ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 8 Job Description: Chief of Operations – Immune System Title: Chief of operations Homeland Security Organization: Immune system Objectives: To create a world-class program for homeland security that ensures the pride, confidence and security of its citizens (body cells). Duties and responsibilities: Command local, regional, national and global public safety and defense programs. Maintain resources to continuously improve the quality and effectiveness of local, regional, national and global operations. Develop and stakeholders. communicate directly and openly with all Establish and utilize appropriate Chain of Command to ensure optimal performance of defense systems. Develop creative approaches to ensure adequate supplies of new recruits. Develop and continuously update continuing educational training and assess personnel to ensure ongoing competence. Establish and regularly asses elite offensive and defensive maneuver training programs in locations throughout the homeland. Establish intelligence and communications agencies and bureaus and oversee the effectiveness and appropriateness of their actions. Qualifications and requirements: Excellent leadership skills. Proven ability to respond quickly and thoughtfully to situations that threaten the safety of the homeland. Proven ability to balance justice and compassion. Extensive knowledge of global issues. Multilingual requirements ( 3 languages). Advanced degrees in strategic planning and strategic maneuvers. ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 9 Advanced leadership, communication degree. Proven ability to instill the principles of honor, justice, valor and pride in serving the homeland. Successful candidate must demonstrate in-depth knowledge of the overall system, as well as partner organs and the importance of the role of each in the successful operation of the overall system. Successful candidate must be detail and process oriented. Lines of Communication: Sophisticated global communication network Excellent communication skills required. Successful candidate must be an effective leader, motivating, mentoring personnel. Successful candidate must demonstrate ability to build strong lines of communication with all stakeholders. Proven ability to communicate effectively on the world stage. Proven ability to remain calm, clear and alert in the most stressful of situations. Times needed Must be available to respond to all homeland safety concerns at the and expense of personal situations. place of work: Extensive travel required (transportation supplied). Virtual home office. Commitment required: Benefits: The Chief of Operations must be committed to a long-term relationship. Honor and respect of nationalists and internationalists. Frustrations: Opportunity to motivate and mentor superiors, peers and subordinates. Possibility of burnout due to repeated stresses. Constant bombardment of questions. Possibility of misinterpretation through national and global relations. ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 10 Immune response One of the many functions of the body is to protect itself from invasion by foreign substances such as viruses, bacteria, fungi, parasites, toxins and poisons. The ability of the body to protect itself from disease-causing agents is known as immunity. This protective role is performed by the immune system – a complex system of specialized cells and organs including lymphoid tissues, immune cells, and chemicals that manage immune functions. The various components of the immune system act similarly to security devices used to protect your home – the immune system contains physiological components that function as surveillance cameras, burglar alarms and detectives with long memories. “Self” and non-self” Two key features of the human immune system are specificity and memory. Specificity enables the body to distinguish “self” from “non-self”. “Self” refers to anything that originated from within my body, while “non-self” refers to anything that did not originate from within my body. Differentiation of self from non-self is important for detection of invading microorganisms that may harm the body. However, when organs or tissues are transplanted from one individual to another, this ability works against us – transplanted tissue may be viewed as “non-self” and be attacked as an invader. To prevent the tissue from being rejected because it is different, testing is performed on the tissue donor and the recipient to determine their compatability and optimize the chance that the recipient’s immune system will consider the new tissue “self”, and accept it without too much complaining. In addition, following a transplant surgery and continuing, sometimes for life, immunosuppressants are administered. Immunosuppressants suppress (hold back) immune response so that the body is less sensitive to differences and, therefore, less likely to attack the foreign tissue that has been transplanted. However, this lack of sensitivity may result in immune system deficiency in recognizing invading microorganisms and may result in an increased risk of infection. Life is all about balance! In some individuals, for poorly understood reasons, the body begins to view its own tissues as “non-self” and attacks them. This “self” attack or “auto” attack may result in any of a number of debilitating and even life-threatening diseases – rheumatoid arthritis is one of these. It is almost as if the immune system is confused. Diseases where the immune system attacks “self” are known as autoimmune diseases. Memory enables the body to mount a stronger, more rapid immune response when specific invaders are encountered following an initial infection or exposure. ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 11 Function of the immune system The immune system performs three major functions: - protects the body from pathogens, pollens, chemicals and other foreign substances - removes dead or damaged tissue and cells (i.e. old red blood cells, dying and dead cells) - recognizes and removes abnormal cells (i.e. cancer cells) Anatomy of the Immune System The immune system is comprised of lymphoid tissues and cells responsible for assisting in body defence. The response potential of the immune system exceeds the potential of our public safety system (military, intelligence and communication agencies, law officers, emergency and fire response). The thymus gland and the bone marrow are the two major lymphoid tissues (headquarters) in the human body where immune system cells involved in immune response form and mature. Link to Normal Bone Marrow Cells: http://www-medlib.med.utah.edu/WebPath/HEMEHTML/HEME153.html In addition to the thymus gland and bone marrow, the spleen (purification and recycling plant) and lymph nodes (check-points where blood and lymph fluid is filtered) are also lymphoid tissues. Link to immune system organs: http://www.bio.davidson.edu/Courses/immunology/hyperhuman/HHH.html) The spleen is the largest lymphoid organ in the body and contains immune cells that monitor the blood for foreign invaders. Similar to a garbage collection center or water purification plant, fluid entering the spleen contains debris, old and abnormal cells, and microorganisms. The blood from old red blood cells is broken down, and the iron and other substances is extracted and transported to the liver for processing. Lymph nodes are oval organs containing clusters of immune cells that act as a filter to intercept pathogens entering the body through the lining of mucous membranes or breaks in the skin. The lymph nodes prevent pathogen spread throughout the body. Lymph nodes contain macrophages, lymphocytes and dendritic cells, and the detection and communication capabilities are much more sophisticated than airport security checkpoints or immigration and customs checkpoints. Macrophages ingest abnormal antigens, cellular debris, and microorganisms, breaking them down and “presenting” the antigens to lymphocytes for interrogation to determine whether the antigen should be detained for further ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 12 questioning to determine its guilt or innocence. Similar to routine checkpoints on a busy highway, some unidentified offenders may pass through undetected, but most are removed from circulation and subjected to further questioning, citation and/or arrest. Lymphatic capillaries collect fluids that have been forced out into the spaces between cells and tissues (interstitial spaces) with the pressure resulting from each contraction of the left ventricle of the heart – sort of like the overflow from major freeways or highways. Lymphatic capillaries carry lymph fluid to larger lymphatic vessels that must also pass through the lymph nodes. Purified lymph fluid then continues out through lymphatic vessels on the other side of the lymph node to the next checkpoint en-route to the vena cava where the fluid re-enters the blood stream. Clusters of immune cells are also located throughout the skin, respiratory, intestinal tract, urinary and reproductive tracts to intercept pathogens before they enter the general circulation. Link to immune system organs: http://www.bio.davidson.edu/Courses/immunology/hyperhuman/HHH.html) White blood cell production All white blood cells descend from a type of cell known as a stem cell. Stem cells originate in bone marrow and develop into one of several cell types – red blood cells, leukocytes, and cells from which platelets are formed (megakaryocytes). Link to cell differentiation: http://www.nucleusinc.com/medicalanimations.php?page_no=1&show_anim=myeloma.mov Link to normal bone marrow smear: medlib.med.utah.edu/WebPath/HEMEHTML/HEME151.html http://www- Types of white blood cells White blood cells (leukocytes) are the main cell type of the immune system; therefore, they are referred to as immune cells. There are six major types of leukocytes, distinguishable in stained tissue samples and blood samples by their morphological characteristics – cell shape and size, nucleus shape and size, cytoplasm characteristics, and characteristics of the cell border: eosinophils basophils neutrophils monocytes lymphocytes dendritic cells ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 13 With the exception of dendritic cells, all of the immune cells listed above are leukocytes and are found normally in blood circulating throughout the body. Leukocytes use the circulatory system as a transportation route from lymphoid tissues where they are formed to tissues where they are required to help fight infection and other foreign invaders. The circulatory system involves a transportation system where arteries lead out to the suburbs (tissues) and veins run from the suburbs back to the city center (heart). In a normal healthy individual, a certain number of leukocytes are normally expected in a specific volume of blood. Cells fall into one of two categories – those containing granules in the cytoplasm (granular; granulocytes) and those that are agranulocytic (do not contain granules). Granulocytes Eosinophils Eosinophils are normally found in relatively low numbers in circulating blood (13% of all leukocytes), and are distinguished from other leukocytes on stained preparations by the presence of bright pink-stained granules in their cytoplasm. Eosinophils fight parasites and are involved in allergic reactions. The life span of eosinophils in the blood is approximately 6-12 hours. Because of their role in defending against parasitic infection, most functioning eosinophils are found in the digestive tract, lungs, connective tissue of the skin, as well as urinary and genital epithelium. Eosinophils are classified as cytotoxic cells, because they release substances that damage or kill pathogens. The main function of eosinophils is defence against parasitic infections caused by helminths (worms); however, they also participate in allergic reactions by releasing toxic enzymes and other substances that contribute to inflammation and tissue damage. Link to Eosinophil image: medlib.med.utah.edu/WebPath/HEMEHTML/HEME004.html http://www- Basophils Basophils are produced in the bone marrow, and are found rarely in the circulating blood (3-5% of total granulocytes in circulation) and are distinguished from other leukocytes on stained preparations by the presence of large, dark violet blue granules in their cytoplasm. Basophils are similar to mast cells, which are found in connective tissue of the skin, lungs, and gastrointestinal tract. ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 14 The granules of mast cells and basophils contain histamine, heparin, cytokines, and other chemicals involved in allergic and immune responses – when granules of these cells release their contents (degranulate), these chemicals are released. The main function of basophils is defence against fleas, lice and ticks - basophils act against antigens in the feces of these little critters, while mast cells are involved in the immune response against pathogens that are inhaled, ingested, or enter the body through breaks in the skin. Link to Basophil image: medlib.med.utah.edu/WebPath/HEMEHTML/HEME005.html http://www- Link to Flea/tick response - http://www.cellsalive.com/mite1.htm Neutrophils Neutrophils are produced in the bone marrow and comprise 50-70% of the total population of leukocytes normally present in the circulating blood. Neutrophils are distinguished from other leukocytes in a stained preparation by the presence of a segmented nucleus (polymorphonuclear) of three to five lobes connected by thin strands of nuclear material. Because of the characteristic nuclear presentation, neutrophils are also known as polymorphonuclear leukocytes. Neutrophils have a life span of only one to two days. Link to Neutrophil image: medlib.med.utah.edu/WebPath/HEMEHTML/HEME002.html http://www- The main function of neutrophils is neutralization of bacteria and viruses. Neutrophils ingest and kill bacteria by a process known as phagocytosis. Surface molecules on the pathogen bind directly to receptors on the phagocyte membrane. The phagocyte receptors close around the invader as it continues to bind to the pathogen surface molecules. The cell cytoskeleton pushes the cell membrane around the pathogen forming a vesicle known as a phagosome. The phagosome pinches off from the cell membrane and moves into the cytoplasm of the cell, where it fuses with a storage vesicle, known as a lysosome. Enzymes within the lysosome digest or break down the bacteria or particles. Link to Cells Alive Phagocytosis: http://www.cellsalive.com/mac.htm Link to Phagocytosis: http://www.bio.davidson.edu/misc/movies/Phago.mov Animation 2.1 – Phagocytosis or Link to Phagocytosis: http://www.sp.uconn.edu/~terry/Common/phago053.html Neutrophils belong to the category of leukocytes known as granulocytes, because they contain inclusions in their cytoplasm that give them a granular appearance – eosinophils and basophils are also granulocytes. The granules of neutrophils release chemicals known as cytokines (chemotaxin) to attract additional forces to the area under attack – these cytokines include pyrogens ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 15 (fever producing cytokines) and other chemicals involved in the inflammatory response. Link to Chemotaxis movie: http://www.cellsalive.com/chemotx.htm Neutrophils spend their lives in circulating blood, but are able to squeeze through pores in the capillary endothelium to attack tissue invaders. Agranulocytic leukocytes Monocytes Monocytes comprise 1-6% of the total population of leukocytes circulating in the blood. Monocytes are precursor cells for tissue macrophages and are found in circulating blood en route from the bone marrow to tissues where they enlarge and mature to macrophages. Macrophages are the equivalent of garbage disposal units or trash compacters, ingesting and destroying bacteria, and other particles like old red blood cells and dead neutrophils. Link to Macrophages taking http://www.bio.davidson.edu/courses/movies.html a walk: Included in the group of leukocytes known as macrophages are monocytes found in the blood and specialized cells found in the liver, skin, brain, bone and lining of the abdomen. Link to Monocyte image: medlib.med.utah.edu/WebPath/HEMEHTML/HEME003.html http://www- Successful hunters display their trophies on walls and mantles and, seeing these, visiting friends seek to emulate them. Similarly, macrophages are also involved in the stimulation of lymphocytes – as antigens are digested, antigen fragments are displayed on the outer surface membranes. And, like the hunter’s visiting friends, visiting lymphocytes are stimulated to produce antibodies against the antigen to obtain kills of their own. Lymphocytes Lymphocytes comprise approximately 20-35% of the total leukocyte population in circulating blood. However, only 5% of all lymphocytes are found in the circulation normally, the remainder are found in the spleen, thymus, lymph nodes and other lymphatic tissue. Link to Lymphocyte image: medlib.med.utah.edu/WebPath/HEMEHTML/HEME002.html http://www- In addition to being grouped by morphological characteristics, leukocytes can also be grouped according to their mode of function – neutrophils, eosinophils, ARO Training & Consulting Bloodborne Pathogens Module 2: The Immune System Page 16 basophils and monocytes are phagocytic cells, while lymphocytes, also referred to as immunocytes, are responsible for specific immune response. Lymphocytes secrete cytokines and are involved in antigen-specific responses. Interleukin is the primary cytokine produced by lymphocytes. There are three main types of lymphocytes: B-lymphocytes – develop into memory cells or plasma cells that secrete antibodies T-lymphocytes – develop either into cells that attack and destroy virusinfected cells or cells that regulate other immune cells Natural killer cells – attack and destroy virus-infected and tumor cells In the course of development from precursor cells into functionally mature forms in the thymus, lymphocytes display a complex pattern of surface antigens on their cell surface – these antigens are known as cluster of differentiation (CD) antigens. CD antigens are also expressed on the surface of macrophages. CD antigens are uniquely expressed on the surface of all lymphocytes, and serve as biochemical markers characteristic for a particular cell type indicating the lineage or stage of maturity. CD antigens are designated CD1, CD2, CD3, CD4, etc. In many instances CD antigens are expressed only at certain stages of development, and the functions of many of the 247 currently recognized CD proteins are still unknown. Dendritic cells Dendritic cells are antigen-presenting cells that patrol skin and other organs. Dendritic cells recognize and capture antigens, then migrate to lymphoid tissues where the antigens bound to the surface of dendritic cells are presented to lymphocytes, thereby activating the lymphocytes. Test your memory – Link to the blood smear and identify the WBCs – to find out if you’re correct, place your mouse on the cell and check your identification against the one that appears in the box at the top of the image http://www-medlib.med.utah.edu/WebPath/HEMEHTML/HEME100.html