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

Page 39:

  • 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

Page 40:

  • 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

Page 41:

  • Phagocytosis process

    1. CHEMOTAXIS

    • Microbe attracts phagocyte

    1. ADHERENCE

    2. INGESTION

    • Pseudopod extends and engulfs microbe

    • Phagosome forms

    • Lysosome fuses with phagosome

    1. DIGESTION

    • Digestive enzymes break down microbe

    • Indigestible material forms residual body

    1. KILLING

    • Microbe is killed

    • Digested material is released

Page 42:

  • Natural Killer (NK) Cells

    • Can lyse and kill cancer cells

    • Can destroy virus-infected cells

    • Secrete potent chemicals that enhance the inflammatory response

Page 43:

  • Inflammation

    • Triggered when body tissues are damaged due to injury, disease, or infection

    • Damaged tissues release chemical mediators (e.g., histamine) which result in:

      1. Vasodilation and increased vessel permeability

      2. Emigration of phagocytes from the blood into the interstitial space and then to the site of damage

      3. Tissue repair

    • Four most common indicators of acute inflammation:

      1. Redness

      2. Heat

      3. Swelling

      4. Pain

Page 44:

  • Inflammation

    • Functions to:

      • Prevent spread of damaging agents

      • Dispose of cell debris and pathogens through phagocytosis

      • Set the stage for repair

Page 45:

  • 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

Page 46:

  • 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

Page 47:

  • Antimicrobial Proteins

    • Either attack microorganisms directly or hinder the multiplication of viruses

    • The most important antimicrobial proteins are:

      • Complement proteins

      • Interferon

Page 48:

  • 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

Page 49:

  • 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

Page 50:

  • 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

Page 51:

  • 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

Page 52:

  • 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

Page 53:

  • 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

Page 54:

  • 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:

    1. Antigen specific — recognizes and acts against particular foreign substances (antigens)

    2. Systemic — not restricted to the initial infection site

    3. Memory — recognizes and mounts a stronger attack on previously encountered pathogens

Page 55:

  • Types of Adaptive Immunity

    1. Humoral immunity = antibody-mediated immunity

    • Provided by antibodies present in body fluids

    1. Cellular immunity = cell-mediated immunity

    • Targets virus-infected cells, cancer cells, and cells of foreign grafts

Page 56:

  • Antigens are foreign agents that elicit an immune response

  • Antigens tend to be foreign, organic, structurally complex, and large

Page 57:

  • 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

Page 58:

  • 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

Page 59:

  • 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

Page 60:

  • 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

Page 61:

  • 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

Page 62:

  • 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

Page 63:

  • 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

Page 64:

  • 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

Page 65:

  • Antibodies, also called immunoglobulins (Igs), are soluble Y-shaped proteins secreted by B cells

  • Antibodies bind specifically to an antigen

Page 66:

  • 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

Page 68:

  • Antibodies have different classes with different roles

  • The five major immunoglobulin classes are IgM, IgA, IgD, IgG, and IgE

Page 70:

  • Antibodies inactivate antigens through complement fixation, neutralization, agglutination, and precipitation

  • All of these mechanisms facilitate phagocytosis

Page 72:

  • 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

Page 74:

  • 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

Page 75:

  • 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

Page 76:

  • 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

Page 77:

  • Sensitization stage

    1. Antigen (allergen) invades body

    2. Plasma cells produce large amounts of class IgE antibodies against allergen

    3. IgE antibodies attach to mast cells in body tissues (and to circulating basophils)

    4. Mast cell granules containing histamine

Page 78:

  • Subsequent (secondary) responses

    1. More of the same allergen invades body

    2. Mast cell granules release allergen contents after binding to IgE

    3. Histamine causes blood vessels to dilate and become leaky

    4. Promotes edema

    5. Stimulates release of large amounts of mucus

    6. Causes smooth muscles to contract

Page 79:

  • 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

Page 80:

  • 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