Lymphatic System & Immune Systems
Page 3: The Immune System
The immune system is the body's defense against pathogens.
It consists of three lines of defense.
The adaptive immune response is carried out by the lymphatic system.
Page 4: The Lymphatic System
The lymphatic system has several functions, including returning interstitial fluid and leaked plasma proteins back to the blood, removing waste products produced by cells, filtering debris and microbes from the lymph, and playing a role in the immune system.
It consists of lymph, lymphatic vessels, and lymphoid tissues and organs.
Page 6: Lymph
Lymph is the fluid that circulates in the lymphatic system.
It forms when interstitial fluid and plasma drain into the lymphatic system.
It contains a high number of lymphocytes and in the digestive system, it is called chyle.
Page 7: Lymphatic Vessels
Lymphatic vessels are a one-way system that always flows toward the heart.
They include lymphatic capillaries, lymphatic collecting vessels, lymphatic trunks, and ducts.
Lymph nodes are located along the lymphatic vessels.
Page 8: Lymphatic Capillaries
Lymphatic capillaries are tiny, thin-walled vessels that pick up interstitial fluid and any pathogens present in the tissues.
They are absent from bones, teeth, bone marrow, and the central nervous system.
Lacteals are specialized lymph capillaries present in the intestinal mucosa that absorb digested fat and deliver fatty lymph to the blood.
Page 10: Lymphatic Collecting Vessels
Lymphatic collecting vessels drain the lymphatic capillaries.
They are similar to veins but have thinner walls and more internal valves.
Nutrients are supplied from branching vasa vasorum.
Page 11: Lymphatic Trunks
Lymphatic trunks drain the lymphatic collecting vessels.
They are formed by the union of the largest collecting vessels, including lumbar, bronchomediastinal, subclavian, jugular, and intestinal trunks.
Page 12: Lymphatic Ducts
Lymphatic ducts drain the lymphatic trunks.
There are two large ducts: the right lymphatic duct and the thoracic duct.
Each duct empties lymph into venous circulation.
Page 13: Lymph Transport
Lymph is moved by the movement of organs and skeletal muscle, peristalsis of the walls of the lymphatic vessels, pressure in the interstitial space, and respiratory movements.
Page 16: Lymphatic Tissues & Organs
The primary lymphatic organs are the bone marrow and thymus, where stem cells divide and become immunocompetent.
The secondary lymphatic organs include the spleen, lymph nodes, and mucosa-associated lymphatic tissue (MALT), where most adaptive immune responses occur.
Page 17: Bone Marrow
Bone marrow is the major hematopoietic organ where blood cells are produced.
B lymphocytes become immunocompetent in the bone marrow, while immature T lymphocytes leave the bone marrow and mature in the thymus gland.
Page 18: Thymus Gland
The thymus gland is located in the mediastinum and functions at peak levels during childhood and puberty.
It is the site where T cells become immunocompetent and undergo maturation, proliferation, and regulation of function.
T cells then leave the thymus and travel to other lymphatic organs.
Page 20: Lymph Nodes
Lymph nodes are bean-shaped organs surrounded by a tough capsule of connective tissue.
They contain a stroma of reticular fibers and are the principal lymphoid organs of the body.
There are about 500-600 lymph nodes scattered along the lymphatic vessels, with many located in clusters near the body surface in inguinal, axillary, and cervical regions.
Lymph Nodes
Lymph enters via afferent lymphatic vessels
Subcapsular sinus and smaller sinuses contain dendritic cells and macrophages
Cortex contains lymphoid follicles for lymphocyte activation and proliferation
Medulla consists of medullary cords of B cells and plasma cells
Medullary sinuses collect lymph
Exits at the hilus via efferent vessels
Fewer efferent vessels cause lymph flow to stagnate, allowing cells to carry out their functions
Lymph nodes filter out debris and microbes before lymph is returned to the blood
Infectious agents taken up by lymphatic capillaries are transported to regional lymph nodes
Fixed cells filter lymph via phagocytosis
Dendritic cells and macrophages internalize and kill pathogens
Other Lymphoid Organs
Spleen is the largest lymphoid organ
Filters blood directly
Red pulp filters blood and acts as a blood reservoir
White pulp is the site of lymphocyte proliferation and immune function
Mucosa-Associated Lymphatic Tissue (MALT) is connective tissue located beneath mucous membranes
Includes tonsils, Peyer's patches, and lymphoid nodules in the bronchi and vagina
Act as sentinels in the digestive, respiratory, and reproductive tracts
Tonsils are small masses of lymphoid tissue around the pharynx
Trap and remove bacteria and foreign materials
Tonsillitis is caused by congestion with bacteria
Peyer's patches are found in the wall of the ileum region of the small intestine
Monitor intestinal bacteria populations and prevent the growth of pathogenic bacteria
Capture and destroy pathogens in the small intestine
The Immune System
The lymphatic system is part of the broader immune system
The immune system has two major divisions: innate (non-specific) defense system and adaptive (specific) defense system
The innate and adaptive defense systems collectively provide three lines of defense
Innate immunity is inborn, non-specific, and responds immediately
Adaptive immunity is specific and acquired, carried out by the lymphatic system
First Line of Defense
Surface barriers act as physical barriers to microorganisms
Skin, mucous membranes
Protective chemicals inhibit or destroy microorganisms
Acidity of skin, urinary tract, and vaginal mucosae
Lipids in sebum and dermcidin in sweat
HCl and protein-digesting enzymes of the stomach
Lysozyme of saliva and lacrimal fluid
Mucus
References
Tortora & Derrickson 2012, Figure 22.6
Tortora & Derrickson 2012, Figure 22.7
Tortora & Derrickson 2012, Figure 22.6
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Second Line of Defense
Necessary if microorganisms breech the first line of defense and invade deeper tissues
Consists of cells and chemicals
Phagocytes: macrophages, neutrophils
Natural killer cells
Inflammatory response: macrophages, mast cells, leukocytes, and inflammatory chemicals
Antimicrobial proteins: interferons and complement proteins
Fever
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Phagocytes
Engulf cellular debris and foreign material into a vacuole which joins with a lysosome
May be fixed or free to migrate
Neutrophils and macrophages can migrate to an infected area
Neutrophils move by diapedesis to clean up damaged tissue and/or bacterial pathogens
Monocytes (in the blood) become macrophages when they move into tissues
Fixed macrophages are found in lymphatic tissues and organs where they filter lymph or blood
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Phagocytosis process
CHEMOTAXIS
Microbe attracts phagocyte
ADHERENCE
INGESTION
Pseudopod extends and engulfs microbe
Phagosome forms
Lysosome fuses with phagosome
DIGESTION
Digestive enzymes break down microbe
Indigestible material forms residual body
KILLING
Microbe is killed
Digested material is released
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Natural Killer (NK) Cells
Can lyse and kill cancer cells
Can destroy virus-infected cells
Secrete potent chemicals that enhance the inflammatory response
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Inflammation
Triggered when body tissues are damaged due to injury, disease, or infection
Damaged tissues release chemical mediators (e.g., histamine) which result in:
Vasodilation and increased vessel permeability
Emigration of phagocytes from the blood into the interstitial space and then to the site of damage
Tissue repair
Four most common indicators of acute inflammation:
Redness
Heat
Swelling
Pain
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Inflammation
Functions to:
Prevent spread of damaging agents
Dispose of cell debris and pathogens through phagocytosis
Set the stage for repair
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Inflammatory response at the site of injury
Thorn injures skin surface
Inflammatory response is triggered
Microbes and dissolved poisonous substances are present
Blood vessels dilate, bringing increased blood flow to the injured area
Phagocytes migrate to the injured area and ingest microbes and other foreign substances
Lymphatic drainage removes dissolved poisonous substances for healing to occur
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Inflammatory response process
Injurious agents cause damage to cells
Cells release kinins, histamine, and other chemicals
Blood vessels dilate and become "leaky"
Neutrophils and monocytes enter the area
Increased blood flow brings more nutrients and oxygen to the area
Redness, heat, pain, and swelling occur
Clotting reaction walls off the region
Temporary limitation of joint movement
Healing occurs
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Antimicrobial Proteins
Either attack microorganisms directly or hinder the multiplication of viruses
The most important antimicrobial proteins are:
Complement proteins
Interferon
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Complement proteins
A group of at least 20 plasma proteins
Damages foreign cell surfaces by creating holes that result in cell lysis
Release vasodilators and chemotaxis chemicals (enhances the inflammatory response)
Causes opsonization
Can be activated when they encounter and attach to cells marked with antibodies (complement fixation)
Interferon
Proteins (cytokines) secreted by virus-infected cells
Binds to healthy cell surface and interferes with the ability of viruses to multiply
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Membrane attack complex forming
Antibodies attached to pathogen's membrane
Activated complement proteins attach to pathogen's membrane in step-by-step sequence, forming a membrane attack complex (a MAC attack) causing cell lysis
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Innate defenses
Internal defenses
Antiviral proteins block viral reproduction
Interferon genes switch DNA on
Interferon binding produces interferon molecules
Interferon stimulates cell to turn on genes for antiviral proteins
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Fever
Abnormally high body temperature due to a change in the set point for body temperature
Hypothalamus heat regulation can be reset by pyrogens (secreted by white blood cells)
Inhibit the release of iron and zinc from the liver and spleen needed for microbial growth
Increases the speed of tissue repair
Fever results from a change in the set point in the hypothalamus whereas hyperthermia is due to a loss of thermoregulation
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Cellular and Chemical Defenses-Second Line of Defense
Phagocytes
Engulf and destroy pathogens that breach surface membrane barriers; macrophages also contribute to the immune response
Natural killer cells
Promote cell lysis by direct cell attack against virus-infected or cancerous body cells; do not depend on specific antigen recognition
Inflammatory response
Prevents spread of injurious agents to adjacent tissues, disposes of pathogens and dead tissue cells, and promotes tissue repair; releases chemical mediators that attract phagocytes (and immunocompetent cells) to the area
Antimicrobial chemicals
Complement: Group of plasma proteins that lyses microorganisms, enhances phagocytosis by opsonization, and intensifies inflammatory response
Interferons: Proteins released by virus-infected cells that protect uninfected tissue cells from viral takeover; mobilize the immune system
Urine
Normally acid pH inhibits bacterial growth; cleanses the lower urinary tract as it flushes from the body
Fever
Systemic response triggered by pyrogens; high body temperature inhibits multiplication of bacteria and enhances body repair processes
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Physical Barriers
Hair: Prevent approach and deny access to pathogens
Secretions: Remove debris and pathogens
Epithelium: Innate Immunity
Phagocytes: Remove debris and pathogens
Fixed macrophage
Free macrophage
Neutrophil
Eosinophil
Monocyte
Natural Killer (NK) Cells: Destroys abnormal cells
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Third Line of Defense
Adaptive and specific
Protects against infectious agents and abnormal body cells
Works with the second line of defense
Amplifies the inflammatory response and activates complement (complement fixation)
Three important aspects of adaptive defense:
Antigen specific — recognizes and acts against particular foreign substances (antigens)
Systemic — not restricted to the initial infection site
Memory — recognizes and mounts a stronger attack on previously encountered pathogens
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Types of Adaptive Immunity
Humoral immunity = antibody-mediated immunity
Provided by antibodies present in body fluids
Cellular immunity = cell-mediated immunity
Targets virus-infected cells, cancer cells, and cells of foreign grafts
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Antigens are foreign agents that elicit an immune response
Antigens tend to be foreign, organic, structurally complex, and large
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Self-antigens are surface proteins on human cells that can trigger an immune response in another person's body
Allergens are small molecules that can link up with our own proteins and trigger a harmful immune response
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B lymphocytes (B cells) are responsible for antibody-mediated immunity
T lymphocytes (T cells) are responsible for cell-mediated immunity
Macrophages activate lymphocytes by presenting antigens to them
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B and T lymphocytes originate from hemocytoblasts in the red bone marrow
B lymphocytes become immunocompetent in the bone marrow
T lymphocytes become immunocompetent in the thymus
Macrophages arise from monocytes and secrete cytokines
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B lymphocytes with specific receptors bind to a specific antigen
The lymphocytes undergo clonal selection, producing a large number of clones
Most B cell clones become plasma cells that produce antibodies
Some B cell clones become long-lived memory cells responsible for the secondary immune response
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B cell receptors recognize unprocessed antigens
Helper T cells activate B cells through costimulation
Clonal selection occurs, leading to the formation of B cell clones
Antibodies are produced by plasma cells and memory B cells
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A second exposure to an antigen causes a faster, stronger, and longer immune response
Memory cells are long-lived and play a role in the secondary immune response
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Active humoral immunity occurs when antibodies are made in response to an antigen
Passive humoral immunity occurs when antibodies are acquired from an external source
Active immunity can be naturally acquired through infections or artificially acquired through vaccines
Passive immunity can be naturally acquired from a mother to her fetus or artificially acquired from immune serum or gamma globulin
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Acquired immunity can be naturally acquired through infection or artificially acquired through vaccination
Active immunity involves the production of antibodies, while passive immunity involves the acquisition of antibodies from an external source
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Antibodies, also called immunoglobulins (Igs), are soluble Y-shaped proteins secreted by B cells
Antibodies bind specifically to an antigen
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Antibodies have a structure consisting of four polypeptide chains linked by disulphide bonds
Each chain has a constant and variable region, with the variable regions combining to form antigen-binding sites
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Antibodies have different classes with different roles
The five major immunoglobulin classes are IgM, IgA, IgD, IgG, and IgE
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Antibodies inactivate antigens through complement fixation, neutralization, agglutination, and precipitation
All of these mechanisms facilitate phagocytosis
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Antigens must be presented by macrophages to T cells for recognition
T cells include cytotoxic T cells, helper T cells, and regulatory T cells
Memory cells are also present in each clone
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Macrophages present antigens to cytotoxic T cells and helper T cells
Cytotoxic T cells kill infected cells, helper T cells recruit other cells to fight invaders, and regulatory T cells suppress the activity of T and B cells
B cells process antigens and secrete antibodies
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Primary lymphatic organs: Red bone marrow, Thymus
Pre-T cells in red bone marrow
Mature T cells in thymus
Antigen Y
Secondary lymphatic organs and tissues
Mature B cells
Cytotoxic T cells
Helper T cells
B cell receptors
T cell receptors
CD8 protein on cytotoxic T cells
CD4 protein on helper T cells
Activation of helper T cell
Formation of helper T cell clone
Memory helper T cells
Active helper T cells
Activation of B cell
Formation of B cell clone
Memory B cells
Active cytotoxic T cells
Antibodies
Plasma cells
Antibodies bind to and inactivate antigens
Attack invading antigens in body fluids
Cell-mediated immunity
Antibody-mediated immunity
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Allergies (Hypersensitivity)
Abnormal, vigorous immune responses
Types of allergies
Immediate hypersensitivity
Triggered by release of histamine from IgE binding to mast cells
Reactions begin within seconds of contact with allergen
Anaphylactic shock — dangerous, systemic response
Delayed hypersensitivity
Triggered by the release of lymphokines from activated helper T cells
Symptoms usually appear within 1–3
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Sensitization stage
Antigen (allergen) invades body
Plasma cells produce large amounts of class IgE antibodies against allergen
IgE antibodies attach to mast cells in body tissues (and to circulating basophils)
Mast cell granules containing histamine
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Subsequent (secondary) responses
More of the same allergen invades body
Mast cell granules release allergen contents after binding to IgE
Histamine causes blood vessels to dilate and become leaky
Promotes edema
Stimulates release of large amounts of mucus
Causes smooth muscles to contract
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Workbook activity
Complete pages: 163, 167-178, 186
Greenwood, T., Bainbridge-Smith, L., Pryor, K., & Allan, R. (2013). Anatomy & Physiology Student Workbook (2nd ed.). New Zealand: Biozone International Ltd
OR
Complete pages: 10, 13-23, 27
Greenwood, T., Bainbridge-Smith, L., Allan, R., & Butler, D. (2007). Health and Disease - Biology Modular Workbook Series. New Zealand: Biozone International Ltd
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References
Greenwood, T., Bainbridge-Smith, L., Pryor, K., & Allan, R. (2013). Anatomy & Physiology Student Workbook (2nd ed.). New Zealand: Biozone International Ltd
Marieb, E. N. (2017). Essentials of human anatomy & physiology (12th ed. Global Edition). USA: Pearson's Higher Ed.
Marieb, E. N. & Hoehn, K. (2007). Human anatomy & physiology (7th ed). USA: Pearson's Higher Ed.
Marieb, E. N. & Keller, S. M. (2018). Essentials of human anatomy and physiology (International/Global Edition 12th ed.). Pearson Education. Australia: Pearson.
Tortora, G. J. & Derrickson, B. (2012). Principles of anatomy and physiology (13 ed.) USA:Wiley