Module 2 - Blood and Immunology PDF Fall 2024

HH/KINE 2011 - HUMAN PHYSIOLOGY I FACULTY OF HEALTH KINESIOLOGY AND HEALTH SCIENCE Fall 2024 MODULE 2 – BLOOD & THE IMMUNE SYSTEM Human Physiology: From Cells to Systems, 5th Edition Lauralee Sherwood; Christopher Ward; Chapter 2 Lecture 1: Learni...

HH/KINE 2011 - HUMAN PHYSIOLOGY I FACULTY OF HEALTH KINESIOLOGY AND HEALTH SCIENCE Fall 2024 MODULE 2 – BLOOD & THE IMMUNE SYSTEM Human Physiology: From Cells to Systems, 5th Edition Lauralee Sherwood; Christopher Ward; Chapter 2 Lecture 1: Learning Objectives By the end of today’s lecture, you should be able to: Distinguish between the different components of the blood and their function Learn about the constituents of plasma Understand the function of red blood cells and the importance of hemoglobin Copyright © 2024 Dr. Abdul-Sater The Blood: Introduction Blood represents about 8 percent of total body weight Average volume: 5 liters in women with packed cell volume (hematocrit) of 42% 5.5 liters in men with hematocrit of 45 % Copyright © 2024 Dr. Abdul-Sater The Blood: Introduction Consists of three types of specialized cellular elements suspended in plasma (liquid portion of blood): Erythrocytes: Red blood cells; important in O2 transport Leukocytes: White blood cells; immune system’s mobile defense units Platelets (thrombocytes): Cell fragments; Important in hemostasis Copyright © 2024 Dr. Abdul-Sater The Blood: Introduction Physiological roles: Carrying: (oxygen, nutrients, hormones, metabolic wastes, heat…) Regulation: (body temperature, pH…) Protection: (clotting, immunoglobulins…) Copyright © 2024 Dr. Abdul-Sater  The Blood: PLASMA ❙ TABLE 11-1 Blood Constituents and Their Functions Constituent Functions Plasma Water Acts as a transport medium; carries heat Electrolytes Are important in membrane excitability; distribute fluid by osmosis between ECF and ICF; buffer pH changes Most abundant electrolytes are sodium (Na+) and chloride (Cl-) Nutrients, wastes, gases, hormones Are transported in blood; blood CO2 plays a role in acid–base balance Plasma proteins In general, exert an osmotic effect important in the distribution of the ECF between the vascular and interstitial compartments; buffer pH changes Albumins Transport many substances; contribute most to colloid osmotic pressure Globulins Alpha and beta Transport many water-insoluble substances; include clotting factors and inactive precursor molecules Gamma Are antibodies Fibrinogen Is an inactive precursor for a clot’s fibrin meshwork Cellular elements Copyright © 2024 Dr. Abdul-Sater Water Acts as a transport medium; carries heat The Blood: PLASMA Electrolytes Are important in membrane excitability; distribute fluid by osmosis between ECF and ICF; buffer pH changes Nutrients, wastes, gases, hormones Are transported in blood; blood CO2 plays a role in acid–base balance Plasma proteins In general, exert an osmotic effect important in the distribution of the ECF between the vascular and interstitial compartments; buffer pH changes Albumins Transport many substances; contribute most to colloid osmotic pressure Non-specific Globulins Alpha and beta (𝛂 and β) Transport many water-insoluble substances; include clotting factors and inactive precursor molecules Specific (e.g. cholesterol, iron, complement, etc…) Gamma (𝛄) Are antibodies Fibrinogen Is an inactive precursor for a clot’s fibrin meshwork Cellular elements Stay in the plasma, where Erythrocytes theyO perform Transport and CO (mainlymany 2 O) 2 valuable functions: 2 dispersed as a colloid Leukocytes because of size, do notEngulf Neutrophils diffuse bacteriathrough and debris capillary wall osmotic pressure partially responsible for Eosinophils plasma’s Attack capacity parasitic worms; play a role into buffer allergic reactionschanges in pH all synthesized by the liver Basophils exceptwhich Release histamine, theis important Gamma globulins in allergic (produced reactions, and byclear fat heparin, which helps from the blood lymphocytes) Monocytes Are in transit to become tissue macrophages Lymphocytes Copyright © 2024 Dr. Abdul-Sater The Blood: Erythrocytes Also called red blood cells (RBCs) 5 billion RBCs / 1 ml of blood! (5x106/mm3) shape and content ideally suited to carry out their primary function transporting O2 (H+ and CO2 to a lesser extent) Copyright © 2024 Dr. Abdul-Sater The Blood: Erythrocytes Biconcave discs (like a doughnut with a flattened center instead of a hole) Provides larger surface area for diffusion of O2 across the membrane Thinness of cell enables O2 to diffuse rapidly between the exterior and innermost regions of the cell Great flexibility of the plasma membrane (diameter 8 µm into 3 µm capillaries!! Copyright © 2024 Dr. Abdul-Sater  The Blood: Erythrocytes Presence of Hemoglobin (Hb) Hemoglobin Found only in red blood cells Heme groups: Globin: Pigment containing iron 4 iron-containing Protein composed Appears reddish when oxygenated non-protein groups of 4 highly folded Appears bluish when deoxygenated Each is bound to polypeptide chains one of the (two 𝛂 subunits polypeptides and two β subunits) Each iron atom can bind reversibly to one oxygen (O2) molecule Copyright © 2024 Dr. Abdul-Sater The Blood: Erythrocytes Hemoglobin (Hb) Primary role is to carry O2: Each Hb molecule can transport 4 O2 molecules O2 is poorly soluble in water 98.5% of O2 is carried in the blood bound to Hb A single RBC is stuffed with more than 250 million Hb molecules! So it can carry more than a billion O2 molecules Copyright © 2024 Dr. Abdul-Sater The Blood: Erythrocytes Hemoglobin (Hb): Also combines with Carbon dioxide (CO2) Acidic hydrogen ion portion (H+) of ionized carbonic acid: generated at the tissue level from CO2 (Buffering capacity) Carbon monoxide (CO): not normally in the blood, but if inhaled CO poisoning (binds irreversibly) Nitric oxide (NO2): Vasodilator (In lungs, NO relaxes and dilates the local arterioles O2-rich blood can make its vital rounds; stabilizes blood pressure) Copyright © 2024 Dr. Abdul-Sater The Blood: Erythrocytes Mature erythrocytes contain no nucleus, organelles or ribosomes (Just a lot of Hb; 250 million of them!) Contain key enzymes: Glycolytic enzymes Necessary for generating energy needed to fuel active transport mechanisms involved in maintaining proper ionic concentrations within cell Rely entirely on glycolysis for ATP formation (no mitochondria) Copyright © 2024 Dr. Abdul-Sater The Blood: Erythrocytes Contain key enzymes: Carbonic anhydrase Critical in CO2 transport Catalyzes reaction that ultimately leads to conversion of metabolically produced CO2 into bicarbonate ion (HCO3−) Primary form in which CO2 is transported in blood (in addition to being bound to Hb) Copyright © 2024 Dr. Abdul-Sater Lecture 2: Learning Objectives By the end of today’s lecture, you should be able to: Know how the body maintains a healthy number of erythrocytes Understand what erythropoiesis is Learn the main types of blood antigens Copyright © 2024 Dr. Abdul-Sater  250 million hemoglobin molecules, excluding almost every- renewing enzyme supplies. Equipped only with initial supplies thing else. (That means each RBC can carry more than 1 billion synthesized before they extrude their nucleus and organelles, The Blood: Erythropoiesis O2 molecules.) Red blood cells contain no nucleus or organ- elles. During the cell’s development, these structures are RBCs survive an average of only 120 days, in contrast to nerve and muscle cells, which last a person’s entire life. During its extruded to make room for more hemoglobin (❙ Figure 11-3). short life span of 4 months, each erythrocyte travels about Thus, an RBC is mainly a plasma membrane–enclosed sac full 700 miles as it circulates through the vasculature. No nucleus/organelles RBCs survive an average of only 120 of hemoglobin. As a red blood cell ages, its plasma membrane, which can- not be repaired, becomes fragile and prone to rupture as the cell days (nerve and Enzymes Key Erythrocyte muscle Only cells last a few crucial, a person’s entire life) nonrenew- squeezes through tight spots in the vascular system. Most old able enzymes remain within a mature erythrocyte: glycolytic RBCs meet their final demise in the spleen because this organ’s At a given enzymes time, and carbonicwe have anhydrase. The about 25-30 glycolytic enzymes necessary for generating the energy needed to fuel the active- are trillion RBC travelling in narrow, winding capillary network is a tight fit for these fragile cells. The spleen lies in the upper left part of the abdomen. In our vessels Turn transport mechanisms over involved of 2-3proper in maintaining millionionic cells per second addition to removing most of the old erythrocytes from circula- concentrations within the cell. Ironically, even though erythro- tion, the spleen has a limited ability to store healthy erythro- Spleenthe removes cytes are the vehiclesmost of for transporting old O to allerythrocytes other tissues of 2 body, for energy production erythrocytes themselves can- from circulation cytes in its pulpy interior, is a reservoir for platelets, and con- tains an abundance of lymphocytes, a type of white blood cell. E r y t h r o p o i e s i s Because Nucleus and Remnants of No nucleus erythrocytes cannot divide to organelles organelles or organelles replenish their own numbers, the old ruptured cells must be replaced by new cells produced in an erythrocyte factory—the bone marrow—which is the soft, highly cellular tissue that Pluripotent stem cell Myeloid stem cell Erythroblast Reticulocyte Erythrocyte fills the internal cavities of ❙ Figure 11-3 Major steps in erythrocyte production (erythropoiesis). Erythrocytes are derived in the red bone marrow bones. The bone marrow nor- from pluripotent stem cells that give rise to all the types of blood cells. Myeloid stem cells are partially differentiated cells that mally generates new red blood give rise to erythrocytes and several other types of blood cells. Nucleated erythroblasts are committed to becoming mature cells, a process known as eryth- erythrocytes. These cells extrude their nucleus and organelles, making more room for hemoglobin. Reticulocytes are imma- ropoiesis, at a rate to keep pace ture red blood cells that contain organelle (mostly ribosome) remnants. Mature erythrocytes are released into the abundant with the Copyright demolition of old © 2024 Dr. Abdul-Sater  250 million hemoglobin molecules, excluding almost every- renewing enzyme supplies. Equipped only with initial suppli thing else. (That means each RBC can carry more than 1 billion synthesized before they extrude their nucleus and organelle The Blood: Erythropoiesis O2 molecules.) Red blood cells contain no nucleus or organ- elles. During the cell’s development, these structures are RBCs survive an average of only 120 days, in contrast to nerv and muscle cells, which last a person’s entire life. During i extruded to make room for more hemoglobin (❙ Figure 11-3). short life span of 4 months, each erythrocyte travels abo Thus, an RBC is mainly a plasma membrane–enclosed sac full 700 miles as it circulates through the vasculature. RBCs cannot divide new cells are produced to replenish dying of hemoglobin. As a red blood cell ages, its plasma membrane, which can not be repaired, becomes fragile and prone to rupture as the ce ones. ThisKey is known Erythrocyte as Erythropoiesis: Enzymes Only a few crucial, nonrenew- squeezes through tight spots in the vascular system. Most o able enzymes remain within a mature erythrocyte: glycolytic RBCs meet their final demise in the spleen because this organ Occursenzymes in red bone and carbonic marrow anhydrase. The glycolytic enzymes are narrow, winding capillary network is a tight fit for these fragi necessary for generating the energy needed to fuel the active- cells. The spleen lies in the upper left part of the abdomen. Pluripotent stem cells transport mechanisms inmaintaining involved in red bone marrow differentiate into proper ionic addition to removing most of the old erythrocytes from circul concentrations within the cell. Ironically, even though erythro- tion, the spleen has a limited ability to store healthy erythr the different types cytes are the vehicles of blood for transporting cells, O to all including other tissues 2 of RBCs and WBCs cytes in its pulpy interior, is a reservoir for platelets, and con the body, for energy production erythrocytes themselves can- tains an abundance of lymphocytes, a type of white blood cel E r y t h r o p o i e s i s Becau Nucleus and Remnants of No nucleus erythrocytes cannot divide organelles organelles or organelles replenish their own number the old ruptured cells must b replaced by new cells produce in an erythrocyte factory—th bone marrow—which is th soft, highly cellular tissue th Pluripotent stem cell Myeloid stem cell Erythroblast Reticulocyte Erythrocyte fills the internal cavities ❙ Figure 11-3 Major steps in erythrocyte production (erythropoiesis). Erythrocytes are derived in the red bone marrow bones. The bone marrow no from pluripotent stem cells that give rise to all the types of blood cells. Myeloid stem cells are partially differentiated cells that mally generates new red bloo give rise to erythrocytes and several other types of blood cells. Nucleated erythroblasts are committed to becoming mature cells, a process known as eryth erythrocytes. These cells extrude their nucleus and organelles, making more room for hemoglobin. Reticulocytes are imma- ropoiesis, Copyright ©at a Dr.rate 2024 to keep pa Abdul-Sater The Blood: Erythropoiesis (EPO) Copyright © 2024 Dr. Abdul-Sater The Blood: Blood Types Blood types depend on surface antigens on erythrocytes large, complex molecule that triggers a specific immune response against itself when it gains entry to the body Lymphocytes recognize antigens and produce antibodies against them bind with the specific antigen against which it is produced and leads to the antigen’s destruction by various means Copyright © 2024 Dr. Abdul-Sater  end on The Blood: Blood Types (Most common blood ❙ TABLE 11-2 ABO Blood Types antigen system) Antigens on Blood Type Erythrocytes Antibodies in Plasma specific A A Anti-B dy. For such as B B Anti-A cognize AB A and B No antibodies n anti- oduced O No antigens Both anti-A and anti-B Thus, the Naturally occurring Antibodies against foreign RBC antigens appear in human plasma after 6 months of ageotherwise noted, all content on this page is © Cengage Learning. Unless Copyright © 2024 Dr. Abdul-Sater  erythrocytes. If thefrom hemoglobin freeruptured hemoglo- donor type A blood Antibody to suchindividuals people a type B blood Antigen A such people are fir bin in erythrocytes. the plasmaIfrisesthe free hemoglo- above a Antibody to type B blood foreign Rh a Antigen A critical level, it precipitates in the a bin in the plasma rises above foreign Rh antigen The Blood: Blood Types kidneyscritical and level, it precipitates blocks the urine- kidneys and blocks the urine- in the positive positive blood. sion of Rh-po sion of Rh-positive blood A su forming structures, leading to duce a transfu forming structures, leading to duce a transfusion acute kidney shutdown. acute kidney shutdown. sensitized sensitized Rh-negaRh Transfusion Reaction: e.g. a transfusion Universal Universal Blood Blood DonorsDonorsand and never positive positive never produce ind individua produc antib reaction resulting from type B blood being Recipients Recipients Because type type Because O individu- O individu- Rh factor Rh factor tha that they als haveals no haveAnoorABorantigens, B antigens, theirtheir sess.sess. Therefo Therefore, Rh transfused into a recipient with type A blood erythrocytes erythrocytes are notareattacked not attacked by either by either Redblood Red bloodcells cells from donoragglutinate donor agglutinate from should shouldbe given be g anti-A or anti-B antibodies, anti-A or anti-B antibodies, so they are so they are blood, whereas blood, where Rh considered universal donors. Their can safely receive ei considered universal donors. Their can safely rec blood can be transfused into people of or Rh-positive bloo blood can be transfused into people of any blood type. However, type O indi- or Rh-positive of particular med ies in the recipient’s Donor with any blood type. According to the American type B blood viduals canHowever, receive only type OO type indi- when ofanparticular Rh-negati lead to a sometimes viduals can Recipient receive with only type blood, because the anti-A and Association O of Blood Banking, fol- when ops antibodies an Rh- aga usion reaction (❙ Figure type A blood, anti-Bblood becauseantibodies the anti-Ainand lowing their are the percentages of blood opsofantibodie cytes an Rh-po lutinated clumps of anti-B plasma antibodies in A or attack either their types B anti- in the ABO and Rh blood cytes aofcon carrying, an donor cells can plug plasmagens attackin incoming either A or blood. In B anti- con- in the United States popula- systems erythroblastosis carrying, a trast, type AB individuals gens in incoming blood. In con- are lytic disease o erythrobla d vessels. In addition, calledABuniversal tion: recipients. A1, 34%; A2, 6%; B1, 9%; Because most lethal conse- trast, type individuals are 2%; AB1, 3%; AB2, 1%; O1, B2, lyticthediseama Lacking both anti-A and anti-B destroy many fet called universal recipients. Because th mismatched transfu- antibodies, they can 38%; acceptand O2, 7%. bone marrow c Antigen B Lackingdonor both anti-A blood and of anyanti-Btype, withdestroy the ratema of e kidney failure caused antibodies, they can donate accept Anti-Rh antibodies are pro- boneimmatumarr although they can blood releases se of large amounts of donor onlyblood ofABany ducedRedonly by Rh-negative Antibody to to other people.type, Because blood cells usually with thesucr erythrocytes, from ruptured donor type A blood although they their can donate erythrocytes haveblood both A individuals rupture when (and if) Clumping blocks blood flow and releases eventuallyim e in capillaries s. If the free hemoglo- Antibody to only to and other AB people. B antigens, theirBecause such cells would people are Red first blood exposed cells usually to the erythrocyte ❙ Figure 11-3), he type B blood Antigen A rupture plasma rises above a be attacked ifhave their erythrocytes bothforeign transfused Ainto Rh antigen present in Rh- Clumping blocks blood flow the condition. and eventu (Se individuals with antibodies Hemoglobin precipitates in kidney, in capillaries cal Reasoning on l, it precipitates in the and B antigens, their cells would positive blood. A with interfering subsequent transfu-Oxygen and nutrient flow kidney function ❙ Figure 11- against either of these antigens. discussion of this d blocks the urine- be attacked if transfused into the conditio The terms universalsion donorof Rh-positive blood could pro-to cells and tissues is Except in ex ructures, leading to individuals with antibodies and universal recipient are duce Hemoglobin mis-ainterfering transfusion precipitates reaction ininkidney, such a reduced cal Reasoni cies, it is safest with kidney function y shutdown. againstleading, either of these antigens. however. sensitized In addition to Oxygenreaction ❙ Figure 11-7 Transfusion reaction. A transfusion Rh-negative person. Rh- and nutrient resulting flow Copyright © from2024 Dr. discussion Abdul-Sater cross-match bloo The Blood: Blood Types Rhesus (Rh) Blood Group CDE system: 50 blood-group antigens with 5 primary antigen groups (D, C, E, c, e) Fisher-Race system e.g. someone with the C antigen will NOT have the c one. (Same pattern follows for the other antigens) – remember there are two alleles! There is no d antigen; sometimes ‘d’ is used to denote the absence of the D antigen The D antigen is commonly found in the population and is the most abundant and most antigenic most important Copyright © 2024 Dr. Abdul-Sater The Blood: Blood Types The older terms Rh factor, Rh positive (Rh+) or Rh negative (Rh-), refer to the D antigen People who have the Rh factor have Rh-positive blood (D) People lacking the Rh factor are Rh-negative (d) No naturally occurring antibodies develop against the Rh factor Anti-Rh antibodies are produced only by Rh-negative people if exposed to Rh-positive blood (after blood transfusion or placental exposure during pregnancy) Notion of universal blood donors (O) and recipients (AB) – This could be misleading (remember other blood Ag systems) Copyright © 2024 Dr. Abdul-Sater Lecture 3: Learning Objectives By the end of today’s lecture, you should be able to: Know the five major types of circulating leukocytes Identify the main function of the different immune cells Learn how leukocytes are produced Copyright © 2024 Dr. Abdul-Sater The Blood: Leukocytes White blood cells (WBCs) Mobile units of body’s immune system Made up of leukocytes, their derivatives, and variety of plasma proteins and immune organs Copyright © 2024 Dr. Abdul-Sater The Blood: Leukocytes The immune system recognizes and destroys or neutralizes materials within body that are foreign to “normal self” defends against invading disease-producing microbes (e.g. bacteria & viruses) functions as a “cleanup crew” removes worn-out cells (e.g. aged RBCs) & tissue debris (e.g. ones damaged by trauma or disease) wound healing & tissue repair identifies and destroys cancer cells that arise in the body “seek out and attack” strategy Copyright © 2024 Dr. Abdul-Sater The Blood: Leukocytes Colorless: lack hemoglobin (stained for visualization by microscopy) Vary in structure, function, & number (unlike uniform RBCs; size > RBCs) Five major different types of circulating leukocytes: Neutrophils Leukocytes Polymorphonuclear granulocytes Mononuclear agranulocytes Eosinophils Neutrophil Eosinophil Basophil Monocyte Lymphocyte Erythrocyte Platelets Basophils Monocytes Lymphocytes 60%–70% 1%–4% 0.25%–0.5% 2%–6% 25%–33% Erythrocyte concentration Platelet concentration = 5 billion/ = 250 million/ Differential WBC count (percentage distribution of types of leukocytes) mL blood mL blood Leukocyte concentration = 7 million/mL blood RBC count Platelet count = 5,000,000/mm3 = 250,000/mm3 WBC count = 7000/mm 3 Copyright © Garland Science 2015 ❙ Figure 11-8 Normal blood cellular elements and typical human blood cell count. There are other important immune cells that don’t primarily circulate Cell types: Courtesy and copyright of the Clinical Chemistry and Hematology Laboratory, Wadsworth Center, NY State Department of Health (http://www.wadsworth.org); platelets: © Peter Arnold, Inc./Alamy in the blood viously cannot engulf a larger parasitic worm, but they do moral, immunity. An antibody binds with and marks for de- attach to the worm and secrete substances that kill it. struction (by phagocytosis or other means)Copyright © 2024 Dr. Abdul-Sater the specific kinds The Blood: Granulocytes Polymorphonuclear (meaning “many-shaped nucleus” PMNs) granulocytes (meaning “granule-containing cells”) Neutrophils: phagocytic specialists engulf and destroy bacteria intracellularly Release web of extracellular fibers called neutrophil extracellular traps (NETs) that contain bacteria-killing chemicals Copyright © Garland Science 2015 Copyright © 2024 Dr. Abdul-Sater The Blood: Granulocytes Polymorphonuclear granulocytes Eosinophils Killing of antibody coated parasites through release of granule contents Copyright © Garland Science 2015 Increase in circulating eosinophils (eosinophilia) is associated with: Allergic conditions such as asthma and hay fever Internal parasite infestations, such as worms Attach to worm and secrete substances to kill it Copyright © 2024 Dr. Abdul-Sater The Blood: Granulocytes Polymorphonuclear granulocytes Basophils Chemotactic factor production Least numerous and most poorly Copyright © Garland Science 2015 understood of the leukocytes (controlling immune responses to parasites) Synthesize and store Histamine: release is important in allergic reactions Heparin: speeds up removal of fat particles from blood after fatty meal Copyright © 2024 Dr. Abdul-Sater The Blood: Mononuclear Cells Mononuclear (“single nucleus”) agranulocytes (“cells lacking granules”) Monocytes Phagocytosis, antigen presentation, cytokine production and cytotoxicity Copyright © Garland Science 2015 Emerge from bone marrow while still immature; circulate for 1-2 days; settle down in various tissues Mature and enlarge in resident tissue macrophages Life span can range from several months to years dies sooner while performing phagocytosis can ingest only a limited amount of foreign material before it succumbs Copyright © 2024 Dr. Abdul-Sater The Blood: Mononuclear Cells Tissue resident Macrophages (macro means “large”; phage means “eater”) first to sense invading microorganisms secrete cytokines/chemokines recruit neutrophils and other leukocytes Copyright © Garland Science 2015 Copyright © 2024 Dr. Abdul-Sater The Blood: Mononuclear Cells Mononuclear agranulocytes Lymphocytes; Two types: 1. Large granular lymphocytes Natural Killer (NK) cells Effector cells of the innate immune response Extremely effective against virally infected cells Release lytic granules to kill infected cells Produce cytokines to limit viral replication Copyright © Garland Science 2015 Copyright © 2024 Dr. Abdul-Sater The Blood: Lymphocytes Lymphocytes; Two types: 1. Small lymphocytes of adaptive immune response Cytokine production, antigen recognition, antibody production, memory, cytotoxicity Two types of lymphocytes: B Lymphocytes: humoral immunity Produce antibodies (as a plasma cell) Responsible to antibody-mediated immunity Copyright © Garland Science 2015 Copyright © 2024 Dr. Abdul-Sater The Blood: Lymphocytes T Lymphocytes: cell-mediated immunity Do not produce antibodies Directly destroy specific target cells by releasing chemicals that punch holes in the victim cell Target cells include body cells invaded by viruses and cancer cells Copyright © Garland Science 2015 Copyright © 2024 Dr. Abdul-Sater The Blood: Leukocyte Production All blood cells ultimately originate from same undifferentiated pluripotent hematopoietic stem cells in red bone marrow Granulocytes and monocytes are produced only in bone marrow Copyright © 2024 Dr. Abdul-Sater The Blood: Leukocyte Production Most new lymphocytes are actually produced (via cell division) by lymphocytes already in lymphoid tissues such as lymph nodes, spleen and tonsils Total number of white cells and percentage of each type may vary considerably to meet changing defense needs Copyright © 2024 Dr. Abdul-Sater The Immune System Body Defenses Lecture 4: Learning Objectives By the end of today’s lecture, you should be able to: Be introduced to the immune system Understand the internal and external body defenses Learn the functions of lymphoid tissues Distinguish between innate and adaptive immunity Copyright © 2014 Dr. Abdul-Sater Immunity: Introduction Immunity is the body’s ability to protect itself by resisting or eliminating potentially harmful foreign invaders (e.g. bacteria and viruses) or abnormal cells (e.g. cancer cells) i.e. foreign to the “normal self” Immune system activities: Defends against invading pathogens Removes “worn-out” cells and tissue damaged by trauma Identifies and destroys abnormal or mutant cells that have originated in the body immune surveillance Mounts inappropriate immune responses that lead either to allergies or to autoimmune diseases Copyright © 2024 Dr. Abdul-Sater Immunity: Pathogenic Microbes Bacteria Non-nucleated, single-celled microorganisms Primarily cause tissue damage and cause disease by releasing enzymes or toxins e.g. Chlamydia, Streptococcus, E. coli, Salmonella Viruses Consists of either DNA or RNA enclosed by a protein coat Cannot carry out metabolism or reproduce without invading a host cell (non-self sustaining entities) e.g. SARS-CoV-2, HIV, HCV, Influenza, Ebola, Polio Copyright © 2024 Dr. Abdul-Sater  Immunity: Pathogenic Microbes Fungi e.g. Aspergillus, Candida Protozoan parasites (e.g. plasmodium malaria) Helminth parasites (worms) Notion of virulence The inherent ability of a pathogen to cause disease Copyright © 2024 Dr. Abdul-Sater Immunity: External Defenses Copyright © 2024 Dr. Abdul-Sater Immunity: Internal Defenses Lymphoid Tissue: Tissues that produce, store, or process lymphocytes, including Bone marrow Thymus Lymph nodes Spleen Tonsils Adenoids Appendix Peyer’s patches or gut-associated lymphoid tissue (GALT) Strategically located to intercept invading microorganisms before they have a chance to spread very far Copyright © 2024 Dr. Abdul-Sater exposure to it. Such responses ening agents. Two categories of provide a first line of internal ❙ Figure 12-1 Lymphoid tissues. patterns call forth the innate Immunity: Functions of Lymphoid Tissues ❙ TABLE 12-1 Functions of Lymphoid Tissues Lymphoid Tissue Functions Bone marrow Origin of all blood cells Site of maturational processing for B lymphocytes Lymph nodes, tonsils, adenoids, Exchange lymphocytes with the lymph (remove, store, produce, and add them) appendix, gut-associated Resident lymphocytes produce antibodies and activated T cells, which are released into the lymph lymphoid tissue (GALT) Resident macrophages remove microbes and other particulate debris from the lymph Spleen Exchanges lymphocytes with the blood (removes, stores, produces, and adds them) Resident lymphocytes produce antibodies and activated T cells, which are released into the blood Resident macrophages remove microbes and other particulate debris, most notably worn-out red blood cells, from the blood Stores a small percentage of red blood cells, which can be added to the blood by splenic contraction as needed Thymus Site of maturational processing for T lymphocytes Secretes the hormone thymosin 406 CHAPTER 12 Unless otherwise noted, all content on this page is © Cengage Learning. Copyright © 2024 Dr. Abdul-Sater Immunity: Immune Responses Two immune responses: Innate and Adaptive Innate responses that nonselectively defend against foreign material First line of defense, “non-specific”, rapid but limited response Defenses include the following: Inflammation Interferons (anti-viral) Natural killer cells (NK) Complement system Dendritic cells Copyright © 2024 Dr. Abdul-Sater Immunity: Immune Responses Two immune responses: Innate and Adaptive Adaptive responses that selectively target particular invaders Antibody-mediated immunity (Humoral) involves production of antibodies by plasma cells (B-lymphocyte derivatives) Cell-mediated immunity involves production of activated T lymphocytes directly attack unwanted cells Copyright © 2024 Dr. Abdul-Sater Lecture 5: Learning Objectives By the end of today’s lecture, you should be able to: Understand the concept and importance of inflammation Identify the function of cytokines, the complement system and dendritic cells Copyright © 2024 Dr. Abdul-Sater  Immunity: Innate vs. Adaptive Immunity Innate Adaptive Response Response Immune Response 1 2 3 4 5 6 7 8 9 10 Days Copyright © 2024 Dr. Abdul-Sater Immunity: Innate Immunity Inflammation: Innate, nonspecific response to tissue injury Recruitment of phagocytes to invaded or injured area Isolate, destroy, or inactivate the invaders Remove debris Prepare for subsequent healing and repair Copyright © 2024 Dr. Abdul-Sater Immunity: Innate Immunity Inflammation: Inflammatory response is similar no matter what the triggering event (Pathogens or sterile) Initiated by resident tissue macrophages release cytokines and chemokines Mast cells are activated release histamine Localized vasodilation Increased capillary permeability Localized edema Walling-off the inflamed area Copyright © 2024 Dr. Abdul-Sater Immunity: Innate Immunity Inflammation: Inflammatory response is similar no matter what the triggering event (Pathogens or sterile) Emigration (recruitment) of leukocytes = neutrophils and monocytes Leukocyte proliferation Marking of bacteria for destruction by opsonins (complement) Leukocytic destruction of bacteria Copyright © 2024 Dr. Abdul-Sater Immunity: Innate Immunity Cytokines: Kill microbes directly Several chemicals (i.e., interleukin (IL)- 1 and 6, TNF) bring about a diverse array of effects EP (endogenous pyrogen) induces fever in the body Decrease plasma concentration of iron Stimulate release of acute phase proteins (e.g. CRP) Trigger clotting and anticlotting systems Copyright © 2024 Dr. Abdul-Sater Immunity: Innate Immunity Ultimate goal Tissue Repair: Cell division replaces lost cells with same kind of cells In non-regenerative tissue (nerve and muscle) Lost cells are replaced with scar tissue Prolonged, unwanted, chronic inflammation: Alzheimer’s disease, atherosclerosis, asthma, diabetes, cancer! NSAIDs, glucocorticoids Interferons: Antiviral effects (indirect) limit viral spread Copyright © 2024 Dr. Abdul-Sater Immunity: Innate Immunity The Complement System: Nonspecific response Composed of plasma proteins that are produced by the liver and circulate in inactive form Three mechanisms of activation: Copyright © Garland Science 2015 1. Spontaneous activation on microbial surfaces 2. Binding to carbohydrate chains present on surfaces of microorganisms but not on human cells 3. Activation by antibody binding to antigens on pathogens Causes destruction of pathogen by two mechanisms: 1. Forms membrane attack complexes (MAC) that punch holes in the pathogen 2. Enhances the uptake of the pathogen by phagocytes (opsonization) Copyright © 2024 Dr. Abdul-Sater Dendritic Cell (DC) Tissue resident cells with a unique star-shaped morphology Immature DC in tissue have very high ability to internalize particles (macropinocytosis) Professional APC Encounter with pathogen causes maturation of DC Mature DC Copyright © 2024 Dr. Abdul-Sater Immunity: From Innate to Adaptive Immunity Copyright © 2024 Dr. Abdul-Sater Lecture 6: Learning Objectives By the end of today’s lecture, you should be able to: Explain the basic functions and structure of antibodies Understand the theory of clonal selection Distinguish between the two major types of T cells Explain how cytotoxic T cells kill their target cells Copyright © 2024 Dr. Abdul-Sater Immunity: Adaptive Immunity Two classes of adaptive immunity: Antibody-mediated or humoral immunity Involves production of antibodies by B lymphocyte derivatives known as plasma cells Cell-mediated immunity Involves production of activated T lymphocytes Directly attack unwanted cells Antigen: Large, foreign, unique complex molecule Induces (elicits) an immune response against itself In general, the more complex a molecule is, the greater its antigenicity Mostly protein in nature Copyright © 2024 Dr. Abdul-Sater Immunity: Adaptive Immunity Specificity Billions of lymphocytes recognizing different antigens Lymphocytes with receptors that recognize the specific Ag will proliferate (clonal expansion or clonal selection) The adaptive immune system acquires immunological memory towards foreign Ag acquired or protective immunity Clonal Selection Theory Copyright © 2024 Dr. Abdul-Sater Immunity: B Lymphocytes Secreted antibodies mediators of humoral immunity Membrane bound on B cell surface function as antigen receptors Initiate B cell activation proliferation and differentiation of antigen-specific B cells plasma cells secretion of soluble form of the antibody (same specificity as the mb bound) Copyright © 2024 Dr. Abdul-Sater Immunity: Antibodies Basic Functions Binding antigens Activate complement system Neutralization: Binding and neutralizing bacterial toxins Inhibiting bacterial access to host cells Inhibiting viral entry into host cells Enhancing phagocytosis of pathogens (opsonization) Copyright © 2024 Dr. Abdul-Sater Immunity: T Lymphocytes Carry out cell-mediated immunity Do not secrete antibodies; directly bind to targets Killer T cells release chemicals that destroy targeted cells Clonal and antigen specific; acquire receptors/mature in the thymus T cells are activated for foreign attack only when the attack is on the surface of a cell that carries foreign antigens presented on self-antigens Copyright © 2024 Dr. Abdul-Sater Immunity: T cells and its Targets T-cell receptor (antigen receptor) peptide fragments (antigen) bound to self proteins called Major Histocompatibility Complex (MHC) displayed on surface of APCs Copyright © 2024 Dr. Abdul-Sater Immunity: Two types of T Cells CD4 cells (mostly helper T cells: Th) Modulate activities of other immune cells and secrete chemicals that amplify the activity of other immune cells Copyright © 2024 Dr. Abdul-Sater Immunity: Two types of T Cells CD8 cells (cytotoxic, or killer T cells: Tc) Destroy host cells harboring anything foreign (viral infected cell; cancer cell) Bind to the viral antigen and self-antigen on the surface of the infected cell May kill cell directly or through enzymes that cause the cell to self-destruct Copyright © 2024 Dr. Abdul-Sater