Lecture 5 Lymphatic and Immune PDF

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HAP2

LECTURE 5

Lymphatic System and Immune Response Reference: Amerman Chapter 20

Dr. Cherylea Browne School of Science and Health

[email protected]

• Test 1

Reminder

– – – –

Next week during normal practical time check vUWS for group allocation worth 10% of final mark WHS induction must be completed or you will not be put on the test list – Assesses knowledge gained from: • • • • • • • • •

Cardiovascular lecture 1 (week 1) Cardiovascular lecture 2 (week 2) Cardiovascular practical 1 (week 2) Cardiovascular practical 2 (week 3) Respiratory lecture 1 (week 3) Respiratory lecture 2 (week 4) Respiratory practical 1 (week 4) Respiratory practical 2 (week 5) Lymphatic and Immune (week 6)

Objectives • Define the function of the lymphatic system • Describe the various types of lymphatic vessels, tissues and organs • Define the composition of lymph fluid • Describe the components and mechanisms of the innate immune response • Describe the components and mechanisms of the adaptive immune response

What is the Lymphatic System? • System that returns fluids that have leaked from blood vessels back to the blood • Consists of three parts: 1. Network of lymphatic vessels (lymphatics) 2. Lymph – fluid in vessels 3. Lymph nodes – cleanse lymph • Pathogens travel throughout body via lymphatics

Venous system

Heart

Lymphatic Vessels (lymphatics) • Return interstitial fluid and leaked plasma proteins back to blood • ~ 3L / day • Once interstitial fluid enters lymphatics, called lymph • One-way system; lymph flows toward heart • Lymphatic vessels include: – Lymphatic capillaries – Collecting lymphatic vessels – Lymphatic trunks and ducts

Arterial system Lymphatic system: Lymph duct Lymph trunk Lymph node Collecting lymphatic vessels, with valves

Lymphatic capillary

Blood capillaries

Tissue fluid Tissue cell

Filaments anchored to connective tissue

Endothelial cell

Flap-like minivalve

Fibroblast in loose connective tissue

Blood capillaries

Lymphatic capillaries

Lymphatic Vessels Lymphatic Capillaries – Similar to blood capillaries, except: • Very permeable (take up proteins, cell debris, pathogens, and cancer cells) – Endothelial cells overlap loosely to form one-way minivalves – Anchored by collagen filaments, preventing collapse of capillaries; increased ECF volume opens the minivalves

Tissue fluid Tissue cell

Blood capillaries

Lymphatic capillaries

Filaments anchored to connective tissue

Endothelial cell

Flaplike minivalve

Fibroblast in loose connective tissue

– Absent from bones, teeth, bone marrow, and CNS – Lacteals: specialized lymph capillaries present in intestinal mucosa • Absorb fat and deliver fatty lymph (chyle) to the blood

Lymphatic Vessels

Lymphatic Collecting Vessels

Venous system

Arterial system Heart Lymphatic system: Lymph duct Lymph trunk Lymph node

– Similar to veins, except: • Have thinner walls, with more internal valves • Anastomose more frequently

– Collecting vessels in skin travel with superficial veins – Deep vessels travel with arteries

Collecting lymphatic vessels, with valves

Blood capillaries

Lymphatic capillary

Tissue fluid Tissue cell

Blood capillaries

Lymphatic capillaries

Lymphatic Vessels

Lymphatic Trunks

– Formed by union of largest collecting ducts • • • • •

Paired lumbar Paired bronchomediastinal Paired subclavian Paired jugular trunks Single intestinal trunk Venous system

Arterial system Heart Lymphatic system: Lymph duct Lymph trunk Lymph node Collecting lymphatic vessels, with valves

Blood capillaries

Lymphatic capillary

Regional lymph nodes:

Internal jugular vein Entrance of right lymphatic duct into vein

Cervical nodes

Entrance of thoracic duct into vein

Axillary nodes

Thoracic duct Cisterna chyli

Aorta

Collecting lymphatic vessels

Drained by the right lymphatic duct Drained by the thoracic duct

Inguinal nodes

Regional lymph nodes:

Internal jugular vein

Lymphatic Vessels Lymphatic Ducts

Entrance of right lymphatic duct into vein

– Lymph delivered into one of two large ducts • Right lymphatic duct drains right upper arm and right side of head and thorax • Thoracic duct arises as cisterna chyli; drains rest of body

– Each empties lymph into venous circulation at junction of internal jugular and subclavian veins on its own side of body

Cervical nodes

Entrance of thoracic duct into vein

Axillary nodes

Thoracic duct Cisterna chyli

Aorta Inguinal nodes

Collecting lymphatic vessels

Drained by the right lymphatic duct Drained by the thoracic duct Venous system Arterial system Heart Lymphatic system: Lymph duct Lymph trunk Lymph node Collecting lymphatic vessels, with valves

Blood capillaries

Lymphatic capillary

Right jugular trunk Right lymphatic duct Right subclavian trunk Right subclavian vein Right bronchomediastinal trunk Brachiocephalic veins Superior vena cava Azygos vein

Internal jugular veins

Esophagus Trachea Left jugular trunk Left subclavian trunk Left subclavian vein Entrance of thoracic duct into vein Left bronchomediastinal trunk Ribs Thoracic duct

Cisterna chyli Right lumbar trunk

Hemiazygos vein

Left lumbar trunk Inferior vena cava

Intestinal trunk Major lymphatic trunks and ducts in relation to veins and surrounding structures. Anterior view of thoracic and abdominal wall.

Lymph Transport • Lymph fluid is propelled by: – Milking action of skeletal muscle – Pressure changes in thorax during breathing – Valves to prevent backflow – Pulsations of nearby arteries – Contractions of smooth muscle in walls of lymphatics

Lymph Fluid

Interstitial Fluid ; water, carbohydrates, fats & protein (but much less than in plasma) Leukocytes (White Blood Cells) – Lymphocytes • Arise in red bone marrow • Protect against foreign antigens – Bacteria and bacterial toxins, viruses, mismatched RBCs, cancer cells

• Mature into one of two main varieties: – T cells (T lymphocytes) » Manage immune response » Attack and destroy infected cells

Reticular fibre Medullary sinus Lymphocytes Reticular cells on reticular fibres Macrophage

– B cells (B lymphocytes) » Produce plasma cells, which secrete antibodies (antibodies mark antigens for destruction by phagocytosis or other means)

– Macrophages • phagocytize foreign substances; help activate T cells

– Dendritic cells • capture antigens and deliver them to lymph nodes; activate T cells

Reticular cells – produce reticular fibre stroma that supports other cells in lymphoid organs

Lymphoid Organs and Tissues • Provide structural basis of immune system • House phagocytic cells and lymphocytes • Structures include spleen, thymus, tonsils, lymph nodes, other lymphoid tissues

Lymphoid Tissue

• Houses, and provides proliferation site for lymphocytes • Surveillance vantage point for lymphocytes and macrophages • Largely reticular connective tissue – type of loose connective tissue • Two main types: – Diffuse lymphoid tissue of lymphoid cells and reticular fibres in ~ every body organ • Larger collections in lamina propria of mucous membranes

– Lymphoid follicles are solid, spherical bodies of tightly packed lymphoid cells and reticular fibres • Germinal centres of proliferating B cells • May form part of larger lymphoid organs • Isolated aggregations of Peyer's patches and in appendix

Lymph Nodes • Principal lymphoid organs of body • Embedded in connective tissue, in clusters along lymphatic vessels • Near body surface in inguinal, axillary, and cervical regions of body • Functions

Regional lymph nodes:

Internal jugular vein Entrance of right lymphatic duct into vein

Cervical nodes

Entrance of thoracic duct into vein

Axillary nodes

Thoracic duct Cisterna chyli

Aorta

Collecting lymphatic vessels

Inguinal nodes

Drained by the right lymphatic duct Drained by the thoracic duct

1. Filter lymph—macrophages destroy microorganisms and debris 2. Immune system activation—lymphocytes activated and mount attack against antigens

Spleen

• Largest lymphoid organ Diaphragm • Served by splenic artery Spleen Adrenal and vein, which enter gland and exit at the hilum Left kidney • Functions: Splenic

artery – Site of lymphocyte Pancreas proliferation, and immune surveillance and response – Cleanses blood of aged cells and platelets; macrophages remove debris – Stores breakdown products of RBCs (e.g., iron) for later reuse – Stores blood platelets, and the precursors of macrophages and dendritic cells

Thymus • Found in inferior neck; extends into mediastinum; partially overlies heart • Stops growing during adolescence, then gradually atrophies

Capsule Cortex Medulla Thymic corpuscles

• Most thymic cells are lymphocytes – Cortex contains rapidly dividing lymphocytes and scattered macrophages

• Medulla contains fewer lymphocytes and thymic corpuscles involved in regulatory T cell development (prevent autoimmunity) • Differs from other lymphoid organs in important ways: – Has no B cells – Does not directly fight antigens • Functions strictly in T lymphocyte maturation- (trains the T cells)

Mucosa-associated Lymphoid Tissue (MALT) • Lymphoid tissues in mucous membranes throughout body • Protects from pathogens trying to enter body • Largest collections of MALT in tonsils, Peyer's patches, appendix • Also in mucosa of respiratory and genitourinary organs; rest of digestive tract

MALT: Tonsils

• Simplest lymphoid organs • Form ring of lymphatic tissue around pharynx (Waldeyer’s Ring)

Pharyngeal tonsil Palatine tonsil Lingual tonsil

– Palatine tonsils: at posterior end of oral cavity – Lingual tonsil: grouped at base of tongue – Pharyngeal tonsil: in posterior wall of nasopharynx – Tubal tonsils: surrounding openings of pharyngotympanic tubes into pharynx

• • • •

Gather and remove pathogens in food or air Germinal centers Tonsillar Contain follicles with germinal centers in lymphoid folliclescrypt Are not fully encapsulated Overlying epithelium invaginates forming tonsillar crypts – Trap and destroy bacteria and particulate matter – Allow immune cells to build memory for pathogens

MALT: Peyer’s Patches and Appendix • Peyer's patches – Clusters of lymphoid follicles – In wall of distal portion of small intestine – Similar structures are also found in the appendix

• Peyer's patches and appendix – Destroy bacteria, preventing them from breaching intestinal wall – Generate "memory" lymphocytes Smooth muscle in the intestinal wall

Follicles of a Peyer’s patch (aggregated lymphoid nodules)

Immune System • Functional system rather than an organ system • Provides lines of defence against foreign material, bacteria, viruses, cancers, etc. • Innate (~born with) and adaptive (~develops over time/exposure) defences intertwined – Innate responses release proteins that alert cells of adaptive system to foreign molecules

Immunity • Resistance to disease • Immune system – Two intrinsic systems • Innate (non-specific) defence system – First line of defence - external body membranes (skin and mucosae) – Second line of defence - antimicrobial proteins, phagocytes, and other cells » Inhibit spread of invaders » Inflammation most important mechanism

• Adaptive (specific) defence system – Third line of defence attacks particular foreign substances via cell-mediated response and humoral response – Takes longer to react than innate system

Innate defences

Surface barriers • Skin • Mucous membranes

1st Line of Defence

Internal defences • Phagocytes • Natural killer cells • Inflammation • Antimicrobial proteins • Fever

2nd Line of Defence

3rd Line of Defence Humoral immunity • B cells Adaptive defences Cellular immunity • T cells

Innate Defences

• Surface barriers:

– provide the first line of defence – ward off invading pathogens • Skin, mucous membranes, and their secretions – Physical barrier to most microorganisms – Keratin resistant to weak acids and bases, bacterial enzymes, and toxins – Mucosae provide similar mechanical barriers

Innate Defences • Surface barriers produce protective chemicals to inhibit or destroy microorganisms – Acidity of skin and secretions • inhibits microorganism growth

– Enzymes: lysozyme of saliva, respiratory mucus, and lacrimal fluid • breakdown/kill many microorganisms

– Defensins: antimicrobial peptides • inhibits microorganism growth

– Other chemicals: lipids in sebum, dermcidin in sweat • toxic to microorganisms

– Respiratory system modifications • Mucus-coated hairs in nose • Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus toward mouth

Innate Defences • If surface barriers are breached by scratches or cuts - second line of defence (internal defences) must protect deeper tissues

Innate Defences

• Internal Defences:

– provide the second line of defence – necessary if microorganisms invade deeper tissues – involve cells and chemicals • Phagocytes • Natural killer (NK) cells • Inflammatory response (leukocytes and inflammatory chemicals) • Antimicrobial proteins (interferons and complement proteins) • Fever

Innate Defences

• Internal Defences: Phagocytes – Neutrophils most abundant but die fighting • Become phagocytic on exposure to infectious material

– Macrophages are the chief phagocytic cells which are very robust • Free macrophages wander through tissue spaces, e.g., alveolar macrophages • Fixed macrophages permanent residents of some organs; e.g., stellate macrophages (liver) and microglia (brain)

A macrophage (purple) uses its cytoplasmic extensions to pull rod-shaped bacteria (green) toward it. Scanning electron micrograph (4800x).

1 Phagocyte adheres to pathogens or debris.

Phagosome (phagocytic vesicle) Lysosome

Acid hydrolase enzymes

2 Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome. 3 Lysosome fuses with the phagocytic vesicle, forming a phagolysosome.

4 Lysosomal enzymes digest the particles, leaving a residual body. 5 Exocytosis of the vesicle removes indigestible and residual material.

Events of phagocytosis. https://www.youtube.com/watch?v=ygkvXT1BmaA

Innate Defences • Internal Defences: Natural Killer (NK) Cells – Non-phagocytic large granular lymphocytes – Attack altered self-cells • Induce apoptosis in cancer cells and virus-infected cells by releasing cytotoxic proteins into the cells

– Secrete potent chemicals that enhance inflammatory response

Innate Defences • Internal Defences: Inflammation – Triggered whenever body tissues injured – Prevents spread of damaging agents – Disposes of cell debris and pathogens – Alerts adaptive immune system – Sets the stage for repair – Cardinal signs of acute inflammation: 1. Redness 2. Heat 3. Swelling 4. Pain (Sometimes 5. Impairment of function)

Inflammatory Response • Begins with chemicals released into ECF by injured tissues, immune cells, blood proteins, etc. • Macrophages and epithelial cells of boundary tissues bear specialised receptors which recognise specific classes of infecting microbes – once these specialised receptors are activated they release chemicals that promote inflammation

• Inflammatory mediators are released – Dilate local arterioles • Causes redness and heat of inflamed region

– Make capillaries leaky – Many attract leukocytes to area – Some have inflammatory roles

Inflammatory Response •  Capillary permeability  exudate to tissues – Fluid containing clotting factors and antibodies – Causes local swelling (oedema) – Swelling pushes on nerve endings  pain • Pain also from bacterial toxins, prostaglandins, and kinins

– Moves foreign material into lymphatic vessels – Delivers clotting proteins and complement

• Clotting factors form fibrin mesh – Scaffold for repair – Isolates injured area so invaders cannot spread

Phagocyte Mobilisation 1. Leukocytosis: release of neutrophils from bone marrow in response to Inflammatory leukocytosis-inducing chemicals 4 Chemotaxis. diffusing factors from injured cells Neutrophils follow from the inflamed chemical trail. site act as 2. Margination: neutrophils Capillary wall chemotactic Basement agents. cling to walls of capillaries membrane Endothelium in inflamed area in response to cell adhesion 2 Margination. 1 Leukocytosis. 3 Diapedesis. molecules Neutrophils enter Neutrophils cling Neutrophils flatten blood from bone and squeeze out of to capillary wall. capillaries. 3. Diapedesis: neutrophils marrow. flatten and squeeze out of • As attack continues, macrophages arrive capillary - These "late-arrivers" replace 4. Chemotaxis: dying neutrophils and remain inflammatory chemicals for clean up prior to repair (chemotactic agent) • If inflammation is due to pathogens, promote positive adaptive immunity elements arrive chemotaxis of neutrophils

•

Innate Defences Internal Defences: Antimicrobial Proteins – Interferons (IFNs) • Family of immune modulating proteins (many types) – Viral-infected cells secrete IFNs (e.g., IFN alpha and beta) to "warn" neighbouring cells » IFNs enter neighbouring cells  produce proteins that block viral reproduction and activate NK cells

– IFN gamma (immune interferon) » Secreted by lymphocytes » Widespread immune mobilizing effects which activates macrophages

– Complement proteins • Proteins that circulate in the blood (many types) • Unleashes inflammatory chemicals that amplify all aspects of inflammatory response • Kills bacteria and certain other cell types by cell lysis • Enhances both innate and adaptive defences

Innate Defences • Internal Defences: Fever – Abnormally high body temperature – Systemic response to invading microorganisms – Leukocytes and macrophages exposed to foreign substances secrete pyrogens – Pyrogens act on body's thermostat in hypothalamus, raising body temperature – Benefits of moderate fever • Causes liver and spleen to sequester iron and zinc (needed by microorganisms) • Increases metabolic rate  faster repair

1st Line of Defence Innate defences

2nd Line of Defence • Fever

3rd Line of Defence Humoral immunity • B cells Adaptive defences Cellular immunity • T cells

Adaptive Defences • Adaptive immune (specific defence) system – – – –

Protects against infectious agents and abnormal body cells Amplifies inflammatory response Has memory – stronger attacks to "known" antigens Uses lymphocytes, Antigen-Presenting Cells (APCs), and specific molecules to identify and destroy non-self substances – Depends upon ability of its cells to: • Reco...