NON SPESIFIK IMMUNITY DEFENSE The human immune system consists of2 branches: 1) theinnate immune system,which is present at birth and provides non-specific protection against microbes; and 2) theadaptive immune system,which provides specific protection against microbes, but must be acquired over time. The innate and adaptive immune branches can be further broken down into3 lines of defensethat work together to protect the body against injury and infection. Thefirst line of defenseis non-specific and is part of theinnate immune system. The firstline of defenseconsists of: 1)physical barriers(skin, mucous membranes, cilia); 2)chemical barriers(saliva, sweat,sebum, tears, lysozyme,digestive enzymes, lactoferrin, urine); and 3)resident bioflora(beneficial microbesliving on our skin and in our bodies that help block infection by disease-causing microbes). Thesecond line of defenseis also part of thenon-specific, innate immune systemand includes: 1)non-specific immune cells(eosinophils, basophils, neutrophils, macrophages); 2)chemical mediators(interleukin-1, interferon, complement); 3)fever; 4)inflammation; and 5)phagocytosis. Thethird line of defense(see chapter 15) is part of theadaptive or acquired immune system. This line of defense provides specific, long-term protection against microbes. The third line of defense includes: 1)T-cells(helper and cytotoxic); 2)B-cells(memory and plasma cells); and 3)antibodies. All blood cells are born or produced in thebone marrow. The 3major types of blood cellsareerythrocytes (red blood cells), thrombocytes (platelets),andleukocytes (white blood cells). Red blood cells help transport oxygen and nutrients to the cells of the body.White blood cells(WBCs) defend the body against infection. The immune system relies upon2 systems for transportof immune cells and proteins: 1) thecirculatory systemand 2) thelymphatic system. Thelymphatic systemincludes thethymus, spleen, tonsils, lymph nodesand other lymph tissues found in the gut (GALT), skin (SALT), mucosal membranes (MALT), and bronchial tubes (BALT).T cells mature in the thymus, the spleen filters out damaged blood cells and microbes, and thelymph nodesserve as the"headquarters"of the immune system. Leukocytes (white blood cells) can be classified as: 1)granulocytes(eosinophils, neutrophils, basophils and mast cells); or 2)agranulocytes(monocytes, macrophages, T-lymphocytes, and B-lymphocytes). Eosinophilsare granular, non-specific immune cells that protect againstparasitic infections. Basophilsare granular, non-specific immune cells found in the blood thatrelease histaminein response to injury, infection and allergens. Mast cellsare granular, non-specific immune cells found in the tissues thatrelease histaminein response to injury, infection and allergens. Neutrophilsare granular, non-specific immune cells that patrol the borders of the body and eliminate microbes by phagocytosis (amateur eaters). Monocytesare agranular, non-specific immune cells that circulate in the blood and mature into macrophages when they migrate into tissues. Macrophagesare agranular, non-specific immune cells that perform the following functions: 1)phagocytosis(professional eaters); 2) sound chemical alarm to alert other immune cells; and 3) present information about the foreign microbes (antigens) to the T cells, which are the generals of the immune army. Phagocytosisis a second line of defense process in which foreign materials (microbes) are engulfed and broken down by neutrophils or macrophages within a digestive compartment known as the lysosome. Inflammationis a non-specific response to tissue injury or infection that: 1) walls off damaged or infected tissue; 2) recruits immune cells to the site of injury or infection; and 3) clears away microbes or damaged cells so tissue repair can occur. There are4 signs of inflammation: 1) rubor; 2) calor; 3) tumor; and 4) dolor. Feveris an increase in body temperature induced by pyrogens (interleukin-1 and LPS) and regulated by the hypothalamus, which decreases bacterial cell growth and increases immune cell activity. Interferonsareanti-viral proteinsreleased by virally-infected cells that help prevent the spread of infection to neighboring cells by degrading viral RNA and blocking production of viral proteins. Complementis a set ofimmune proteinsthat aid or "complement" immune function. Complement proteins C3a and C5a induce inflammation. Complement protein C3b opsonizes or binds to microbial cells marking them for destruction by phagocytes. Complement proteins C5-C9 form the membrane attack complex, which forms holes on the surface of targeted microbes and leads to their lysis. 3 Linesof Immune DefenseThe body utilizes2 types of immunityto defend against microbial invaders:InnateandAcquired Immunity.Innate immunityis a type of natural, built-in defense system that provides non-specific protection against pathogens. Innate immunity includes the1st line of defense(physical & chemical barriers & resident bioflora) and the2nd line of defense(inflammation, fever, phagocytosis and non-specific immune cells).Acquired immunityis a specific, long-term form of protection that develops over time. Acquired immunity represents the3rd line of defenseand is mediated by specific immune cells (T cells and B cells).Non-Specific (Innate) ImmunityInnate immunityis a natural defense system present at birth that provides non-specific protection against a wide range of pathogens. Although theinnate immunesystem cannot specifically recognize or remember individual pathogens, it does NOT require prior exposure to the pathogen in order to be effective against it. This means it can protect you from microbes that your body has never encountered before. The innate immune system consists of the1st and 2nd lines of defense.

Thefirst line of defenseis non-specific and consists of: 1)physical barriers(skin, mucous membranes, cilia); 2)chemical barriers(saliva, sweat, sebum, tears, lysozyme, digestive enzymes, lactoferrin, urine); and 3)resident bioflora(beneficial microbes living on our skin and in our bodies that help block infection by disease-causing microbes).

1st Line of Defense: Physical Barriers (p. 415-417)Physical barriers,which include the outer layer of skin (epidermis), cilia, and mucous membranes, block the entry of pathogens into the body, much like a castle wall blocks or prevents foreign invaders from entering the castle.The skin consists of anouter layercalled theepidermis, which is composed of multiple layers of tightly packed skin cells that serve as aphysical barrieragainst infection. As new cells are produced in the layers below, thedead outermost layers of the epidermis are shed.Any microbes attached to these dead skin layers are shed along with the dead skin cells. The dermis, which lies just beneath the epidermis, containscollagen fibersthat give the skin strength and flexibility. This layer containssweat glandsthat use salty perspiration to flush microbes and other contaminants out of the pores. Sweat also contains a special enzyme calledlysozyme, that breaks down the bacterial cell wall. In addition to sweat glands, the skin also hassebaceous glandsthat coat the skin withsebum,which is an oily substance that contains fatty acids that lower the pH of the skin surface to inhibit microbial growth.As the dead outermost layers of the epidermis are shed, any infectious microbes attached to this layer are also shed from the body. For this reason, you should always wash your sheets, towels, and other personal clothing items after you have been ill, as the microbes attached to these dead skin layers can remain infectious!So, where does all of that dead skin go? Dead skin cells can be found on our sheets, pillows, clothes, and even in the dust particles that form in our homes. Dead skin cells are broken down by dust mites, which are microscopic parasites that live on our skin, hair, and eyelashes.Mucous membranesline the respiratory, urinary, gastrointestinal, and reproductive tracts. Mucous membranes consist of a single layer of tightly-packedciliated epithelial cells. Neighboringgoblet cellssecrete a thick, sticky substance calledmucus, which coats the epithelial cells. Mucus contains lysozyme, which is an enzyme that breaks down the bacterial cell wall. As bacteria and other debris become trapped in the thick mucus, cilia sweep it up and out of the respiratory tract, where it is expelled from the body bycoughing,sneezing, or evenswallowing!

1st Line of Defense: Chemical Barriers (p. 417)Chemical barriers(tears, saliva, sweat,sebum, lysozyme, digestive enzymes, lactoferrin, urine) help break down or destroy microbial invaders. Lysozyme, an enzyme found in tears, sweat, mucus, saliva and urine, acts by destroying the peptidoglycan cell wall of bacteria. Sweat also contains salt, which creates a hypertonic environment that can lead to dehydration of microbial cells. Fatty acids found in sebum contain fatty acids, which give the skin an acidic pH of 5. The stomach maintains an acidic pH (below 7) and contains digestive enzymes that can break down microbes that pass through the gastrointestinal (GI) tract. Bile is found in the intestinal tract, where it contributes to a basic or alkaline pH (above 7) that inhibits growth of some microbes. Vaginal and prostrate secretions containlactoferrin, which is an iron-binding protein that prevents microbes from attaching to and using free iron to enhance their metabolism.

Can you answer the questions below?

1st Line of Defense: Resident Bioflora (p. 416-417)Normal biofloraare beneficial microbes living on our skin and in our bodies that help block infection by disease-causing microbes. Resident bioflora provide non-specific protection to the host by competing with pathogens for nutrients and blocking attachment to the host, and by secreting toxins (bacteriocidins) that inhibit or kill microbes. These beneficial microbes also aid in digestion and absorption of our food.Staphylococcus epidermidisis a normal resident of the skin andEscherichia coliis a normal resident of the intestinal tract. Current research also shows that by maintaining a constant level of beneficial bacteria in our body, we keep the second line of defense active and ready to fight off infection if needed. Frequent or chronic antibiotic use can destroy many of the beneficial bacteria that live in the GI tract, making us more susceptible to other types of infection.2nd Line of Defense (p.418, 426-438)If pathogens do gain entry into the body, the body's 2nd line of defense comes into play. Thesecond line of defenseis also part of thenon-specific, innate immune systemand includes: 1)non-specific immune cells(eosinophils, basophils, neutrophils, macrophages); 2)antimicrobial chemicals(interleukin-1, interferon, complement); 3)fever; 4)inflammation; and 5)phagocytosis.Role of Blood & Lymph in Immune Defense (p. 421-424)Blood consists ofcellsandplasma,which is a fluid that contains ions, dissolved gases, nutrients, and proteins involved in inflammation (complement proteins) and blood clotting. There are 3 major types of blood cells: 1)erythrocytes(red blood cells); 2)thrombocytes(platelets); and 3)leukocytes(white blood cells). Erythrocytes transport oxygen and carbon dioxide gases between the cells and the lungs. The average adult male has4-6 million red blood cells per microliterof blood, whereas the average female has4-5 million red blood cells per microliterof blood. Leukocytes (white blood cells) defend the body against infection and injury. The average person has between4500-11,000 per microliter of blood.All blood cells originate in thebone marrow, within the hollow cavities of the large bones. In a process calledhematopoiesis, stem cells are used to produce each of the3 major types of blood cells: 1)erythrocytes(red blood cells), which arise from erythroid stem cells; 2)thrombocytes(platelets), which arise from myeloid stem cells; and 3)leukocytes(white blood cells), which arise from both myeloid and lymphoid stem cells.

White blood cellshave specialized receptors on their surface that enable them to determine what is"self"and belongs in the body and what is"non-self"and does not belong. When "non-self" proteins are encountered, an immune response is mounted to destroy the foreign (non-self) substance.

Immune Transport: The Circulatory & Lymphatic Systems (p. 424-426)Immune cellsmove throughout the body via thecirculatory system(with vessels that run in opposite directions, like an interstate) and thelymphatic system(with vessels that run in only one direction, like a one-way street). Blood and immune cells are transported quickly through thecirculatory systemvia a pump (heart), while lymph is moved slowly back toward the heart through the contraction of skeletal muscles. This dependence on muscle movement explains why bed- or wheel-chair ridden patients tend to have swelling or edema of the hands and feet.Lymphoid organsinclude thethymus(site of T-lymphocyte maturation), thespleen(filters out damaged red blood cells and pathogens from the blood),lymph nodes(immune system headquarterswhere white blood cells attack foreign invaders),tonsils, gut-associated lymphoid tissue (GALT) which includes the appendix and intestinal Peyer's patch, mucosal-associated lymphoid tissue (MALT), skin-associated lymphoid tissue (SALT) and broncial-associated lymphoid tissue (BALT).One of the functions of the lymphatic system is thereabsorption of extracellular body fluids, which are returned to the heart via the lymph vessels. Lymphatic fluid is filtered in the lymph nodes (immune system headquarters), allowing immune cells within the nodes to see and respond to foreign cells or antigens. Disruption of the lymphatic system by parasites, such as the filarial worm (shown below), can interfere with the reabsorption of extracellular body fluids and lead to edema or swelling.Leukocytes: Warriors of the Immune SystemLeukocytes (white blood cells) are microscopic immune warriors that protect us from injury and infection caused by invading microbes and disease-causing pathogens. Produced in thebone marrow, leukocytes (white blood cells) include basophils, eosinophils, mast cells, neutrophils, monocytes, macrophages and lymphocytes.T-lymphocytes leave the bone marrow and mature in the thymus. There are several types of T-lymphocytes produced in the body-- cytotoxic, helper, memory and suppressor T-cells. B-lymphocytes are born and mature in the bone marrow. After activation, B-lymphocytes can become plasma cells that secrete antibodies or memory cells. Some cells within the lymphatic system become antigen-presenting cells (APCs). Macrophages are one type of APC that eat microbial invaders and then display foreign antigens to the generals of the immune arrmy, the CD4+ T helper cells.

Non-Specific Immune Cells (p. 422-424)Leukocytes (white blood cells) can be divided into 2 groups based upon their appearance under the microscope: 1)granulocytes; or 2)agranulocytes. Granulocytes contain large granules or compartments that store pre-formed chemicals such as histamine, leukotrienes and prostaglandins.Granulocytesinclude: eosinophils, neutrophils, basophils and mast cells. In contrast,agranulocytesdo not appear to have granules when viewed under a light microscope.Agranulocytesinclude:monocytes, macrophages, T-lymphocytes, and B-lymphocytes.

Granulocytes (p. 422-423)Granulocytes account for 75% of all leukocytes (white blood cells) and contain large granules or compartments that store pre-formed chemicals such as histamine, leukotrienes and prostaglandins.Granulocytesinclude: eosinophils, neutrophils, basophils and mast cells.

Eosinophils (2-4%) are non-specific immune cells (granulocytes) involved in eliminating allergens and parasites. Eosinophils primarilyattack parasitic wormsby attaching to their surface. Eosinophils then release digestive enzymes, such as peroxidase, lysozyme, and perforin, which act to break down the large parasite into smaller parts that can be consumed by macrophages. Eosinophilia, an abnormally high number of eosinophils in the blood, is often an indication that the patient has a parasitic infection.Basophils account for 0.5-1% of all leukocytes (white blood cells). Found circulating in the blood, basophils release histamine in response to injury, infection and allergic responses. The release of histamine causes vasodilation of the blood vessels, which results in increased blood flow and the recruitment of WBCs into the infected or injured tissue. Although similar in function to basophils,mast cellsare found in thetissueswhere theyrelease histaminein response to injury, infection and allergens.Neutrophils are non-specific immune cells that patrol the borders of our body. Always on the lookout for foregin invaders, neutrophils are the 1st cells to arrive at the site of injury or infection. The primary function of the neutrophil is to eat and digest invading microbes by phagocytosis (amateur eaters). Although neutrophils account for 55-65% (25 billion cells) of all white blood cells (WBCs), they are short-lived and only survive 3-8 days before dying and forming pus. Substances that induce pus formation are calledpyogens.For example,Streptococcuspyogenes, causes the formation of white nodules at the back of the throat.Non-Specific Immune Cells: Agranulocytes (p. 423-424)Agranulocytesdo not appear to have granules when viewed under a light microscope.Agranulocytesinclude: monocytes, macrophages, dendritic cells, T-lymphocytes, and B-lymphocytes.

Monocytes & Macrophages (p. 432-433)Monocytesare agranular, non-specific immune cells that circulate in the blood andmature into macrophageswhen they migrate into tissues.Macrophagesperform 3 important functions within the non-specific immune system: 1)phagocytosis(professional eaters); 2)release chemical messengersto alert other immune cells; and 3)present informationabout the foreign microbes (antigens) to the T cells, which are the generals of the immune army.

Macrophages that migrate into specific tissues are named for their location in the body. For example,alveolar macrophagesare found in the lungs,Kuppfer cellsare found in the liver,dendritic cellsare found in the skin and mucous membranes, andmicrogliaare found in the brain.

Chemical Messengers: Cytokines & Interleukins (p. 428-429)Immune cells communicate usingchemical messengerscalledcytokines. Cytokines are small, regulatory proteins essential for communication between cells. Cytokines are produced by many types of cells including, monocytes, macrophages, lymphocytes, fibroblasts, mast cells, platelets, and endothelial cells. Cytokines have several different functions within the body: 1) they can mediate non-specific immune reactions such as inflammation, fever, and phagocytosis; 2) they regulate the growth and activation of the specific immune system lymphocytes; 3) stimulate hematopoiesis in the bone marrow; amd 4) they can either expand (vasodilate) or constrict (vasoconstrict) blood vessels.Interleukinsare a special class of cytokine that allow immune cells (leukocytes) to communicate with each other and the rest of the body. For example,interleukin-1 (IL-1)is produced by macrophages in response to infection. This chemical messenger activates the hypothalamus and induces fever.Histamineis a vasoactive chemical messenger produced by mast cells and basophils, that causes vasodilation and increased vascular permeability.Leukotrienesalso increase vascular permeability.Prostaglandins,which can be produced by most body cells, can trigger inflammation and pain.

2nd Line of Defense: Fever (p. 431-432)Feveris an increase in body temperature induced by endogenous (interleukin-1, IL-1) or exogenous (Lipopolysaccharide found on Gram-negative bacterial cells) pyrogens. Fever is induced when chemical messengers such as IL-1 stimulate the hypothalamus to raise body temperature. Fever acts to slow down microbial metabolism while, at the same time, ehances immune cell function.

What Causes Chills?If the thermostat (hypothalamus) has been set by the pyrogen (interleukin-1 or LPS) at 102F, but the blood temperature is only at 99F, then the muscles are stimulated to contract or shiver to produce heat. At the same time, vessels in the skin constrict (become smaller) and the piloerector muscles in the skin cause "goosebumps" to form. In contrast, when the thermostat is reset to 98.6F, but the blood is still at 102F, the body will cause the vessels to dilate (expand) and the body will sweat in an attempt to release heat and lower the body's temperature.2nd Line of Defense: Inflammation (p. 426-431)Inflammationis a non-specific response to tissue injury or infection that limits the spread of pathogens, removes damaged cells or tissues, destroys pathogens, and stimulates tissue repair.4 Signs of InflammationInflammation is characterized by 4 signs: rubor, calor, tumor, and dolor.

Inflammation begins when injured or infected tissuesrelease chemical distress signals, such ashistamine, that causevasodilation. Vasodilation leads toincreased blood flowand therecruitment of non-specific immune cellsto the site of injury. Non-specific immune cells migrate in response to the chemical distress signal released by infected or injured cells via a process called chemotaxis and leave the blood vessel to enter the tissue viadiapedesis.

Steps in Inflammation1. Mast cells release chemical messengers (histamineandleukotrienes) in response to tissue injury or infection. These factors create a"chemical trail"for the immune cells to follow to the site of injury or infection via a process calledchemotaxis.2.Histaminecauses vasodilation or expansion of the blood vessels. This causes redness (rubor) and increased heat (calor) in the affected region.Leukotrienesmake the blood vessel walls more permeable or leaky.

3. Neutrophils & macrophages crawl out of the blood vessels by diapedesis. This causes swelling (tumor) in the affected tissue.Neutrophilsandmacrophagesremove microbes or damaged tissue by phagocytosis (eating) and pus is formed.

4. Tissue damage is repaired and scars can form if fibroblasts are involved.Inflammation can either be acute or chronic.Acute inflammationis a localized response that develops immediately upon injury and lasts for a short period of time. Acute inflammation is typically beneficial and results in the destruction of microbes and tissue repair.Chronic inflammationis a more slow-progressing form of inflammation that persists for a longer period of time (months to years). Chronic inflammation can cause damage to surrounding host tissues.

Bothsteroidal(corticosteroids) andnon-steroidal anti-inflammatory drugs (NSAIDs)can be used asanti-inflammatory drugsto reduce pain and swelling. NSAIDS, which include drugs like aspirin and ibuprofen, prevent prostaglandins from being synthesized. They achieve this by inhibiting the cyclooxygenase (COX) enzyme. In contrast, other products, such as Tylenol (acetaminophen) can be used to reduce pain (analgesic), but cannot reverse the effects of inflammation.2nd Line of Defense: Phagocytosis (p. 432-434)Phagocytosis involves: 1) chemotaxis; 2) attachment to the microbe; 3)endocytosis; 4)fusion with a lysosome; 5) digestion of the microbe; 6) formation of residual waste; and 7) release of waste by exocytosis.

Antimicrobial Secretions: Interferon (p. 434-435)Non-specific immune cells produce and secrete a variety of antimicrobial substances including interleukins, lactoferrins, peroxides, free radical, lysins, complement and interferon. These substances act to destroy the invading microbe or inhibit microbial metabolism. Interferon is ananti-viral cytokineproduced by virally infected cells that helps prevent the spread of infection to neighboring cells.Antimicrobial Secretions: Complement (p. 435-438)Thecomplement systemis a series of 9 blood proteins that are activated in response to microbial invasion. When activated, these proteins either bind to pathogens or antibody-pathogen complexes to target them for destruction by phagocytosis or form a membrane attack complex to lyse the invading cell. Complement proteinsC3a & C5ainducechemotaxisandinflammation. Complement proteinC3bcoats or opsonizes the surface of microbes to enhance phagocytosis (cellular eating) by macrophages. Complement proteins C5-9 form themembrane attack complex (MAC)and induce lysis of the microbe.

Preview of Specific Immunity (Chapter 15)The3rd line of defenseinvolves the activation of thespecific or acquiredimmune system. Once activated, the specific immune system mounts a defense that is specific to the invader, global, and long-lasting. The specific immune response is mediated by B- and T-lymphocytes, which work together but utilize different mechanisms to destroy the microbial invader. Only B- or T-cells