Chapter 9 Respiratory System PDF

1 ANATOMY PHYSIOLOGY Respiratory System BHS407 Dec-24  LEARNING OUTCOMES At the end of the lessons, student will be able to: Understand the anatomy of the respiratory system Understand the function of the respiratory...

1 ANATOMY PHYSIOLOGY Respiratory System BHS407 Dec-24  LEARNING OUTCOMES At the end of the lessons, student will be able to: Understand the anatomy of the respiratory system Understand the function of the respiratory system Understand the process of gas exchange and gas transport Understand the regulation of respiration Dec-24 BHS407 2  * urti-upper respiratory tract infections The structures of the respiratory system can be divided into the upper respiratory tract and the lower respiratory tract. The upper respiratory tract refers to the nose, pharynx, nasal cavity and paranasal sinuses. The lower respiratory tract includes the larynx, trachea, bronchi, bronchioles and alveoli. Dec-24 BHS407 3  the to transport air ↑ The respiratory system can also be separated into a conducting zone and a respiratory zone. The conducting zone refers to structures that transport air but play no role in gas exchange. It includes: nasal cavity, nasopharynx, oropharynx, laryngopharynx, larynx, trachea, bronchi, and all bronchioles except for respiratory bronchioles. These structures are involved in transporting, filtering, humidifying, and warming air. tiny hair in nose = filter Dec-24 BHS407 4  The respiratory zone refers to structures where exchange of O2 and CO2 occurs. Sites of gas exchange are known as alveoli (single alveolus). All respiratory zone structures contain alveoli alveoli and include: respiratory - -respiratory bronchioles bronchioles, alveolar ducts, and - alveolar ducts alveolar sacs. - alveolar 9 acS Dec-24 BHS407 5  nasal's opening two lobes three lobes ↑ location of most important muscle heart BHS407 6 Dec-24  The Respiratory System: An Introduction Functions of the respiratory system Gas exchange between air and circulating blood Moving air from the exchange surface of the lungs Protection of respiratory surfaces Production of sound t superior part of has al aed Provision for olfactory sensations - cavity Dec-24 BHS407 7  Respiratory Mucosa #Maraa Respiratory epithelium (Columnar and B Shape not standardized pseudostratified) and underlying connective tissue Respiratory membrane, supported by Irose connective Tissue lamina propria, changes along tract Lines conducting portion of respiratory tract Protected from contamination by respiratory defense system *this with present of cilia-mucus > - lines -> helps protection layer (dust stuck in mucus Dec-24 BHS407 8  Nasal Cavity nasal carity left and night of separate > - Nasal septum = divider between nasal cavity Hard palate = floor for nasal cavity ; separate 2. - between nasal cavity and mouth cavity - Bony ridges called conchae = increase surface area ↳ of nasal cavity and cause air to churn ad a fulang yang terkelnar sikit * Baby takde gang - hard palate sumbing Dec-24 BHS407 9  Paranasal sinus open into nasal cavity and line with mucous membrane Nasolacrimal ducts = eyes to nasal cavity Olfactory receptor at superior part of nasal cavity Cavity is lining with stratified squamous epithelium tissue with coarse hair = trap dust or large particles in the air - ↓ Near to pharynx, cavity lining by pseudostratified columnar associated with goblet cells produces e Sneeze reflex stratified to column an Dec-24 BHS407 10  sinus = chamber located between bone 11 within maxillae bone within sphenoid bone BHS407 Dec-24  The pharynx Shared by the digestive and respiratory systems Divided into three sections: – Nasopharynx (pseudostratified columnar) – superior portion ; enclose by uvulva during > - > swallowing tekak anak same level as – Oropharynx (Stratified squamous) – navity continuous with the oral cavity or a Sebelah – Laryngopharynx – from tip of epiglottis until esophagus - ↳ actas door laryax to close (voice box) the pharynx Dec-24 BHS407 12  - Dec-24 BHS407 13  The Larynx (voicebox ( Air passes through the glottis on the way to the lungs (C4 – C6) Larynx protects the glottis (pathway ( D9 Cartilages of the larynx Three large cartilages 3 – Thyroid, cricoid, and epiglottis Paired cartilages 6 – Cuneiform, Corniculate and Arytenoids – Arytenoids : change the position and tension of vocal cords Dec-24 BHS407 14  & containst elasiare hyaline cartilage ↳.I a ord BHS407 15 Dec-24  Vocal cord Primary source of voice production Two pairs of ligament at thyroid cartilage extended posteriorly to arytenoid cartilage Superior ligament – vestibular fold (false vocal cord) Inferior ligament – true vocal cord Control by posterior and lateral cricoarytenoid muscle Dec-24 BHS407 16  Moving air pass through vocal cord cause them to vibrate and produce sound Male has thick and long vocal fold (influence by testosterone) – Vibrate more slowly and produce low pitch voice The articulators (tongue, palate, cheek and lips) – Control laryngeal airflow to strengthen it or weaken it as a sound source. – https://www.youtube.com/watch?v=JF8rlKu SoFM Dec-24 BHS407 17  >Anythenoid relate cartage - Aadapaksaan angin keluar , diaakanatte - Dec-24 BHS407 18  The laryngeal musculature Muscles of the neck and pharynx position and stabilize the larynx When swallowing, these muscles elevate the larynx large Cartilage Bend the epiglottis over the glottis Intrinsic muscles control tension on the vocal folds and open the glottis Dec-24 BHS407 19 20 BHS407 Dec-24  Trachea Inferior to cricoid cartilage large cartilage - Extends from the larynx to the mediastinum Divide into left and right primary bronchi at 5th Thoracic vertebra Lined by pseudostratified epithelium associated with goblet cells - mucus secretion – due to its abundant seromucous glands. mucus banyak-seromucous glands mucus sikit-goblet cells Dec-24 BHS407 21  16 – 20 C shape of hyaline cartilage Prevents air passage from collapsed Strengthen by ligament Posterior wall of trachea has no cartilage - connective tissue and smooth muscle Contract during cough Provides the esophagus with room to expand when a large bolus of food is swallowed Dec-24 BHS407 22 BHS407 23 Dec-24  Anterior to esophagus The last tracheal cartilage is expanded and contains a sensitive posterior projection known as the carina. – The mucous membrane in the carina is the most sensitive than the larynx and trachea – Trigger cough reflex The right primary bronchus is more vertical, shorter and broader than the left Dec-24 BHS407 24  wider more more horizontal more , Vertical Shorter less Article Dec-24 25 BHS407  Bronchi The trachea divides into 2 main bronchi. The right main bronchus is wider, shorter, and more vertical than the left. – More likely to be obstructed by a foreign object. Air reaching the bronchi has been significantly filtered, warmed, and humidified. – Line by pseudostratified columnar epithelium and supported by C shape cartilage Dec-24 BHS407 26  The bronchial tree Each main bronchus divides into lobar bronchi (secondary bronchi). There are 3 lobar bronchi on the right (one for each of the 3 lobes of the right lung) and 2 lobar bronchi on the left (one for each of the 2 lobes of the left lung). Dec-24 BHS407 27  Lobar bronchi divide to yield segmental bronchi (tertiary bronchi) that divide to yield smaller and smaller bronchi until about 23 branchings have occurred. Tertiary bronchi supply air to a single bronchopulmonary segment Once the passageways have a diameter first – A thin layer of fluid - layer – Alveolar epithelium (SSQ) – Basement membrane – Intersitial space – Basement membrane of capillary endothelium – Capillary endothelium (SSQ) Dec-24 BHS407 35  Dec-24 BHS407 36  Cells of the respiratory membrane include compose ~ the wall of kalantakde Alveoli will & Alveolar cell (Pneumocyte 1) alveolar collapse & Line the alveolar surface repeat ~ Septal & cells (Pneumocyte 2) Palar takde reduce Secrete D langs surfactant – lipid-rich fall will water material to reduce surface tension surface tension Scattered randomly in the respiratory membrane Alveolar Macrophage – dust cell Engulf foreign particles BHS407 37 - respiratory distress single Dec-24 BHS407 38 Dec-24  The pleural cavities and pleural membranes Each lung is covered by one pleura Pleura – serous membranes lining the pleural cavity – Parietal - attaches to the walls of the pleural cavity – Visceral - adheres to the surface of the lungs Pleural fluid – fills and lubricates the space between the pleura ↳ reduce friction parietal visceral Dec-24 BHS407 39 * intrapleural-between  angie to prevent + 50 , I lungs ↑ apse Pt than outer P4 - Lp in body lesser than / nav I to prevent lungs to BHS407 40 totally Collapse Dec-24  Pressure changes during inhalation and exhalation The relationship between intrapulmonary pressure and atmospheric pressure determines the direction of airflow Intrapleural pressure maintains pull on the lungs – Pressure in the space between parietal and visceral pleura – Must always lower than alveolar pressure (prevents alveolar from collapsing) Dec-24 BHS407 41  Dec-24 42 BHS407  Pulmonary Ventilation Inspiration The physical movement of air into and out of the lungs Movement of air depends upon Boyle’s Law - Pressure and volume inverse relationship Volume depends on the movement of the diaphragm and ribs Pressure and airflow to the lungs VIPt Dec-24 BHS407 43  Pulmonary Ventilation Expiration Inspiration External intercostal External intercostal relaxed contract Rib cage move Rib cage move downwards upwards Diaphragm elevated Diaphragm move and curved upwards inferiorly (flattened) Thoracic volume Thoracic volume Pt decrease increase Air flows out from the Air flows into the lungs Pt-pt lungs from Dec-24 44 BHS407  Po more to Pt Dec-24 BHS407 45  Respiration is associated with 4 processes: 1. Pulmonary ventilation is the movement of air into/out of the lungs 2. External respiration is the movement of O2 from the lungs to the blood and CO2 from the blood to the lungs. 3. Gas transport refers to the mechanisms by which O2 and CO2 are moved through the blood. 4. Internal respiration is the movement of O2 from the blood to the cell interior and CO2 from the cell interior to the blood. Dec-24 BHS407 46  ↑P > - Ph GAS LAWS IN RESPIRATION eg Pienvironment = 50 % = Pinfinid 50 % kep adae an autung k & its equivalent bary e berMatt a ↓  Dalton law and partial pressure Individual gases in a mixture exert pressure proportional to their abundance Diffusion between liquid and gases (Henry’s law) The amount of gas in solution is directly proportional to their partial pressure Dec-24 BHS407 47 48 750mmtg normal calculation down to the sea PpT Ost 20 84. x 700 = 158 4. ↓ , in BHS407 Pt Dec-24 004x760 03 3 = 0  Gas Exchange Gas exchange across the respiratory membrane is efficient due to: the higher of partial pressure, Differences in partial pressure the efficient Small diffusion distance diffusion process Soluble gases Large surface area of all alveoli small Alveoli - Coordination of blood flow and airflow Gas Exchange and Partial Pressures, Animation Dec-24 BHS407 49  drop Pair = Pfiuid Sbb dan ben er, Man Sbbdanse sendcorting CO 02 pH ↓ > trigger - chemoreceptor Dec-24 BHS407 50 51 External respiration BHS407 Dec-24 52 Internal respiration occur tissue at Pt P4 BHS407 Dec-24  Oxygen transport  Carried mainly by RBCs, bound to haemoglobin  The amount of oxygen haemoglobin can carried is dependent upon: PO2 ↑ hemoglobin bind > - v PCO2 to bind with haemoglobin on pH&- reduce capability be released - Temperature ↑ easy for Of to - Structure lath Fetal ( hemoglobinC has a higher O2 affinity than adult hemoglobin CO (Carbon Monoxide) Oxygen Hemoglobin Dissociation Curve | Oxygen transport | Gas Exchange | Respiratory Physiology - YouTube Dec-24 BHS407 53  thePt the higher the affinity towards O2 54 more acidic , higher p(senange 02 BHS407 Dec-24 55 affinitytowards o -higher BOMR's effect BHS407 Dec-24  Carbon dioxide transport 7% dissolved in plasma 70% carried as carbonic acid in plasma buffer system 23% bound to hemoglobin Carbaminohemoglobin How Red Blood Cell Carry Oxygen and Carbon Dioxide, Animation Dec-24 BHS407 56 57 BHS407 Dec-24  Summary of gas transport Driven by differences in partial pressure Oxygen enters blood at lungs and leaves at tissues Carbon dioxide enters at tissues and leaves at lungs Dec-24 BHS407 58  breathing ratet CO2 * Respiratory centers of Carbanic Acid + the brain P chemoreceptor Medullary centers Respiratory rhythmicity centers set the pace Dorsal Respiratory Group (DRG) Ventral Respiratory Group (VRG) Pons Apneustic and pneumotaxic centers Dec-24 BHS407 59  adhibitary & enter promote DRG - Group promote exhalation borsal - promote inhalation promotration more - contract upwards Dec-24 BHS407 60  Respiratory reflexes Respiratory centers are modified by sensory information including Chemoreceptor reflexes Level of carbon dioxide > - form carsonic Heid Baroreceptors reflexes I stretch receptors ) inhale lung stretch-lung Hering-Breuer reflexes - aftets Protective reflexes - some pathogen residently Sneeze and cough reflex enter trigger coughing , reflex -activate pneumotaxie Dec-24. BHS407 61 center stop mualeb exhale -  62 - something can control hyperventilate - Anxiety person fast breathing - BHS407 Dec-24 Control diaphragm (  change PM moredic - promote Apneustic center Dec-24 BHS407 63  r trigger sneezing and coughing Dec-24 BHS407 64 - stop breathing temporary 65 Voluntary control of respiration Conscious thought can affect the respiratory rate by stimulating centres in the hypothalamus Emotional states (limbic system) can affect respiratory rate by stimulating the sympathetic or parasympathetic nervous system Control of Ventilation, Animation BHS407 Dec-24 66 detected when as cost promoteation pendentilati BHS407 Dec-24  Respiratory capacity 67 110m/ tak paksa 125ml paksa maximumly paksa BHS407 Dec-24  Aging and the Respiratory System The efficiency of the respiratory system decreases with age as: Elastic tissue deteriorates causing lower lung compliance and vital capacity Chest movements are restricted by arthritic changes Some degree of emphysema normally occurs Dec-24 BHS407 68  amphesyma Dec-24 BHS407 69  banyaa ung's al inalveda decrease D-tissue already scarring SoB lungkeras Dec-24 BHS407 70 71 Who said smoking is COOL?? BHS407 Dec-24 72 BHS407 Dec-24 LYMPHATIC SYSTEM DR FARRAH SHAFEERA @ ANN IBRAHIM annshafeera@FSK UiTM'09 1 annshafeera@FSK UiTM'09 2 annshafeera@FSK UiTM'09 3  Immunity or Resistance n Ability to ward off damage or disease through our defenses n 2 types of immunity n Innate or nonspecific immunity – present at birth n No specific recognition of invaders, no memory component n 1st and 2nd line of defenses n Adaptive or specific immunity n Specific recognition of invaders with a memory component 4  Lymphatic system structure and function n Consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue, red bone marrow n Functions of the lymphatic system 1. Drain excess interstitial fluid 2. Transport dietary lipid 3. Carry our immune responses 5 Components of the Lymphatic System annshafeera@FSK UiTM'09 6  Lymphatic vessels and lymph circulation n Vesselsbegin as lymphatic capillaries n Closed at one end n Uniteto form large lymphatic vessels n Resemble veins in structure but thinner walls and more valves n Passes through lymph nodes n Encapsulated organs with masses and B and T cells 7  Lymphatic capillaries n Slightly large diameter than blood capillaries n Unique one-way structure n Permits interstitial fluid to flow in but not out n Anchoring filaments pull openings wider when interstitial fluid accumulates 8 Lymphatic Capillaries 9  Lymph trunks and ducts n Vessels unite to form lymph trunks n Principal trunks are the lumbar, intestinal, bronchomediastinal, subclavian and jugular n Passes from lymph trunks into 2 main channels (thoracic and right lymphatic ducts) before draining into venous blood 10 annshafeera@FSK UiTM'09 11 Routes for drainage of lymph annshafeera@FSK UiTM'09 12  Formation and flow of lymph n More fluid filters out of blood capillaries than returns to them by reabsorption n Excess filtered fluid – about 3L/day – drains into lymphatic vessels and become lymph n Important function of lymphatic vessels to return lost plasma proteins to blood stream n Contain valves n Same 2 “pumps” aiding venous return also used n Skeletal muscle pump – milking action n Respiratory pump – pressure changes during breathing 13  Relationship of the Lymphatic System to the Cardiovascular System 14  1. Lymphoid Cells n Lymphocytes are the main cells involved in the immune response n Two main varieties (protect fr antigen) n T cells n B cells 15  Lymphocytes n T cells and B cells protect the body against antigens n Antigen – anything the body perceives as foreign n Bacteria and their toxins; viruses n cancer cells 16  Lymphocytes n T cells n Manage the immune response n Attack and destroy foreign cells n B cells n Produce plasma cells, which secrete antibodies n Antibodies immobilize antigens 17  Other Lymphoid Cells n Macrophages – phagocytize foreign substances and help activate T cells n Dendritic cells – spiny-looking cells with functions similar to macrophages(capture antigen&bring them back to the lymph nodes) n Reticular cells – fibroblast–like cells that produce a stroma, or network, that supports other cell types in lymphoid organs 18  Lymphatic tissues and organs n 2 groups based on function 1. Primary lymphatic organs n Sites where stem cells divide and become immunocompetent (to produce a normal immune reponse) n Red bone marrow and thymus 2. Secondary lymphatic organs n Sites where most immune response occurs n Lymph nodes, spleen, lymphatic nodules 19 Lymphoid Organs annshafeera@FSK UiTM'09 20 Figure 20.5  1. Thymus Internal Anatomy n Thymic lobes contain an outer cortex and inner medulla n Cortex contains densely packed lymphocytes and scattered macrophages n Medulla contains fewer lymphocytes and thymic (Hassall’s) corpuscles 21 n The thymus differs from other lymphoid organs in important ways n It functions strictly in T lymphocyte maturation n It does not directly fight antigens n The stroma of the thymus consists of star-shaped epithelial cells (not reticular fibers) n These thymocytes secrete the hormones that stimulate lymphocytes to become immunocompetent 22 n Thymus n Outer cortex composed of large number of T cells n Immature T cells migrate here from red bone marrow where they proliferate and begin to mature n Dendritic cells derived from monocytes assist in T cell maturation n Specialized epithelial cells help educate T cells through positive selection – only about 25% survive n Macrophages clear out dead and dying cells n Medulla n More mature T cells migrate here from cortex n More epithelial cells, dendritic cells and macrophages n Thymus shrinks with age from 70g in infants to 3g in old age 23 24  2. Lymph nodes n Located along lymphatic vessels n Scattered throughout body n Stroma – supporting connective tissue n Capsule, trabeculae, reticular fibers and fibroblasts n Parenchyma – functional part n Outer cortex – aggregates of B cells called lymphatic nodules (follicles) – site of plasma cell and memory B cell formation n Inner cortex – mainly T cells and dendritic cells n Medulla – B cells, antibody producing plasma cells from cortex, and macrophages 25  annshafeera@FSK UiTM'09 26 Structure of a Lymph Node  Lymph n Lymph flows through a node in 1 direction only n Enters through afferent lymphatic vessels n Directs lymph inward n Lymph enters sinuses (irregular channels) n Into medulla n Medullary sinuses drain into efferent lymphatic vessels n Conveys lymph, antibodies and activated T cells out of the node n Lymph nodes function as a filter n Foreign substances trapped n Destroyed by macrophages or immune response of lymphocytes 27 n Two basic functions: a) Filtration – macrophages destroy microorganisms and debris b) Immune system activation – monitor for antigens and mount an attack against them 28  Structure of a Lymph Node n Nodes are bean shaped and surrounded by a fibrous capsule n Trabeculae extended inward from the capsule and divide the node into compartments n Nodes have two histologically distinct regions: a cortex and a medulla 29 Figure 20.4a  Structure of a Lymph Node n Cortex contains follicles with germinal centers, heavy with dividing B cells n Dendritic cells nearly encapsulate the follicles n Deep cortex houses T cells in transit n T cells circulate continuously among the blood, lymph nodes, and lymphatic stream 30  3. Spleen n Largest single mass of lymphatic tissue in the body n Stroma – capsule, trabeculae, reticular fibers, and fibroblasts n Parenchyma n White pulp – lymphatic tissue (lymphocytes and macrophages) n B cells and T cells carry out immune function n Red pulp 31 n Redpulp – blood-filled venous sinuses and splenic (Bilroth’s) cords – red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes n Macrophages remove ruptured, worn out or defective blood cells n Storage of up to 1/3 of body’s platelet supply n Production of blood cells during fetal life 32 n Functions: n Site of lymphocyte proliferation n Immune surveillance and response n Cleanses the blood n Stores breakdown products of RBCs for later reuse n Spleen macrophages salvage and store iron for later use by bone marrow n Site of fetal erythrocyte production (normally ceases after birth) n Stores blood platelets 33 Structure of the Spleen annshafeera@FSK UiTM'09 34  4. Lymphatic nodules n Not surrounded by a capsule n Scattered throughout lamina propria of mucous membranes lining GI, urinary, reproductive tract n Mucosa-associated lymphatic tissue (MALT) of respiratory tract n Most small and solitary n Some larger – tonsils, Peyer’s patches, appendix 35 Lymphoid Organs annshafeera@FSK UiTM'09 36 Figure 20.5 Let’s recap https://quizlet.com/86740961/lymphatic-system- organs-functions-flash-cards/ 37 annshafeera@FSK UiTM'09 38 39 INNATE IMMUNITY 40  First line of defenses: Skin and mucous membranes n Provide both physical and chemical barriers n Physical barriers n Epidermis – closely packed, keratinized cells n Mucous membranes n Mucus traps microbes and foreign substances n Nose hairs trap and filter n Cilia of upper respiratory tract propel trapped particles up and out 41 n Fluids n Lacrimal apparatus of eye n Washing action of tears n Lysozyme breaks down bacterial cell walls – n Saliva washes mouth (by salivary gland) n Urine cleanses urinary system n Vaginal secretions, defecation and vomiting-expel the microbes n Chemicals n Sebaceous (oil) glands secrete sebum – protective film, acid n gastric juice(HCl,mucus,enzymes), vaginal secretions – all acidic-discourage bacterial growth 42  Second line of defenses: 4 Internal defenses A) Antimicrobial substances 1. Interferons nProduced by lymphocytes, macrophages, and fibroblasts infected by viruses nPrevents replication in neighboring uninfected cells 43  Second line of defenses: 4 Internal defenses A) Antimicrobial substances 2. Complement nProteins in blood plasma and plasma membranes n“complement” or enhance certain immune reactions nCauses cytolysis of microbes, promotes phagocytosis, contributes to inflammation 44 3.Iron-binding proteins nInhibit growth of bacteria by reducing available iron nTransferrin(blood and tissue fluids), lactoferin(milk,saliva,mucus), ferritin(liver spleen ,rbm), hemoglobin (rbc) 4.Antimicrobial proteins (AMPs) nShort peptides that have a broad spectrum of antimicrobial activity nCan attract dendritic cells and mast cells that participate in immune responses 45 B) Natural Killer (NK) cells n Lymphocyte but not a B or T cell n Ability to kill wide variety of infected body cells and certain tumor cells n Attack any body cell displaying abnormal or unusual plasma membrane proteins n Cause cellular detruction by releasing proteins that destroy the target cell’s membrane C) Phagocytes n Neutrophils and macrophages (from monocytes) n Migrate to infected area n 5 steps in phagocytosis 46 Phagocytosis of a microbe annshafeera@FSK UiTM'09 47  1 CHEMOTAXIS Microbe 1 CHEMOTAXIS Microbe Phagocyte Phagocyte 2 ADHERENCE 3 INGESTION 2 ADHERENCE 3 INGESTION Pseudopod Pseudopod Lysosome 4 DIGESTION Lysosome 4 DIGESTION Plasma Digested microbe membrane in phagolysosome Plasma membrane Residual body 5 KILLING (indigestible Digestive material) enzymes Digestive enzymes Phases of phagocytosis Phases of phagocytosis D) Inflammation n Nonspecific, defensive response of body to tissue damage n 4 signs and symptoms – redness, pain, heat and swelling n Attempt to dispose of microbes, prevent spread, and prepare site for tissue repair n 3 basic stages n Vasodilation and increased blood vessel permeability n Emigration n Tissue repair annshafeera@FSK UiTM'09 49 i) Vasodilation and increased permeability of blood vessels n Increased diameter of arterioles allows more blood flow through area bringing supplies and removing debris n Increased permeability means substances normally retained in the blood are permitted to pass out – antibodies and clotting factors n Histamine, kinins, prostaglandins (PGs), leukotrienes (LTs), complement 50 Inflammation annshafeera@FSK UiTM'09 51  ii) Emigration of phagocytes n Within an hour after inflammation process starts, phagocyte appear on the scene.Neutrophils start to stick to the inner surface of endotheluim of blood vessel. n The neutrophils begin to squeeze through the wall of blood vessel to reach the damaged cells (emigration) n N attempt to destroy the microbes by phagocytosis n Depends on chemotaxis n Neutrophils predominate in early stages but die off quickly n Monocytes transform into macrophages n More potent than neutrophils n Pus – pocket of dead phagocytes and damaged tissue annshafeera@FSK UiTM'09 52 annshafeera@FSK UiTM'09 53 ADAPTIVE IMMUNITY annshafeera@FSK UiTM'09 54  Adaptive immunity n Ability of the body to defend itself against specific invading agents n Antigens (Ags) – substances recognized as foreign and provoking an immune response n Distinguished from innate immunity by n Specificity n Memory annshafeera@FSK UiTM'09 55  1. Maturation of T cells and B cells n Both develop from pluripotent stem cells originating in red bone marrow n B cells complete their development in red bone marrow n T cells develop from pre-T cells that migrate from red bone marrow to the thymus n Helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T cells) n Immunocompetence – ability to carry out adaptive immune response n Have antigen receptors(make protein that r inserted into their plasma membranes): to identify specific antigen 56  2. types of adaptive immunity n Cell-mediated n Cytotoxic T cells directly attack invading antigens n Particularly effective against intracellular pathogens(viruses, bacteria,fungi), some cancer cells and foreign tissue transplants(inside cell) n Involve cells attacking cells n Antibody-mediated n B cells transform into plasma cells making antibodies (Abs) or immunoglobulins n Works against extracellular pathogens in fluids outside cells n Helper T cells aid in both types n CM & AM often work together to get rid of large no. of copies of particular antigen from th body annshafeera@FSK UiTM'09 57  Cell-mediated and antibody-mediated immunity Lymph nodes,spleen ,lymp nodules annshafeera@FSK UiTM'09 58  3. Clonal selection n Process by which a lymphocyte proliferates and differentiates (highly specialized cell) in response to a specific antigen n Clone – population of identical cells all recognizing the same antigen as original cell n Occur in secondary lymphatic organ & tissue n Indicator : swollen lymph nodes+tonsils when you were sick n Lymphocyte undergoes clonal selection to produce n Effector cell (inactivation of the antigen)– active helper T cell, active cytotoxic T cell, plasma cell, die after immune response n Memory cell – do not participate in initial immune response, respond to 2nd invasion by proliferating and differentiating into more effector and memory cells, long life spans destroy the ANTG fast & vigorous b4 any sign & symptom of disease can occur 59  4. Who is Antigens???? n Antigens have 2 characteristics n Immunogenicity – ability to provoke immune response n Reactivity – ability of antigen to react specifically with antibodies it provoked n Entire microbes may act as antigen n Typically, just certain small parts of large antigen molecule triggers response (epitope or antigenic determinant) 60  Diversity of antigen receptors n Human immune system able to recognize and bind to at least a billion different epitopes n An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells n Major Histocompatibility Complex Antigens (protein self antigen: located at the plasma membrane surface of most body cells) n MHC or human leukocyte antigens (HLA) n Normal function to help T cells recognize foreign or self 61  5. Pathways of antigen processing n B cells can recognize and bind to antigens(lymph, interstitial fluid, or blood plasma) n T cells only recognize fragments of antigens that are processed and presented in a certain way n Antigen processing n Antigenic proteins are broken down into peptide fragments and associated with MHC molecules n Antigen presentation – antigen-MHC complex inserted into plasma membrane n Pathway depends on whether antigen is outside or inside body cells 62 Antigen presenting cell: -process and present the antigen -APC’s include :dendritic cells, macrophage, B cell -location: place that antigen like to penetrate (skin: langerhans cell is dendritic cell)mucous membranes of resp, gastro, urinary, reproductive tract, lymph nodes. -post action: APC’s migrate from tissue via lymphatic vessels to lymph nodes 63  Exogenous and Endogenous Antigens n Exogenous antigens – present in fluid outside body cells n Antigen-presenting cells (APCs) include dendritic cells, macrophages and B cells n Ingest antigen, process, place next to MHC-II molecule in plasma membrane, and present to T cells n Endogenous antigens – antigens inside body cells n Infected cell displays antigen next to MHC-I AFTER PROCESS AN ANTIGEN APC MIGRATE TO LYMPHATIC TISSUE TO PRESENT ANTIGEN TO T CELLS T CELL BIND WITH ANTIGEN FRAGMENT MHC COMLEX TRIGGER CELL MEDIATD / ANTIBODY MDIATED IMMUNE RESPONSE 64 Exogenous Antigens annshafeera@FSK UiTM'09 65  Key: 5 Vesicles containing antigen Antigen peptide fragments and peptide 1 Phagocytosis or MHC-II molecules fuse fragments Exogenous 6 Antigen peptide endocytosis of antigen antigen fragments bind to MHC-II MHC-II molecules self-antigen Phagosome or endosome 7 Vesicle undergoes 2 Digestion of exocytosis and antigen into antigen–MHC-II peptide fragments complexes are inserted Antigen- 4 Packaging of MHC-II presenting molecules into a vesicle into plasma membrane cell (APC) Endoplasmic reticulum 3 Synthesis of MHC-II molecules APCs present exogenous antigens in association with MHC-II molecules Endogenous Antigens annshafeera@FSK UiTM'09 67 Cell-mediated immunity 68  Cell-mediated immunity n Activation of T cells n First signal in activation n T-cell receptors (TCRs) recognize and bind to a specific foreign antigen fragments that are presented in antigen-MHC complexes n CD4 and CD8 proteins are coreceptors n Second signal required for activation n Costimulation – 20 known substances (cytokines, plasma membrane molecules)interleukin 2 n May prevent immune response from occurring accidentally n Anergy – recognition without costimulation (in both B and T cells) leads to prolonged state of inactivity 69  Activation and clonal selection of helper T cells n Most that display CD4 develop into helper T cells (CD4 T cells) n Recognize exogenous antigen fragments associated with MHC-II molecules on the surface of an APC n After activation undergoes clonal selection n Makes active helper T cells and memory helper T cells n Function:help other cells of adaptive immune response combat intruders n Active helper T cells secrete variety of cytokines n Interleukin-2 (IL-2)(costimulator) needed for virtually all immune responses(enhance activation/poliferate of restingT,B,NK cell) n Memory helper T cells are not active cells – can quickly proliferate and differentiate if the antigen appears again annshafeera@FSK UiTM'09 70 Activation and clonal selection of a helper T cell annshafeera@FSK UiTM'09 71  Activation and clonal selection of cytotoxic T cells n Most that display CD8 develop into cytotoxic T cells (CD8 T cells) n Recognize antigens combined with MHC-I n Maximal activation also requires presentation of antigen with MHC-II to cause helper T cells to produce IL-2 n Undergoes clonal selection n Active cytotoxic T cells attack body cells that have been infected n Memory cytotoxic T cells do not attack but wait for a antigen to appear again annshafeera@FSK UiTM'09 72 Activation and clonal selection of a cytoxic T cell annshafeera@FSK UiTM'09 73  Elimination of invaders n Cytotoxic T cells migrate to seek out and destroy infected target cells n Kill like natural killer cells n Major difference is T cells have specific receptor for particular microbe while NK cells destroy a wide variety of microbe-infected cells n 2 ways to kill cells n Granzymes cause apoptosis (fragmentation of cellular contents) once the infected cell is destroyed the released microbs are killed by phagocytocyte n Release 2 protein from their granule : Perforin and/ or granulysin causes cytolysis (cell bursting) n Immunological surveillance n Tumor antigens displayed on cancerous cells targeted by cytotoxic T cells, macrophages and natural killer cells 74 Activity of cytoxic T cells annshafeera@FSK UiTM'09 75 Antibody-mediated immunity 76  Antibody-mediated immunity n Activation and clonal selection of B cells n During activation, antigen binds to B cell receptor (BCRs) n Can respond to unprocessed antigen n Response much more intense when B cell processes antigen*antigen processing stage n Antigen taken into B cell, combined with MHC-II, moved to plasma membrane, helper T cell binds and delivers costimulation (interleukin-2 and other cytokines) n Once activated, B cell undergoes clonal selection.Produce: n Plasma cells secrete antibodies (4-5 days until plasma cell die) n Antibody travel in lymph and blood to the invasion site) n Memory B cells do not secrete antibodies but wait for reappearance of antigen 77 Activation and clonal selection of B cells annshafeera@FSK UiTM'09 78  Antibodies (Ab) n Can combine specifically with epitope of the antigen that triggered its production n Belong to group of glycoproteins called globulins n Ab are immunoglobulins (Igs) n 4 polypeptide chains – 2 heavy (H) chains, 2 light (L) chains n Hinge region – antibody can be T shape or Y shape n Variable (V) region at tips of each H and L chain n 2 antigen-binding sites - bivalent n Constant (C) region – remainder of H and L chain n Same in each 5 classes – determines type of reaction 79 Chemical structure of the immunoglobin (IgG) class of antibody 80  Antibody actions n Neutralizing antigen (antibody+antigen) - neutralize & prevents attachments of some virues to body cells n Immobilizing bacteria (limits bacterial spread) - To lose their motility (limits bacterial spread into nearby tissues) n Agglutinating and precipitating antigen (clumping together) - antigen antibody complex activate compleent proteinsà cytolysisàmicrobe removed n Enhancing phagocytosis (attrction) - antigen antibody bind: antibody (flag) attract phagocytes. 81  Immunological memory n Thousands of memory cells exist after initial encounter with an antigen n Next time antigen appears can proliferate and differentiate within hours n Antibody titer measure of immunological memory n Amount of Ab in serum n Primary response n Secondary response faster and stronger 82  Self-recognition and self- tolerance n Your T cells must have n Self-recognition – be able to recognize your own MHC n Self-tolerance – lack reactivity to peptide fragments from your own proteins n Pre-T cells in thymus develop self-recognition via positive selection – cells that can’t recognize your own MHC undergo apoptosis n Self-tolerance occurs through negative selection in which T and B cells that recognize self peptide fragments are eliminated n Deletion – undergo apoptosis n Anergy – remian alive but are unresponsive 83 Development of self- recognition and self-tolerance annshafeera@FSK UiTM'09 84