Immune & Lymphatic Systems

The Immune & Lymphatic Systems

• The lymphatic and immune systems' components and functions are identified. Structure of the role and antibodies in the immune responses are discussed. Different types of immunity, mechanisms of inflammation, its mediators, signs, symptoms, and tissue healing are also covered.

The Lymphatic System

• Returns excess interstitial fluid to the cardiovascular system, working in concert with venous circulation. Both the heart and blood vessels are interdependent and contribute to the structure.
• Lymph, lymph vessels, lymphatic tissues, lymph nodes and nodules, spleen, thymus gland, red bone marrow, and tonsils are components.
• It facilitates fluid movement, removes excess fluid, proteins and waste products. It also filters & destroys foreign material, initiates immune response, and absorbs lipids from the GI tract.

Lymph

• Mostly water/plasma consisting of excess interstitial fluid that enters lymph capillaries, and is returned to the blood through lymphatic vessels. This is an important function to maintain blood volume and BP
• Lymph contains leukocytes, proteins, electrolytes, urea, creatinine, and other waste products.

Lymphatic System

• Lymphatics collapse easier under pressure and have thinner walls than veins.
• Lymph is first absorbed at the capillary level, channeled through small vessels (pre-collectors) then larger vessels (collectors).
• Collectors have smooth muscle and valves.
• Larger vessels merge into trunks and then ducts, where the right lymphatic duct drains lymph from the upper right quadrant and the thoracic duct drains the rest.
• Cisterna chyli collects lymph from the abdomen and drains into the thoracic duct.
• Lymphatic ducts transfer lymph fluid to the subclavian veins.

Lymph Movement

• Lymph fluid moves via diffusion, filtration, and additional mechanisms that include nerve stimulations, mild tissue stimulation, arterial pulsation adjacent to lymph vessels, also muscle contractions, and abdominal/thoracic cavity pressure.
• Lymphangion is the functional unit of lymph vessels, in the portion of vessels between adjacent valves. It contains smooth muscle in the walls, and an intrinsic pumping mechanism triggered by pressure in the vessel.

Lymph Nodes

• Encapsulated and range between 1 and 2 cm in diameter, being found in groups along lymph vessel pathways.
• Lymph enters via afferent lymph vessels and leaves via efferent vessels.
• Lymph node’s function is to filter lymph fluids to phagocytize bacteria and other foreign materials with macrophages. Plasma cells develop from B lymphocytes exposed to pathogens to create antibodies.

Lymph Nodules

• Range from fractions of mm to several mms in size and do not have a capsule.
• Nodules are located just beneath the mucous membranes' epithelium in respiratory, digestive, urinary, and reproductive tracts.
• Tonsils are lymph nodules in the pharynx, where palatine, pharyngeal (adenoid), and lingual tonsils form a ring of lymphatic tissue around the pharynx. the Peyer's patches, are lymph nodules in the small intestine.

Spleen

• Located in upper left quadrant of the abdomen.
• The spleen produces RBCs when in the fetus but its main function following birth is to; filter blood, contain plasma cells, produce antibodies in response to foreign antigens, and store platelets.
• The spleen contains monocytes and fixed macrophages that can phagocytize foreign substances, and monocytes can also enter circulation when tissue is damaged/needs cleaning.

Thymus

• Located inferior to the thyroid, and gets smaller with age.
• Stem cells produce T lymphocytes (T cells) which create thymic hormones and enable cell competence. Immature T Cells learn self-recognition during development.

The Immune System

• Lymphoid structures & tissues and specific locations are key for immune cell development.
• Bone marrow originates all immune cells.
• Thymus is responsible for T lymphocyte maturation.
• The immune cells contain leukocytes and macrophages.

Innate Vs. Adaptive Immunity

• Innate immunity has a non-specific response including anatomic and physiological barriers, phagocytic and defensive cells, and inflammatory processes. Efficiency does not repeat with repeated exposure.
• Adaptive immunity is specific, driven by lymphocytes and macrophages. It also becomes more efficient, and involves both cell-mediated and antibody-mediated processes.

Immune Response

• Key elements for immune responses include antigens such as cell surface antigens, which are part of the HLA complex of genes specific to protein production. They distinguish what is "self" versus "non-self" to know what must be ignored/tolerated.
• "Non-self" cells are recognized as foreign by the body which then develops a specific response. Memory cells are produced so that the immune system can respond more rapidly when the antigen is encountered again.

Major Immune Response Cells

• Mast cells, Neutrophils, Basophils, Eosinophils, Monocytes, Macrophages, Dendritic cells, and Lymphocytes are the major cells of immune response.
• Mast cells release histamine & other chemical mediators during inflammation.
• Neutrophils participate in phagocytosis during inflammation.
• Basophils are involved in allergic reactions.
• Eosinophils are involved in bactericidal and allergic responses.
• Monocytes circulate in blood; mature into macrophages and migrate to tissues.
• Macrophages will phagocytosis, process/present antigens.
• Dendritic cells phagocytosis, and present antigens.
• Lymphocytes contain T cells, B cells, and Natural killer cells.

Cells of the Immune System: Macrophages

• Macrophages present/ initiate the body’s overall immune response, by developing from monocytes.
• They engulf foreign material and proceed to display foreign antigen material on their membranes.
• Lymphocytes respond by triggering the appropriate immune response, using chemicals such as monokines and interleukins.

Cells of the Immune System: Lymphocytes

• Lymphocyte origin is the lymphoblast which then produces B lymphocytes, T lymphocytes, and natural killer cells.
• T lymphocytes originate from bone marrow stem cells and differentiate and mature in the thymus. Major functions include cytotoxicity, support, memory and regulation of immune response by cytotoxic killer cells. Memory is made possible with memory T cells.
• Cytotoxic T killer cells bind to antigens & release enzymes and chemicals to assist in destroying cells, in order to regulate the immune system. “Messenger cytokines” activate B and T cells.
• Memory T cells stay in lymph nodes, in order to respond quick if the same antigen presents in the future.
• Regulatory T cells are able to keep the immune response from running rampant, suppressing immune response when no longer needed.

B Lymphocytes

• B lymphocytes are responsible for the production of antibodies (immunoglobulins), and are found outside of cells fighting bacteria or viruses.
• B cells mature in bone marrow then proceed to the spleen.
• B cells have 2 forms being plasma cells which produce the antibodies, and memory cells which can quickly form clones of plasma cells at a rapid rate.

Natural Killer Cells

• Natural killer cells vary from B and T cells and will destroy tumor cells, virally infected cells and other foreign cells without prior exposure
• NK cells respond to localized infected cytokines by destroying cells, without prior exposure.

Types of Adaptive Immunity

• Cell-mediated immunity is achieved lymphocytes programmed to attack non-self cells. It develops when T cells recognize protein receptors on the target itself, destroying invading antigens. “Programmed”T cells then reproduce to battle the antigens.
• Antibody-mediated (humoral) immunity involves the body creating antibodies, and B cells becoming plasma cells after exposure to antigens.

Development of Humoral Immunities

• Lymphoblasts originating from marrow stem, mature in either the thymus (T cells) or Bone Marrow (B cells). Then both migrate to lymph nodes where they can be exposed to different antigens, which stimulates cellular responses and antibody creation.

Antibodies

• Antibodies also known as immunoglobulins are found within the circulation.
• Antibodies are divided into 5 classes based on their constrant region structrure and immune function.
• Constant regions are attaches to macrophages and will determine the classification of the antibodies.
• Variable regions has a unique structure with a set of a.a.’s which binds to a specific antigen.

Antibody Structure

• Antibodies are built with a constant and variable region to destroy antigens. The specificity of antibody binding is driven by the variable region with the constant region used for destroying antigens, classified by the specific Ig.

Major Antibody Classes

• IgG is the most abundant antibody in the circulation, found in blood and extracellular fluids. IgG contains antiviral and antibacterial properties and contributes to antitoxin antibody production, and can travel across the placenta.
• IgM is bound to B lymphocytes in the circulation, and increase in immune response.
• IgA provides localized defense and is found in secretions and mucosal membranes.
• IgE binds to mast cells or membranes and is involved in responses resulting in inflammation.
• IgD are involved in regulating B cell function and maturation within bone marrow

Immune System Actions

• The complement system involves a group of inactive proteins circulating in blood referred to as C1 to C9.
• The complement is activated during innate and adaptive immune responses, and when antigen-antibody complexes bind with C1, a cascade of rxns sets off.
• This system is responsible for cell damage and inflammation.

Acquired (Adaptive) Immunity

• A two-step process, adaptive immunity is achieved through a Primary and Secondary response.
• Primary response presents with the 1st exposure to an antigen
• The antigen is recognized/processed, which leads to the subsequent antibody production of the antigen. This then occurs within 1-2 weeks for an antibody level to reach its full strength.
• Secondary response involves repeat exposure to that same antigen. This causes more rapid response, with efficacy occurring in 1-3 days.

Passive Immunity

• Passive natural immunity involves IgG transferred from a mother to fetus through placenta and breast milk, protecting until they are a few months old or until weaned.
• Passive artificial immunity is protection via an antibody injection delivering short-term protection.

Active Immunity

• Active natural immunity: Natural exposure causes development of antibodies.
• Active artificial immunity: Introduce antigen purposefully to cause immunizations.

Types of Acquired Immunity

The Inflammatory Response

• Body defenses consist of three lines of defense, starting with Line 1- nonspecific mechanical barriers, through unbroken skin & mucous membranes.
• Secretions contain enzymes which assist in breaking down the surface of bacteria.
• Second Line of Defense- nonspecific phagocytosis of bacteria, cell debris & foreign material, which are engulfed. The next step in the inflammatory response.
• Third Line of defense, is defense-specific, cell or antibody mediated immunity.

Inflammation

• Physiological responses can be warning signs.
• Inflammation is a defense mechanism that’s normal, and that occurs regardlesss of cause.
• The inflammatory process can present despite inflammation and infection. It occurs whenever the cellular matrix triggers the immune response.

Common Causes of Inflammation

• Direct physical damage, Caustic chemicals, Ischemia or infarction, Allergic reactions, Extremes of hot or cold, Foreign bodies and Infection are possible causes of Inflammation.

Acute Inflammation

• Chemical mediators affect blood vessels and cause vasodilation as well as relaxation.
• Increased capillary permeability allows toxic material to dilute so that the body can form an immune reaction.
• Blood clotting wall offs area.
• Lastly, leukocytes are released to further act on a chemical stimulus.

Local Effects of Inflammation

• 5 signs make up inflammation: redness, warmth/heat, swelling, pain, and loss of function.
• Increased blood flow results in redness and warmth.
• Shift in protein and fluid into the interstitial space results in swelling/edema.
• Increased pressure of fluids on the nerve tissue, can cause Pain due to release of chemical mediators such has bradykinins.
• Lastly, Loss of function occurs if there is a lack of cell nutrients, in addition to experiencing edema & pain.

Signs of Inflammation

• More general manifestations of inflammation include mild fever called pyrexia which results from WBC or Macrophage release, in addition to general Malaise, Fatigue, Headache, Anorexia.

Key Actions Driving the Inflammatory Response

Blood Value Changes Due to Inflammation

• Blood value changes that come from blood inflammation cause increased ESR and necrotic processes.

Chronic Inflammation

• May follow acute if cause is not resolved and may come from irritating long term issues.
• Less exudate and swelling, but presence of more macrophages & lymphocytes occurs.
• Granulomas will develop, with increased fibrous scar tissue.

Potential Complications of Inflammation

• Complications will depend on the site & cause of inflammation, such as infection,muscle spasm, ulcers or immune suppression.

Immune Suppression

• Some microbes resist and can penetrate edematous tissue, so that inflammatory exudate also provides a microorganism medium. Then muscle spasms, ulcers, immune suppression, may be initiated by cell necrosis and risk of infection.

Types of Healing include

• Resolution: Occurs when damaged cells recovers.
• Regeneration: Occurs when damaged tissues undergo mitosis (epithelial cells), resulting in proliferation of nearby cells to be replaced with identical cells. These processes take time at different rates.
• Replacement: Functional tissue is replaced by scar tissue, also known as fibrosis. Cardiac and brain tissue function is lost and chronic scarring will occur.

The Healing Process

• Primary intention involves healing of wound edges by re-approximating non traumatic tissue. During smaller and post-operative cuts, this will lead to thinner scars than in the case of larger wounds.
• Secondary intention deals with large breaks in tissue as normal appoximation cannot proceed. This causes more inflammation and thus takes longer and causes more scarring.
• Clot formation sealing an area begins the healing after 3-4 day period, which removes debris from monocytes and macrophages. Granulation occurs as "gap" appears, resulting in “Red and pink” vessels within the tissues. These structures can be broken by stress or microorganism.

Healing Tissue

• Granulation tissue fills in the wound, nearby epithelial cells go under mitosis, fibroblasts appear, and new cells move across the wound inward. Collagen will form causing tight scar tissue by connecting the epithelial structure.
• The process shrinks, causing vessel color is removed, leaving the structure to mature around 12-18 months.

Factors for Promotion

• Certain items can push healing forward as well and includes.
• Effective circulation and Adequate Hemoglobin.
• Factors that delay healing: Advancing age and current smoking habits.

Factors Delaying Healing