Anatomy and Physiology for Blood and Blood Related

ANATOMY AND PHYSIOLOGY

Blood

Blood is a connective tissue composed of a liquid extracellular matrix called blood plasma that dissolves and suspends various cells and cell fragments. Interstitial fluid is the fluid that bathes body cells. Blood transports oxygen from the lungs and nutrients from the gastrointestinal tract. The oxygen and nutrients subsequently diffuse from the blood into the interstitial fluid and then into body cells. Carbon dioxide and other wastes mo e in the reverse direction, from body cells to interstitial fluid to blood. Blood then transports the wastes to various organs- the lungs, kidneys, and skin- for elimination from the body.

Functions of Blood

Blood, which is a liquid connective tissue, has three general functions:

1.    Transportation. As you just learned, blood transports oxygen from the lungs to the cells of the body and carbon dioxide from the body cells to the lungs for exhalation.

2.    Regulation. Circulating blood helps maintain homeostasis of all body fluids. Blood helps regulate pH through the use of buffers.

3.    Protection. Blood can clot, which protects against its excessive loss from the cardiovascular system after an injury.

 

 Physical characteristics of blood:

Blood is denser and more viscous than water and feels slightly sticky. The temperature of blood is 38 degree Celsius, about 1 degree Celsius higher than oral or rectal body temperature, and it has a slightly alkaline pH ranging from 7.35 to 7.45. Blood constitutes about 20% of extracellular fluid, amounting to 8% of the total body mass. The blood volume is 5-6 L in an average-sized adult male and 4-5 L in an average-sized adult female. Several hormones, regulated by negative feedback, ensure that blood volume and osmotic pressure remain relatively constant.

 

 Components of Blood

Blood has two components:

1.    Blood plasma, a watery liquid extracellular matrix that contains dissolved substances

2.    Formed elements, which are cells and cell fragments

  Formation of blood cells

Although some lymphocytes have a lifetime measured in years, most formed elements of the blood last only hours, days, or weeks, and must be replaced continually. Negative feedback systems regulate the total number of RBC’s and platelets in circulation and their numbers normally remain steady.

The process by which the formed elements of bleed develop is called hepoiesis of hematopoiesis. Before birth, hemopoiesis first occurs in the yolk sac of an embryo and later in the liver, spleen, thymus, and lymph nodes of a fetus.

Red bone marrow is a highly vascularised connective tissue located in the microscopic spaces between trabeculae of spongy bone tissue. It is present chiefly in bones of the axial skeleton, pectoral and pelvic girdles, and the proximal epiphyses o the humerus and femur.

Red blood cells

            Are also called erythrocytes which contain the oxygen-carrying protein haemoglobin, which is a pigment that gives while blood its red color.

RBC Anatomy

            RBCs are biconcave discs with a diameter of 7-8 um. Mature red blood cells have a simple structure. Their plasma membrane is both strong and flexible, which allows them to deform without rupturing as that squeeze through narrow capillaries.

RBC Physiology

            RBCs are highly specialized for their oxygen transport function. Because mature RBCs have no nucleus, all their internal space is available for oxygen transport. Because RBCs lack mitochondria and generate ATP anaerobically, they do not use up any of the oxygen they transport.

            Each RBC contains about 280 million haemoglobin molecules. A haemoglobin molecule consists of a protein called globin, composed of four polypeptide chains; a ringlike nonprotein pigment called heme is bound to each of the four chains.

            Hemoglobin also transports about 23% of the total carbon dioxide a waste product of metabolism.

            In addition to its key role in transporting oxygen and carbon dioxide, haemoglobin also plays a role in the regulation of blood flow and blood pressure.

RBC life cycle

RBC live only about 120 days because of the wear and tear their plasma  membranes undergo as they squeeze through blood capillaries. Without a nucleus and other organelles, RBCs cannot synthesize new components to replace damaged ones.

Erythropoiesis: Production of RBC’s

            The production of RBCs starts in the reed bone marrow with a precursor cell called proerythroblast. Ultimately, a cell near the end of the development sequence ejects its nucleus becomes a reticulocyte. Cellula deficiency called hypoxia, may occur if too little oxygen enters the blood.

Types of WBCs

            White blood cells or leukocytes have nuclei and do not contain haemoglobin. WBCs are classified as either granular or agranular; depending on whether they contain conspicuous chemical-filled cytoplasmic granules that are made visible by staining.

Grandular leukocytes

            After staining, each of the three types of granular leukocytes displays conspicuous granules with distinctive coloration that can be recognized under a ligh microscope. The large, uniform-sized granules within an eosinophil are eosinophilic- they stain red-orange with obscure the nucleus, which most often has two lobes connected by a thick strand of chromatin. The round, variable-sized franules of a basophil are basoholic- they stain blue-purple with basic dyes. The granules commonly obscure the nucleus, which has two evenly distributed, and pale lilac in color; they are often called polymorphonuclear leukocytes, polymorphs, or polyps. Younger neutrophils are often called bands because their nucleus is more rod-shaped.

Agranular Leukocytes

Even though so-called granular leukocytes possess cytoplasmic granules. The granules are not visible under a light microscope because of their small size and poor staining qualities.

            The lymphocyte is round or slightly indented and stains darkly. The cytoplasm stains sky blue and forms a rim around the nucleus. The larger the cell, the more cytoplasm is visible.

            Monocytes are 12-20 um in diameter. The nucleus of a monocyre is usually kidney has a foamy appearance. The color and appearance are due to very fine azurophilic granules, which are lysosomes.

            White blood cells and all other nucleated cells in the body have proteins.called major histocompatibility antigens, protruding from their plasma membrane into the extracellular fluid.

Functions of WBC

            In a healthy body, some WBCs, especially lymphocytes, can live for several months or years, but most lives only a few days. During a period of infectin, plhagocytic WBCs may live only a few hours.

            The skin and mucous membranes of the body are continuously exposed to microbes and their toxins. Some of these microbes can invade deeper tissues to cause disease. Once the pathogens enter the body, the general function of white blood cells is to combat them by phagocytosis or immune responses.

            WBCs leave the bloodstream by a process termed emigration, formerly called diapedesis, in which they roll along the endothelium, stick to it, and them squeeze between endothelial cells. The precise signals that stimulate emigration through a particular blood vessel vary for the different types of WBCs. Molecules known as adhesion molecules help WBCs stick to the endothelium. For example, endothelial cells display adhesion molecules called selectins in response to nearby injury and inflammation, selectins stick to carbohydrates on the surface of neutrophils, causing them to slow down and roll along the endothelial surface.

            Neutrophils and macro[hages are active in phagocytosis; they can ingest bacteria and dispose of dead matter. Several different chemicals relealsed by microbes and inflamed tissues attract phagocvtes, a phenomenon called chemotaxis.

            Among WBCs, neutrophils respond most quickly to tissue destruction by bacteria. After engulfing a pathogen during phagocytosis, a neutrophil unleashes several chemicals to destroy the pathogen. These chemicals include the enzyme lysozyme, which destroys certain bacteria, and strong oxidants, such as the superoxide anion, hydrogen peroxide, and the hypochlorite anion, which is similar to household bleach. Neutrophils also contain defensins proteins that exhibit a broad range of antibiotic activity against bacteria and fungi.

            Monocytes take longer to reach a site of infection than do neutrophils, but they arrive in larger numbers and destroy more microbes.

            At sites of inflammation, basophils leave capillaries, enter tissues, and release granules that contain heparin, histamine, and serotonin. These substances intensify the inflammatory reaction and are involved in hypersensitivity reactions.

            Eisonophils leave the capillaries and enter tissue fluid. They are believed to release enzymes, such as histaminases, that combat the effects of histamine and other substances involved in inflammation during allergic reactions.

            Lymphocytes are the major solders in immune system battles. Three main types of lymphocytes are B cells. T cells and natural killer cells.

Hemostasis

            Not to be confused with the very similar term homeostasis, is a sequence of responses that stops bleeding. When blood vessels are damaged or ruptured, the hemostatic response must be quick, localized to the region of damage, and carefully controlled in order to be defective.

Platelet

Besides the immature cell types that develop into erythrocytes and leukocytes, hematopoietic stem cells also differentiate into cells that produce platelets.Under the influence of the hormone thrombopoietin, myeloid stem cells develop into megakaryocyte-colony-forming cells that, in turn, develop into precursor cells called the megakaryoblast. Megakaryoblast transform into megakaryocytes , huge cells that splinter 2000 to 3000 fragments. Each fragment enclosed by a piece of plasma membrane, is a platelet.

Platelet help stop blood loss from damage blood vessels by forming platelet plug. Their granules also contain chemicals that, once released, promote blood clotting. Platelet have a short life span , normally just 5-9 days. Age and dead platelets are removed by fixed macrophages in the spleen and liver.

Vascular spasm

            When arteries or arterioles are damaged, the circularly arrange smooth muscle in their walls contracts immediately, a reaction called vascular spasm.

Platelet plug formation

            Considering their small size, platelers store an impressive array of chemicals. Within many vesicles are clotting factors, ADPL ATP, Ca2+, and serotonin. Also present are enzymes that produce thromboxane A2, a prostaglandin; fibrin-stabilizing factor, which helps to strengthen a blood clot; lysosomes; some mitochondria; membrane systems that take up and store calcium and provide channels for release of the contents of granules; and glycogen.

            A platelet plug is very effective in preventing blood loss in a small vessel. Although initially the platelet plug is loose, it becomes quite tight when reinforced by fibrin thread s formed during clotting. A platelet plug can stop blood loss completely if the hole in blood vessel is not too large.

Blood clotting

            Normally, blood remains in its liquid form as long as it stays within in its vessels. If it is drawn from the body, however, it thickens and forms a gel. Eventually, the gel separates from the liquid. The straw-colored liquid, called serum, is simply blood plasma minus the clotting proteins. The gel is called a clot. It consists of a network of insoluble protein fibers called fibrin in which the formed elements of blood are trapped.

            The process of gel formation, called clotting or coagulation, is series of chemical reactions that culminates in formation, is a series of chemical reactions that culminates in formation of fibrin threads.

            Clotting involves several substances known as clotting factors. These factors include calcium ions, several involves several substances known as clotting factors. These factors include calcium ions, several inactive enzymes that are synthesized by hepatocytes and release into the bloodstream, and various molecules associated with platelets or released by damaged tissues.

            Clotting is complex cascade of enzymatic reactions in which each clotting factor activates many molecules of the next one in a fixed sequence.

The Extrinsic pathway

            This pathway of blood clotting has fewer steps than the intrinsic pathway and occurs rapidly- within a matter of seconds if trauma is severe. It is also named because a tissue protein called tissue factor also known as thromboplastin, leaks into the blood from cells outside blood vessels and initiates the formation of prothrombinase.

The Intrinsic pathway

            This pathway of blood clotting is more complex than the extrinsic pathway, and it occurs more slowly, usually requiring several minutes the intrinsic pathway is so named because its activators are either in direct contact with blood or contained within the blood; outside tissue damages is not needed.  If endothelial cells become roughenedor damaged blood can come in contact with collagen fibers in the connective tissue around the endothelium of the blood vessel.

The common pathway

            The formation of prothrombinase marks the beginning og the common pathway. In the second stage of blood clotting, prothrombinase and Ca2+ catalyze the conversion of prothrombin to thrombin. In the third stage, thrombin, in the presence of Ca2+, converts fibrinogen, which is soluble, to loose fibrin threads, which are insoluble.

Clot Retraction

            Once the clot is formed, it plugs the ruptured area of the blood vessel and thus stops blood loss. Clot retraction is the consolidation or tightening of the fibrin clot. The fibrin threads attached to the damaged surfaces of the blood vessel gradually contract as platelets pull on them. As the clot retracts, it pulls the edges of the damaged vessel closer together, decreasing the risk of further damage.

Role of vitamin K in clotting

            Normal clotting depends on adequate levels of vitamin K in the body  although vitamin K is not involved in actual clot formation, it is required for the synthesis of four clotting factors. Normally produced by bacteria that inhibit the large intestine, vitamin K is a fat-soluble vitamin that can be absorbed through the lining of the intestine and into the blood if absorption of lipids is normal. People suffering from disorders that slow absorption of lipids often experience uncontrolled bleeding as a consequence of vitamin K deficiency.

Hemostatic control mechanisms

            Many times a day little clots start to form, often at a site of minor roughness or at a developing atherosclerotic plaque inside a blood vessel. Because blood clotting involves amplification and positive feedback cycles, a clot has a tendency to enlarge, creating the potential for impairment of blood flow through undamaged vessels. The fibrinolytic system dissolves small, inappropriate clots; it also dissolves clots at a site of damage once the damage is repaired. When a clot is formed, an inactive plasma enzyme called plasminogen is incorporated into the clot. Both body tissues and blood contain substances are thrombin, activated factor XII, and tissue plasminogen activator, which is synthesized in endothelial cells of most tissues and liberated into the blood. Once plasmin is formed, it can dissolve the clot by digestion fibrin threads and inactivation substances such as fibrinogen, prothrombin, and factors V and XII.

            Even though thrombin has a positive feedback effect on blood clotting, clot formation normally remains localized at the site of damage. A clot does not extend beyond a wound site into the general circulation, in part because fibrin absorbs thrombin into the clot.

            Several other mechanisms also control blood clotting. For example, endothelial cells and whit e blood cells produce a prostaglandin called prostacyclin that opposes the actions of thromboxane A2. Proscyclin is a powerful inhibitor of platelet adhesion and release.

            In addition substances that delay, suppress, or prevent blood clotting, called anticoagulants, are present in blood. These include antithrombin, which blocks the action of several factors. Including XII, X, and II. Heparin, an anticoagulant that is produced by mast cclottinf factorsells and basophils, combines with antithrombin and increase its effectiveness in blocking thrombin. Another coagulant, activated protein C inactivates the two major clotting factors not blocked by antithrombin, and enhances activity of plasminogen activators. Babies that lack the ability to produce APC due to a genetic mutation usually die of blood clots in infancy.

ANTCOAGULANTS

            Patients who are at increased risk of forming blood clots may receive anticoagulants. Examples are warfarin or heparin. Heparin is often administered during hemodialysis and open heart surgery. Warfarin acts as an antagonist to vitamin K and thus blocks synthesis of four clotting factors. Warfarin is slower acting than heparin. To prevent clotting in donated blood, blood banks and laboratories often ads substances that remove calcium; example are EDTA

( ethylene diamine tetraaccetic acid) and CPD ( citrate phosphate dextrose).

INTRAVASCULAR CLOTTING

            Despite the anticoagulating and fibrinolytic mechanisms, blood clots sometimes form with in the cardiovascular system. Such clots may be initiated by roughened endothelial surfaces of a blood vessel resulting from atherosclerosis, trauma, or infection. These conditions induce adhesion of platelets. Intravascular clots may also form when blood flows too slowly (stasis), allowing clotting factors to accumulate locally in high enough concentrations to initiate coagulation. Clotting in an unbroken blood vessel (usually a vein) is called thrombosis. The clot itself, called a thrombus, may dissolve spontaneously. If it remains intact, however, the thrombus may become dislodged and be swept away in the blood. A blood clot, bubble of air, fat from broken bones, or a piece of debris transported by the bloodstream is called an embolus, an embolus that breaks away from an arterial wall may lodge in a smaller-diameter artery downstream and block blood flow to a vital organ. When an embolus lodges in the lungs, the condition is called pulmonary embolism.

Figure  SEQ Figure \* ARABIC 2. Thrombocytes and Clotting

LYMPHATIC SYSTEM

Lymphatic system structure and function

The lymphatic system consists of a fluid called lymph, vessels called lymphatic vessels that transport the lymph, a number of structures and organs containing lymphatic tissue, and red bone marrow, where stem cells develop into the various types of blood cells, including lymphocytes. It assists in circulation body fluids and helps defend the body against disease-causing agents. As you will see shortly, most components of blood plasma filter through blood capillary walls to form interstitial fluid. After interstitial fluid passes into lymphatic vessels, it is called lymph. The major difference between interstitial fluid and lymph is location: interstitial fluid is found between cells, and lymph is located within lymphatic vessels and lymphatic tissue.

Lymphatic tissue is a specialized form of reticular connective tissue that contains large numbers of lymphocytes.

Functions of the lymphatic system:

1.    Draining excess interstitial fluid. Lymphatic vessels drain excess interstitial fluid from tissue spaces and return it to the blood.

2.    Transporting dietary lipids. Lymphatic vessels transport lipids and lipid-soluble vitamins absorbed by the gastrointestinal tract to the blood.

3.    Carrying out immune responses. Lymphatic tissue initiates highly specific responses directed against particular microbes or abnormal cells. T cells and b cell, aided by macrophages, recognize foreign cells, microbes, toxins and cancer cells and respond to them in two basic ways: a.) in cell mediated immune responses, T cells destroy the intruders by causing them to rupture or by releasing cytotoxic (cell-killing) substances b.) in antibody mediated immune responses, B cells differentiate into plasma cells that protect us against disease by producing antibodies, proteins that combine with and cause destruction specific foreign substances.

  Lymphatic vessels and lymph circulation

Lymphatic vessels begin as lymphatic capillaries. These tiny vessels, which are located in the spaces between cells, are closed at one end. Just as blood capillaries converge to form venules and then veins, lymphatic capillaries unite to form larger lymphatic vessels, which resemble veins in structure but have thinner walls and more valves. At intervals along the lymphatic vessels, lymph flows through lymph nodes, encapsulated bean-shaped organs consisting of masses of B cell and T cells.

 Lymphatic capillaries

Lymphatic capillaries are slightly larger in diameter than blood capillaries and have a unique one- way structure that permits interstitial fluid to flow into them but not out. The ends of endothelial cells that make up the wall of a lymphatic capillary overlap. When pressure is greater in the interstitial fluid than in lymph, the cells separate slightly, like the opening of a one-way swinging door, and interstitial fluid enters the lymphatic capillary. When the pressure is greater inside the lymphatic capillary, the cells adhere more closely and lymph cannot escape back into interstitial fluid. The pressure is relieved as lymph moves further down the lymphatic capillary.

      In the small intestine, specialized lymphatic capillaries called lacteals carry dietary lipids presence of these lipids causes the lymph draining from the small intestine to appear creamy- white; such lymph is referred to as chlye. Elsewhere, lymph is a clear, pale-yellow fluid.

  

Lymph trunks and ducts

      As lymphatic vessels exit lymph nodes in particular region of the body, they unite to form lymph trunks. The principal trunks are the lumbar, intestinal, bronchomediastinal, subclavian, and jugular trunks. The lumbar trunks drain lymph from the lower limbs, the wall and viscera of the pelvis, the kidneys, the adrenal glands, and the abdominal wall. The intestinal trunk drains lymph from the thoracic wall, lung, heart, the subclavian trunks drain the upper limbs. The jugular trunks drain the head and neck.

      Lymph passes from lymph trunks into two main channels. The thoracic duct and the right lymphatic duct, and then drains into venous blood. The thoracic duct is about 38-45 cm long and begins as a dilation called the cistern chlyli anterior to the second lumbar vertebra.

      The right lymphatic duct is about 1.2 com long and receives lymph from the right jugular, right subclavian, and right bronchomediastinal trunks. Thus, the right lymphatic duct receives lymph from the upper right side of the body. From the right lymphatic duct, lymph drains into venous blood at the junction of the right internal jugular and right subclavian veins.

   Formation and flow of lymph

      Most components of blood plasma filter freely through the capillary wall tot form interstitial fluid, but more fluid filters out of blood capillaries than returns to them by reabsorption. Because most plasma proteins are too large to leave blood vessels, interstitial fluid contains only a small amount of protein

      Like veins, lymphatic vessels contain valves, which ensure the one-way movement of lymph, as noted previously, lymph drains into venous blood through the right lymphatic duct and the thoracic duct at the junction of the internal jugular and subclavian veins.

 Lymphatic organs and tissues

            The widely distributed lymphatic organs and tissues are classified into two groups based on their functions. Primary lymphatic organs are the sites where stem cells divide and become immunocompetent, that is, ccapable of nounting and immune response. The primary lymphatic organs are the red bone marrow and the thymus.

  

Nonspecific resistance: innate defences

      Although several mechanisms contribute to innate defences, also called nonspecific resistance to disease, they all have two things in common. They are present at birth, and they offer immediate protection against a wide variety of pathogens and foreign substance.

First line of defense: skin and mucous membranes

      The skin and mucous membranes of the body are the first line of defense against pathogens. These structures provide both physical and chemical barriers that discourage pathogens and foreign substances from penetrating the body and causing disease.

      With its many layers of closely packed. Keratinized cells, the outer epithelial layer of the skin- the epidermis- provides a formidable physical barrier to the entrance of microbes of epidermal cells helps remove microbes at the skin surface. Bacteria rarely penetrate the intact surface of healthy epidermis. If this surface is broken by cuts, burns, or punctures, however, pathogens can penetrate the intact surface of healthy epidermis.

      The epithelial layer of mucous membranes, which line body cavities, secretes a fluid called mucus that lubricates and moistens the cavity surface. Because mucus is slightly viscous, it traps many microbes and foreign substances.

      Other fluids produced by various organs also help protect epithelial surfaces of the skin and mucous membranes. The lacrimal apparatus of the eyes manufactures and drains away tears in response to irritants.

      Certain chemicals also contribute to the high degree of resistance of the skin and mucous membranes to microbial invasion. Sebaceous gland of the skin secretes an oily substance called sebum that forms a protective film over the surface of the skin.

Second line of defense: internal defences

      When pathogens penetrate the mechanical and chemical barriers of the skin and mucous membranes, they encounter a second line of defense: internal antimicrobial proteins, phagocytes, natural killer cells, inflammation, and fever.

  Antimicrobial proteins

      Blood and interstitial fluids contain three main types of antimicrobial proteins that discourage microbial growth: interferons, complement, and transferrins.

1.     Lymphocytes, macrophages, and fibroblalsts infected with virus produce proteins called interferons.

2.    A group of normally inactive proteins in blood plasma and on plasma membranes makes up the complement system.

3.    Iron- binding proteins called transferrins inhibit the growth of certain bacteria by reducing the amount of available iron.

Natural killer cells and phagocytes

When microbes penetrate other skin and mucous membranes or bypass the antimicrobial proteins in blood, the next nonspecific defense consist of natural killer cells and phagocytes. They are present in the spleen. Lymph nodes, and red bone marrow.

            The binding of NK cells to a target cell, such as in infected human cell causes the release of granules containing toxic substances from NK cells. Some granules contain a protein called perforin that inserts into the plasma membrane of the target cell and creates channels in the membrane.

Phagocytes are specialized cells that perform phagocytosis, the ingestion of microbes or other particles such as cellular debris. The two major sites of  phagocytes are neutrophils and macrophages. When an infection occurs, neutriphils and monocytes migrate to the infected area.

Phagocytosis occurs in five phases:

1.    Chemotaxis

2.    Adherence

3.    Ingestion

4.    Digestion

5.    Killing

Inflammation

            Inflammation is a nonspecific, defensive response of the body to tissue damage. Among the conditions that may produce inflammation are pathogens, abrasions, and chemical irritations, distortion or substances of cells, and extreme temperatures. The four characteristic signs and symptoms of inflammation are redness, pain, heat, and swelling. Inflammation can also cause the loss of function in the injured area, depending on the site and extent of the injury. Inflammation is and an attempt to dispose of microbes, toxins, or foreign material at the site of injury, to prevent their spread to other tissues, and to prepare the site for tissue repair in an attempt to restore tissue homeostasis.

            Because inflammation is one of the body’s nonspecific resistance mechanisms, the response of tissue to a cut is similar to the response to damage caused by burns, radiation, or bacterial or viral invasion. In each case, the inflammatory response has three basic stages: vasodilatation and increased permeability of blood vessels, emigration of phagocytes from the blood into interstitial fluid and ultimately and tissue repair.

Vasodilation and increase permeability of blood vessels

            Two immediate changes occur in the blood vessels in a region of tissue injury: vasodilation of arterioles and increased permeability of capillaries. Increased permeability means that substances normally retained in blood are permitted to pass from the bleed vessel. Vasodilation allows more blood to flow through the damaged are, and increased permeability permits defensive proteins such as antibodies and clotting factors to enter the injured area from the blood. The increased blood flow also helps remove microbial toxins and dead cells.

            Among the substances that contribute to vasodilation, increased permeability, and other aspects of the inflammatory response are the ff:

1.    Histamine

2.    Kinins

3.    Prostaglandins

4.    Leukitrienes

5.    Complement

Dilation of arterioles and increased permeability of capillaries produce three of the symptoms of inflammation: heat, redness, and swelling. Heat and redness result from the large amount of blood that accumulates in the damaged area. As the local temperature rises slightly, metabolic reactions proceed more rapidly and release additional heat. Edema results from increased permeability o f blood vessels, which permits more fluid to move from blood plasma into tissue spaces.

Pain is   a prime symptom of inflammation. It results from injury to neurons and from injury to neurons and from toxic chemicals released by microbes. Kinins affect some nerve endings, causing much of the pain associated with inflammation. Prostaglandins intensify and prolong the pain associated with inflammation. Pain also be due to increased from edema.

Emigration of phagocytes

            Within an hour after the inflammatory process starts, phagocytes appear on the scene. As large amounts of blood accumulate, neutrophils begin to stick to the inner surface of the endothelium of blood vessels.  Then the neutrophils begin to squeeze through the wall g the blood vessel to reach the damaged area. This process, called emigration, depends on chemotaxis. Neutrophils attempt to destroy the invading microbes by phagocytosis. A steady stream of neutrophils is ensured by the production and release of additional cells from bone marrow.

Fever

            -is an abnormally high body temperature that occurs because the hypothalamic thermostat is reset. It commonly occurs during infection and inflammation. Many bacterial toxins elevate body temperature, sometimes by triggering release of fever-causing cytokines such as interleukin-1 from macrophages. Elevated body temperature intensifies the effects of interferons. Inhibits the growth of some microbes, and speeds up body reactions that aid repair.

Specific resistance: immunity

The ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues is called specific resistance or immunity. Substances that are recognized as foreign and provoke immune responses are called antigens.

Pathways of antigen processing

            For an immune response to occur, B cells and T cells must recognize that a foreign antigen is present. B cells can recognize and bind to antigens in lymph, interstitial fluid, or blood plasma. T cells only recognise fragments of antigenic proteins that are processed and presented in a certain way. In antigen processing, antigenic proteins are broken down into peptide fragments that then associate with MHC molecules. Next the antigen-MHC complex is inserted into the plasma membrane of a body cell.

Cytokines

            Cytokines are small protein hormones that stimulate or inhibit many normal cell functions, such as cell growth and differentiation. Lymphocytes and antigen- presenting cells secrete cytokines, as do fibroblasts, endothelial cells, monocytes, hepatocytes, and kidney cells. Some cytokines stimulate proliferation of progenitor blood cells in red bone marrow. Others regulate activities of cells involved in nonspecific defences or immune responses.

Types of T Cells

1.    Helper T Cells

Most T cells that display CD4 develop into helper T cells, also known as CD4 T cells. With the aid of the CD4 protein, the helper T cell and APC interact with each other (antigenic recognition), costimulation occurs, and the helper T cell becomes activated.

Within hours after costimulation, activated helper T cells start secreting a variety of cytokines. One very important cytokine produced by helper T cells is interleukin- 2 (IL- 2), which is needed for virtually all immune responses and is the prime trigger of T cell proliferation. IL-2 can act as a costimulator for resting helper T cells or cytotoxic T cells, and it enhances activation and proliferation of T cells, B cells, and natural killer cells.

           Some actions of interlukin- 2 provide a good example of a beneficial positive feedback system. As the helper T cells proliferate, a positive feedback effects occurs because they secrete more IL-2, which causes further cell division. Il-2 may also act in a paracrine manner by binding to Il-2 receptors on neighbouring helper T cells, cytotoxic T cells, or B cells. if any of these neighbouring cells have already bound an antigen, IL-2 serves as a costimulator.

2.)  Cytotoxic T Cells

T cells that display CD8 develop into cytotoxic T cells, also termed CD8 cells. Cytotoxic T cells recognized foreign antigens combined with major histocompatibility complex class 1 (MHC-1) molecules on the surfaces of:

*Body cells infected by microbes

*Some tumor cells of a tissue transplant.

*Recognition requires the TCR and CD8 protein to maintain the coupling with MHC-1. Following antigenic recognition, costimulation occurs in order to become activated; cytotoxic T cells require costimulation by interleukin-2 or other cytotokines produced by helper T cells.

3.)  Memory T Cells

T cells that remain from a proliferated clone after a cellmediated immune response are termed memory T cells. The second response usually is so fast and so vigorous that the pathogens are destroyed before any signs or symptoms of disease can occur.

Figure  SEQ Figure \* ARABIC 1. Lymphocyte

Complement system

Complement system is a defensive system consisting of over 30 proteins produced by the liver and found circulating in blood serum and within tissues throughout the body. Together, proteins of the complement system destroy microbes by cytolysis inflammation and by phagocytosis and also prevent excessive damage to host tissue. Complement proteins are usually designated by an uppercase letter C. The proteins are numbered C1 trough C9 .The products are activated proteins and are indicated by the lower case letter a and b. Complement  proteins act in a cascade, that is triggers another which , in turn triggers another .Also, as part of the cascade more product is formed with each succeeding reaction so that the effect is amplified as the reaction  continue.

The result of compliment Activation

C3 can be activated by three mechanisms that will describe shortly:

a.    When C3 is activated its split in C3a and C3b

b.    C3b enhances phagocytosis, C3b binds to the surface of an invading microbe, and receptor of phagocytes on phagocytes attach to C3b.Recall that this enhancement of phagocytosis by coating a microbe is called opsonisation or immune adherence. It promotes attachment of a phagocyte to a microbe.

c.    C3b also initiates a series of reaction that result in cytolysis. First, C3b splits C5. Fragment C5 then bind to C6 and C7, attach to the invading cells plasma membrane. Next ,C8 and several C9 molecules join the other complement proteins and together form a cylinder shaped membrane attack complex which inserts itself through the membrane.

d.    The MAC creates transmembrane channels in the membrane. This causes water to enter the cell and ions to leave cells, resulting cytolysis.

e.    C3a and C5a bind to mast cell and cause them to release histamine and other chemical that increase blood vessels permeability during in inflammation .C5a also functions as very powerful chemo tactic factors that attracts phagocytes to the site of an infection.

Host cell plasma membrane contain protect against lysis by preventing attachment of the MAC proteins to their surfaces. Also MAC forms the basis for the compliment fixation test used to diagnose some diseases.