J.+IMMUNOLOGY

= ** Immunology **

** ﻿ ** =

__OVERVIEW __ This Chapter covers the Immune System and its Defense Mechanisms, inlcuding Innate (Nonspecific) Immunity and Adaptive (specific) immunity. Also gets into the Lympocytes and Lymphoid organs and talks about T lymphocytes aka T cells and also B Lymphocytes aka B cells. Explains cell-mediated immunity, humoral immunity and also primary lymphoid organs (bone marrow and thymus) and secondary lymphoid organs ( lymph nodes, tonsils, and areas called Peyer's patches under the mucosa of the intestine). This section also describes local inflammation where osponization and chemotaxis is defined. Mast cells are described and how they secrete histamine. Explains the symptoms of local inflammation, which are redness, warmth, pain, swelling, pus. Explains the events that occur during a local inflammation. Next Functions of B Lymphocytes are discussed. This includes antibodies, antibody structure and diversity of antibodies. Also the complement system where osponization, complement, complement fixation, classic and alternative pathway, membrane attack complex are discussed. Also in this section Active Immunity and the Clonal Selection Theory is discussed. Immunologival Toleralance is discussed and also Passive Immunity. Next in the chapter is Tumor Immunology where natural killer cells, immunotherapy for cancer and effects of aging and stress are all discussed. The last topic in the chapter is diseases caused by the immune system such as autoimmune diseases such as Graves' disease or DM type 1, and immune complex diseases such as SLE or rheumatoid arthritis. Allergies are also discussed in where there is immediate hypersensitvity where allergic rhinitis, conjuntivitis, allergic asthma, or atopic dermatits occurs whereas in delayed hypersensitivity symptoms take longer to develop and an example of this would be contact dermatitis or the mantoux test.

//Sources://
//Fox, Stuart Ira. (2009). Human Physiology. New York, NY: McGraw-Hill.//

B lymphocytes are important for the immune system to fight off infection. The "B" comes from research that was done of chickens. The chickens have an organ called the bursa of Fabricius which makes the B cells in the chickens. Humans, however, do not have a bursa of Fabricius so the "B" is sometimes refered to as "the bursa equivalent." B cells do however come from the bone marrow so the "B" could also stand for bone marrow. B cells are responsible mostly for bacterial infection and on occation will get involved in a viral infection. B cells secrete antibodies in the lymph fluid and the blood to help fight off infections. The type of immunity provided by the B cells is called antibody-mediated immunity or humoral immunity because there are humors invoved, blood and lymph fluid. There are specific antibodies on the B cells that are meant for specific antigens. Some B cells will become meomory cells and some will become plasma cells. Plasma cells will make thousands of antibodies that will provide active immunity. When a B cell binds with an antigen complement will be activated. Compliment will kill cells that have antigens on them, or infected cells and activate phagocytosis. B cells are only a small part of our immunity but they do a great deal to keep us healthy.

__ESSENTIAL QUESTIONS __  **Compare and contrast: ** **Active immunity vs. Passive immunity ** Active immunity is immunity that is //produced by the body// in response to a pathogen. It can take //5 to 14// days before a measurable amount of antibodies appear in the primary response. The lymphocytes with specificity for that antigen are stimulated to divide many times and produce a clone which is active immunity. During a secondary response to the same specific pathogen the body can produce antibodies in as few as a few hours and last longer than the primary response antibodies. Vaccinations also produce an active immunity as the body is injected with a specific //antigen//, a weakened version of the pathogen, or a "killed" pathogen that the body can fight off to form lymphocytic clones to combat the pathogens in a secondary response. Vaccination induced active immunity //last as long as the body creates the lymphocytic clone cells maybe even years//. Vaccinations need to be given //before exposure// to a pathogen in order to be effective. Passive immunity involves injecting the body with //antibodies// from a human or animal donor that had created an active immunity. This injection of antibodies is //short lasting// as the body does not create its own lymphocytic clones it does however //act immediately upon injection// but it is short //lasting from days to maybe weeks// then is ineffective. Passive immunity injections can be given **before or after exposure** to a pathogen. Passive immunity can also be //transferred from mother to fetus// during pregnancy making the fetus and newborn immune to the same antigens as the mother. This passive immunity disappears because the baby does not produce lymphocytic clones to form antibodies. Passive immunity can be used to treat virulent infection or toxins. Active and Passive immunity are similar in that they both protect the body from pathogens. They can also both be given before exposure to a pathogen as long as exposure takes place before the injection wares off.

**Innate immunity vs. Adaptive immunity ** Innate immunity is inherited immunity that combat an entire category of pathogens which are identified by the presence of particular molecules on their surface. It includes external and internal defenses and are the first line of defense against pathogens. If pathogens do cross the external defense mechanisms(skin, digestive enzymes, respiratory mucus, and GI tract acid) the innate defenses are activated. Toll-like receptors recognizes PAMPs displayed on the surface of pathogens that are specific for a type of molecule that is not characteristic of human cells. If dendritic cells or macrophages are stimulated they release cytokines to recruit other immune cells and promote phagocytosis and fever. Adaptive immunity in contrast is acquired to defend against specific pathogens based on prior exposure to the pathogens. It recognizes specific features of pathogens known as antigens. When antigens are recognized as foreign to the body it stimulates the production of antibodies which bind to the foreign antigens. Innate and adaptive immunity work together. The cytokines release in innate immunity by dendritic cells and macrophages activate the B and T lymphocytes of the adaptive immune system. The complement system also integrate immune response. Plasma proteins and other body fluids that are activated by antibodies bond to antigens and complement proteins promote phagocytosis, lysis of target cells, and aspects of local inflammation. They are the same because they both identify foreign molecules which activates an immune response that may consist of both innate and adaptive immunity.

**Cell-mediated immunity vs. Humoral immunity ** Both cell-mediated immunity and humoral immunity are a form of specific immunity. Both have receptors on their surface for antigens. In contrast however humoral immunity is produced by B lymphocytes which are produced in the bone marrow while cell mediated immunity is produced by T lymphocytes produced in the thymus. Also humoral immunity fights infections by secreting antibodies into the blood and lymph while cell mediated immunity must come into close proximity with the victim cell or have physical contact with the cell to destroy it. Humoral immunity has surface antigens for antibodies and have surface antibodies while cell mediated immunity has receptors for antigens related to immunoglobulin's and do not have detectable surface antibodies.

**Describe the process of a local inflammatory response. **   **<span style="font-family: "Arial","sans-serif"; font-size: 10pt; line-height: 150%;">(include characteristic symptoms) ** <span style="font-family: "Arial","sans-serif"; font-size: 10pt; line-height: 150%;">Local inflammation is a complicated event. First bacteria enters through a break in the skin which is part of innate immunity. Next the inflammatory reaction starts with phagocytosis and complement activation. Then the adaptive immunity begins when the B lymphocytes are stimulated to produce antibodies against antigens on the bacteria. The produced antibodies attach to the antigens on the bacteria which stimulates opsonization. Complement proteins and bacterial products serve as chemokines which draw leukocytes toward the infection through chemotaxis and promote phagocytosis. When neutrophils arrive for phagocytosis they release chemicals that recruit monocytes, lymphocytes, and other immune cells to the infection. Through the action of proteases the neutrophils liquefy the surrounding tissues which creates pus. Pus creates pressure that closes lymphatic and blood capillaries, which in turn clocks the spread of bacteria. The mast cells in the tissue release histamine which promotes capillary permeability attracting leukocytes to the area of infection. Mast cells then release inflammatory prostaglandins and leukotrienes and cytokines to promote inflammation. Mast cells and macrophages secrete tumor necrosis factor attracting more neutrophils. Together these all produce symptoms of local inflammation including, redness and warmth from the histamine stimulated vasodilation, edema, pus, and pain. If the infection continues to grow leukocytes and macrophages release endogenous pyrogen producing a fever. <span style="font-family: "Arial","sans-serif"; font-size: 8pt;"> <span style="font-family: "Arial","sans-serif"; font-size: 10pt;">

__<span style="color: #800080; font-family: 'Arial Black',Gadget,sans-serif;">SUMMARY __ __**Major Histocompatibility Complex (MHC)**__: MHC is a molecule encoded on chromosome #6 in the Human Genome; it plays an important role in the immune system and autoimmunity. MHC is located inside all cells except mature RBC's that will display a fragment of the cell's proteins on the cell's surface. By having the MHC protein complex displayed on the cell's surface, it acts as a flag for the T cell or the natural killer cell, to recognizer the protein as itself or as an invader (and destroy it). MHC is what will cause the itchy response to poison ivy, because MHC display the "bad" protein on its cell surface and it causes the immune system to react and kill the cell. This MHC is vitally important to understand when it comes to organ transplants because if the transplanted organ does not have the same or similar MHC molecules, it will cause the immune system to attack the transplanted tissue/organ as a foreign object and destroy it. The bad news is there are hundreds of different MHC molecules, the good news is each person only has four, two from each parent. This is why biological family is check for compatibility first is a transfusion is needed.

http://upload.wikimedia.org/wikipedia/commons/8/85/TCR-MHC_bindings.png

Natural Killer Cells are lymphocytes and part of the innate (nonspecific) immune system. They do not have surface receptors specific for a particular antigen, but, have numerous receptors that allow them to determine if the cell is foreign or itself. They are considered the first line of cell-mediated defense because they destroy the cells displaying foreign antigens non-specifically, and they require no prior exposure to the foreign antigen to react to it. Natural Killer Cells are activated in response to interferons and are cytotoxic. When a cell is target by the Natural Killer Cell, it releases perforin proteins and the granzyme enzyme. Perforins enter the cells plasma membrane and make a hole in it; granzyme is taken into the cell and will lead to the destruction of its DNA, thus, destroying the "bad" cell. While this is taking place, the Natural Killer Cell secretes cytokines, which let the B and T Lymphocytes know they are needed for assistance. Natural Killer Cells are special, they destroy tumor and malignant cells daily. Due to their unique ability to kill with out prior exposure, many bad cells, viruses, etc. are destroyed before we even know we have a problem.
 * __Natural Killer Cells:__**

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http://www.rkm.com.au/IMMUNOLOGY/immune-images/Natural-Killer-Cell.jpg

Autoimmunity is when the immune system can't tell the difference between healthy body cells (self-antigens) and antigens from cancer cells, viruses, bacteria, toxins, and other cells not normally found in the body, and destroys itself. Normally dendritic cells, macrophages, and antigen activated B cells are the ones who produce what is known as MHC-2 molecules, which carry the antigen of a foreign substance (ex:virus), displays it on its cell surface and then helper T cells will recognize it and secretes a lymphokine called interleukin-2, which signals the Killer T cells to come and destroy the foreign antigen (substance). 5-7% of the population is affected by an autoimmune disease and 2/3 of this population is women. Once common autoimmune disease is Type 1 diabetes. In type 1 diabetes, for example, the beta cells of the pancreatic islets abnormally produce the MHC-2 molecules. As we learned before, only dendritic cells, macrophages, and antigen activated B cells normally do this because they will be destroyed by the Killer T cells. So, if the beta cells produce the MHC-2 molecule, they too will be destroyed, causing the destruction of the insulin-producing cells. Listed below are some examples of autoimmune diseases.
 * __Autoimmunity:__**



Sources:
<span style="font-family: 'Times New Roman','serif';">Fox, Stuart Ira. (2009). //Human Physiology//. New York, NY: McGraw-Hill. <span style="font-family: 'Times New Roman','serif';">http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb62_1.html[| MHC] http://www.cancerfoundation.com/NKcells.html

__<span style="color: #800080; font-family: 'Arial Black',Gadget,sans-serif;">APPLICATION __

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As a clinic nurse I should know the differences between active immunity and passive immunity. I will use this information for education purposes, for example, when explaining to new parents how vaccinations work and why they are so important to their new child. Immunizations are very important because it protects them from dangerous childhood diseases. I will know what immunizations the child needs, when they start and how many of each they need. Of course I will explain to the parents that there can be side effects such as slight fever, rash, or soreness at the site of injection, and that it is normal for the child to experience slight discomfort but not to be alarmed. I would also tell them not to wait to vaccinate because children under the age of five do not have a built up immune system and are very susceptible to disease. I also realize that receiving all of this information at once can be overwhelming so I will have available information for them to take home or refer them to the Centers for Disease Control and Prevention on the internet so they can view the information at their own pace and not feel overwhelmed.

[|Centers for Disease Control and Prevention: Vaccines] [|10 Things You Need to Know About Immunizations]



Resources: Education.com Centers for Disease Control and Prevention

As a nurse I will need to be able to recognize the signs of an infection such as redness, swelling, warmth, pus, and sometimes pain. An example could be, a 5 year old boy comes in with a a fever of 103.2 degrees F. Blood draw shows high elevation of white blood cells. During examination you notice that the child seems to be favoring his left leg. You ask to examine the leg and find what appears to be a deep bite mark on the lower calf. The area has a 2 inch inflamed area around the 3 puncture wounds that are secreting pus. Possible treatment could be cleansing of the wound, stitches, application of clean bandages, and a prescription of an antibiotic.

__<span style="color: #800080; font-family: 'Arial Black',Gadget,sans-serif;">CASE STUDY __ **[|A Bad Reaction]** [|Immunofluorescence] image of the eukaryotic [|cytoskeleton]. [|Actin] filaments are shown in red, [|microtubules] in green, and the [|nuclei] in blue.

An antigen is a molecule able to induce the production of antibodies and to react in a specific manner with antibodies. An allergen is an antigen that brings on an allergic response instead of a normal response. An unusually severe allergic reaction that can result in cardiovascular shock and death. There are 5 major classes of plasma proteins: albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin. The gamma globulin plasma protein is the class that contains antibodies. Peanut allergies are associated Immunoglobulin E (IgE).
 * What is the difference between an "allergen" and an "antigen"?**
 * What is meant by "anaphylaxis"?**
 * What are the different classes of antibodies that our bodies produce? Which class is associated with the peanut allergy?**

Antibody isotypes of mammals(http://en.wikipedia.org/wiki/Antibody) Antibody isotypes of mammals|| **Name** || **Types** || **Description** || **Antibody Complexes** || A mast cell is a type of connective tissue cell that produces and secretes histamine and heparin.
 * [|IgA] || 2 || Found in [|mucosal] areas, such as the [|gut], [|respiratory tract] and [|urogenital tract], and prevents colonization by [|pathogens].[|[][|10][|]] Also found in saliva, tears, and breast milk. || [[image:http://upload.wikimedia.org/wikipedia/commons/thumb/3/31/Mono-und-Polymere.svg/170px-Mono-und-Polymere.svg.png width="170" height="209" caption="Some antibodies form complexes that bind to multiple antigen molecules." link="http://en.wikipedia.org/wiki/File:Mono-und-Polymere.svg"]] ||
 * [|IgD] || 1 || Functions mainly as an antigen receptor on B cells that have not been exposed to antigens.[|[][|11][|]] It has been shown to activate basophils and mast cells to produce antimicrobial factors.[|[][|12][|]] ||^  ||
 * [|IgE] || 1 || Binds to [|allergens] and triggers [|histamine] release from [|mast cells] and [|basophils], and is involved in [|allergy]. Also protects against [|parasitic worms].[|[][|6][|]] ||^  ||
 * [|IgG] || 4 || In its four forms, provides the majority of antibody-based immunity against invading pathogens.[|[][|6][|]] The only antibody capable of crossing the placenta to give passive immunity to fetus. ||^  ||
 * [|IgM] || 1 || Expressed on the surface of B cells and in a secreted form with very high avidity. Eliminates pathogens in the early stages of B cell mediated (humoral) immunity before there is sufficient IgG.[|[][|6][|]][|[][|11][|]] ||^  ||
 * What is a mast cell? What role do mast cells play in the immune response?**


 * Hypersensitivities can be described as immediate, subacute, or delayed. How do these sensitivities differ? What evidence did the doctors use to determine that the peanut allergy was an immediate hypersensitivity?**

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