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Lymphatic and Immune Systems

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Lion Den -> Anatomy & Physiology -> Course Info -> A&P 2 -> A&P 2 Outlines -> LYMPHATIC - IMMUNE

Reading assignment: 
Chapter 20 & 21
(Thibodeau & Patton Anatomy & Physiology)

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GA  Gray's Anatomy
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Lymphatic System
Immune System

(Previews are found at WebCT)

Lymphatic System

General structure and function

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Part of "circulatory system"

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Principal organs/tissues    pp
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Lymph (lymphatic fluid)

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Lymphatic vessels

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Lymph nodes and nodules

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Tonsils

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Thymus

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Spleen

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Functions    pp
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Fluid balance (returns water, proteins, etc. from tissues back to blood)

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Immunity

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Transports lipids from the digestive tract
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Lacteals (lymph capillaries) in intestine transport fatty lymph called chyle

 

Starling's Law of the Capillaries
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In a capillary, there are inwardly directed forces and outwardly directed forces that are balanced or imbalanced
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Osmotic pressure

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Hydrostatic pressure (pressure of fluid against a membrane)

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At the arterial end of a capillary
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Outwardly directed forces (mostly blood pressure) causes net diffusion of water and small solutes OUT of the blood (and into the IF [interstitial fluid])

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At the venous end of a capillary
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Inwardly directed forces (mostly tissue fluid pressure and osmotic pressure of the blood plasma) causes net diffusion of water and small solutes INTO the blood (and out of the IF)

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About 10% (varies greatly) of the fluid that OUGHT to return to the blood capillary does not
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This "extra" interstitial fluid (IF) in the tissue may accumulate, causing painful swelling and potentially fatal damage to the tissue
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Blood would also loose too much fluid to maintain health

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The lymphatic system includes a system of vessels that drains this excess fluid away and returns it to the blood supply

 

Lymphatic drainage
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Lymphatic capillaries    pp     GA    GA
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Blind-end tubules that begin in a tissue and continue as tributaries to larger and larger vessels, like creeks running into large streams, into rivers, into the lake

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Lumen (hollow part) of capillaries is "always open" like storm drainage pipe because tiny fibers attached to surrounding tissue cells hold it open from the outside
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This allows water and small particles to drain into the capillaries easily (without much of a pressure gradient)

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The drained fluid is now called "lymph" or "lymphatic fluid"

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Numerous SL (semilunar) valves keep lymph from flowing back toward tissue

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Drain away excess fluid as described above
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Also drain away fats absorbed in the digestive tract (otherwise the fats would increase blood viscosity and slow blood flow during absorption of a meal)

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Lymphatic vessels and ducts     GA
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Lymphatic vessels eventually all drain into the:
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Right lymphatic duct
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drains lymph from the superior right quadrant of body ---into the right subclavian vein (just before the systemic blood enters the right atrium of the heart)

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Thoracic duct 
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drains lymph from the lower right quadrant and entire left side of body into the left subclavian vein

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Numerous SL valves and lymph nodes (and other lymphoid organs)

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Lymphokinesis (kinesis = "movement")
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One-way flow (linear;  unlike "circular flow" of cardiovascular system) toward the blood/heart

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Lymphatic pump
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Similar to venous pumps

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Lymphokinesis averages about 125 ml/hr (that's 3 L/day)

Elephantiasis

Also known as lymphatic filariasis, this condition occurs when parasitic worms (any of several types of filaria worms) infest the lymphatic system.  The filaria are transmitted by mosquitoes to the blood and can build a population in the lymph nodes, blocking fluid drainage from arms, legs, genitals, or breasts.  It is called elephantiasis (literally, "elephant condition") because in extreme cases, the arms and legs look like the limbs of an elephant. Elephantiasis affects over a 100 million people around the world.  However, most cases are not as extreme as in this photo!

wpe4.gif (62634 bytes)
Click to enlarge

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Lymphatic drainage of the breasts -- a special case     GA
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Superficial lymphatics

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Deep lymphatics

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Lymphatic anastomoses
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Superficial with deep

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Across median

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With abdominal lymphatics

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With pectoral muscles

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Important in infections (mastitis) and cancer (breast cancer) because bacteria or cancer cells can easily migrate to other parts of the body, making things even more serious

 

Lymphoid organs

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Lymphoid organs have flow-through of lymph (and/or blood)

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Lymphoid organs have lymphoid tissue, which is made up of developing WBCs

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Lymph nodes
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Each is a tiny (1-20+ mm) fibrous capsule divided into many chambers
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Usually found in clusters (not evenly distributed throughout body)     GA

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Each chamber or "sinus" has may fine (reticular) fibers suspending a lymph nodule made up of lymphoid tissue       GA
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Lymphoid tissue is packed WBCs

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Germinal center is the the interior portion of a nodule
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Where B-lymphocytes begin the last stages of development (then are released from outer part of nodule)

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Lymph enters node through afferent lymphatic vessels and leaves the node through efferent lymphatic vessels

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As lymph flows through lymph node, lymph is mechanically filtered by fibers (large chunks get stuck)    pp

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Lymph is biologically filtered when phagocytes (reticuloendothelial cells) consume the particles or otherwise attack the particles

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Tonsils
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Three sets of lymph nodules in throat
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Pharyngeal lymphoid ring - a protecting ring of tonsils around the entrance of digestive and respiratory tracts     GA

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Lingual tonsils - base of tongue

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Pharyngeal tonsils - posterior wall of nasopharynx (above soft palate)
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Called "adenoids" if they become enlarged, possibly blocking breathing

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Palatine tonsils
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Oval thickening of mucosa on each side of oropharynx

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Most prominent of all tonsils; have 10-20 pits (crypts)

bulletPeyer's patches
bulletNow more often called aggregated lymphoid nodules
bulletLocated in the instestinal wall
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Thymus
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Also an endocrine gland, found in chest in front of or slightly above the heart (mediastinum)     GA

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Largest at puberty, then shrinks slowly over time (almost gone in advanced old age [twice Kevin's age])

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Cortex: lymphoid tissue     GA
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Site of T-lymphocyte (T-cell) development (lymphocytes become T-cells under the influence of thymosin hormones)

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Medulla: thymic corpuscles (function not clear; may be be where older cells are broken down)

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Spleen     GA
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Located in left upper part of abdomen, under diaphragm and tucked behind the stomach (left hypochondrium)

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Like a giant lymph node for blood: 
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Capsule with many sinuses that contain lymphoid tissue (incl. reticuloendothelial cells) for the filtering of blood (including RBC/platelet destruction)     GA

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Hematopoiesis
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RBCs (before birth)

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Nongranular leukocytes

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Blood reservoir

 

Immunity

Hint: Review types of pathogens in "Mechanisms of Disease" at end of Chapter 1 of textbook: bacteria, viruses, protozoa, fungi, worms, etc.

Immunity is protection/defense     pp
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Often, a military warfare model is used to illustrate immune function    pp

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Immunity is carried out by many cells and tissues of the body, not just those classically identified as "immune cells" or "immune tissues"

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Defense / protection against variety of "enemies"
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Nonself particles have unique identifying marker molecules
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Similar to the insignia of enemy aircraft, vehicles, soldiers

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Self-tolerance--we do not attack our own cells

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Examples of "enemies"
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Pathogens (see above)

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Cancer cells (your own cells that have become cancerous)

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Physical damage (burns, cuts, etc.)

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Two strategies of immunity    pp
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Innate immunity
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Called "innate" immunity because it does not require prior exposure to a pathogen

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Also called nonspecific immunity
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Mechanisms that are "on standby" at all times and are effective against a variety of different "enemies"

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Innate immune mechanisms respond rapidly (always "on alert")

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Adaptive immunity
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Called "adaptive immunity" or "acquired immunity" because it changes to work against new pathogens upon exposure to them

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Also called specific immunity
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Mechanisms that are effective against specific (one kind only) "enemies"

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Adaptive immune mechanisms respond more slowly because they take time to prepare and develop

Note: Immunology is a complex and rapidly changing discipline. We will be looking at a simple overview of immunology to prepare you for further work in this area later in your studies.

Innate (nonspecific) defenses
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There are many innate strategies; here we discuss just a few of them
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Many of these innate defenses also work in cooperation with, or are supplemented by, additional adaptive defense mechanisms

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Species resistance

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Lines of defense (as in military model)

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Surface barriers - skin and mucous membranes

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Phagocytes - neutrophils, eosinophils, macrophages
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Antigen-presenting cells (APCs) digest the enemy particle and display the unique protein markers to signal the adaptive immune system

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Examples
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Macrophages = large, phagocytic cells found in many areas of the body

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Dendritic cells (DCs) = branched phagocytes, often at/near external barriers

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Natural killer (NK) cells
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NK cells are lymphocytes that "patrol" the body, looking for abnormal cells (esp. cancer cells and virus-infected cells) to kill

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NK cells kill by direct contact with enemy cell
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NK cells each have two receptors
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Killer-activating receptor binds to common cell markers (thus, binds even to self cells)

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Killer-inhibiting receptor binds to certain self markers, thus preventing killing of self cells
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The self markers are MHC (major histocompatibility complex) proteins unique to every individual

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Kill by various methods
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May release perforins, which are proteins that form holes in the plasma membrane of the cell to be killed
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Sodium diffuses in, then water osmoses inward, causing the cell to swell and burst (cytolysis)

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In nucleated cells, this influx of ions may trigger apoptosis (programmed cell death), also resulting in cytolysis

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May also release granzymes that can enter the cell and trigger apoptosis

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Defensive proteins (cytokines)
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Interferons (IFNs) are released by dying, virus-infected lymphocyte or other cell     pp
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Interferons "call in" other immune cells (NK cells and macrophages) that destroy virus-infected cells, protecting the body from further spread of viral infection

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Interferons also "interfere" with the ability of viruses to replicate in other nearby cells --also stopping the viral infection

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Interferons are paracrine agents, regulating nearby cells

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Complement is a group of about 20 different plasma proteins
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Individual complement proteins are designated C1, C2, C3, and so on

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Complement molecules are activated in a cascade of chemical reactions triggered by innate or adaptive mechanisms

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Complement can act directly, as do perforins
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Form MACs (membrane attack complexes) that poke holes in the outer membrane

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Complement can act indirectly as a chemotactic agent or regulating immune cells in some other way

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Chemotaxis    pp
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Chemical attractants are released from damaged tissue cells and immune system cells to "call over" immune cells to the site of injury

 
Interferon activity in a virus-infected cell.
bulletClick the image to enlarge it
bullet Click here for the animated version (PowerPoint slide)

 

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Inflammation (the inflammatory response)
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Set of reactions in response to injury
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Four principle signs of inflammation: redness, warmth, pain, swelling

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Inflammation mediators are chemicals that regulate the inflammatory response

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Summarized in textbook Figure 21-3

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Fever 
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Pyrogens (literally "fire makers")
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Chemical factors released by pathogens or immune cells

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Causes hypothalamus ("thermostat"  of the body) to "reset" setpoint body temperature a little higher

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Cause liver / spleen to remove iron from the blood, making it unavailable for pathogens

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Mild, moderate fever increases body temp slightly
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Increases efficiency of immune mechanisms

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Decreases efficiency of pathogen function

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 High or prolonged fever
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Can denature (change shape of) proteins, thus disrupting enzyme activity bodywide --perhaps leading to death

Adaptive (specific) defenses
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Two strategies of adaptive defense    pp
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Antibody-mediated immunity uses antibodies (immunoglobulins [Ig])
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Also called humoral immunity because antibodies are dispersed in the blood plasma (humor = "body fluid")

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Antibodies are Y-shaped plasma proteins made by B-lymphocytes (B-cells) that bind to specific antigens (markers or particles that have a complementary shape to the active site on an antibody molecule) and cause them harm 

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Antibody-mediated immunity is like "shelling" the "enemy"  --the antibodies are like "homing missiles" directed as specific distant targets

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Cell-mediated immunity (or cellular immunity) uses cells (T-lymphocytes = T cells) that directly attack another cell such as an infected cell or cancer cell

bulletSpecialized lymphocytes carry out adaptive immunity
bulletThus, lymphocytes are the "soldiers" of adaptive immunity
bulletLymphocytes are often identified by their CD (cluster differentiation) markers
bulletCD4 or CD8, for example
bulletTriggering adaptive responses requires BOTH of two signals    pp
bulletStimulate antigen receptor
bulletAntigens are markers that identify nonself particles
bulletFor example, antigens presented by APCs (see above)
bulletB cells can also detect free-floating antigens in the plasma
bulletPrior to recognizing an antigen, lymphocytes are known a naïve cells, or virgin cells, or inactive cells
bulletStimulate cytokine receptor
bulletCytokines are regulating chemicals
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Effector and memory cells
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Effector cells are the cells that actively participate in "the battle" against "the enemy"
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Effector cells usually die during or just after the "battle"

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Memory cells are inactive copies of the effector cells that are held as "reserves" in case the same enemy attacks later
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Memory T cells and memory B cells can quickly be activated or "called up to the front" and become effector cells if the same enemy attacks again at a later time

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Sounding the alarm
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Macrophages, DCs, or other APCs (antigen-presenting cells) ingest the "enemy" and incorporate the enemy markers on the surface of the APC

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This display of "enemy antigens" then triggers a helper T cell (= T4 cell = CD4 cell) with complementary receptors by releasing interleukin 1

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Interleukin 1 activates the helper T cell, which divides into many identical daughter cells (the group of identical cells is called a clone)
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Some of the cells remain inactive "reservists" as memory helper T cells