Lymphatics and the Immune System

Lymphatic System

• One-way system: towards the heart.
• Returns collected excess tissue fluid.
• Returns leaked protein.
• Lymph: fluid within the lymphatic system.
• Edema: swelling due to blocked or surgically removed lymphatic system.

Lymph Capillaries

• One-way mini valves: allow excess fluid to enter but not leave.
• Picks up: bacteria, viruses, proteins, electrolytes, and fluid.
• Lymph nodes: destroy most pathogens.

Lymphatic Vessels

• Absent: bone, bone marrow, teeth, CNS.
• Lymphatic collecting vessels.
• Similar to blood vessels (three layers) but thin and delicate.
• Superficial: in skin, travel with superficial veins.
• Deep: trunk and digestive viscera, travel with deep arteries.
• Very low pressure.
• Lymphangiography: distinctive appearance.
• Drain into lymph nodes.

Lymph Nodes

• Bean-shaped organs along lymphatic collecting vessels.
• Size: Up to 1 inch.
• Clusters: Both deep and superficial.
• Fibrous capsule sends in dividing trabeculae.
• Afferent and efferent lymphatic vessels.
• Lymph percolates through lymph sinuses.
• Follicles: masses of lymphoid tissue (outer cortex & inner medulla).
• Macrophages on reticular fibers consume pathogens and foreign particles.
• Usually pathogen-free lymph enters lymph trunks.

Lymph Node Groups and Drainage

• Superficial Groups:
  • Cervical
  • Axillary
  • Inguinal
• Deep Groups:
  • Tracheobronchial
  • Aortic
  • Iliac
• Drainage:
  • Superior Right 1/4 of body: Right lymphatic duct
  • The rest: Thoracic duct

Lymphatic Trunks

• Lumbar: paired.
• Intestinal: Receives fatty lymph (chyle) absorbed through lacteals in villi of intestines; unpaired.
• Broncho-mediastinal: paired.
• Subclavian: paired.
• Jugular: paired.

Lymph Ducts

• Thoracic Duct: everyone has one.
• Right Lymphatic Duct: 20% of people also have one.

The Immune System

• Recognizes Specific Foreign Molecules.
• Exposure Effectivity: Each exposure to the same pathogen increases the effectiveness of the response.
• Lymphoid Organs:
  • Lymph nodes
  • Spleen
  • Thymus
  • Tonsils
  • Small intestine & appendix aggregated lymphoid nodules.

Basic Immunology

• Distinguishes Between: Self and non-self molecules.
• Self Molecules: Components of an organism's body distinguished from foreign substances by the immune system.
• Autoimmunity: Immune reaction against self-molecules, causing various diseases.
• Non-Self Molecules: Recognized as foreign molecules.
• Antigens: Substances that bind to specific immune receptors and elicit an immune response (antibody generators).

Lymphocytes

• Primary cells of the lymphoid system.
• Respond to:
  • Invading Organisms
  • Abnormal body cells (virus-infected or cancer cells).
  • Foreign Proteins (toxins released by bacteria).
• Types of lymphocytes:
  • T cells (thymus-dependent)
  • B cells (bone marrow-derived)
  • NK cells (natural killer)

T Cells

• 80% of circulating lymphocytes.
• Types:
  • Cytotoxic T cells: Attack foreign cells or virus-infected cells (cell-mediated immunity).
  • Regulatory T cells: Helper and suppressor T cells, control B cell activation.
  • Memory T cells: Produced after exposure to a particular antigen, remain on reserve for later exposure.

B Cells

• 10-15% of circulating lymphocytes.
• Differentiate: into plasmocytes (plasma cells) when stimulated by an antigen.
• Plasma Cells: Produce antibodies (immunoglobulins or Ig’s), which react with antigens.
• Mediates: Humoral immunity (antibody-mediated immunity).
• Memory B cells: Produced after exposure to a particular antigen, remain on reserve for later exposure.

NK Cells

• 5-10% of circulating lymphocytes.
• Attack foreign cells, virus-infected cells, and cancer cells.
• Immunologic Surveillance.

Humoral vs. Cell-Mediated Immunity

• Cell-mediated immunity: Direct attack by activated T cells reacting with foreign antigens on other host cells.
• Antibody-mediated (humoral) immunity: Attack by circulating antibodies (immunoglobulins) released by plasma cells derived from activated B cells.
• Humor: Old-fashioned word for stuff in the blood.
• Interaction: These two systems interact with each other.

B Lymphocytes

• Antigen Receptor: Antibody on B cell surface.
• Respond: Can respond to millions of foreign antigens.
• Capability: Exists before exposure to any antigens.
• Each lineage: Expresses a different antibody.
• Complete Set: Represents all antibodies the body can manufacture.
• Identification: B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigen.
• Antigen/Antibody Complex: Taken up by the B cell and processed into peptides.
• Clonal Expansion: Activated B cell divides, offspring secrete millions of copies of the antibody.
• Circulation: Antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen, and mark them for destruction.
• Antibodies: Can also neutralize challenges directly by binding to bacterial toxins or interfering with the receptors viruses and bacteria use to infect cells.

Immune System Needs

• Attack Infected Cells: T cells target cells with altered (antigenic) proteins on their surfaces due to viral infection or cancerous changes.
• Handle Extracellular Antigens: Antibodies made by plasma cells bind to antigens on bacteria, marking them for destruction by macrophages.

Definitions

• Cells: in our bone marrow, thymus, and the lymphatic system of ducts and nodes, spleen, and blood that function to protect us.
• Antigen: Anything causing an immune response, usually foreign material but may be our own tissues.
• Pathogen: Any disease-causing microorganism.
• Tolerance: Non-reactivity of the immune system, usually refers to "self" but may include foreign tissue in organ transplants.
• Autoimmunity: A failure of tolerance, the immune system reacts to self.
• Chemokines: Molecules released by pathogens and infected tissues to attract cells of the immune system.
• Cytokines: Signaling molecules released by one cell to cause a response in another.
• Innate Immunity: Protection that is always present. Includes phagocytic (cells that eat other cells) macrophages and dendritic cells.
• Adaptive Immunity: Protection that arises by an immune response, including humoral immunity producing antibodies and cellular immunity.

Lymphocyte Development

• Originate: in bone marrow from lymphoid stem cells.
• B Cells: Stay in bone marrow, hence "B" cells.
• T Cells: Mature in thymus, hence "T" cells.
• Division: These divide rapidly into families.
• Immunocompetence: Each has surface receptors able to recognize one unique type of antigen.

Lymphocyte Activation

• Naive immunocompetent lymphocytes "seed" secondary lymphoid organs (especially lymph nodes).
• Antigenic Challenge: Full activation upon meeting and binding with specific antigen.
• The B cell’s antigen receptor is an antibody
• Full Activation
  • Gains ability to attack its antigen
  • Proliferates rapidly producing mature lymphocytes
• Mature lymphocytes re-circulate seeking same pathogens

Immunologic Memory

• Offspring: When B cells and T cells are activated and begin to replicate, some offspring become long-lived memory cells.
• Lifetime: Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again.
• Adaptive: This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges.
• Immunity: For example immunity to chicken pox after you’ve had it.
• Immunological Memory: can either be in the form of passive short-term memory or active long-term memory.
• Example: Passive immunity in breast milk (wanes within a short time, weeks to months).

Immune System Defenses

• Physical Barriers: Prevent pathogens from entering the body.
• Innate Immune System: An immediate, but non-specific response.
• Adaptive Immune System: Adapts its response during an infection to improve its recognition of the pathogen.
• Immunological Memory: This improved response is retained after the pathogen has been eliminated, allowing for faster and stronger attacks upon subsequent encounters.

Components of Immune System

• Innate Immune System:
  • Response is non-specific.
  • Exposure leads to immediate maximal response.
  • Cell-mediated and humoral components.
  • No immunological memory.
  • Found in nearly all forms of life (plants & animals).
• Adaptive Immune System:
  • Pathogen and antigen specific response.
  • Lag time between exposure and maximal response.
  • Cell-mediated and humoral components.
  • Exposure leads to immunologic memory.
  • Found only in jawed vertebrates.

Innate Immunity

• Dominant system: of host defense in most organisms.
• Inflammation: one of the first responses.
• Redness, swelling, heat and pain.
• Chemical and cellular response.
• Chemotaxis: During the acute phase of inflammation, neutrophils migrate toward the site of inflammation.

Innate Immunity - Leukocytes

• Phagocytes: (macrophages, neutrophils, and dendritic cells).
• Other Cells: mast cells, eosinophils, basophils, and natural killer cells.
• Function: Identify and eliminate pathogens.
• Mechanism: Attacking larger pathogens through contact or engulfing and killing microorganisms.
• Mediators: Important mediators in the activation of the adaptive immune system.

Innate Immunity - Macrophages

• Versatile cells: reside within tissues.
• Produce Wide Array: Enzymes, complement proteins, and regulatory factors such as interleukin 1.
• Scavengers: Ridding the body of worn-out cells and other debris.
• Act as Antigen-Presenting Cells: Activate the adaptive immune system.

Innate Immunity - Dendritic Cells

• Phagocytes: in tissues that are in contact with the external environment.
• Location: mainly in the skin, nose, lungs, stomach, and intestines.
• Link: Serve as a link between the innate and adaptive immune systems.
• Function: Present antigens to T cells, one of the key cell types of the adaptive immune system.

Innate Immunity - Mast Cells

• Reside: in connective tissues and mucous membranes.
• Inflammatory Response: Regulate the inflammatory response.
• Association: Most often associated with allergy and anaphylaxis (release histamine, antihistamines help allergic reactions).

Phagocytosis

• Cellular Innate Immunity: Performed by cells called 'phagocytes' that engulf, or eat, pathogens or particles.
• Patrolling: Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines.
• Pathogen Destruction: The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome.
• Ancient Defense: Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals.

Adaptive Immunity

• Evolution: Evolved in early vertebrates.
• Stronger Response: Allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by its signature antigen.
• Antigen-Specific: Requires the recognition of specific “non-self” antigens during a process called antigen presentation.
• Tailored Responses: Allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells.
• Memory Cells: The ability to mount these tailored responses is maintained in the body by "memory cells“.
• Quick Elimination: Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.

Major Histocompatibility Complex (MHC)

• Self Proteins.
• Class 1: on most nucleated cells.
• Class II: only on a few cells (B lymphocytes & macrophages) which interact with Th cells.
• CD8+: proteins associated with Tc (cytotoxic or killer T cells).
• CD4+: proteins associated with Th (helper T cells).
• Reduced in AIDS.

MHC and T Cell Interactions

• MHC = Major Histocompatibility
• Are “self” proteins, and have the most genetic (person to person) variability
• Class I: on most nucleated cells
• Class II: only on a few cells (B lymphocytes & macrophages) which interact with Th cells
• CD8 is a protein on Tc’s (cytotoxic or killer T cells) which recognizes class I MHCs
  • The class I MHC binds the Ag inside the body’s cell (any cell) which is being made because of its infection, and takes it to the surface of the cell
  • The Tc cell recognizes Ag as foreign so treats this cell of the body as foreign and sends a chemical signal to cell for it to self-destruct (by apoptosis = programmed cell death)
• CD4 is a protein on Th (helper T cells) which recognizes class II MHCs
  • Class II MHC cells are only B lymphocytes and macrophages: these take up extracellular antigens, e.g. bacteria which multiply outside cells, toxins produced by bacteria, etc.; MCH II binds these, takes them to surface, so the lymphocyte become an “antigen presenting cell”
  • Helper (CD4) T cells secrete cytokines which stimulate the proliferation of activated B cells, cytotoxic T cells (CD8+) and macrophages and amplify their response

Lymphoid Organs

• Lymph nodes
• Spleen
• Thymus
• Tonsils
• Small intestine & appendix aggregated lymphoid nodules

Lymphoid Tissue

• Specialized connective tissue with vast quantities of lymphocytes
• Lymphocytes become activated.
• Memory.
• Macrophages & dentritic cells also.
• Clusters of lymphoid nodules or follicles.

Thymus

• Prominent in newborns, almost disappears by old age.
• Function: T lymphocyte maturation (immunocompetence).
• Has no follicles because no B cells.

Lymph Nodes

• Lymphatic and immune systems intersect.
• Masses of lymphoid tissue between lymph sinuses (see next slide).
• Some of antigens leak out of lymph into lymphoid tissue.
• Antigens destroyed and B and T lymphocytes are activated: memory (aiding long-term immunity).

Lymph Node Structure

• Follicles: masses of lymphoid tissue divided into outer cortex & inner medulla
• All follicles and most B cells: outer cortex
• Deeper cortex: T cells, especially helper T cells
• Medullary cords: T & B lymphocytes and plasma cells

Spleen

• Largest lymphoid tissue; in LUQ posterior to stomach.
• Functions
  • Removal of blood-borne antigens: “white pulp”
  • Removal & destruction of aged or defective blood cells: “red pulp”
  • Stores platelets
  • In fetus: site of hematopoiesis
• Susceptible to injury; splenectomy increases risk of bacterial infection.

Tonsils

• Palatine (usual tonsillitis)
• Lingual (tongue)
• Pharyngeal (“adenoids”)
• Tubal
• Simplest lymphoid tissue: swellings of mucosa, form a circle
• Crypts get infected in childhood

Aggregated Lymphoid Nodules

• (“Peyer’s Patches”)
• About 40 follicles, 1 cm wide
• Distal small intestine (ileum)
• Appendix
• Parts of the intestine are so densely packed with MALT (mucosa-associated lymphoid tissue) that they are considered lymphoid organs.