Lymphatic and Immune System: Overview

Lymphatic & Immune Systems Overview

• The goal is to understand components and function of lymphatic and immune systems.
• The goal is to discuss antibody structure, role in immune response.
• The goal is to describe different types of immunity.
• The goal is to learn mechanisms of inflammatory response and mediators involved.
• The goal is to describe cardinal signs/symptoms of inflammation
• The goal is to breakdown basic mechanisms of tissue healing and factors involved.

Lymphatic System Relationship to Circulatory

• Returns excess interstitial fluid to cardiovascular system, working with venous circulation.
• Lymphatics, heart, and blood vessels function interdependently.

Lymphatic System Components

• Lymph is a component.
• Lymph vessels transports lymph.
• Lymphatic tissues play a role.
• Lymph nodes & nodules.
• Spleen plays a role.
• Thymus gland is a component.
• Red bone marrow is where blood cells are produced.
• Tonsils act as a first line of defense.

Lymphatic System Function

• Facilitates fluid movement.
• Removes excess fluid, proteins, and waste products.
• Filters and destroys foreign material.
• Initiates immune response:
• Absorbs lipids from the gastrointestinal tract.

Lymph Composition

• Mostly water/plasma
• Contains excess interstitial fluid entering lymph capillaries.
• Returns fluid to blood via lymphatic vessels to maintain blood volume and blood pressure.
• Contains leukocytes as immune cells.
• Contains proteins.
• Contains electrolytes.
• Contains waste products like urea and creatinine.

Lymphatic System Details

• Lymphatics have thinner walls than veins and collapse more easily under pressure.
• Lymph is absorbed at the capillary level.
• Lymph channeled through pre-collectors, then larger collectors.
• Collectors have smooth muscle and valves.
• Larger vessels merge into trunks and then ducts.
• The right lymphatic duct drains lymph from the upper right quadrant.
• The thoracic duct drains the rest.

Lymphatic System Components

• Cisterna chyli collects lymph from abdomen and drains in thoracic duct.
• Lymphatic ducts return lymph fluid to subclavian veins.

Lymph Movement

• Movement driven by diffusion and filtration processes.
• Movement also driven by nerve stimulation.
• Movement also driven by mild stimulation of dermal tissue.
• Movement also driven by arterial pulsation, skeletal muscle pump, or respiratory pump.

Lymphangion

• Lymphangion is the functional unit of lymph vessel and exists between adjacent valves.
• Lymphangions' walls contain smooth muscle; its intrinsic pumping mechanism is pressure sensitive.

Lymph Nodes Details

• Encapsulated structures with a diameter of 1 to 2 cm.
• Found along lymph vessel pathways.
• Lymph enters via afferent vessels and exits via efferent vessels.
• Filter lymph, phagocytizing bacteria and foreign materials by macrophages.
• Plasma cells are developed from B lymphocytes exposed to pathogens and produce antibodies.

Lymph Nodules Details

• Size ranges from a fraction of a millimeter to several millimeters.
• Lack a capsule.
• Located beneath the epithelium of mucous membranes. Examples include:
• Respiratory, digestive, urinary, and reproductive tracts.
• Tonsils, lymph nodules in the pharynx, including palatine, pharyngeal (adenoid), and lingual tonsils.
• Peyer's patches, lymph nodules in the small intestine.

Spleen Location/Function

• Located in the upper left quadrant of the abdominal cavity, below the diaphragm and behind the stomach.
• Produces RBCs in a fetus. The Spleen functions after birth by:
• Filtering blood.
• Housing plasma cells that produce antibodies against foreign antigens.
• Housing monocytes and fixed macrophages to phagocytize foreign material in the blood.
• Monocytes enter circulation for tissue damage clean up/repair.
• Stores and destroys platelets.

Thymus Location/Function

• Inferior to the thyroid.
• Decreases in size with age.
• Stem cells produce T lymphocytes (T cells).
• Thymic hormones and other cells enable immunological competence of T cells.
• Immature T cells introduced to the body to develop self-recognition and self-tolerance.

Components of Immune System

• Lymphoid structures and tissues.
• Locations of immune cell development.
• Bone marrow: origin of immune cells.
• Thymus: maturation of T lymphocytes.
• Immune cells.
• Leukocytes.
• Macrophages.

Innate vs. Adaptive Immunity

• Innate immunity.
• Non-specific response.
• Includes anatomic/physiological barriers, phagocytic/defensive cells, inflammatory process along with chemical secretions.
• Does not increase in efficiency with repeated exposure.
• Adaptive immunity.
• Specific.
• Carried out by lymphocytes and macrophages.
• Includes cell-mediated and antibody-mediated processes.
• Becomes more efficient w/ repeat exposure.

Elements of Immune Response: Self Antigens

• Cell surface antigens are found on cell membranes.
• HLA complex: group of genes coding for the production of specific proteins used to distinguish body's own proteins from foreign substances.
• The immune system normally ignores self cells/antigens due to self-recognition and self-tolerance.

Elements of Immune Response: Non-self Antigens

• Immune system recognizes NON-self antigens as foreign.
• Creates specific response to target antigen.
• Memory cells produced to respond quickly when encountered again.

Major Immune Cells

• Mast cells.
• Neutrophils.
• Basophils.
• Eosinophils.
• Monocytes.
• Macrophages.
• Dendritic cells.
• Lymphocytes.

Immune Cell Functions

• Mast cells release histamine and chemical mediators in inflammatory response.
• Neutrophils phagocytize and are active in inflammatory process.
• Basophils play a major role in allergic reactions, releasing histamine and binding to IgE.
• Eosinophils respond to allergies. Eosinophils phagocytize, are antiparasitic, and bactericidal.
• Monocytes mature into macrophages upon migration into tissues because of infection/inflammation.
• Macrophages phagocytize, process, and present antigens to lymphocytes.
• Dendritic cells phagocytize, and act as antigen presenting cells.

Lymphocyte Types

• Lymphocytes include T cells, B cells, & NK (natural killer) cells.

Cells of Immune System/Macrophages

• Macrophages present throughout body.
• Macrophages initiate immune response, developing from monocytes.
• Macrophages engulf foreign material and process/display foreign antigen on their cell membranes.
• Lymphocytes respond to the display, triggering an immune response. Secrete Chemicals:
• Examples: monokines and interleukins.

Lymphocyte Types

• Lymphocytes include B Lymphocytes, T Lymphocytes, and Natural Killer Cells

T Lymphocytes (T Cells)

• T cells arise from bone marrow stem cells and then differentiate and mature in the thymus.
• Have a major role in cell-mediated immunity and include cytotoxic, helper, memory, and regulatory T cells.

T Lymphocyte Details

• Cytotoxic T killer cells bind to antigen and release cytotoxic enzymes and chemicals.
• Helper T cells regulate the entire immune system via secretion of messenger molecules for specific actions.
• The primary task of helper T cells is to activate B cells and cytotoxic T cells.
• Memory T cells remain in lymph nodes for years and respond if exposed to the same antigen in the future.
• Regulatory T cells suppress the immune response when no longer needed.

B Lymphocytes (B Cells)

• Responsible for antibody/immunoglobulin production.
• Mature in bone marrow and moves to spleen & lymphoid tissue.
• Involved in fighting bacteria and viruses that are outside of cells. Two types:
• Plasma cells produce antibodies
• B memory cells form clone of plasma cells.

Natural Killer Cells

• Natural killer cells are distinct from T and B cells.
• Natural killer cells destroy tumor and virus-infected cells without prior exposure.
• Localized to infected tissue in response to cytokines as a chemical signal.

Adaptive Immunity Types

• Cell-mediated immunity (CMI).
• Programmed lymphocytes attack non-self cells.
• Develops when T cells with protein receptors on cell surface recognize and destroy invading antigens on target cells.
• Programmed T cells reproduce, creating more cells to battle the antigen.
• Antibody-mediated (humoral) immunity.
• Antibodies protect the body.
• B cells become plasma cells after exposure to antigens to release antibodies.

Antibody Details

• Antibodies also known as immunoglobulins.
• Antibodies are found within general circulation and lymphoid tissues,
• There are five major classes of immunoglobulins.
• Classes are based on their constant region structure & immune function. The two regions include:
• Constant region: attaches to macrophages & other effector cells with immunoglobulin.
• Variable region: unique set of amino acids that binds to a specific antigen.

Antibody Structure

• Contains a 'C' or constant region which determines the mechanism used to destroy an antigen related to its Immunoglobulin class.
• Contains a 'V' or variable region that allows for specific binding of a given antigen.

Classes of Antibodies

• IgG: Most abundant, crosses placenta, and includes antiviral/antibacterial/antitoxin antibodies.
• IgM: Usually first to increase in immune response and is bound to B lymphocytes and don't require helper T cells.
• IgA: Provides localized defense, and is found in secretions.
• IgE: Binds to mast cells or basophils and causes histamine release.
• IgD: Activates B cells in bone marrow.

Complement System

• Group of inactive proteins circulating in blood (C1 to C9).
• Activated in innate and adaptive immune response.
• Cascade of reactions is initiated w/ antigen-antibody complex binds with C1.
• Activation results in cell damage & further inflammation.

Acquired (Adaptive) Immunity: Two Step Process

• Primary response occurs with first exposure to antigen:
• Antigen recognized and processed, sensitizing T lymphocyte, and developing antibodies.
  • This takes 1-2 weeks for the antibody level reaches full efficacy.
• Secondary response occurs with repeat exposure to the same antigen:
  • Antibodies can be produced is with efficacy taking between 1-3 day.

Acquired (Adaptive) Immunity Types

• Passive natural immunity.
  • IgG transferred from mother to fetus (across placenta or through breast milk) to protect infant for the first few months.
• Passive artificial immunity.
  • Injection of antibodies for short-term protection.
• Active natural immunity.
  • Natural exposure to antigen that develops antibodies.
• Active artificial immunity.
  • Antigen purposefully introduced to body to stimulate antibody production, such as immunizations.

Acquired Immunity Types Summary

• Natural active: Pathogens enter body and cause illness, which forms antibodies with memory. For example Chickenpox.
• Artificial active: Vaccine is injected into a person with no illness but antibody formation with memory. For example Measles.
• Natural passive: Antibodies are passed directly from mother to child, there are temporary so there is no memory, for example through Placental passage.
• Artificial passive: Antibodies injected or given intravenously to provide temporary protection with no memory, for example with Gammaglobulin.

Inflammatory Response Overview

• Body's first line of defense is nonspecific and a mechanical barrier such as skin or mucous.
• Body's second line of defense is also nonspecific in which bacteria, cell debris, and foreign material are engulfed and destroyed.
• Body's third line of defense is specific, such as antibody or cell-mediated immunity.

Physiology of Inflammation Details

• Inflammation is a normal defense mechanism, serving as a warning sign.
• Problems may be hidden within the body.
• Inflammation process is the same, regardless of cause; note inflammation is unlike infection. "itis" suffix to denote inflammation

Common Causes of Inflammation

• Direct physical damage: cut or sprain.
• Caustic chemicals: strong acid and drain cleaner type products.
• Ischemia or infarction.
• Allergic reactions.
• Extremes of heat or cold.
• Foreign bodies such as splinters.
• Infections.

Acute Inflammation Events

• Chemical mediators affect blood vessels & nerves in damaged area.
• Vasodilation occurs because of relaxation of smooth muscles, which then increases diameter of arterioles.
• Hyperemia occurs, increasing blood flow to damaged area.
• Increase in capillary permeability causes plasma proteins to move into interstitial space along with more fluid.
• Fibrinogen is activated, forming fibrin mesh to localize the injurious agent (blood clotting "walls off" area.)
• Chemotaxis attracts leukocytes by movement of a substance or cell in response to a chemical stimulus released at inflammation site.

Local Effects of Inflammation Details

Cardinal Signs of Inflammation:

• Redness caused by increased blood flow to damaged area.
• Warmth or heat from increased blood flow to the damaged area.
• Swelling (edema) from shift of protein and fluid into the interstitial space.
• Pain from increased pressure of fluid on nerves; release of chemical mediators (e.g., bradykinins).
• Loss of function due to possible lack of nutrients and/or edema/pain that interferes with motion.

Systemic Effects of Inflammation

• More general manifestations of inflammation:
• Mild fever (pyrexia).
• Commonly occurs with extensive inflammation because of pyrogens with WBC/Macrophages.
• More severe fever occurs if infection is also present.
• Malaise: generalized feeling of being unwell.
• Fatigue.
• Headache.
• Anorexia: lack of appetite.

Chemical Mediators

• Histamine: Vasodilation and increased capillary permeability to form exudate.
• Chemotactic factors: Attract leukocytes to site.
• Platelet activating factor (PAF): Activates neutrophils which causes platelet aggregation.
• Cytokines (interleukins and tumor necrosis factor): Increase protein, increase ESR, induce fever, cause chemotaxis and leukocytosis.
• Leukotrienes: vasodilation and increases capillary permeability which causes chemotaxis.
• Prostaglandins: Causes vasodilation, capillary permeability and potentiates histamine effect triggering pain and fever.
• Kinins (bradykinin): Vasodilation which increases capillary permeability triggering chemotaxis and pain.
• Complement System increases vasodilation, capillary permeability, chemotaxis and histamine release.

Blood Value Changes with Inflammation

• Leukocytosis is the increased number of WBCs, especially neutrophils.
• Differential count is WBC proportions depend on inflammation cause. Increased plasma proteins related to increased fibrinogen and prothrombin.
• C-reactive protein appears with acute inflammation and necrosis.
• Increases ESR (SED rate) because of increased plasma proteins.
• Increased cellular enzymes because of released from necrotic cells and tissue fluids & blood.

Overview of Chronic Inflammation

• May follow acute inflammation if cause is not completely resolved.
• Can occur w/ long-term irritation/autoimmune conditions.
• Compared to acute inflammation its has: less swelling/exudate, increase presence of lymphocytes/macrophages/fibroblasts and more scar tissues.
• Continued presence promotes tissue destruction.
• May develop granuloma by presence of smalls cell masses with necrotic center covered by connective tissue.

Inflammation Complications

• Complications depends on site and cause and relates to:
  • Infection which leads to microorganisms penetrating edematous tissues.
  • Muscle spasms as a protective pain response.
  • Ulcerations.
• Suppressed immune system is also a complication.

Types of Healing: Resolution

• Resolution occurs when there is minimal tissue damage.
• Damaged cells recover.
• Tissue returns to normal within a short time period.
• Example: mild sunburn.

Types of Healing: Regeneration

• Regeneration occurs in damaged tissues with cells capable of mitosis.
• Some epithelial cells constantly replicate, but others don't.
• Types of tissue have a greater potential for regeneration when replaced by mitosis.
• Nearby cells proliferate to replace identical cells.

Types of Healing: Replacement

• Replacement happens when functional tissue is replaced by scar tissue or fibrous tissue.
• Replacement for cells incapable of mitosis or excessive damage like Cardiac or Brain tissue. Loss of function can occur.
• Chronic inflammation and infection lead to scarring.

Healing by First Intention

• Primary intentions in wound is closesly re-approximated.
• It occurs readily when wound is clean, free of foreign material and in a non necrotic state.
• It is a normal healing process in post op procedures or small wounds.
• It yields thinner scars as a result of healing.

Healing by Second Intention

• Occurs with large tissue breaks in which edges cannot be approximated.
• Often has more inflammation and a longer healing period.
• More scar formation occurs.

Healing Process Step-by-Step

• Healing starts when a clot forms to seal the area.
• 3-4 days after injury, foreign material and cell debris are removed by phagocytes, monocytes & macrophages.
• Granulation tissue, rich with blood supply (highly vascularized), grows from nearby connective tissue and fills in the "gap".
• It is moist and pink in appearance and contains new capillary buds, as well as fragile tissue to protect them.
• Near wounds, nearby epithelial cells undergo mitosis.
  • New formed cells extends across the wound towards outside edges inwardly.
• Fibroblasts then begin to form collagen, creating growth factors which stimulate epithelial cell proliferation and new blood flow.
• Collagen fiber cross linking leads to the development of a tight strong scar.
• Capillaries then decrease leading to scar color gradually fading after 12-18 months.

Factors Promoting and Delaying Healing

• Promoting Younger age, Effective circulation, Adequate hemoglobin and Proper nutritional consumption of Protien/ Vitamins A & C

• Delaying such as Smoking / Poor Circulation, Advanced age/Chronic conditions,Anemia/ Dehydration, Prolonged steroid use or radiation treatment can lead to delayed the rates of healing.