The Lymphatic System and the Blood

The Lymphatic System and the BloodOverviewWhy needed? Origin: Blood vessels form from mesodermBlood produced 2 wks after vessels are formed, during the 5th week of life

What is blood?Connective tissue?Different from othersMatrix not a solid or semi-solid materialMatrix of blood is plasmawatery substanceYellowish90% Water7% protein1% minerals2% other materials incl. atmospheric gases, chem signals, and nutrients

More on plasmaContains:Atmospheric gases: oxygen, carbon dioxide, and nitrogenComprises 55% of blood volume

Formed elements(= Cellular components)Remaining 45% of blood volume:Erythrocytes (RBCs)Leukocytes (WBCs)Thrombocytes (platelets)

HematocritCalculates the volume of red blood cells making up the blood

Included in a CBCFYI: CBC (on medical shows) = complete blood count

Complete Blood Count includesHematocritThe number of RBCsThe number of WBCsThe total amount ofhemoglobinin the bloodAlso provides information about the following measurements:Average red blood cell size (MCV)Hemoglobinamount per red blood cell (MCH)The amount of hemoglobin relative to the size of the cell (hemoglobin concentration) per red blood cell (MCHC)Theplatelet countis 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

Red Blood CellsNo mature nucleus (lost in dev.)No DNA, so.Use enzymes to carry out their tasksReticulocytes (immature RBC) have mesh-like network of rRNA become mature in ~24 hoursLive max 120 daysNo way to repair & replace damaged cellular componentsAppear red b/c of hemoglobinContains iron facilitates transport of O2 and CO2 4.8 million RBC/mm3 in women5.4 million RBC/mm3 in men

Blood TypeGeneticDetermined by the antigens on the surface of the RBC membraneA,B,O blood group system most common (30 possible in full blood type classification!)Blood will attack non-selfImportant to match blood types for transfusionsTherefore AB universal acceptorO universal donor-has no proteins on the membrane

Rh FactorThe D proteinMost 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 fetalisTreat negative mothers with Rhogam, a preventative measurePrevents formation of antibodies to Rh moleculeGiven 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+ cellsCan you answer these questions?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

White Blood CellsWBC : RBC ratio = 1 : 500 or 1000Use blood, lymph to move from bone marrow to the tissues5 types (differential WBC count measures them)Neutrophils (Most abundant)LymphocytesEosinophilsMonocytesBasophils (Least abundant)

WBCsAgranulocytesGranulocytesNucleus is polymorphic, lobed, unusually shapedNoticeable granules that produce specialized secretions for fighting infectionLack visible granules in cytoplasmAKA : MononuclearMonocytesEosinophils, basophils, neutrophilsLymphocytesT & B cellsNeutrophilsGranulocyteMost common WBCNucleus = 2-5 lobesFound in the bloodFirst responders in the inflammation response due to environmental exposure, some cancers, bacterial infection Predominant cell in pus

EosinophilsGranulocyte5% of WBCsBi-lobed nucleusCombats parasitic infections (protists, worms)Secretions produced related to allergiesNormally in thymus GI, ovaries, testes, spleen, uterus, lymph nodesNOT in lungs, esophagus, or skin if found here, indicates disease/pathology

BasophilsGranulocyte (least common)Susceptible to basic dyesLarge, bi-lobed nucleus (similar to mast cells) Granules obscure the nucleusBas-ically all granulesInvolved in allergies.Stores, secrete histamine & heparin (anticoagulant)Found where allergic reactions are taking place

Agranulocytes LymphocytesImmune cells: NK (natural killer) cells (no prior activation needed)T lymphocytes (mature in thymus)Helper: direct immune responseCytotoxic: release cytotoxin to kill pathogen infected cellsB lymphocytes (mature in bone marrow): Use antibodies to neutralize pathogens

MonocytesAgranulocyteLargest of WBCs - shaped nucleusMono = kissing = Love = heartMany vesicles in cytoplasm for processing pathogensPerform phagocytosis - uptake & digestion of pathogensFragments of eaten pathogen signal T-lymphocytes to the area

PlateletsCell fragments derived from larger cells called megakaryocytes.Have sticky proteinsReduce blood flow to an affected area.Reduce blood lossSensitive 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 WBCsWhy are platelets called the Band-Aids of the blood?Blood Cell Function

Red Blood Cell FunctionCarry oxygen from the lungs to the bodyCarry carbon dioxide from the body to the lungs

Alveoli-where gasexchange happens in the lungsRBC in the capillaries that surround the alveoli oxygen entersOnly if the partial pressure of oxygen outside is higher than insideIn cytoplasm of RBC oxygen binds to Hemoglobin

HemoglobinFour oxygen molecules bind to hemoglobin (w/ the iron)Carries CO2 also; binds to a different area than O2Percent saturation: amount of oxygen that is dissolved in a solution of hemoglobin moleculesO2 sats = 98% or aboveSimilar to with myoglobin in muscleGreater affinity for oxygenHemoglobin 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 appropriateSome cellular wastes stimulate the release of the oxygen from the hemoglobinAllows RBC to give more O2 to tissues w/ high metabolic needs

Carbon DioxideCarried 3 ways in the blood1. Carried in the blood as a gas (10%)2. Binds to empty hemoglobin: carbaminohemoglobin3. As a bicarbonate ion (HCO3-)CO2 can dissolve in water, forming bicarbonate ionDissolves in the blood plasmaCarbonic anhydrase: enzyme in RBC that stims the formation of carbonic anhydrase, which dissociates to form bicarbonate ions and H+ ionsEventually excreted

33Movement of gasesDiffusion: High concentration low concentrationFor Oxygen:Partial pressure is higher in blood than in tissuesFor Carbon Dioxide:Partial pressure is higher in tissues than in bloodCarbon dioxide intoxicationOccurs when the CO2 is extremely high in the environment or the bloodAcute: high levels in the airSubacute: toxicity caused by the bodys failure to eliminate carbon dioxideDecreases bloods pH (what kind of acid does CO2 form when it dissolves in water?)Carbonic acid!35Can you answer these questions?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?

White Blood Cell FunctionIn general:Fight infections & diseaseGranulocytes: granules of toxic chemicals that kill microorganisms regulate reactions to foreign materials in the bodyNeutrophil functionPass through capillaries to tissues to with infections.Attracted to affected areas by factors secreted by damaged cells/tissuesStick to injured tissues, use phagocytosis to engulf remains of bacteria and damaged cellsSecretes antibiotics-harms/kills bacteriaSecretes other chemicals that stim. Inflammation blood flow to the area & WBC concentration

Eosinophil functionSecretions defend against parasitic infections esp. protists& worms in eosinophils = parasitic infectionGranules contain major basic protein to kill the parasitesSecrete chemicals associated w/ allergies

Basophil functionSecrete histamine stim the immune responseOverproduction of histamine runny nose, sneezing, watery eyesMast cells (special kind of basophil)Cause inflammation of tissues Secrete chemical that attract neutrophilsFound in walls of small bl. vessels

Monocyte functionClear granules give cytoplasm a grey appearanceWhen they leave the bone marrow they become either:Circulating monocytesDetect infections in bloodBone growth & maintenanceTissue monocytes (macrophages)Remove dead cellsAttack microorganisms that are difficult to kill (fungi)

Lymphocyte functionStay tuned! Welltalk about it later.for now, they carry out most of theduties of the immune system

Can you answer these questions?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?Platelets functionBlood clottingPlatelets adhere to injured areaActivation of blood clot formationImportant that clot forms by injury onlyIntact cells secrete prostacyclin (prevents platelet activation)

Clotting Cascade

Clotting Cascade (simplified)1.) BV damaged, releases distress chemicals 2.) Clotting factors stim. other factors that indicates presence of damaged tissuesa.) platelets stick to damaged tissues & each otherb.) Platelets secrete prothrombin activator & Ca2+Catalyze conversion of prothrombin to thrombin c.) Thrombin causes fibrinogen fibrind.) 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 tissuesCalcium ions = catalyze PT to TVitamin K = synthesis of clotting factors

ProthrombinThrombinFibrinogenFibrinWhy is the cascade so complicated?So the blood doesnt clot unintentionally!They arent permanentPlasminogenplasmin (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? Whats the difference?Blood Cell FormationIn GeneralAdults: bone marrowEmbryo: LiverDifferent forms of Hb throughout development allow fetus to adapt to varying metabolic needs for oxygen11 million/sec in an adult1 WBC produced for every ~500 RBCs

51In GeneralAdults: bone marrowEmbryo: Liver11 million/sec in an adult1 WBC produced for every 700 RBCs

Hematopoietic stem cellOrMultipotent stem cellOrPluripotent stem cellMyeloid stem cell (progenitor)Lymphoid stem cell (progenitor)GFGFLympohid give rise to WBC of lymphatic systemMyeloid give rise to platelets, RBCs, and WBCs that circulate in the bloodGrowth factors: stimulate the production of a particular blood cell lineageGrowth factors from various organs regulate the formation of blood cells52

53The life history of erythrocytes (RBCs)Blood oxygen decreasesStimulates erythropoietin production from kidneys and liverErythropoietin Erythropoiesis in red bone marrow (where is this found?)Immature erythrocytes have a large nucleusHb production begins in basophilic erythroblastsReticulocytes: lose nucleus, after 1-2 days in circulation lose organelles

ErythropoeisisIf 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 daysNormal bone marrow has an abundance of newly formed RBCs and megakaryocytes (which produce platelets)Old erythrocytes get gobbled up!Removed by macrophagesGlobin (protein) is broken into individual amino acids & recycledIron is recycledParts of the molecule are converted to bilirubinProcessed in liver, secreted in bile in small intestineBacteria convert into pigments feces colorSome excreted in urine yellow color

A bit about WBCs:Lifespan = 13-20 days Destroyed in lymphatic systemWhen released from bone marrow called stabs or bandsEsp. neutrophils b/c their nuclei arent lobed, yet, and look like a rod (stab = German for rod) or bandsThe Lymphatic SystemFunctions of Lymphatic System1.) Maintain fluid balance in the tissues30L fluid from capillaries to interstitial and only 27L pass from interstitial back into capillaries qd (every day) If fluid left in the body tissue damage3L fluid enter lymph capillaries, called lymphThen to lymph vessels & return to blood2.) Absorb fats & other substances from digestive tract (chyle)3.) DefenseNodes filter lymph & spleen filters blood of microorganisms & foreign substances

Lymphatic System StructuresLymph Like plasma: ions, nutrients, wastes from interstitial spacesHormones, enzymes from cells in tissuesLymphocytesLymph vesselsFlow of lymph produced by gravity or skeletal muscle, passively drains to lower body from upperValves-no backflowLymphatic trunks drain lymph from larger areas of bodyClusters of lymphatic tissue

Lymphatic System StructuresLymph nodesCollections of lymphatic tissue covered by connective-tissue capsulesEliminate antigens from lymph as lymph flows thru the node.In groups along the larger lymphatic vessels

62Lymph node structure2 divisions: Cortex (outer) & Medulla (inner)CortexHas compartments called lymphatic nodules2 layers: inner layer called germinal center where B-lymphocytes are found. In the wall surrounding the germinal center is where T-lymphocytes are found.Nodules are sepd by trabeculaeextensions of the capsulefibrous covering of the nodeCortical sinus: spaces where lymph flows throughMedullaMedullary sinus = space where lymph flows throught he center of the node, contains macrophagesMedullary cord = contains lymphocytes

Capsule covers.Extension of capsule = trabeculaeReticular fibers, macrophages, and lymphocytes form lymphatic tissueOutside layer: cortexInner layer: medullaCortex & medulla have open spaces called sinuses, lined with phagocytic cells that remove bacteria and other foreign materialEfferent and afferent lymph vessels. Afferent = enter via cortex. Efferent = exit from opposite sideCells of lymph nodes consist of lymphocytes, macrophages and reticular cells. Microorganisms or other foreign substances in the lymph can stimulate lymphocytes throughout the lymph node to undergo cell division with proliferation esp. evident in the lymph nodules of the cortex. Areas of rapid lymphocyte division are germinal centers.Newly produced lymphocytes are released into the lymph and eventually reach the blood stream where they circulate, can enter other lymph tissuesEfferent Blood vessels enter via hilumLymph vessels enter thru various openings in the capsule and exit via hilum64Lymphatic System StructuresTonsilsSwollen cluster of lymphatic tissue in throatForm protective ring of lymphatic tissue around the openings between the nasal and oral cavities & pharynxProvide protection against bac and other harmful materialEventually disappear in adultsSpleenDetects and responds to foreign substances in the bloodDestroys worn out red blood cellsActs as a blood reservoirStructureLeft side of the extreme superior, posterior corner of ab cavityWhite pulp: Contains T & B lymphocytesAssist body with infections that require a large immune responseRed pulp: removes old/damaged RBCs

Lymphatic System StructureThymusDeep to manubriumIn newborn, extends length of thorax & grows until puberty, then decreases in sizeFunctionProduce lymphocytes that move to other lymph tissues, but most degenerate before moving onProduces secretions that mature T-lymphocytesCant destroy normal body cells (Self-tolerance)Immune ResponseImmunity 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 immunityAcquired immunity

Why an immune system?We are outnumbered! Viruses and bacteria are everywhere!Humans offer limitless resources for pathogens EnergyReproductive potentialGetting into the body isnt easy!

Meet the enemyBacteriaFree-livingNot all are bad!Pathogenic ones produce toxins that damage human tissueVirusesObligate parasitesHijack human cells; convert to virus-producers, killing host cell in the process(And fungi, protozoa too)A human fortress: PreventionSkin is thick hard to penetrateProduces 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 trappedStomach acid kills ingested invaders

but we do get sick!Enter through weak points:FoodNoseBreak in skin/scrapesCells 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:Barriers (First line of defense)Generalized defenders (Second line of defense)Specific defenders AND memory (Third line of defense)

Consist of:Several types of cellsProteins

The Complement SystemPart of second line of defenseFree-flowing proteins found in bloodQuickly reach site of invasionReact to antigensWhen activated, canTrigger inflammationAttract eater cells (macrophages)Coat pathogen (make macrophages job easier)Kill intruder directly

PhagocytesFind and eat bacteria, viruses, dead/injured body cells by phagocytosis3 types: NeutrophilsMacrophagesDendritic cells

NeutrophilsOften first to site of infectionNumerousShort lifespanPus in infected wounds chiefly composed of neutrophils

MacrophageBig eatersSlower to respond to invader than neutrophilLarger, longer-lived, more capableHelp alert rest of immune system to invaderStart as monocytes; become macrophages when entering bloodstream

Dendritic cellsEater cells Help with immune system activation act as antigen-presenting cellsFilter bodily fluids to clear foreign organisms and particles

Lymphocytes: Third Line of DefenseT and B cellsOriginate in bone marrowMigrate to lymph nodes, spleen, thymus to matureLymph vessels transport, store lymphocytesFeeds cells into bodyFilter out dead cells/invading organisms

ReceptorsEach lymphatic cell contains surface receptors Recognize foreign antigensSpecialized for a particular antigen

T cellsTwo types: helper and killerT = thymus Mature here

Helper T cellMain regulator of third line of defensePrimary task: activate B cells and killer T cellsActivated by macrophages/dendritic cells (antigen presentation)

Killer T cellAttacks body cells infected by pathogen, cancer cellsReceptors used to determine if each cell encountered is self/non-self (compare to accepted receptors, MHC)

B lymphocyte cellSearches for antigens matching receptorIf a match is foundConnects to antigenTriggering signal set offT helper proteins help fully activate B cellProduces 1000s of clones: differentiate into plasma cells or B memory cells

Plasma CellProduces antibodiesResponds to same antigen matched by B cell receptorSeek out intruders, help destroy themRelease tens of thousands/second

AntibodiesY-shapedAttach to matching antigensEnhance phagocytosis of macrophages (label for capture)Neutralize toxinsIncapacitate viruses (coat surface proteins)Group pathogens by linking (agglutination)

ImmunoglobinsIgG: most common, fight general infections, pass from mom to child in pregnancy (G= moms 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)88Memory cellsProlonged lifespanRemember specific intrudersBoth B and T cells have memory cellsHelps trigger immune system to respond more quickly if invader reappears

InflammationOutcome of acquired immune responseIncreases blood circulation to affected areaBvs dialate to increase blood flowImmune cells go to injured areaImmune resp. takes place at the site its neededTissues = red and warm b/c of the blood that enters the area, in temp = anti-microbialPain from pressure of swollen tissues on nerve endingsNormal functions return when the tissue is fully recoveredImmunization & VaccinationNatural ImmunityNatural: exposed to foreign antigens as a part of everyday life.Active immunity body responds to foreign antigens and develops immunity using B and T lymphocytesPassive immunity Embryological development when antibodies (Igs) from the mothers blood stream are passed to the fetusBreastfeeding baby receives antibodies via milk

Artificial ImmunityActive: Immunization Therapeutic exposure to antigensStimulates the primary response by introducing pathogenic material (inactivated, attenuated, or partial) into the bodyVaccines are typically used for viruses! Antibiotics are only for bacteriaPassive: Antibody TransferPatient receives (via injection) large amounts of antibodies to fight diseaseGlobulin injections can remove certain microorganisms from the body.