystem make up the conducting zone . During the trip that air takes through the conducting zone, it is humidified, cleaned, and warmed so that it does not harm any an y of delicate organs that it  passes through. When the air finally reaches the a lveoli, it is closer to the air in the tropics, which is the kind of air that your lungs prefer.

The Nose The nose is the first and last organ that air passes through. The nose serves some very most important functions. As part of the conducting zone, it cleans the air of dust and other impurities, warms the air if it is too cool, and moistens the air if it is dry. Though not related to respiration, your nose also helps you to speak, and is the organ that gives you the power to smell. After passing through the external nares (nostrils), it passes through the nasal cavities. Your  nasal septum separates the two nasal cavities. Immediately after passing through the nostrils into the nasal cavities, the air begins to be purified, humidified and warmed. The skin of the vestibule, the part of the nasal cavities cav ities behind the nostrils, has sebaceous and sweat g lands and hair follicles, which catch the dirt or other impurities that may be in the air. The hair growing out of the follicles are called vibrissae. The olfactory mucosa is what detects scents that you inhale. The serous glands excrete enough eno ugh lysozyme, an enzyme that destroys bacteria, to keep the air you breathe mostly pure. That is about a quart a day. It will kill the bacteria that is caught by the vibrissae.

In the pharynx, the cilia moves bacteria up away from the lungs so that you can swallow it into your stomach, where the bacteria can do little harm. Because of the shape of your organs, air  swirls and twists as it moves down. This make sit virtually impossible for impurities to not make contact with the mucous lining your organs. This will catch most particles larger than 4µm.

The Pharynx The pharynx, most commonly known as the throat, serves duel purposes. Not only does it move the air into your lungs, but it also moves food into your stomach. About five inches long, the  pharynx is separated into three distinct regions, chosen b y location and function: the nasopharynx, the oropharynx, and the laryngopharynx. The Nasopharynx 

The nasopharynx is located above the part of the pharynx that food enters. At the base of the nasopharynx are the soft palate and its pendulous uvula. When swallowing, there is a dangerous possibility: that food will enter into your nasopharynx and nose. This would disrupt severely your breathing. So, when you swallow, the soft palate and its pendulous uvula u vula point upwards blocking of  the nasopharynx so that neither air nor food can pass through it. The auditory, equally poorly known as the eustachian, connects the middle ear to the wall of the nasopharynx so that ear e ar pressure can be equalized. Infections in the nasopharynx are commonly followed by ear infections because of this. The Oropharynx 

The mouth leads into the oropharynx. The mucous lining the walls of the oropharynx change slightly to adapt for handling food as well as air. It is here that the two tonsils are located. One is at the entrance from the mouth into the oropharynx, and the other is somewhat deeper. The Laryngopharyn Laryngopharynx  x 

The laryngopharynx too serves as a common passageway for both food and air. At the base of the laryngopharynx is the esophagus, which directs food and air to where they should be. Sometimes it can get confused and make mistakes. Swallowing air can lead to burping more often. often . Inhaling food or liquid causes you to cough until it is expelled.

The Larynx Also known as the voice box, the pharynx is what allows you to speak. The larynx has an inlet at the top that allows substances to pass through it or not. When food is being swallowed, the inlet is closed, forcing food into the stomach. When air is being breathed, the inlet is wide open so that air can enter your lungs. l ungs. With the exception of the epiglottis, all larynx cartilage is hyaline cartilage. The Adam's apple is really the laryngeal prominence, where the curved disc shaped thyroid cartilage bond.

The Trachea The trachea, or windpipe connects the larynx to the bronchi. This organ differs from others in the neck in that it is flexible, stretching to be between four and five inches long, and about one inch in ch in diameter. The trachea is lined with mucous called the mucociliary escalator, which represents the th e mucous and cilia and carry the foreign substances up to be swallowed. The trachea is made up of between 16 and 20 cartilage rings in the shape of a "C". Because the trachea is so flexible and twistable, without these cartilage rings, it would collapse under the partial vacuum formed when inhaling. The open part of the "C" shape is covered with the Trachealis muscle, which can stretch itself to prevent tracheal tearing when swallowing large things. When you cough, the muscle also contracts to force air out at a faster speed to dislodge food or other foreign objects stuck.

The Bronchi The trachea branches off into two main bronchi, your left and right primary bronchi, which lead to the left lef t and right lung respectively. Your right lung is slightly wider, shorter, and taller that the left, which makes it more vulnerable to foreign invasion. At this point in breathing, the air has been moistened, purified and warmed. Each bronchi enters its lung and begins on a series of branches, called the bronchial or respiratory tree. The first of these branches is the lobar (secondary) branch. On the left, there are two lobar branches, while on the right, there are three. Each lobar branches into one lobe. The next branch is called the segmental (tertiary) branch. Each branch continues to branch into smaller and smaller bronchioles. The final branch is called the terminal bronchioles. These bronchioles are smaller than 0.5 mm in diameter. The first few levels of bronchi are supported by rings of cartilage. Branches after that are supported by irregularly shaped discs of cartilage, while the latest levels of the tree have no support whatsoever.

Respiratory Zone Respiration begins when the terminal bronchioles lead into the respiratory bronchioles. These bronchioles are covered with thin-skinned air sacs that allow for gasses to pass through them. These sacs, which contain alveoli, are called alveolar sacs, and are at the end of alveolar ducts. The alveoli are very small curves in the sac walls. Your lung has many millions of alveoli, which gives your lungs an incredible surface area for gas exchange. Though fairly impossible to measure exactly, that surface area is approximated to 70 - 80 square meters, or a

square between eight and nine meters on each side! The alveoli are covered in inter linking capillaries through which blood flows. The alveoli and the capillary walls form the respiratory membrane. Your lungs rely simply on diffusion to exchange the gasses, and that moves enough gas to have a steady supply of oxygen in your body. The respiratory membrane is only 0.5 - 1µm thick, so diffusion happens pretty efficiently. For maximum efficiency, the amount of blood passing though a capillary on an alveoli and the amount of  gas exchange should match precisely. When there is not enough gas in that alveoli, certain pulmonary vessels tighten, slowing the flow of blood, which causes more blood to flow elsewhere. When there is a lot of gas exchange happening, those vessels widen, allowing for more blood to pass pa ss though. A similar process happens to bronchioles. When an alveoli has a lot of carbon dioxide in it, the bronchioles that connects it to the outside air widen, allowing it to leave more quickly. With the lungs coming in direct contact with the air, you would think that it could supply it's own blood supply. This isn't so. The bronchial arteries, which branch from the aorta, supply the lungs with oxygen, and the bronchial and pulmonary veins take old blood away.

The Pleurae The Pleurae is a thin, double-layered tissue which lines the walls of the lungs and heart«link» . Due to the fact that it produces pleural fluid, the pleurae helps the lungs to glide easily against the rib-lining tissues, the thoracic wall, when the lungs take in air. Also, the pleural is essential to breathing because it serves as potential space. This important function helps the lungs form a vacuum which sucks in air from the atmosphere. In addition, its capability to stretch and divide the lungs into two compartments, a lower lung and a upper lung, allows other organs to move without interfering with respiration.

Inspiration and Respiration As mentioned before, respiration is the result of a vacuum formed inside your lungs. Your lungs themselves don't have muscles, so they cannot force themselves to expand. Instead of each alveoli or bronchiole having a muscle, you have one big muscle, the diaphragm. The diaphragm lines the lower part of your chest ch est cavity, sealing it off air-tight from the rest of your body. When you want to inhale, your dome-shaped diaphragm contracts, straightening itself out. This lowers the pressure in your chest cavity causing air outside your lungs to rush in to fill the space. Though air can expand, and does for a short time, the low pressure inside pulls in air to equalize the pressure. Your lungs, connected at the ends by cartilage, expand, stretching the cartilage to allow room for the lungs to hold air. With the ribs expanding outward only a few millimeters, and the

diaphragm lowers only a few millimeters, this increases the volume of the chest cavity by about half a liter, which is the average inhaling amount. The exact opposite is the cause for expiration. When the diaphragm relaxes, moving upwards, the chest cavity becomes less in volume, raising air pressure inside the lungs, forcing air out into the th e atmosphere. Muscles, such as the diaphragm, cannot push out, but only contract. When you inhale, different tissues in your chest cavity stretch. Relaxing the diaphragm allows them to return to normal size, which raises the pressure, thus forcing air out. That is quiet respiration. If you need to exhale quickly, such as in coughing and sneezing, your abdominal walls can contract, doing the same things that the stretched tissues do. That elasticity is incredibly important. Sufferers of emphysema e mphysema can testify to this personally. Their lungs of lost most of their original elasticity, so they must actively breath out instead of it happening automatically. The triples or even quadruples the amount of energy required to breath, which is a reason so many emphysema sufferers have little energy most of the time. Dangers of surface tension

Blood, like any liquid, has a tendency to form a surface that is reluctant to break  and mix with other substances. The danger comes in that if the blood pushes on the alveoli instead of passing through it, it could easily e asily collapse every sac in your lungs (which is what happens in IRDS, or infant respiratory distress syndrome, because the premature infants have commonly not developed far enough to hold the sacs patent, or open continuously). Though this is not fatal, having to completely reinflate your lungs is very draining. To break the surface tension of  the blood, a surfactant is released. A surfactant acts like the soap you wash your hands and clothes with. The soap breaks the surface of the water allowing it to wash more effectively and pass through the minute openings between fiber strands.

Internal Respiration Internal respiration is the exchange of carbon dioxide and oxygen in the cells of  the body. It happens in much the same way as gas exchange in the lungs, diffusion. Red blood cells carry the oxygen to the body, and brings back the th e carbon dioxide to the lungs.

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