CVS: Blood & Lymph PDF

CVS: Blood & Lymph Nawale Rajesh Bhaskar Body fluid Dilute watery solution present in body Intracellular (ICF): within the cell Extra cellular (ECF): outside body cell Interstitial: ECF fill in narrow space between cells & tissue Intra vascular: with in blood vessels Lymph: in lymph vesse...

CVS: Blood & Lymph Nawale Rajesh Bhaskar Body fluid Dilute watery solution present in body Intracellular (ICF): within the cell Extra cellular (ECF): outside body cell Interstitial: ECF fill in narrow space between cells & tissue Intra vascular: with in blood vessels Lymph: in lymph vessels Cerebrospinal: surrounding spinal cord and brain Synovial: with in joints of body Aqueous Humor / Vitreous: ECF of eye Blood & its function Blood is fluid connective tissue It is interstitial fluid The extracellular matric is plasma Cells are suspended in plasma Three basic function Transportation Oxygen, carbon dioxide, nutrient, hormones, west products etc Regulation By circulation - pH, temperature, osmotic pressure, water etc. Protection Coagulation, WBC – Phagocytosis, Blood proteins – antigen, antibody, interferon Blood physical characteristics Denser & viscous than water, Feel slightly sticky Temperature 38 Deg. Centi, Slightly alkaline in pH (7.5 to 7.45) Red colour (Hb in RBC) varies depending of oxygen level Is 20% extra cellular fluid and 8% body mass Average volume – 5 to 6 lit. (male) and 4 to 5 lit. (female) On centrifugation Denser RBC settle down (99% formed elements) Buffy coat (WBC and Platelets) Superior layer - Plasma Blood and Its Blood (8%) composition Plasma (55%) Formed Elements (45%) Water (91.5%) Protein (7%) Other solutes (1.5%) RBC WBC Platelets Electrolytes Granulocytes Agranulocytes Albumin (54%) Nutrients Neutrophils Monocytes Globulin (38%) Gases Basophils Lymphocytes Fibrinogen (7%) Regulating Eosinophils substances Other (1%) Waste Products Blood plasma Straw color liquid. Its is 91.5% water & 8.5% solutes (7% protein & 1.5 % other substances) Some proteins are also found in other body. But when its is in blood termed as plasma protein. Some blood cell develop gamma globulin – known as antibodies / immunoglobulins – as immune response (for foreign substances) Other solutes – electrolytes, hormones, gases, enzymes, nutrients, west products (urea, uric acid, creatinine, ammonia, bilirubin etc.) When coagulating protein are removed from plasma – known as serum Formed Elements RBC / Red Blood cells / Erythrocytes – non nucleated, carry oxygen & carbon dioxide WBC / White blood cells / Leukocytes – nucleated, have different types, protect body from invasion, defense mechanism of body Platelets / Thrombocytes – Fragments of cells, release chemical of clotting Percentage of total blood volume occupied by RBC is called as hematocrit Drop in hematocrit indicate anemia & high is polycythemia  Hemopoiesis Process of formation of blood cell is hemopoiesis Hemopoiesis occurs from stem cells by proliferation and differentiation Occur in red bone marrow (3 month after birth) Before birth in yolk sac After birth in liver, spleen, thymus, lymph nodes of fetus Hormone hemopoietic growth factor regulate proliferation and differentiation. Erythropoietin (produced by kidney) decides number of RBC Thrombopoietin (produced by liver) stimulates formation of WBC Different cytokines regulate development of cell types RBC/HB Oxygen carrying cells (using Hemoglobin/HB) Also carry carbon dioxide and nitric oxide RBC contain enzyme carbonic anhydrase RBC live only 120 days. Due wear and tear by squeeze through blood vessels (no nucleus to repair) they break. Ruptured RBC removed from circulation. Destroyed by phagocytes in liver and spleen. Breakdown products are recycled WBC These are nucleated cells. Full components of other organelles. Do not contain hemoglobin. Classified as granulocytes and agranulocytes depending on conspicuous chemicals filled in cytoplasm. Granules are made visible by differential staining (under microscope) Granulocytes After differential staining – show three types of granules (distinct color) Neutrophil Smaller granules, lilac color (both red & blue), Nucleus with 2 – 5 lobes connected with thin strand. Eosinophil Large uniform size granules, Stain red-orange color Granule do not cover nucleus. Nucleus 2 lobes connected with thin strand. Basophil Round variable size nucleus, Stain blue-purple Granule cover nucleus. Nucleus 2 lobes Agranulocyte Granules are small size, poor staining, not visible under light microscope Lymphocytes Nucleus stain dark, round shape, cytoplasm stain blue, rim around nucleus Depending on diameter are classified as large lymphocytes (10-14 micro M) and small lymphocytes (6-9 Micro M) Large lymphocytes has diagnostic significant in acute viral infection and immunodeficient diseases Monocytes Kidney / horse shoes shape nucleus. Cytoplasm blue – gray, foamy appearance Migrates from blood to tissue – enlarge and differentiate in to macrophages. If fixed to tissue, reside in particular tissue – Fix macrophages. Other wandering macrophages – roam the tissue, gather at site of infection / inflammation WBC Function WBC are far less in number than RBC (5 to 10 T) – 700:1 In healthy body WBC live long life (month to years). During period of infection they live for few hours Leucocytosis is increase in number of WBC (above 10,000) – Invading microbes, strenuous exercise, anaesthesia, surgery etc Leukopenia is decrease in number of WBC (less than 5000) – radiation, shock, chemotherapeutic agents etc Skin and mucous continuously expose to microbes and toxins – invade deeper tissue – WBC combats WBC leave bloodstream (emigration / diapedesis) and gather at site of infection. WBC Function Neutrophils and microphases are active in phagocytosis. Ingest bacteria and dispose dead matter Several chemical released by microbes and inflamed tissue attract phagocytes – phenomenon is known as chemotaxis Neutrophils response more quickly. Unleashes several chemicals like lysozymes, strong oxidants (super peroxides, hydrogen peroxide, hypochlorite ions etc and Neutrophils also contain defensine - protein - strong antibiotic property. Eosinophil leave capillary and enter body tissue. Release enzyme histaminase. High count indicate allergic condition / parasitic infection Combat effect of histamine and other inflammagens and allergens. Eosinophils phagocytes antigen-antibody complex.  WBC Function Basophil leave capillary and enter inflammation site. Release granules containing heparin, histamine, serotonin. These substances intensify inflammation reaction, involved in hypersensitivity / allergic reaction. Lymphocytes are major soldiers of battle. B lymphocytes destroy bacteria and inactivate their toxins T lymphocytes attach infected body cells and tumor cells, Natural killer cells attack infected body cell and tumor cells Monocytes arrived late at site but large in number & destroy more microbes. On arrival they enlarge, differentiate and phagocytes microbes Platelets Stem cell differentiate under influence of thrombopoietin to form platelets Normal count 150,000 to 400,000 (size 2 to 4 micro M) Have short lifespan (5 to 9 days) Granules contains chemicals promotes coagulation. Stop blood loss from damaged blood vessels by forming platelet plug. Aged and dead platelets are removed by fixed microphases in spleen and liver  Anemia Condition where oxygen carrying capacity of blood is reduced Reduced number of RBC or amount of Hb in blood. Individual feel fatigue and intolerant to cold due to lack of oxygen. Skin become pale. Types of anemia Iron deficiency: Most common. Women are at greater risk (menstruation / pregnancy). Insufficient iron intake, inadequate absorption of iron, excess loss of iron, increased iron requirement. Megaloblastic anemia: Inadequate intake of Vit. B12 and/or folic acid. Red bone marrow produce large, abnormal RBC (megaloblast) Pernicious anemia: Insufficient hemopoiesis. Inability of stomach to produce intrinsic factor needed for absorption of Vit B12. Hemorrhagic anemia: Excessive loss of RBC by bleeding, large wound, stomach ulcer, heavy menstruation etc. Hemolytic anemia: RBC membrane rupture immaturely. Hb pour in plasma. Damage to nephron. Condition due to lack in inherent enzyme, parasite, toxins, antibodies from transfusion fluid. Thalassemia: Deficient synthesis of Hb. RBC are small (microcytic) pale (hypochromic) & short lived. Aplastic anemia: Destruction of red bone marrow. Caused by toxins, gamma radiation, medication etc.  Sickle cell Disease (SCD) Contain Hb-S, an abnormal kind of hemoglobin It forms long, stiff, rodlike that bend RBC into sickle shape Sickle cell rupture rapidly leading to anaemia, shortness of breath, fatigue, paleness, delayed growth of child. Rapid RBC destruction lead to jaundice. Yellowing of eye and skin. Sickle cell does not move easily, stick together, form clump, block blood vessel. Deprive organ of oxygen & cause pain, serious infection, organ damage (lung, brain, spleen, kidney etc.) Other symptoms – fever, rapid HR, swelling, inflammation, leg ulcer, eye damage, excessive thirst, frequent urination, painful and prolong erection (male) Is inherited, genes have identified for SCD. Treatment – Analgesics, fluid, oxygen, antibiotics, blood trnasfusion Hemophilia & Leukemia Hemophilia Inherited deficiency of clotting – spontaneous bleeding, trauma. Deficiency of different clotting factors. It is oldest known heritable disease, Usually affect males. Known as Royal disease. Characterized by spontaneous traumatic subcutaneous and intramuscular hemorrhage, nose bleeding, blood in urine, joints (produces pain & tissue damage) Leukemia Disorder – group of red bone marrow cancer Abnormal WBC multiply uncontrollably. Accumulation of cancerous WBC in red bone marrow interfere with production of blood cell. Reduced oxygen carrying capacity (due to anaemia), increased susceptibility to infection, abnormal blood coagulation, enlargement of lymph nodes, liver, spleen. Other - weight loss, fever, night sweeting, excessive bleeding, recurrent infection etc. Two types: Acute (symptoms develop rapidly), & chronic (take years to develop) Hemostasis Is sequence of events that stops bleeding Three mechanism involved in this Vascular spasm Platelet plug formation Blood coagulation Occurs in localized region of damage Prevent loss of large amount of blood (hemorrhage) from small blood vessels. Large blood vessels requires medical intervention. Vascular Spasm & Platelet plug formation Arteries and arterioles damaged - Circular smooth muscle constricts immediately (vascular spasm) - Reduces blood flow Damage also break platelet cells (containing array of chemicals). Release clotting factors, ADP, ATP, Ca++, serotonin and many more Process takes place in three steps Platelet adhesion: Cell contact and stick to part of damaged blood vessels Platelet release reaction: adhesion make them active and liberate content in to vesicles initiates reaction like – activating other platelet, vasoconstriction, decreased blood flow Platelet aggregation: ADP make other platelet and area sticky and cause them to adhere and gather more cells and formation of platelet plug. Plug is effective in preventing blood loss and stop bleeding. Blood Clotting Process of gel formation is known as clotting / coagulation Is series of chemical reactions (cascade enzymatic reaction) causes formation fibrine thread resulting in thrombus formation It involves several factors – clotting factors (13 universal factors) Process involves three stages Extrinsic pathway Intrinsic pathway Common pathway Extrinsic and Intrinsic Pathway Extrinsic Pathway Few steps, occurs within seconds of trauma Involves tissue protein tissue factor (TF) / thromboplastin – leak into blood from outside. TF in presence of Ca++ activates clotting factor X. Active factor X combined with factor V and promote formation of Prothrombinase Intrinsic Pathway More complex, Occurs slowly, Requires several mins. Activators are present within blood (outside tissue damage is not needed) Damaged platelet activates clotting factor XII subsequently activates factor X. Activated factor X combined with factor V to form active enzyme Prothrombinase.  Common Pathway Formation of prothrombinase (Stage 1) is beginning of common pathway Stage 2: Prothrombinase and C++ catalyzes conversion of Prothrombin to thrombin Stage 3: In presence of Ca++ thrombin convert fibrinogen to insoluble fibrin thread. Thrombin also activate factor XIII. Activated factor XIII strengthen and stabilizes fibrinogen threads to sturdy clot. Clot retraction: Once clot is formed, its plug ruptured blood vessels and stops blood loss. Clot retraction is consolidation / tightening of fibrin clot. Vitamin K Normal coagulation of blood depend on adequate level of vitamin K in body Vitamin K is not directly involved in coagulation process Requires for synthesis of four clotting factors ( factors II, VII, IX, X) and also Protein C and S. Factors II: Prothrombin Factor VII: Stable factor / proconvertin Factor IX: Chrismas factor / Antihemophilic factor B Factor X: Stuart factor, Prower factor, or thrombokinase Is a fat soluble vitamin, absorbed through lining of intestine. Individual suffering from slow absorption of lipid from intestine experience uncontrolled bleeding (due to Vit. K deficiency) Clotting (Coagulation) factors Homeostatic control Small clots are formed due to rough surface of blood vessels. These small clot act as nucleus for large clot to form. The fibrinolytic mechanism dissolves these small clots (fibrinolysis) Several anticoagulant substances in blood prevent / delay / suppress clotting Antithrombin: Block action of several factors II, X and XII Heparin: Produced by mast cells and basophils Combined together these increases effectiveness in blocking thrombin. Activated protein C: Inactivates Enhance activity of plasmogen activators. Despite anticoagulant and fibrinolytic mechanism blood clot (thrombus) form in CVS known as intravascular clotting. This clot block the blood vessels – embolism. When embolus lodges in lung - pulmonary embolism. Blood Grouping and Typing Surface of RBC contained genetically determined Antigen – agglutinogen Based on antigen – antibody present in plasma – agglutinin Base on presence / absence of antigen blood group are categorized More than 100 antigen and around 24 different blood groups are determined but two major blood groupings are ABO and Rh Blood Transfusion - significance Transfusion is transfer of whole / part of blood components (specially RBC) into the bloodstream Give to alleviate anaemia, increase blood volume, improve immunity. Normal antigen-antibody reaction can trigger damaging response to recipient (agglutination – clumping of RBC) Donated RBC plasma membrane make leaky causing haemolysis/rupture of RBC Liberate Hb in blood and this Hb damages kidney by clogging filtration Reaction always take place between doners cell to recipients plasma. Transfusion – Not allowed Transfusion – Allowed (donors and acceptors) Rh Factor Names Rh blood group – Rh antigen / Rh factor found in Rhesus monkey Individual who have Rh antigen on RBC are Rh + ve (Rh positive) Individual who do not have Rh antigen RBC are Rh – ve (Rh negative) Plasma does not contain any corresponding antibody (Anti Rh antibody) If Rh – ve person receives Rh + ve blood, immune system start developing Anti Rh antibody and remain in blood. If second transfusion or Rh + ve blood is received the previous form antibody and antigen will cause agglutination reaction and hemolysis of RBC in donated blood. Hemolytic Disease of newborn Blood group detection To avoid blood-type mismatch, laboratory blood group detection of donor and recipient is must. Blood group detection kit contains different antisera containing antibodies. One drop of blood mixed with antisera (Both anti A and Anti B – separately) and agglutination reaction is observed. For Rh factor determination – drop of blood is mixed with antisera containing anti Rh antibody. If agglutination occur Rh + ve. If not then Rh – ve Lymphatic System  Lymphatic System A defense system that deals with invading microbes Immunity / resistance is ability to ward off damage or disease using defense system. Lack of resistance is susceptibility. Two types of immunity Innate: Defense that present by birth. Do not require recognition of specific microbes, Act against all types in same way. Give early warning to prevent entry. First line: Physical & chemical barrier of skin & mucous membrane. Second Line: Antimicrobial substances, natural killer cells, phagocytes, inflammation & fever Adaptive: Involves specific recognition. Involves specific response to specific microbes / invader (i.e. adopted for specific type only). It involves lymphocytes (T and B). Body system responsible for adaptive and some part of innate immunity is lymphatic system. Is closely aligned with CVS. Function with digestive system. Lymphatic Organ and Tissue Lymphatic system consists of Flowing fluid – Lymph – fluid passes from blood to interstitial fluid (in between cell) and then to lymphatic vessels – known as lymph. Vessels – Lymph vessels, that transports lymph Tissue – Lymphatic tissues - nodes, filtering tissue, red bone marrow etc. Lymphatic tissue is specialized reticular connective tissue containing large number of lymphocytes. Function of Lymphatic system Drain excess interstitial fluid Drain excess fluid from tissue space and return it to blood (closely link to CVS) It help in maintaining circulating blood volume Transport dietary lipids Transports lipid absorbed by GIT Transports lipid soluble vitamins (A, D, E and K) Carryout immune response Initiates highly specific response against particular microbes or abnormal cells. Lymphatic Vessels Lymphatic vessels begin as lymphatic capillary Located in between space of cell & have close end Lymphatic capillary unit to form lymphatic vessels At interval along lymphatic vessels lymph flow through lymph nodes (encapsulated bean shape organ consist of mass of B and T cells) In skin lymph vessels lies subcutaneously and follow same route of veins Lymphatic capillaries Have greater permeability than blood capillaries Absorbs molecules like protein, lipids. Have slightly larger diameter than blood capillary Have unique one-way structure that permit interstitial fluid to enter lymph capillary. When pressure in interstitial fluid is greater, it opens swinging door and fluid enter the lymph capillary When pressure in lymph capillary is greater than interstitial fluid, cell adhere closely and lymph can not escape back to interstitial space. Lymph Trunks and Ducts Lymph passes – lymph capillaries to lymph vessels & then to lymph nodes. Lymphatic vessels exit lymph nodes to form lymph trunks. The main lymph trunk are – lumber, intestinal, bronchomediastinal, subclavian, jugular. They drain lymph from organs as follows Lumber trunk – lower limb, the wall of viscera pelvis, kidney, adrenal gland, abdominal wall Intestinal trunk – stomach, intestine, pancreas, spleen, part of liver Bronchomediastinal trunk – thoracic wall, lung and heart Subclavian trunk – upper limbs, Jugular trunk – head and neck These trunk independently (right & left) open into venous system on anterior surface of junction of the internal jugular and subclavian vein.  Formation & flow of Lymph Most components (nutrients, gases, hormones) filter from capillary to interstitial fluid but can not return back. This fluid (around 3 lit./day) drain in to lymphatic vessels & become lymph. Proteins can not reenter blood from interstitial fluid passes in to lymph vessels. Lymph vessels contain valves that ensure one-way movement of lymph Sequence of fluid flow: Blood capillary -> interstitial space -> lymphatic capillary -> lymphatic vessels -> lymphatic trunk/duck -> jugular/subclavian vein -> blood Lymphatic organ & tissue Are of two groups Primary Lymphatic organs Site where stem cell divide and become immunocompetent. Capable of mounting immune response. Organs – Red bone marrow, Thymus, Stem cells that matures to Immunocompetent B cell and T cells Secondary Lymphatic organs Site where most immune response occur. Include – thymus, lymph node, spleen Thymus Bilobed organ located in mediastinum between sternum and aorta Each lobe contain cortex and medulla. Cortex contain large number of T cells & scattered dendritic cells, epithelial cells, macrophages. Immature T cell migrate from red bone marrow to thymus cortex and become mature. Medulla consists of widely scattered more mature T cells epithelial cells, dendritic cells and macrophages. It contain high content of lymphoid tissue and rich blood supply, thymus has reddish appearance.  Lymph Nodes Located along lymph vessels. About 600 bean-shaped lymph nodes scattered throughout body (superficially and deep). Lymph nodes are 1-25 mm long like thymus, covered by capsule of dense connective tissue that extend in to node. Parenchyma (functional part) is divided in to superficial cortex and deeper medulla Cortex has two parts – outer cortex and inner cortex. Outer cortex contains egg-shaped aggregates of B cells called lymphatic nodules (follicles) they develop antibody in response to antigen. The inner cortex does not contain lymphatic nodules. It contains T cells & dendritic cells. Medulla contain B cells, antibody producing plasma cells that have migrated out of cortex to medulla and macrophages  Spleen Oval shape single largest mass of lymphatic tissue. Soft encapsulated. Located in hypochondriac region between stomach and diaphragm. Parenchyma contain two types of tissues White pulp: Lymphatic tissue containing lymphocytes and macrophages arranged around branches of splenic artery. Red pulp: Blood filled venous sinuses and cord of splenic tissue (splenic cord). Splenic cord contains RBC, macrophages, lymphocytes, plasma cells, granulocytes Blood flow in to the spleen enter white pulp, B and T cell carryout immune function. Spleen macrophages destroys blood born pathogen by phagocytosis. Spleen perform three function Macrophages remove worn out, defective, ruptured blood cell & platelets Storage of platelets up to 1/3 of the body supply Production of blood cells (hemopoiesis) during foetal life Innate Immunity: First line defense Skin and mucous membrane (epidermis) provide physical and chemical barrier for entry of pathogen and foreign substance. Periodic shedding removes microbes, rarely penetrate intact skin. Broken, cut, burns, punctures can penetrate epidermis and invade blood. Secretion of mucus (viscus) trap microbes. Hair act as trap and filter. Cilia on epithelial waving action propel out side. Coughing, sneezing accelerate removal. Swallowing destroy by gastric acid. Lacrimal apparatus of eye secrete tears & blinking give washing. Tear contain enzyme lysozyme (breakdown cell walls of bacteria). Flow of urine, vaginal fluid, defecation, vomiting expels bacteria out side body. Innate Immunity: Second line defense Antimicrobial substance Lymphocytes, macrophages, fibroblasts produces protein interferon. Interferon induces synthesis of antiviral protein that interferes with viral replication. Complement system active compliment protein & enhance immunity Transferrin, lactoferrin, ferritin hemoglobin inhibit growth of certain bacteria Antimicrobial short peptides with broad antimicrobial activity - dermicidin (sweat gland) defencin & cathelicidins (neutrophils) thrombocidin (platelets) Natural killer cells and phagocytes When microbes pass first line defense natural killer cells (NK) kills them. NK release perforin (creates perforation / channels), cytokines (inflammation reaction), granzyme (protein digesting enzyme) Phagocytes (neutrophils, macrophages - wondering and fixed) ingests microbes.  Innate Immunity: Second line defense Inflammation Is non specific defense response of body to tissue damage Caused by - pathogens, abrasions, chemical irritations, distortion or disturbances of cells, and extreme temperatures Is attempt to dispose, microbes, toxins, foreign material at site of injury to prevent spread to other tissue and prepare site for tissue repair. PRISH Pain due to release of chemicals Redness due to more blood rush to area Immobility from loss of function Swelling by accumulation of fluid Heat due to more blood rush to affected area Histamine, kinin, Prostaglandin, leukotriene, complimentary system contributes for PRISH Emigration of phagocytes occur with hr. Phagocytosis kill microbes along with macrophages. Collection of dead phagocytes and damaged tissues in pocket along with fluid is called pus. Innate Immunity: Second line defense Fever Abnormally high body temperature due to hypothalamic thermostat reset. Commonly occur during infection and inflammation Many bacterial toxins elevates body temperature. Some time by triggering cytokines Elevated body temperature intensify effect of interferons, inhibit growth of microbes, speedup repair reaction.  Phagocytosis Chemotaxis: Chemically stimulated movement of phagocytes to site of damage. Chemical come from microbes, WBC, damage tissue cells, activated complementary protein Adherence: attachment of phagocytes to microbes. Complimentary protein enhance adhesion. Ingestion: Phagocytes pseudopods engulf microbes. Engulfed microbes in phagocytes are called phagosomes. Digestion: Phagosomes on entering cytoplasm merges with lysosomes to form phagolysosomes. Lysosomes contributes break down of microbes cell walls, degrades carbohydrate, protein, lipid and nucleic acid. Phagocytes also forms lethal oxidants (superoxide, hypo chloride, hydrogen peroxide) causing oxidative burst. Killing: Lysozymes, digestive enzymes, oxidants, with phagolysosomes quickly kills many types of microbes Adaptive Immunity Is ability of body to defend itself against invading agents such as bacteria, toxins, viruses, foreign tissue Substance that are recognized as foreign provokes this immune response is Antigen (Antibody generator). Adaptive immunity is Specific for particular foreign molecule (antigen) which are also distinguishing itself from non specific molecules/ Has memory for most previously encountered antigens so that a second encounter prompts an even more rapid and vigorous response. When challenged by antigen is called immunology. System consists of cells and tissues that carry out immune response  Adaptive Immunity Maturation of T and B cells Involves T and B lymphocytes and develop immunocompetency (ability to carry out adaptive immunity). These cells make several distinctive protein. Some function as antigen receptor (capable of recognizing specific antigen) Major two types of T cells – helper T cells (CD4) and cytotoxic T cells (CD8) Type of adaptive immunity Cell mediated: Cytotoxic T cells directly attach invading antigens. Antibody mediated: B cell transform into plasma cell which synthesizes and secretes specific protein (antibody / immunoglobulins). The antibody can bind and inactivate specific antigen. Cell mediated immunity is particularly effective against Intracellular pathogen (virus, fungi, bacteria); Cancer cell; Foreign tissue transplant Antibody mediated immunity works against extracellular pathogens. (virus, fungi, bacteria). In this immunity antibody bind to antigen in body humors / fluid (blood, lymph) known as humoral immunity  Adaptive Immunity Clonal selection Once antigen bind to antigen receptor, lymphocytes receives a stimulatory cues (instruction) undergoes clonal selection. Clonal selection is process by which lymphocytes undergo proliferation and differentiation in response to specific antigen. Result of clonal selection – formation of population of identical cells called clone. Clone recognizes specific antigen as that of lymphocyte. On first exposure very few antigen were recognized. After clonal selection thousand cells can recognize antigen. Memory cell do not actively participate in immunity. If antigen enter body in future. Thousand of memory cell clone (proliferation and differentiation) to combat antigen.  Adaptive Immunity Antigen and antigen receptors Antigen have two properties – immunogenicity (ability to provoke immune response by production of specific antibody) and reactivity (ability of antigen to react specifically with antibody). Antigens are large, complex, proteins, nucleic acids, lipoproteins, glycoproteins, large polysaccharides. The diversity in antigen receptor (in T & B cells) – shuffling & rearranging hundreds versions of several small genes segments. Process is known as genetic recombination. Cytokines Are small protein molecules that stimulate or inhibit many normal cell function (growth, differentiation). Lymphocytes and antigen presenting cells secretes cytokines also from fibroblast, endothelial cells, monocytes, hepatocytes, kidney cells Some cytokines stimulate proliferation of blood cells, other regulates activity of innate defense and adaptive immunity.  Cell mediated Immunity Activation of T cells At any given time most T cells are inactive. T cell become activated when it bind to foreign antigen and receive second signal – process is known as costimulation. More than 20 costimulators – like cytokines (interleukin), other plasma membrane molecules. Invasion of antigen, recognition of specific antigen, leads to costimulation, this prevent immune response occurrence accidently. Antigen binding to receptor without costimulation – prolong state of inactivity called anergy in both B and T cells. Elimination of invaders Cytotoxic T cells are soldiers march battel with foreign invaders. They leave lymphatic organs and migrate to destroy infected target cells, cancer cells, transplanted cells Cytotoxic T cells recognizes and attach target body cells. Like natural killer cells. Cytotoxic T cells are receptor specific for particular microbe and thus kill only target body cell infected with microbe. Immunological surveillance When normal cell transforms into cancerous cell – displays novel cell surface called tumor antigen. If immunity recognize this antigen – destroy cancer cell. This is immunological surveillance. Carried out by cytotoxic T cells, macrophages, natural killer cells. Is most effective in eliminating tumor by virus.  Antibody mediated immunity Body contain million different T & B cells. Respond to specific antigen. In response to antigen plasma cell secretes antibodies in 4 to 5 days Antibodies: antigen-antibody structure matches like lock and key. Antibody structure: is a group of glycoprotein (globulins) – hence known as immunoglobulins. Most antibody contain 4 polypeptide chains (two identical). Heavy (H) chain & light (L) chain. Each contain about 220 amino acid and disulphide bonds. Antibody action: Action of antibody include – Neutralizing antigen: Antigen – antibody reaction neutralizes toxins Immobilizing bacteria: antigen-antibody reaction cause bacteria to loos mobility, limit spread. Agglutinating & precipitating antigen: antigen-antibody reaction crosslink pathogen – clumping together Activating complement: antigen-antibody complex inhibit classical pathway of complementary system Enhancing phagocytosis,: Antibody enhances activity of phagocytes by agglutination & precipitation Role of compliment system in immunity: is made up of 30 proteins produced by liver and circulating blood plasma. Compliment protein destroy microbes by causing phagocytosis, cytolysis and inflammation.  Antibody mediated immunity Immunological memory: Hallmarks of immunity is memory for specific antigen triggered immune response in past. Immunological memory is due to presence of long-lasting antibody and very long living lymphocytes arise during clonal selection. Immune response (cell or antibody mediated) are much quicker and more intense after second or subsequent exposure to antigen. Measure of immunological memory is antibody titer (amount of antibody in serum). After initial contact with antigen – no antibody present for several days. Then slow rise in antibody followed by gradual decline in antibody. Memory cells remain for decades. Every new encounter with same antigen results rapid proliferation of memory cells. Immunological memory provide basis for immunization. Vaccines are attenuated (weakened) or killed microbes or portion of microbes. B and T cells are activated and provides immunity  Self recognition & Tolerance To function properly our cells must have two traits They must recognize own major histocompatibility complex protein, process known as self recognition. Must lack reactivity to peptide fragments of own protein, process known as self-tolerance B cell display self tolerance. Loss of self tolerance leads to autoimmune disease. Pre-T cells in thymus develops capability for self recognition Self-tolerance occur by weeding-out process call negative selection. In this process T cell with receptor that recognize self-peptide fragment or other self-antigen are eliminated or inactivated. Negative selection occur via both deletion and anergy. In deletion self-reactive T cells undergo apoptosis and die, in anergy they remain alive but unresponsive to antigenic stimulation. Thanks