Immunology

Unit Overview: The study of all aspects of immunity, including allergy, hypersensitivity, and how it fights disease. In this section you will learn how the your defense system works to protect you from diseases and infections. For example you have two different types of defense that work against pathogens; One is innate (nonspecific) immunity and the other one is adaptive (specific) immunity. You will also learn about Natural Killer cells (NK) that provide a cell-mediated defense for your body. You will also read about the diseases in that can happen in the immune system which can be put into three different kinds of categories.



Concepts:
1.Defense Mechanisms-
Your body has two different types of defense against pathogens. They are innate and adaptive immunity. These two are different in how they go about protecting the body, but at the same time there are areas that they tend to overlap.
Innate are nonspecific immunity are inherited in the structure of each organism to help fight off pathogens. They recognize the body's tissue cells as "self" which allows them to recognize invaders. The best for detecting these invaders are the lipopolysaccharides. The first layer of defense is the top layer of skin called the epidermis. Many pathogens don't get passed this barrier. Along with the epidermis, gastric juice also helps fight off microogranisms before they can enter the body. External and internal defense mechanisms are both part of innate immunity. Once a pathogen gets through the epithelial tissue it is in the connective tissues and is now called a toxin. From there it can go into the persons blood stream or into the lymphatic capillaries where it then can travel to any other place in the body. Innate is also the first defense set off once a toxin is in the body to see if it can't get rid of it. There is a thing called the complement system that helps out the innate and adaptive immune responses. It does this by when the antibodies attach to their targets, which actives the plasma proteins (which is the complement system), this then sends out phagocytosis to destroy the cells that were targeted. With phagocytosis there are three major groups. First you have the neutrophils that are located in the blood and all the body's tissues, then comes the mononuclear phagocyte system that is found in connective tissues and lastly you have the organ-specific phogocytes that are located in the liver, spleen, brain, lungs, and lymphnodes. Fixed phagocytes are phagocytes that cant move from the place that they are in. For example, Kupffer cells are only found in the body's liver. One of the jobs of phagocytes is to rid the body of debris like dead cells which usually is a result of apoptosis. Because of this phagocytes often work outside of the immune system. Neutrophils show up first at the site of an infection, then monocytes, which develop into macrophages at the fight goes on. A fever and or sleepiness may develop as a result of the defense mechanism of innate immunity underway.

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On the other hand, adaptive or specific immunity is something you can get by having the pathogen come into the body and once its fought off the lymphocytes acquire the ability to fight it off next time right away because it already knows how to kill it. According to the scientist Emil Adolf von Behring, antibodies is what makes up this immunity. But only certain antibodies would on certain infections, it depends on which ones were there for when the pathogen first came in order for it to build up its immunity against it for the next time. Since the body can recognize its own "self" it can go against antigens that are a foreign molecule to the body's fluids such as blood.


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Local Inflammation
Above this is a picture of what happens in a local inflammation. "The antigens on the surface of bacterial cells, first bind to antibodies, then this activates complement and promotes phagocytosis by neutrophils and macrophages. This also stimulates mast cells to release histamine and other mediators of inflammation, including chemicals that promote capillary permeability and extravasation of leukocytes" which go to the part of the body that is inflamed. Fox, Stuart.
In the bone marrow, Leukocytes, erythrocytes, and platelets in the blood are made. Lymphocytes that go to the thymus mature into T cells (T lymphocytes). The rest of the lymphocytes that don't go to the thymus to become T cells, form into B cells (B lymphocytes). Because of the forming of B and T cells, both the thymus and the bone marrow are known as the primary lymphoid organs. B and T cells are a form of specific immunity. It is said that the B cells give a person humoral immunity because it goes against bacterial and some virus infections in the blood. It is also then said that T cells are cell-mediated immunity because in order to kill a cell it has to come very close if not in actual contact with it. The thymus is located under the thyroid. The thymus grows as children age but stops soon usually after they hit puberty. Even though T cells have a very long life span, they still need to be reproduced all the time especially when a person is having chemotherapy.



2. Functions of B Lymphocytes and T lymphocytes

B lymphocytes secrete antibodies that bind to specific antigens. A system of plasma proteins called complement is activated by the bonding that stimulates a cascade of reactions. Resulting in a more effective defense against pathogens, some of the activated complement proteins kill the cells containing the antigen and others promote phagocytosis.

A lymphocyte circulates throughout the body, going from on secondary lymphoid organ to another until it encounters the antigen that is specific to its receptors. Memory cells are visually indistinguishable from the original cell and are important for active immunity. Plasma cells are derived from B lymphocytes that produce and secrete large amounts of antibodies. They are responsible for humoral immunity. Plasma cells are protein factories that produce about 2,000 antibody proteins per second.


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Antibodies are immunoglobulin proteins that are secreted by B lymphocytes that have transformed into plasma cells. Antibodies are also responsible for humoral immunity. Their synthesis is induced by specific antigens and the combine with these specific antigens but not with unrelated antigens. Electrophoresis is the technique that separates plasma proteins into five major classes. The five major classes of plasma proteins are albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin. Immunoglobulins (Ig) are also known as antibody proteins. There are five immunoglobulin subclasses: IgG, IgA, IgM, IgD, and IgE.

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The complement system is part of nonspecific defense system. Immune destruction of bacteria is also promoted by antibody-induced activation of a system of serum proteins known as a complement. Opsonization is the process that antibodies increase the ability of phagocytic cells to attack bacteria. Complement proteins constitute a nonspecific defense system that is activated by the bonding of antibodies to antigens. These proteins are present in an inactive state within plasma and other body fluids and become activated. The complement proteins can be subdivided into three components. The attack phase of complement fixation where complement proteins attach to the cell membrane and destroy the victim cell.
Classic pathway is initiated by the binding of antibodies of the IgG and IgM subclasses to antigens on the invading cell;s membrane. Alternative pathway is more rapid and efficient because it is initiated by the unique polysaccharides that coat bacterial cells. The membrane attack comple is a large pore that can kill the bacterial cell through the osmotic influx of water.

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T cells are activated only by antigen-presenting cells. Activated helper T cells produce lymphokines that stimulate other cells of the immune system. Killer T cells effect cell-mediated destruction of specific victim cells, and helper and suppressor T cells play supporting roles.
Killer T lymphocytes (or cytotoxic) function is to destroy body cells that carry foreign molecules or antigens. They carry CD8 cell surface molecule. Killer T cells kill by cell-mediated destruction by coming in contact with the victim cell. They kill by secreting perforins and enzymes called granzymes which creates a pore in a victim's membrane and causes lysis.
Helper T lymphocytes carry a surface molecule called CD4. These cells enhance the immune response by improving the ability of B lymphocytes to differentiate into plasma cells and secrete specific antibodies. They also enhance the ability of cytotoxic lymphocytes to mount a cell-mediated immune response. Regulatory T lymphocytes, suppressor, provide a brake on the specific immune response. They inhibit the activity of killer T lymphocytes and B lymphocytes.


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A lymphokine refers to the cytokines of lymphocytes. They are any group of chemicals released from T cells that contribute to cell-mediated immunity and secrete a number of polypeptides that serve as autocrine regulators of the immune system.


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3. Active and Passive Immunity15.20.jpg

Active immunity can protect the person from getting the disease upon subsequent exposures. When a person is exposed to a particular pathogen for the first time, the sluggish response is the primary response. It may not be sufficient to protect the person against the disease caused by the pathogen. If a person is exposed to the same antigen, it results in a secondary response. Antibody production, compared to the first response, is much more rapid in the second response. The rapid rise in antibody production is usually sufficient to prevent the person from developing the disease.

Active immunity involves sensitization, in which antibody production is stimulated by prior exposure to an antigen. Vaccinations are clinical immunization programs that induce primary responses into people with pathogens whose virulence has been affected or destroyed. Vaccines may use live viruses to provoke strong immune responses against the virulent virus. They also may use killed virulent viruses that don't cause the disease. Some vaccines may recombinant viral proteins, produced through genetic engineering and given by themselves. Adjuvants can boost the immune response when delivered with the vaccine antigens. Adjuvants are molecules associated with microbes and they enhance the adaptive immune response by boosting the antigen-presenting cells' ability to activate T lymphocytes.




Passive immunity is the specific immunity granted by the administration of antibodies made by another organism. It is the immune protection that can be produced by the transfer of antibodies to a recipient from a human or animal donor. Passive immunity occurs naturally in the transfer of immunity from mother to fetus during pregnancy and from mother to baby during nursing. Immunological competence,developing about a month after birth, is the ability to mount a specific immune response. The immune system of the mother is fully competent but does not usually respond to fetal antigens. The fetus and the newborn baby are immune to the same antigens as the mother. Passive immunizations are used clinically to protect people who have been exposed to extreme infections or toxins. Monoclonal antibodies are produced by a single clone of lymphocytes. They are generated medically to bind a single antigenic determinant site of a molecule.

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4. Tumor Immunology & Diseases Caused by the Immune System

Tumor Immunology

Immunological surveillance against cancer is provided mainly by killer T lymphocytes and natural killer cells.

Tumor cells dedifferentiate or become less specialized like cells of an embryo. These or other antigens may be presented to lymphocytes in association with abnormally produced class-2 MHC antigens. They produce surface antigens that are normally recognized by immunological surveillance and destroyed.

Because they were absent at the time immunological competence was established, the body treats these antigens as foreign. With the presence of these antigens it provides a basis of laboratory diagnostic testing for some cancers.

Natural killer cells (NK) are nonspecific lymphocytes, whereas T lymphocytes are directed against specific antigens on the cancer cell surface. NK's are related to t-cells thought and provide the first line of cell-mediated defense. Which means the cells themselves have contact with pathogens or cancerous cells. They are considered to be part of the innate immune system and possess an array of surface receptors that allow them to fight viruses, bacteria, parasites, and malignant cells. They destroy tumors in a non-specific fashion which are then backed up by the specific response of killer T-cells. NK's are stimulated by interferons from the T-cells. They also lack class-1 MHC antigens and kill with perforins and granzymes.

Immunological surveillance against cancer is weakened by stress.

Immunotherapy for cancer
Monoclonal antibodies- used to combat some forms of cancers. One example is about 20-25% of breast cancer patients have HER2 receptors on the plasma membrane of tumor cells. The monoclonal antibodies for these receptors is commercially available as Hereceptin, which blocks these receptors. Human interferons- obtained from genetically engineered bacteria are now available. They have been used for treatment of some types of lymphomas, renal carcinoma, and melanoma

Effects of aging and stress
Little is known about why susceptibility to cancer is so variable.
Cancer risk increases with age, one factor may be that aging lymphocytes accumulate genetic errors that decrease effectiveness, as well as the thymus function declining with age and with a decrease in cell-mediated immune competence. It has also been proven that tumors grow faster in stressed animals. The stress hormones (corticosteroids) causes decreased immune function.


Diseases Caused by the Immune System

Diseases Caused by the immune system
Can be grouped into 3 categories: autoimmune diseases, immune complex diseases, and allergies.
- all are caused by abnormal function of immune system.


I. Autoimmune diseases are produced by failure of immune system to recognize and tolerate self-antigens and may be caused by the production of autoantibodies against self-antigens, or they may result from the development of autoreactive T lymphocytes. It afflicts women twice as often as men.

Failure of self-tolerance may be due to:
1. An antigen that does not normally circulate in blood being presented to immune system.- Example Hashimoto's Thyroiditis
2. Combination of a self-antigen, that is otherwise tolerated, with a foreign hapten.- Example Thrombocytopenia
3. Antibodies being produced that are directed against other antibodies.- Example Rheumatoid Arthritis
4. Antibodies against foreign antigens cross-reacting with self-antigens.- Example Rheumatic Fever
5. Self-antigens being presented to helper T cells together with class-2 MHC molecules.- Example Type 1 Diabetes

II. Immune complex diseases are those caused by the inflammation that results when free antigens are bound antibodies. Involve formation of immune complexes that are free and not attached to a cell. These activate complement proteins and promote inflammation. But can also damage tissues as well. Can result from infections by bacteria, parasites, viruses. Can result from formation of complexes between self-antigens and autoantibodies this occurs in rheumatoid arthritis and lupus.

III. An Allergy is an abnormal immune response to allergens.
There are two types of allergic responses: immediate hypersensitivity and delayed hypersensitivity .

Immediate hypersensitivity results when an allergen provokes the production of antibodies in the IgE class= Dendritic cells stimulate a class of helper Ts to secrete interleukin-4 and -13 which causes B and plasma cells to secrete IgE antibodies. These antibodies attach to tissue mast cells and stimulate the release of chemicals from the mast cells= IgE antibodies don't circulate in blood; are attached to mast cells and basophils.The immediate is due to abnormal B-cell response to allergen; causes effects in secs to mins. and happens very fast.- caused by food, bee stings, or pollen.


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Mast cells secrete histamine, leukotrienes, and prostaglandins, which are believed to produce the symptoms of allergy. When re-exposed to same allergen, antibodies on mast cells and basophils bind it and stimulate secretion of histamine, leukotrienes, and prostaglandin D. Producing allergy symptoms such as watery eyes, and a runny nose. Histamine increases capillary permeability and enhances immune response. Inappropriate immune response to an unharmful thing.
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Delayed hypersensitivity, as in contact dermatitis, is a cell-mediated response of T lymphocytes that causes symptoms 24-72 hrs after exposure.
Symptoms are caused by secretion of lymphokines, not histamine so antihistamines provide little benefit to this reaction. Examples include contact dermatitis caused by poison ivy, oak, or sumac (any of various shrubs or small trees.)

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Poison Ivy

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Poison Oak


























Essential Questions:
-Compare and contrast the following categories:
-Active immunity vs. passive immunity
Active immunity is when a person gets the infection but recovers and has memory B and T cells left to help fight infections later on. Active immunity could also come from a vaccine.
Passive immunity is immunity that a person can receive by injections from someone else or from an animal.
-Innate immunity vs. adaptive immunity
Innate immunity is something that is already in a persons body after they are born because it is inherited. So it fights off pathogens without having to first become immune to it.
Adaptive immunity is immunity against a pathogen after you got the virus. So then it knows how to fight it off right away the next time.
-Cell-mediated immunity vs. humoral immunity
Cell-mediated immunity doesn't consist of antibodies but consists of NK cells, macrophages, and or cytotoxic T cells.
Humoral immunity is immunity that comes from the body making antibodies against infections and diseases.
-Describe the process of a local inflammatory response. Make sure to include characteristic symptoms of a local inflammation.
At a local inflammatory response the first thing that happens is that T cells are released and neutrophils show up to kill the pathogens that came into the body and to stimulate recruiting cells to come. Later B cells arrive to make a specific antigen against this certain kind of pathogen. The blood vessels in that area constrict allowing less area to the area that is inflamed. The characteristics that show up during local inflammation is redness and warmth that is the result of the blood vessels dilating. Another one is swelling which is a result of extra fluid build up in that area, with swelling you could also have pus as a result which is just dead WBC. Last there is pain which is different level for every person but its usually there in some kind of form whether its throbbing, sharp, dull and so on.

How this applies to PTA:
This would be very important for us to know in our particular field of study because we will be working with patients that are going to have open wounds that may be affected or may become infected and we need to know the how the persons immune system may act and what to look for if swelling is occurring. If we are aware of these things we can try to keep the healing process progressing in a positive way. It is also very important that we know if our Patients have allergies. Because of some of the products we use to help treat injuries, such as compression bandages which may have latex in it to stretch and hold around the injury, it could cause an allergic reaction and delay healing. Being aware of their allergies will help us keep them safe.

1.Fox, Stuart I. "Human Physiology." New York: McGraw-Hill, 2011. Print.
2.http://highered.mcgraw-hill.com/sites/0073378119/student_view0/chapter15/textbook_images.html
3. http://www.cosmetic-lasersurg.com/main/images/stories/images/poison_ivy_oak.jpg
4. http://www.mayoclinic.com/images/image_popup/sn7_cdermatitis3.jpg