Immune & Lymphatic Systems

The Immune & Lymphatic Systems

• The objectives are to describe the components of the lymphatic and immune systems and their functions, discuss antibody structure and roles in immune response, describe various types of immunity, the mechanisms involved in the inflammatory response and specific mediators, cardinal signs and symptoms associated with inflammation, and the basic mechanisms and factors in tissue healing

The Lymphatic System

• The lymphatic system returns excess interstitial fluid to the cardiovascular system while working concert with venous circulation.
• Lymphatics, heart, and blood vessel functions are interdependent.
• It consists of lymph, lymph vessels, lymphatic tissues, lymph nodes/nodules, spleen, thymus gland, red bone marrow, and tonsils.
• Its functions are to facilitate fluid movement, remove excess fluid/proteins/waste, filter/destroy foreign material, initiate immune response, and absorb lipids from the GI tract.

Lymph

• Lymph is mostly water/plasma.
• Lymph capillaries collect excess interstitial fluid.
• It is returned to the blood supply via lymphatic vessels.
• Lymph contains leukocytes, proteins electrolytes, urea, creatinine, and other waste products.
• Maintaining blood volume and blood pressure are important functions of lymph.

Lymphatic Vessels

• Lymphatics have walls thinner than veins and collapse more easily under pressure.
• Absorption is initiated at the capillary level.
• The lymph is channeled through small vessels (pre-collectors), then larger vessels (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 everything else.

Lymph Moving Through System

• The cisterna chyli collects lymph from the abdomen and drains into the thoracic duct.
• Lymphatic ducts return lymph fluid to the subclavian veins.
• Movement of lymph fluid is achieved through diffusion and filtration.
• Additional mechanisms that aid movement includes nerve stimulation or mild stimulation of dermal tissue.
• Lymphatic movement also relies on arterial pulsation adjacent to lymph vessels.
• Muscle contraction adjacent to lymph vessels, or the skeletal muscle pump and abdominal/thoracic cavity (respiratory pump) can affect lymph moving through the system.

Lymphangion

• The lymphangion represents the functional unit of a lymph vessel.
• It is situated between adjacent valves.
• It contains smooth muscle in walls, and an intrinsic pumping mechanism triggered by pressure in the vessel.

Lymph Nodes

• Lymph nodes are encapsulated and measure 1-2 cm in diameter.
• Lymph nodes are found in groups along lymph vessel pathways.
• Lymph enters via afferent lymph vessels and leaves via efferent vessels.
• Lymph nodes filter lymph: bacteria and foreign materials are phagocytized by macrophages.
• Plasma cells develop from B lymphocytes exposed to pathogens in lymph, and produce antibodies.

Lymph Nodules

• Lymph nodules are a fraction of a millimeter to several millimeters in size.
• Lymph nodules lack a capsule.
• Lymph nodules are located just beneath the epithelium of mucous membranes in respiratory, digestive, urinary, and reproductive tracts.
• Tonsils are lymph nodules in the pharynx.
• Palatine/pharyngeal (adenoid) and lingual tonsils form a ring of lymphatic tissue around the pharynx.
• Peyer's patches are lymph nodules in the small intestine.

Spleen

• The spleen is located in the upper left quadrant (ULQ) of the abdominal cavity, just below the diaphragm, behind the stomach.
• The spleen produces red blood cells in the fetus; it filters blood after birth.
• Plasma cells producing antibodies in response to foreign antigens are produced in the spleen.
• Monocytes and fixed macrophages in the spleen phagocytize pathogens or foreign material in blood.
• Monocytes may enter circulation when tissue is damaged and cleaning up/repair is needed.
• The speen stores platelets and destroys them when no longer needed.

Thymus

• The thymus is located inferior to the thyroid.
• This gland gets smaller as we age.
• Stem cells of the thymus produce T lymphocytes (T cells).
• Thymic hormones and other cells give rise to immunological competence of T cells.
• Immature T cells are introduced to the body's cells and organic molecules.
• Self-recognition and self-tolerance develop in the thymus.

The Immune System

• Key components of the immune system include lymphoid structures, tissues, and immune cells.
• Bone marrow is the source of immune cell development and origination point for all immune cells.
• The thymus is the maturation location of T lymphocytes.
• Immune cells are leukocytes and macrophages.

Innate vs. Adaptive Immunity

• Innate immunity represents a nonspecific response and includes anatomic/physiological barriers, phagocytic and other defensive cells, and chemical secretions and the inflammatory process.
• Efficiency does not increase with repeated exposure with innate immune response.
• Adaptive immunity is more specific, carried out by lymphocytes/macrophages.
• It includes cell-mediated/antibody-mediated processes.
• Adaptive immunity becomes more efficient with repeat exposure.

Elements of the Immune Response: Antigens

• Cell surface antigens are found on the cell membrane and are "self" substances.
• The HLA complex is a group of genes coding for specific protein production; it helps the immune system to distinguish its own proteins from foreign substances.
• The immune system normally ignores self-cells/antigens due to self-recognition and self-tolerance.
• The immune system recognizes specific non-self antigens as foreign, prompting development of a specific response.
• Memory cells are produced to respond more quickly to an antigen the next time it is encountered.

Major Cells of Immune Response

• Leukocytes include mast cells, neutrophils, basophils, eosinophils, monocytes, macrophages, dendritic cells, and lymphocytes.

Specific Immune Cell Functions

• Mast cells release histamine and other chemical mediators in inflammatory response.
• Neutrophils are phagocytic and active in inflammatory processes.
• Basophils play major role in allergic reactions, and release histamine, while binding to IgE.
• Eosinophils function in allergic responses and phagocytosis, and exert antiparasitic and bactericidal activity.
• Monocytes circulate in blood, and upon migration into tissues in response to infection/inflammation mature into macrophages.
• Macrophages are phagocytic and present antigens to lymphocytes for immune response.
• Dendritic cells are phagocytic antigen presenting cells.
• Lymphocytes include T cells, B cells, and NK cells.

Macrophages

• Macrophages are present throughout the body.
• Macrophages initiate immune response, develop from monocytes, and engulf foreign material.
• The cells process and display foreign antigen material on cell membranes, causing lymphocytes to respond, which triggers the immune response.
• Examples of chemicals secreted are monokines and interleukins

Lymphocytes

• Lymphocytes have a variety of cells.
• T lymphocytes (T cells) arise from bone marrow stem cells, and differentiate and mature in the thymus, and exerting a major role in cell-mediated-immunity.

Subtypes of T Cells

• Cytotoxic T or Killer T cells: Bind to antigen and release cytotoxic enzymes/chemicals
• Helper T cells: Regulate all the cells of the immune system via secretion of messenger cytokines. 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, responding if exposed to any of the same antigen in the future.
• Regulatory T cells: Suppress immune response when is no longer needed.

B Lymphocytes

• B lymphocytes (B cells) produce antibodies, or immunoglobulins.
• Mature in bone marrow and they proceed to spleen and lymphoid tissue.
• Play a role in fighting bacteria and viruses that are outside of cells.
• Plasma cells produce antibodies.
• B memory cells quickly form clone of plasma cells.

NK Cells

• (Natural killer cells) are distinct from T and B cells.
• NK cells destroy tumor cells, cells infected with viruses, and other foreign cells, without prior exposure.
• NK cells are localized to infected tissue in response to cytokines.

Types of Adaptive Immunity

• Cell-mediated immunity (CMI) involves lymphocytes being programmed to attack non-self cells.
• It develops when T cells with protein receptors on cell surfaces recognize antigens on target cells to destroy invading antigens.
• Programmed T cells reproduce and more cells are created to battle the antigen.
• Antibody-mediated (humoral) immunity involves antibodies being produced to protect the body.
• B cells subsequently become plasma cells after exposure to antigens.

Development of Cellular & Humoral Immunities

• Originates with lymphoblasts developing into bone marrow stem cells
• It is followed by maturation that develops in the thymus or bone marrow causing T or B cells.
• These move into the Lymph nodes
• A foreign substance is introduced which induces the antigen stimulation
• Forms various types of sensitized T cells in the circulation
• Then antibodies are produced and memory B cells are created

Antibodies

• Antibodies, also known as immunoglobulins, are found within general circulation and lymphoid tissues.
• There are five major classes of immunoglobulins.
• Immunoglobulins have a constant region that attaches to macrophages and other effector cells and refers to type/class of the immunoglobulin, and a variable region, which is a unique set of amino acids.
• These unique sets bind to specific antigens

Antibody Structure

• The constant region determines the mechanism used to destroy an antigen (related to the class of Ig).
• The variable region gives the antibody its specificity for a given binding antigen.

Major Classes of Antibodies

• IgG is the most abundant antibody in the circulation, found in blood and extracellular fluid, including antiviral, antibacterial, and antitoxin antibodies. It crosses the placenta, and creates passive immunity in newborns.
• IgM is bound to B lymphocytes in the circulation. It usually is the first to increase in immune response but does not require helper T cells. Also involved in ABO blood type incompatibility reactions.
• IgA provides localized defense and is found in secretions (tears, saliva, mucous membranes, and colostrum).
• IgE binds to mast cells or basophils in skin and mucous membranes, promoting allergic response and causing the release of histamine and other mediators, ultimately resulting in inflammation.
• IgD is attached to B cells.and activates B cells and assists them in leaving bone marrow.

Immune System: Complement System

• Refers to a group of inactive proteins, C1 to C9, which are circulating in blood. It is activated in innate and adaptive immune response. When specifically an antigen-antibody complex binds with C1, it sets off a cascade of reactions ultimately causing cell damage and further inflammation when activated.

Acquired Immunity

• Acquired or Adaptive Immunity is a 2 step process
• Primary response occurs with the first exposure to antigen.
• The antigen is recognized and processed, and subsequent antibody production or sensitization of T lymphocyte occurs, often 1-2 weeks before antibody level reaches full efficacy
• Secondary response occurs with repeat exposure to the same antigen and is a more rapid response, with efficacy in 1-3 days

Passive Immunity

• This is "borrowed" immunity from an outside source.
• IgG can be transferred from mother to fetus across the placenta or through breast milk.
• This gives the infant protection for the first few months of life or until weaned.
• Passive artificial immunity can be achieved with injection of antibodies .
• This provides only short-term protection.

Active Immunity

• Active Natural Immunity, body encounters things on its own.
• Natural exposure to antigen occurs leading to development of antibodies
• Active Artificial Immunity, the body is purposefully introduced to produce antibodies through Stimulation of antibody production and receiving Immunizations

Summary of Acquired Immunity

• Natural Active Immunity: occurs with pathogens entering the body and the cause the illness which causes the antibodies to form in the host.
• Artificial Active Immunity: is injected into a person who does not experience illness, but the antibodies form anyway. For example receiving immunity after a Measles Vaccine
• Natural Passive Immunity: are passed directly from a mother to their child. Which leads to a temporary protection
• Artificial Passive Immunity:is injected or administered via the IV. This causes a temporary protection or to try and minimize the effects and conditions of infections.

The Inflammatory Response

• The body has multiple lines of defense to protect itself.
• The first line of Defense is a Nonspecific process by means of mechanical barriers.
• An unbroken skin, mucous membranes,tears, saliva and gastric juices have enzymes to destroy bacteria.
• The second line of Defense represents the body's Nonspecific defense.
• Phagocytosis engulf bacteria, cell debris and other foreign material, to destroy.
• Inflammation is an overall series of events that happen to limit effects of injury or harmful event in the body
• The 3rd line of defense is more Specific due to antibody either directly or indirectly destroying the cells

Physiology of Inflammation

• Inflammation is a normal, necessary defense mechanism as inflammation helps our body heal
• Signs and symptoms indicate that something is going wrong with the body
• Problem may be hidden within the body
• Inflammatory process is the same, regardless of what the cause is
• Inflammation is not the same as when there is actual infection
• However, infection may cause inflammation Medical Terminology:
• Itis is the medical terminology for inflammation

Common Causes of Inflammation

• Direct physical damage
• Cut, sprain etc.
• Caustic chemicals
• Acid, drain cleaner etc
• Allergic reactions
• Extremes of hot or cold reactions
• Foreign bodies
• Splinter, glass etc
• Ischemia or infarction
• Infection

Acute Inflammation

• Chemical Mediators stimulate nerves and blood vessels
• Vasodilation occurs: The smooth muscles relax, thus resulting in an increase in the overall diameter of the arterioles Increased diameter leads to Increased Blood: Hyperemia
• Leads to Increase in capillary permeability Allows the plasma proteins to flood more into interstitial space along with more fluids
• Dilutes all toxic materials at site
• Forms a fibrinogen, which forms a meshing of the blood cells to target area also called "wall off" area.
• Chemotaxis which causes leukocytes to be summoned. Movement of cells that respond to chemical stimulus

Local Effects of Inflamation

• Cardinal Signs which refer to the Reddening of the specific site
• This is caused by the increase In blood flow to the exact site of inflammation
• Warmth can also affect the specified site
• This is caused by the increase In blood flow to the exact site of inflammation
• Swelling (edema)
• This results when a shift of fluid and protein moves into the interstitial space
• Increased pressure of fluid on nerves leads to Pain
• Release of chemical, bradykinins causes more problems
• Loss of function
• If cells happen to lag behind and cause edema can occur
• The motion will be interfered and hurt a lot

Systemic Effects of Inflammation

• Mild Fever or Pyrexia can lead to extensive inflammation which is very common
• Release of pyrogens occurs
• Subtances that are fever reducing are caused by WBC
• Macrophages
• General feeling of being unwell Malase
• Fatigue
• Headache
• Anorexia: Lack of appetite

Chemical Mediators In The Inflammatory Response

• Histamine cause an immediate vasodilation and increased capillary permeability that will form exudate
• Chemotactic factors are used to attract the leukocytes to that inflammation site
• Platelet activating factor will engage the neutrophils and aggregate the platelet
• Cytokines increase the plasma proteins and increase the Erythrocytes Sedimentation Rate(ESR)   Induces leukocytes, fever, and chemotaxis
• Leukotrienes occur because of vasodilations which create a delayed but increased capillary permeability.
• Prostaglandins will heighten histamine cause pain and then lead to a fever at the same time
• Kinins (bradykinin) cause increase in vasodilation and increased capillary permeability which will lead to chemotaxis and trigger pain.
• Complement factor which have a high level of chemotaxis. Has a high release of histamine. Causing vasodilation which directly increases the level of chemotaxis.

Inflamation Change In The Blood

• The increased value, the increased inflammation in the body
•  Leukocytosis(leukocytes): has an increased count of WBCs and neutrophil
•  Differential count: alters the WBC and depends on the specific cause of the inflammation.
•  Plasma proteins: leads to an increased abundance of prothrombin and fibrinogenthat is directly present in the bloodstream.
•  C-reactive protein: is not normally present in the blood. But with acute inflammation and necrosis it comes within 24-48 (hrs)
• Increased ESR (SEDr Rate): this causes plasma protein to increase on the red blood cells which causes them to settle at a more rapid rate in an sample of fluid
•  Cellular Enzymes: Release from necotrotic and tissue fluids and the Blood

Chronic Inflammation

• May follow acute inflammation, but could be chronic irritation too
• The primary cause can be, lung long irritation or a second hand hand smoke or even autoimmune disease.
• Presence of macrophages
• More fibrous
• granuloma forms from a foreign object with a cell mass.
• Has a necrotic factor and the mass surrounds the connecting tissue

Potential Complications of Inflammation

• Complications come from the overall of inflammation and will depend on the location or the overall cause of the inflammation.
• The common complications are a result of the basic inflammation process
• Can be causes by
• Muscular Spasm
• Infection
• Ulcerations
• Immune Suppression

Cause for Infection to become possible.

• Causes microorganism can easily go through edematous tissue more easily
• Microbes: that are extremely resistan to phagocytosis .Inflammation also provides a medium for other microorganisms
• Skeletal Muscular Spasms often accompany infections
• This is the body’s response to pain and or infection. Ulcers are possible infections Can be caused by cell decay Will lead to a perforation of organs Suppression of the Immune system increases the risk of the further infections and the severity

Resolution - One of The Type of Healing

• Damage occurs and the cell reverses back to their original state
• Reversal of the cell happens inside the short period of time
• Example: mild sunburns or mild inflammation from a cut

Regegeration - One of The Type of Healing

• The cells are replaced, the regeneration comes from stem cells
• Constanitly replicating calls are the ones to most often regegerate
• Nearby cells make more nearby cells

Replacement - One of The Type of Healing

• If the cell has sustained damage
• Functional tissue is replaced during the scar tissue, the fibrous tissue
• Extensive tissue that is too hard for tissue or if the cells are not able to replicate by mitosis
• Cardiac
• Brain tissue
• Lost Tissue Factor
• Scars

Healing Process - Primary

• 1st intention of healing
• Happens when wound in wound edges are close
• It is relatively easy to treat when wound us pure and safe.
• smaller cuts /wounds on the skin
• Post op sutures, using strip

Healing Process - Secondary

• Caused when
• The overall tissue is broken and the area requires
• More information in the area
• Slower healing process
• More time to heal
• Scar tissue

Various processes after skin have an injury.

• Clots form to stop and seal area, will then develop into granulation tissue.
• 3-4 day cycle,
• Area will be mostly removed by cell waste
• Monocytes Macrophages
• Granulation, grows into a the damaged nearby connective tissue
• Will mostly be pink, moist and reddish in color Capillary buds will be very thin.

Overall steps to completely heal the wounded tissue.

• First- Skin tissue will fill more and undergo mitosis
• Cells enter a new zone
• Cell growth in factors Stimulates Epithelial Migration Development of capillary development known as angiogenesis
• Connective tissue becomes collagen, and fiber
• Collagen fibers
• Capillary decreases color goes away
• Scar tissue takes 2 years

Promote Healing Factors

• Younger age
• Effective Circulation
• Adequate Hemoglobin
• Clean /Undisturbed wound Absence of movement in that specific area. Good nutrition protein, vitamins A& C.

Delay Healing Factors

• Advanced age
• Smoking
• poor circulation
• Other medical conditions
•  Chemotherapy
• Prolonged use of steroids
• Anemia
• Poor Nutrition
• Dehydration
• Excessive bleeding
• Excess Movement