Overview Why needed? Origin: Blood vessels form from mesoderm Blood produced 2 wks after vessels are formed, during the 5th week of life What is blood? Connective tissue? Different from others Matrix not a solid or semi-solid material Matrix of blood is plasma watery substance Yellowish ○ 90% Water ○ 7% protein ○ 1% minerals ○ 2% other materials incl. atmospheric gases, chem signals, and nutrients More on plasma Contains: Atmospheric gases: oxygen, carbon dioxide, and nitrogen Comprises 55% of blood volume Formed elements (= Cellular components) Remaining 45% of blood volume: Erythrocytes (RBCs) Leukocytes (WBCs) Thrombocytes (platelets) Hematocrit Calculates the volume of red blood cells making up the blood Included in a CBC FYI: CBC (on medical shows) = complete blood count Complete Blood Count includes… Hematocrit The number of RBCs The number of WBCs The total amount of hemoglobin in the blood Also provides information about the following measurements: Average red blood cell size (MCV) Hemoglobin amount per red blood cell (MCH) The amount of hemoglobin relative to the size of the cell (hemoglobin concentration) per red blood cell (MCHC) The platelet count is also usually included in the CBC. Can you answer these questions? What is the blood composed of? Why is the blood unlike any other connective tissue? What does a hematocrit tell you? Red Blood Cells No mature nucleus (lost in dev.) No DNA, so…. ○ Use enzymes to carry out their tasks Reticulocytes (immature RBC) – have mesh-like network of rRNA… become mature in ~24 hours ○ Live max 120 days ○ No way to repair & replace damaged cellular components Appear red b/c of hemoglobin ○ Contains iron facilitates transport of O2 and CO2 4.8 million RBC/mm3 in women 5.4 million RBC/mm3 in men Blood Type Genetic Determined by the antigens on the surface of the RBC membrane A,B,O blood group system most common (30 possible in full blood type classification!) Blood will attack “non-self” Important to match blood types for transfusions Therefore… AB universal acceptor O universal donor-has no proteins on the membrane Rh Factor The “D” protein Most are positive (depends on geography) If a woman is negative and conceives with a positive man, problems can arise— erythroblastosis fetalis This can lead to anemia, a condition marked by weakness and fatigue. Severe anemia can lead to heart failure and death. The breakdown of RBC leads to the buildup of bilirubin which can lead to jaundice and brain damage. Prevention of erythroblastosis fetalis Treat negative mothers with Rhogam, a preventative measure Prevents formation of antibodies to Rh molecule Given whenever there is a possibility of fetal blood mixing with maternal blood following childbirth, abortion, miscarriage, prenatal testing. Once sensitized the woman will always react against Rh+ cells Can you answer these questions? 1. 2. 3. 4. 5. 6. How are RBCs different from most other cells? How does the lack of a nucleus affect RBCs lifespan? What is hemoglobin and what does it do? Why are RBCs red? What is blood type? What do the different blood types mean? Why is it dangerous for an Rh- woman to have an Rh+ baby? White Blood Cells WBC : RBC ratio = 1 : 500 or 1000 Use blood, lymph to move from bone marrow to the tissues 5 types (differential WBC count measures them) Neutrophils (Most abundant) Lymphocytes Eosinophils Monocytes Basophils (Least abundant) Agranulocytes AKA : Mononuclear Lack visible granules in cytoplasm Granulocytes Noticeable granules that produce specialized secretions for fighting infection Nucleus is polymorphic, lobed, unusually shaped Monocytes Lymphocytes T & B cells Eosinophils, basophils, neutrophils Neutrophils Granulocyte Most common WBC Nucleus = 2-5 lobes Found in the blood First responders in the inflammation response due to environmental exposure, some cancers, bacterial infection Predominant cell in pus Eosinophils Granulocyte 5% of WBCs Bi-lobed nucleus Combats parasitic infections (protists, worms) Secretions produced related to allergies Normally in thymus GI, ovaries, testes, spleen, uterus, lymph nodes NOT in lungs, esophagus, or skin if found here, indicates disease/pathology Basophils Granulocyte (least common) Susceptible to basic dyes Large, bi-lobed nucleus (similar to mast cells) Granules obscure the nucleus “Bas-ically all granules” Involved in allergies. Stores, secrete histamine & heparin (anticoagulant) Found where allergic reactions are taking place Agranulocytes Lymphocytes “Immune” cells: NK (natural killer) cells (no prior activation needed) T lymphocytes (mature in thymus) ○ Helper: direct immune response ○ Cytotoxic: release cytotoxin to kill pathogen infected cells B lymphocytes (mature in bone marrow): Use antibodies to neutralize pathogens Monocytes Agranulocyte Largest of WBCs - shaped nucleus Mono = kissing = Love = heart Many vesicles in cytoplasm for processing pathogens Perform phagocytosis - uptake & digestion of pathogens Fragments of “eaten” pathogen signal T- lymphocytes to the area Platelets Cell fragments derived from larger cells called megakaryocytes. Have “sticky” proteins Reduce blood flow to an affected area. Reduce blood loss Sensitive to many types of hazardous chemicals and pollutants Can you answer these questions? Describe the characteristics & functions of all granulocytes, agranulocytes, and platelets. Compare and contrast the structure & function of RBCs and WBCs Why are platelets called the “Band-Aids” of the blood? Carry oxygen from the lungs to the body Carry carbon dioxide from the body to the lungs Alveoli-where gas exchange happens in the lungs RBC in the capillaries that surround the alveoli oxygen enters Only if the partial pressure of oxygen outside is higher than inside In cytoplasm of RBC oxygen binds to Hemoglobin Four oxygen molecules bind to hemoglobin (w/ the iron) Carries CO2 also; binds to a different area than O2 Percent saturation: amount of oxygen that is dissolved in a solution of hemoglobin molecules O2 sats = 98% or above Similar to with myoglobin in muscle Greater affinity for oxygen Hemoglobin collects oxygen a low partial pressures In the tissues the oxygen is released and carbon dioxide enters the RBC, binds to Hemoglobin. Partial pressures of the gases must appropriate Some cellular wastes stimulate the release of the oxygen from the hemoglobin ○ Allows RBC to give more O2 to tissues w/ high metabolic needs Carried 3 ways in the blood 1. Carried in the blood as a gas (10%) 2. Binds to empty hemoglobin: carbaminohemoglobin 3. As a bicarbonate ion (HCO3-) ○ CO2 can dissolve in water, forming bicarbonate ion ○ Dissolves in the blood plasma Carbonic anhydrase: enzyme in RBC that stim’s the formation of carbonic anhydrase, which dissociates to form bicarbonate ions and H+ ions - Eventually excreted Diffusion: High concentration low concentration For Oxygen: Partial pressure is higher in blood than in tissues For Carbon Dioxide: Partial pressure is higher in tissues than in blood Occurs when the CO2 is extremely high in the environment or the blood Acute: high levels in the air Subacute: toxicity caused by the body’s failure to eliminate carbon dioxide Decreases blood’s pH (what kind of acid does CO2 form when it dissolves in water?) ○ Carbonic acid! What is the purpose of RBCs? Where does oxygen bind to the Hb molecule? Where does Hb collect oxygen? Then what happens? Describe the partial pressures that must be present for oxygen to diffuse from RBC to tissues and for carbon dioxide to move to the cells? In general: Fight infections & disease Granulocytes: ○ granules of toxic chemicals that kill microorganisms ○ regulate reactions to foreign materials in the body Pass through capillaries to tissues to with infections. Attracted to affected areas by factors secreted by damaged cells/tissues Stick to injured tissues, use phagocytosis to engulf remains of bacteria and damaged cells Secretes antibiotics-harms/kills bacteria Secretes other chemicals that stim. Inflammation ↑ blood flow to the area & ↑ WBC concentration Secretions defend against parasitic infections esp. protists & worms ↑ in eosinophils = parasitic infection Granules contain major basic protein to kill the parasites Secrete chemicals associated w/ allergies Secrete histamine stim the immune response Overproduction of histamine runny nose, sneezing, watery eyes Mast cells (special kind of basophil) Cause inflammation of tissues Secrete chemical that attract neutrophils Found in walls of small bl. vessels Clear granules give cytoplasm a grey appearance When they leave the bone marrow they become either: Circulating monocytes ○ Detect infections in blood ○ Bone growth & maintenance Tissue monocytes (macrophages) ○ Remove dead cells ○ Attack microorganisms that are difficult to kill (fungi) Stay tuned! We’ll talk about it later….for now, they carry out most of the duties of the immune system Which WBC is in charge of engulfing bacteria? Which WBC is in charge of protecting us from parasites? Which WBC differentiates into cells that assist in bone growth and maintenance or are macrophages that protect against fungal infections? Which WBC secretes major basic protein? Blood clotting Platelets adhere to injured area Activation of blood clot formation Important that clot forms by injury only Intact cells secrete prostacyclin (prevents platelet activation) 1.) BV damaged, releases “distress chemicals” 2.) Clotting factors stim. other factors that indicates presence of damaged tissues a.) platelets stick to damaged tissues & each other b.) Platelets secrete prothrombin activator & Ca2+ - Catalyze conversion of prothrombin to thrombin c.) Thrombin causes fibrinogen fibrin d.) Fibrin forms a sticky mesh that adheres to thrombocytes and other blood components (clot) - Clot forms a barrier that prevents blood loss & impedes the passage of microorganisms into tissues - Calcium ions = catalyze PT to T - Vitamin K = synthesis of clotting factors Prothrombin Thrombin Fibrinogen Fibrin So the blood doesn’t clot unintentionally! They aren’t permanent Plasminogenplasmin (digests fibrin and dissolves a clot) Healthy cells near the clot secrete TPA (tissue plasminogen activator)dissolves fibrin as well. Can you answer these questions? 1.) What is the purpose of prostacyclin? 2.) What is the purpose of a clot? 3.) What are the steps of the clotting cascade? 4.) What is the role of calcium and vitamin K in clot formation? 5.) Why is the clot cascade so complex? 6.) What do plasmin and tissue plasminogen have in common? What’s the difference? Adults: bone marrow Embryo: Liver Different forms of Hb throughout development allow fetus to adapt to varying metabolic needs for oxygen 11 million/sec in an adult 1 WBC produced for every ~500 RBCs Adults: bone marrow Embryo: Liver 11 million/sec in an adult 1 WBC produced for every 700 RBCs GF Myeloid stem cell (progenitor) Hematopoietic stem cell Or Multipotent stem cell Or Pluripotent stem cell GF Lymphoid stem cell (progenitor) The life history of erythrocytes (RBCs) Blood oxygen decreases Stimulates erythropoietin production from kidneys and liver Erythropoietin Erythropoiesis in red bone marrow (where is this found?) Immature erythrocytes have a large nucleus Hb production begins in basophilic erythroblasts Reticulocytes: lose nucleus, after 1-2 days in circulation lose organelles If the need for oxygen is great, erythropoiesis will occur at an increased rate. This means an increased amount of polychromatic erythroblasts will enter the blood stream Erythropoiesis of a single erythrocyte takes approximately 4 days Normal bone marrow has an abundance of newly formed RBCs and megakaryocytes (which produce platelets) Removed by macrophages Globin (protein) is broken into individual amino acids & recycled Iron is recycled Parts of the molecule are converted to bilirubin Processed in liver, secreted in bile in small intestine ○ Bacteria convert into pigments feces color ○ Some excreted in urine yellow color Lifespan = 13-20 days Destroyed in lymphatic system When released from bone marrow called stabs or bands Esp. neutrophils b/c their nuclei aren’t lobed, yet, and look like a rod (stab = German for rod) or bands Functions of Lymphatic System 1.) Maintain fluid balance in the tissues ○ 30L fluid from capillaries to interstitial and only 27L pass from interstitial back into capillaries qd (every day) ○ If fluid left in the body tissue damage ○ 3L fluid enter lymph capillaries, called lymph Then to lymph vessels & return to blood 2.) Absorb fats & other substances from digestive tract (chyle) 3.) Defense ○ Nodes filter lymph & spleen filters blood of microorganisms & foreign substances Lymphatic System Structures Lymph Like plasma: ions, nutrients, wastes from interstitial spaces Hormones, enzymes from cells in tissues Lymphocytes Lymph vessels ○ Flow of lymph produced by gravity or skeletal muscle, passively drains to lower body from upper ○ Valves-no backflow ○ Lymphatic trunks drain lymph from larger areas of body Clusters of lymphatic tissue Lymphatic System Structures Lymph nodes Collections of lymphatic tissue covered by connective-tissue capsules Eliminate antigens from lymph as lymph flows thru the node. In groups along the larger lymphatic vessels Lymph node structure 2 divisions: Cortex (outer) & Medulla (inner) Cortex ○ Has “compartments” called lymphatic nodules ○ 2 layers: inner layer called germinal center where Blymphocytes are found. In the “wall” surrounding the germinal center is where T-lymphocytes are found. ○ Nodules are sep’d by trabeculae—extensions of the capsule—fibrous covering of the node ○ Cortical sinus: spaces where lymph flows through Medulla ○ Medullary sinus = space where lymph flows throught he center of the node, contains macrophages ○ Medullary cord = contains lymphocytes Lymphatic System Structures Tonsils Swollen cluster of lymphatic tissue in throat Form protective ring of lymphatic tissue around the openings between the nasal and oral cavities & pharynx Provide protection against bac and other harmful material Eventually disappear in adults Spleen Detects and responds to foreign substances in the blood Destroys worn out red blood cells Acts as a blood reservoir Structure ○ Left side of the extreme superior, posterior corner of ab cavity ○ White pulp: Contains T & B lymphocytes Assist body with infections that require a large immune response ○ Red pulp: removes old/damaged RBCs Lymphatic System Structure Thymus Deep to manubrium In newborn, extends length of thorax & grows until puberty, then decreases in size Function ○ Produce lymphocytes that move to other lymph tissues, but most degenerate before moving on ○ Produces secretions that mature T-lymphocytes Can’t destroy normal body cells (Self-tolerance) Immunity words to know: Antigen: a substance that can induce an immune response. Hapten: A molecule that can cause an immune response when attached to blood proteins. Two ways the immune system can respond to disease: Innate immunity Acquired immunity Why an immune system? We are outnumbered! Viruses and bacteria are everywhere! Humans offer limitless resources for pathogens Energy Reproductive potential Getting into the body isn’t easy! Meet the enemy Bacteria Free-living Not all are bad! Pathogenic ones produce toxins that damage human tissue Viruses Obligate parasites Hijack human cells; convert to virus- producers, killing host cell in the process (And fungi, protozoa too…) A human fortress: Prevention Skin is thick – hard to penetrate Produces substances that deter invasion: Skin pH (not favorable) Mucus (sticky trap) Lysozymes (digest bacteria) Specialized traps around vulnerable areas (Eyes, nose, mouth) Cilia sweep away invaders that are trapped Stomach acid kills ingested invaders …but we do get sick! Enter through weak points: Food Nose Break in skin/scrapes Cells are damaged/destroyed Dying cells release distress chemicals (histamine) ○ Triggers inflammation (blood vessel dilation, increased blood flow) ○ Draws defensive cells to area (generalized white blood cells) How do we tell “friend” from “foe”? All cells present antigens – surface protein molecules that identify identity (antigen = antibody generator) Immune system reacts to foreign antigens A complex system! Several “lines” of defense: 1. Barriers (First line of defense) 2. Generalized defenders (Second line of defense) 3. Specific defenders AND memory (Third line of defense) Consist of: Several types of cells Proteins The Complement System Part of second line of defense Free-flowing proteins found in blood Quickly reach site of invasion React to antigens When activated, can Trigger inflammation Attract “eater cells” (macrophages) Coat pathogen (make macrophages’ job easier) Kill intruder directly Phagocytes Find and “eat” bacteria, viruses, dead/injured body cells by phagocytosis 3 types: Neutrophils Macrophages Dendritic cells Neutrophils Often first to site of infection Numerous Short lifespan “Pus” in infected wounds chiefly composed of neutrophils Macrophage “Big eaters” Slower to respond to invader than neutrophil Larger, longer-lived, more capable Help alert rest of immune system to invader Start as monocytes; become macrophages when entering bloodstream Dendritic cells “Eater” cells Help with immune system activation – act as antigen-presenting cells Filter bodily fluids to clear foreign organisms and particles Lymphocytes: Third Line of Defense T and B cells Originate in bone marrow Migrate to lymph nodes, spleen, thymus to mature Lymph vessels transport, store lymphocytes Feeds cells into body Filter out dead cells/invading organisms Receptors Each lymphatic cell contains surface receptors Recognize foreign antigens Specialized for a particular antigen T cells Two types: helper and killer T = thymus Mature here Helper T cell Main regulator of third line of defense Primary task: activate B cells and killer T cells Activated by macrophages/dendritic cells (antigen presentation) Killer T cell Attacks body cells infected by pathogen, cancer cells Receptors used to determine if each cell encountered is self/non-self (compare to accepted receptors, MHC) B lymphocyte cell Searches for antigens matching receptor If a match is found… Connects to antigen Triggering signal set off… ○ T helper proteins help fully activate B cell Produces 1000’s of clones: differentiate into plasma cells or B memory cells Plasma Cell Produces antibodies Responds to same antigen matched by B cell receptor Seek out intruders, help destroy them Release tens of thousands/second Antibodies Y-shaped Attach to matching antigens Enhance phagocytosis of macrophages (label for capture) Neutralize toxins Incapacitate viruses (coat surface proteins) Group pathogens by linking (agglutination) Immunoglobins IgG: most common, fight general infections, pass from mom to child in pregnancy (G= mom’s gift) IgA: in mucous membranes of the digestive system, milk, tears, saliva (A= a lot of mucus) IgM: natural defenses against general bacterial infections (M=most bacteria) IgE: stim basophils and mast cells to defend against parasites fungi and worms (E=eeww!) IgD: on membranes of B-lymphocytes, form plasma and memory cells (D=defend blood) Memory cells Prolonged lifespan “Remember” specific intruders Both B and T cells have memory cells Helps trigger immune system to respond more quickly if invader reappears Inflammation Outcome of acquired immune response Increases blood circulation to affected area Bv’s dialate to increase blood flow Immune cells go to injured area Immune resp. takes place at the site it’s needed Tissues = red and warm b/c of the blood that enters the area, ↑ in temp = anti-microbial Pain from pressure of swollen tissues on nerve endings Normal functions return when the tissue is fully recovered Natural Immunity Natural: exposed to foreign antigens as a part of everyday life. Active immunity – body responds to foreign antigens and develops immunity using B and T lymphocytes Passive immunity – ○ Embryological development when antibodies (Ig’s) from the mother’s blood stream are passed to the fetus ○ Breastfeeding – baby receives antibodies via milk Artificial Immunity Active: Immunization Therapeutic exposure to antigens Stimulates the primary response by introducing pathogenic material (inactivated, attenuated, or partial) into the body Vaccines are typically used for viruses! Antibiotics are only for bacteria Passive: Antibody Transfer Patient receives (via injection) large amounts of antibodies to fight disease ○ Globulin injections can remove certain microorganisms from the body.