Anatomy and Physiology

1
Anatomy and Physiology

• Chapter 14
• Lymphatic System and Immunity

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Introduction to the Lymphatic System

• Network of vessels that transports fluids
• Consists of a collection of cells and
  biochemicals that travel in lymphatic vessels and
  the organs and glands that produce them
• Carries away excess fluid from interstitial
  spaces in most tissues and returns it to
  bloodstream

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Link to unlabeled diagram
Schematic representation of lymphatic vessels
transporting fluid from interstitial spaces to
the bloodstream
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• Lacteals special lymphatic capillaries located
  in the lining of the small intestine that absorb
  digested fats and transports them to venous
  circulation.
• Cells and biochemicals of the lymphatic system
  launch both generalized and targeted attacks
  against foreign particles enabling the body to
  destroy infectious microorganisms and viruses
• Also attacks toxins and cancer cells
• When abnormal, can cause allergies or cancer,
  autoimmune disorders in which the body attacks
  itself

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Lymphatic Pathways

• Begin as lymphatic capillaries which merge to
  form larger and larger vessels that unite with
  veins in the thorax
• Lymphatic capillaries are microscopic
  closed-ended tubes that extend into interstitial
  spaces forming complex networks that parallel
  those of blood capillaries

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Lymphatic capillaries are microscopic,
closed-ended tubes that begin in the interstitial
spaces of most tissues.
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• Walls of capillaries (like those of blood
  capillaries) are formed from a single layer of
  squamous epithelial cells.
• Thin layer makes it possible for tissue fluid to
  enter lymphatic capillaries
• Lymph fluid inside lymphatic capillaries
• Lymphatic Vessels
• Walls similar to those of veins but thinner
• Have flaplike valves that help prevent backflow
  (similar to veins)
• Lead to lymph nodes then merge to larger vessels
  called lymphatic trunks

Light micrograph of the flaplike valve (arrow)
within a lymphatic vessel
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Lymph enters and leaves a lymph node through
lymphatic vessels.
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• Lymphatic trunks
• Drain lymph
• Named for the regions they serve
• Join one of 2 collecting ducts thoracic duct
  and right lymphatic duct

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• Thoracic Duct
• Larger and longer
• Receives lymph from the lower limbs and abdominal
  regions, left upper limb and left side of thorax,
  head and neck
• Empties into the left subclavian vein near the
  left jugular vein.

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• Right Lymphatic Duct
• Receive lymph from the right side of the head and
  neck, right upper limb and right thorax
• Empties into the right subclavian vein near the
  right jugular vein.

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Lymphatic Pathways. The right lymphatic duct
drains lymph from the upper right side of the
body, whereas the thoracic duct drains lymph from
the rest of the body.
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• After leaving collecting ducts, lymph enters the
  venous system to become part of plasma just
  before blood returns to the right atrium.
• The skin has many lymphatic capillaries. If skin
  is broken or something is injected (venom from
  insect sting), foreign substances rapidly enter
  the lymphatic system.

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Lymphatic Pathway

• Lymphatic capillary
• Vessel
• Node
• Vessel
• Trunk
• Collecting duct
• Subclavian vein

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Tissue Fluid and Lymph

• Lymph is tissue fluid that has entered a
  lymphatic capillary, thus lymph formation depends
  upon tissue fluid formation.
• Tissue fluid originates from blood plasma
• Composed of water and dissolved substances that
  leave blood capillaries
• Capillary blood pressure causes filtration of
  water and small molecules from the plasma

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• Resulting fluid has much the same composition as
  blood plasma (nutrients, gases, hormones) except
  plasma proteins, which are too large to pass
  through capillary walls.
• Osmotic effect of the plasma proteins helps draw
  fluid back into the capillaries by osmosis
  (plasma colloid osmotic pressure)

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Lymph Formation and Function

• Filtration from plasma normally exceeds
  reabsorption leading to net formation of tissue
  fluid (interstitial fluid)
• This increases interstitial fluid hydrostatic
  pressure favoring movement of tissue fluid into
  lymphatic capillaries forming lymph.
• Lymph returns most of the small proteins to the
  blood stream and transports foreign particles
  (bacteria, virus) to the lymph nodes.

Step through of net movement of fluids
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Lymph Movement

• Hydrostatic pressure of tissue fluid drives the
  entry of lymph into lymphatic capillaries
  (pressure is low, similar to venous blood)
• Other forces that influence the movement of
  lymph
• Contraction of skeletal muscles that compress
  lymphatic vessels
• Contraction of smooth muscles in walls of larger
  lymphatic trunks
• Pressure changes associated with breathing

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• Valves prevent backflow
• Continuous movement of fluid stabilizes the
  volume of fluid in these spaces.

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Edema

• Swelling that results from interference of lymph
  movement causing tissue fluids to accumulate
  within interstitial spaces
• May occur when surgery removes lymphatic tissue,
  obstructing vessels.
• Ex. Breast cancer surgery often includes removal
  of nearby lymph nodes to prevent associated
  vessels from transporting cancer cells to other
  sites. This can interfere with drainage from
  upper limb.

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Lymph drainage of the right breast illustrates a
localized function of the lymphatic system.
Surgery to remove a cancerous breast can disrupt
this drainage, causing painful swelling.
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Lymph Nodes

• Located along lymphatic pathways throughout the
  body, but absent in CNS
• Contain large numbers of lymphocytes and
  macrophages that fight invading microorganisms

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Structure of a Lymph Node

• Vary in size and shape. Usually less than 2.5 cm
  long and bean-shaped.
• Hilum indented region where blood vessels and
  nerves join a lymph node
• Afferent vessels (leading to a node) enter at
  various points on its concave surface
• Efferent vessels (leaving node) exit from the
  hilum
• Capsule of connective tissue encloses each lymph
  node and subdivides it into compartments called
  lymph nodules

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A section of a lymph node.
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Major locations of lymph nodes.
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Lymph Nodules

• The structural units of a lymph node
• Occur singly or in groups associated with mucous
  membranes of the respiratory and digestive
  tracts.
• Contain dense masses of lymphocytes and
  macrophages
• Tonsils partially encapsulated lymph nodules
• Peyers patches aggregations of nodules.
  Scattered throughout the mucosal lining of the
  ileum of the small intestine

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Lymph Sinuses

• Spaces within a node
• Provide complex network of chambers and channels
  through which lymph circulates
• Macrophages most highly concentrated

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Functions of Lymph Nodes

• Filtering potentially harmful particles from
  lymph before returning it to the bloodstream
• Immune surveillance
• Provided by lymphocytes and macrophages.
• Nodes are centers for lymphocyte production.
• Lymphocytes attack invading viruses, bacteria,
  and other parasitic cells
• Macrophages engulf and destroy foreign
  substances, damaged cells and cellular debris

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Lymphangitis

• Superficial lymphatic vessels inflamed by
  bacterial infection.
• Appear as red streaks beneath the skin

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Lymphadenitis

• Inflammation of lymph nodes
• Nodes enlarge and may be quite painful
• Often follows lymphangitis

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Thymus

• Soft, bi-lobed structure enclosed in a connective
  tissue capsule
• Located anterior to the aorta and posterior to
  the upper part of the sternum.
• Relatively large during infancy and early
  childhood but shrinks after puberty.
• Small in adult
• In elderly, replaced by adipose and connective
  tissue
• By age 70, the thymus is 1/10th the size it was
  at age 10. The immune system is only 25 as
  powerful

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Thymus and Spleen. The thymus gland is bilobed
and located between the lungs and superior to the
heart. The spleen is located inferior to the
diaphragm and posterior and lateral to the
stomach.
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• Lobules
• Sub-divisions of the thymus
• Contain lymphocytes called thrombocytes that are
  inactive, but some mature into T cells (T
  lymphocytes)
• T cells leave the thymus and provide immunity
• Epithelial cells in the thymus secrete hormones
  called thymosins, which stimulate maturation of T
  cells after they leave the thymus and migrate to
  other lymphatic tissues

A cross section of the thymus. Note how the gland
is subdivided into lobules.
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Spleen

• Largest lymphatic organ
• Located in the upper left portion of the
  abdominal cavity, just inferior to the diaphragm
  and posterior and lateral to the stomach.
• Resembles a large lymph node
• Sub-divided into lobules
• Venous sinuses of spleen contain blood instead of
  lymph (unlike sinuses of lymph node)
• 2 types of tissues White pulp and Red pulp

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The spleen resembles a large lymph node.
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White Pulp

• Distributed throughout the spleen in tiny
  islands.
• Composed of splenic nodules similar to those in
  lymph nodes
• Contains many lymphocytes

Light micrograph of the spleen
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Red Pulp

• fills the remaining spaces of the lobules.
  Surrounds the venous sinuses.
• Contains numerous RBCs which give it color, plus
  many lymphocytes and macrophages
• Blood capillaries within red pulp are permeable
  RBCs can squeeze through pores in capillary
  walls and enter venous sinuses.
• Older RBCs may rupture as they pass through
  pores. Cellular debris removed by phagocytic
  macrophages within splenic sinuses.
• Macrophages also engulf and destroy foreign
  particles in the blood

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Body Defenses Against Infection

• Infection the presence and multiplication of a
  disease-causing agent or pathogen (virus,
  bacteria, fungi, protozoan)
• Non-specific and Specific defenses work together
  to protect the body

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Non-specific Defense

• Also called Innate Immunity (inborn protection)
• General mechanisms that protect against many
  types of pathogens
• Response is rapid.
• Mechanisms include
• Species resistance
• Mechanical barriers
• Chemical barriers (enzyme action and interferon)
• Fever
• Inflammation
• Phagocytosis

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Specific Defense / Immunity

• Also called Acquired or Adaptive Immunity
  (stimulated by environmental factors)
• Precise defense mechanisms that target certain
  pathogens.
• Specialized lymphocytes recognize foreign
  molecules (non-self antigens) and respond to
  execute specific defense.
• Slower response

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Nonspecific Defenses
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Species Resistance

• Refers to the fact that a given kind of organisms
  (species) develops a set of diseases that is
  unique to it.
• Species may be resistant to diseases that affect
  other species.
• Tissues fail to provide the temperature or
  chemical environment that a particular pathogen
  requires.

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Mechanical Barriers

• First line of defense that prevents entry of
  some infectious agents. Must remain intact. (All
  other nonspecific defenses are the 2nd line of
  defense)
• Hair of the skin
• Skin
• Mucous membranes lining passageways of the
  respiratory, digestive, urinary, and reproductive
  systems.
• Fluids (sweat and mucous) rinse away
  microorganisms

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Chemical Barriers

• Enzymes in body fluids
• Gastric juice contains the protein-splitting
  enzyme pepsin. Has a low pH due to HCl lethal to
  many pathogens that enter the stomach.
• Tears contain enzyme lysozyme which has
  antibacterial action against certain pathogens
  that get onto the eye surface
• Salt from perspiration kills certain bacteria on
  the skin

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• Interferons
• Hormone-like peptides produced by lymphocytes and
  fibroblasts in response to viruses or tumor cells
• Once released from virus-infected cell,
  interferon binds to receptors on uninfected cells
  stimulating them to synthesize anti-viral
  proteins that block replication of a variety of
  viruses
• Interferon also stimulates phagocytosis and
  enhances activity of other cells that help the
  body resist infections and growth of tumors.

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Fever

• Elevated body temperature
• Causes liver and spleen to sequester iron,
  reducing levels in blood
• Bacteria and Fungi require more iron as
  temperature rises. Their growth and reproduction
  in fever-ridden body slows or ceases
• Phagocytic cells attack more vigorously when
  temperature rises.

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Inflammation

• Tissue response to injury or infection producing
  localized redness, swelling, heat and pain.
• Redness results from blood vessels dilation and
  increased blood volume within affected tissues.
  More phagocytes to remove microorganisms
• Swelling is due to increased permeability of
  nearby capillaries causing edema
• Heat comes from blood from deeper body parts.
  Speeds phagocytic activity
• Pain results from stimulation of nearby pain
  receptors

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• Infected cells release chemicals that attract
  WBCs to inflammation sites to phagocytize
  pathogens.
• Pus thick fluid formed of WBCs, bacterial
  cells, and damaged tissue from an infection
• Body fluids containing fibrinogen and other
  clotting factors collect inflamed tissue
• Clotting forms a network of fibrin threads within
  the affected region.
• Fibroblasts arrive and secrete fibers until area
  is enclosed in a sac of connective tissue with
  many fibers which inhibits the spread of
  pathogens and toxic substances.

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Phagocytosis

• Bloods most active phagocytic cells are
  neutrophils and monocytes
• Can leave bloodstream by squeezing between the
  cells of blood vessel walls (diapedesis)
• Chemicals released from injured tissues attract
  these cells (chemotaxis)
• Neutrophils engulf and digest smaller particles
  monocytes phagocytize larger ones
• Monocytes give rise to macrophages (histocytes)
  which become fixed in various tissues and attach
  to the inner walls of blood and lymphatic vessels
• Found in lymph nodes, spleen, liver, and lungs.
  Makes up the Mononuclear Phagocytic System
  (Reticuloendothelial System)
• Phagocytosis removes foreign particles from the
  lymph as it moves from interstitial spaces to the
  blood stream.

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Specific Defenses / Immunity
Scanning electron micrograph of a human
circulating lymphocyte.
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Specific Defenses

• Third line of defense
• Resistance to particular pathogens or to their
  toxins or metabolic byproducts
• Includes lymphocytes and macrophages that
  recognize and remember specific foreign molecules
  and carry out immune responses

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Antigens

• May be proteins, polysaccharides, glycoproteins,
  or glycolipids located on a cells surface.
• Before birth, body cells inventory the proteins
  and other large molecules in the body learning
  to recognize them as self
• Receptors on the lymphocytes surface recognize
  and respond to nonself or foreign antigens.
  (normally no response to self)

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• Antigens most effective in eliciting an immune
  response are large and complex with few repeating
  parts.
• Hapten smaller molecule that combines with
  larger ones to be able to elicit an immune
  response.
• Found in certain drugs (penicillin), household
  and industrial chemicals, dust particles, and
  dander.

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Lymphocyte Origins

• During fetal development, red bone marrow
  releases undifferentiated lymphocytes into
  circulation
• Half reach thymus and specialize into T-cells and
  become 70-80 of the circulating lymphocytes
• Others reside in lymphatic organs (especially
  lymphnodes, thoracic duct, and spleen)
• Other lymphocytes remain in red bone marrow until
  they differentiate into B cells (B lymphocytes)
• Blood distributes B cells (20-30 of circulating
  lymphocytes)
• Settle in lymphatic organs along with T cells.
  Abundant in lymph nodes, spleen, bone marrow, and
  intestinal linings

Link to step through of bone marrow releasing
lymphocytes
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Bone marrow releases undifferentiated
lymphocytes, which after processing become T
cells (T lymphocytes) or B cells (B lymphocytes).
Note that in the fetus, the medullary cavity
contains red marrow.
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Lymphatic Functions

• Each person has millions of varieties of T and B
  cells
• The members of each variety have a particular
  type of antigen receptor on their cell membranes
  that can respond only to a specific antigen.
• Clone identical cells originating from the
  division of a single cell.
• T and B cells respond to antigens in different
  ways.
• T Cells and the Cellular Immune Response
• B Cells and the Humoral Immune Response

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Cellular Immune Response

• T cells attach to foreign, antigen-bearing cells
  (bacteria) and interact directly by cell-to-cell
  contact.
• Also called Cell-mediated Immunity
• T cells and some macrophages also synthesize and
  secrete polypeptides called cytokines
  (specifically, lymphokines) that enhance certain
  cellular responses to antigens.
• Stimulate other T cells to synthesize cytokines
• Help activate T cells
• Cause T cells to proliferate
• Stimulate leukocyte production in red bone marrow
  causing B cells to grow and mature and activate
  macrophages
• T cells may also secrete toxins that kill their
  antigen-bearing target cells.
• Growth-inhibiting factors that prevent
  target-cell growth
• Interferon that inhibits the proliferation of
  viruses and tumor cells

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T Cell Activation

• A lymphocyte must be activated before it can
  respond to an antigen.
• T cell activation requires the presence of
  processed fragments attached to the surface of an
  accessory cell (antigen-presenting cell) such as
  a macrophage or a B cell
• T cell activation begins when a macrophage
  phagocytizes a bacterium, digesting it in its
  lysosomes

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• Some bacterial antigens exit lysosomes and move
  to the macrophages surface.
• Antigens are displayed on the cell membrane near
  certain protein molecules called the major
  histocompatibility complex (MHC)
• Helper T cell becomes activated if it contacts,
  fits and combines with a displayed foreign
  antigen.
• Activated helper T cell stimulates B cell to
  produce antibodies specific for the displayed
  antigen.

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Link to antigen processing animation
Link to step through of this diagram
T cell and B cell activation. 1.) After digesting
antigen-bearing agents, a macrophage displays
antigens on its surface. 2.) Helper T cells
become activated when they contact displayed
antigens that fit their antigen receptors. 3.) An
activated helper T cell interacts with a B cell
that has combined with an identical antigewn and
causes the B cell to proliferate.
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Cytotoxic T Cell

• Recognizes nonself antigens that cancerous cells
  or virally infected cells display on their
  surfaces near MHC proteins.
• Becomes activated when it combines with an
  antigen that fits its receptors.
• T cell proliferates, enlarging its clone of cells.

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• Cytotoxic T cells then bind to the surfaces of
  antigen-bearing cells and release a protein that
  cuts porelike openings, destroying these cells.
• Continually monitor body cells, recognizing and
  eliminating tumor cells and cells infected with
  virus.
• Some do not respond to antigen on first exposure
  but remain as memory cells which can immediately
  differentiate into cytotoxic T cells upon
  subsequent exposure to same antigen.

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Humoral Immune Response

• B cells attack foreign antigens in a different
  way.
• Differentiate into plasma cells which produce and
  secrete larger globular proteins called
  antibodies or immunoglobins
• Body fluids carry antibodies which then react in
  various ways to destroy specific antigens or
  antigen-bearing particles. (humoral fluid)
• Also called Antibody-mediated Immune Response

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B Cell Activation

• B cell becomes activated when it encounters an
  antigen whose molecular shape fits the shape of
  its receptors.
• B cell divides repeatedly expanding its clone.
• Most require T cell help to become activated.
• When activated, helper T encounters B cell that
  has already combined with identical foreign
  antigen.
• Helper T releases cytokines which stimulate B
  cell to proliferate and enlarge clone of
  antibody-producing cells.
• Cytokines also attract macrophages and leukocytes
  into inflamed tissues and help keep them there.

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• Some activated B cells clone differentiate
  further into memory cells. Memory B cells respond
  rapidly to subsequent exposure to a specific
  antigen.
• Others differentiate into Plasma Cells which
  secrete antibodies
• Antibodies are similar in structure to the
  antigen receptor molecules on the original B
  cells surface.
• Antibodies can combine with the antigen-bearing
  agent that has invaded and react against it.
• An individuals B cells can produce an estimated
  10mil -1bil different varieties of antibodies.
  Each reacting against a specific antigen
  (pathogen)
• Secrete 2000 identical antibodies/second during
  its lifespan
• Antibodies are soluble, globular proteins that
  constitute the gamma globulin fraction of plasma
  proteins.

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Link to step through of this diagram
An activated B cell proliferates after
stimulation by cytokines released by helper T
cells. The B cells clone enlarges. Some cells of
the clone give rise to anti-body-secreting plasma
cells and others to dormant memory cells.
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Types of Antibodies (immunoglobins)

• Immunoglobulin G (IgG) In plasma and tissue
  fluids. Effective against bacteria, viruses, and
  toxins. Activates complement
• Immunoglobulin A (IgA) Commonly found in
  exocrine gland secretions in breast milk,
  tears, nasal fluid, gastric juice, intestinal
  juice, bile, and urine
• Immunoglobulin M (IgM) Develops in blood plasma
  in response to contact with antigens in foods or
  bacteria. Anti A and Anti B are examples. Also
  activates complement

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• Immunoglobulin D (IgD) Found on surfaces of most
  B cells, especially infants. Important in
  activating B cells.
• Immunogloulin E (IgE) Appears in exocrine
  secretions along with IgA. Associated with
  allergic reactions.

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• Newborn does not yet have its own antibodies.
• Retains IgG passed through placenta from mother.
  Protects against some illnesses to which the
  mother is immune.
• Receive IgA from colostrum, which protects
  against certain digestive and respiratory
  infections.

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Antibody Actions

• Directly attack antigens
• Activate complement to attack antigens
• Stimulate changes in local areas that help
  prevent the spread of antigens

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Direct Attack

• Antibodies combine with antigens and cause them
  to clump together (agglutinate) or to form
  insoluble substances (precipitate)
• Make it easier for phagocytic cells to engulf the
  antigen-bearing agents and eliminate them.
• Antibodies cover the toxic portions of antigen
  molecules and neutralize their effects.

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Complement

• More important than direct attack
• A group of proteins in plasma and other body
  fluids
• IgG or IgM combine with antigens and expose
  reactive sites on antibody molecules, triggering
  a series of reactions leading to activation of
  complement proteins.

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• Effects of Complement Proteins include
• Coating the antigen-antibody complexes
  (opsonization) making them more susceptible to
  phagocytosis
• Attracting macrophages and neutrophils into
  region (chemotaxis)
• Clumping antigen-bearing agents
• Rupturing membranes of foreign cells (lysis)
• Altering molecular structure of viruses rendering
  them harmless
• Promote inflammation which helps prevent the
  spread of infectious agents

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Actions of the Complement System
77
Immune Responses

• Primary Immune Response
• Secondary Immune Response

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Primary Immune Response

• When B and T cells become activated after first
  encountering their matching antigen
• Plasma cells release antibodies (IgM, then IgG)
  into lymph
• Antibodies enter the blood and distribute
  throughout body where they help destroy
  antigen-bearing agents.
• As a result of primary immune response,
  detectable concentrations of antibodies usually
  appear in the body fluids within 5-10 days
  following an exposure to antigens
• Continues for several weeks.

79
A primary immune response produces a lesser
concentration of antibodies than does a secondary
immune response
80
Secondary Immune Response

• Circulating memory B and memory T cells enlarge
  clone and respond rapidly with IgG if they come
  into contact with the antigen to which they were
  previously sensitized.
• Body may produce additional antibodies within a
  day or two.
• Secondary response is faster and produces a
  higher antibody concentration
• Newly formed antibodies may persist in the body
  for a few months or years. Memory cells live much
  longer.

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Superantigens

• Foreign antigens that elicit unusually vigorous
  lymphocyte responses
• Staphylococcus aureus 2 types
• 1 type causes food poisoning until digestive
  enzymes destroy it
• 2nd type causes toxic shock syndrome. Plummeting
  blood pressure, confusion, high fever, diarrhea,
  vomiting, potentially fatal

82
Practical Classification of Immunity
83
Vaccines

• Stimulate active immunity against a variety of
  diseases
• Consists of
• Bacteria or viruses that have been killed or
  weakened so that they cannot cause a serious
  infection
• A toxoid, which is a toxin from an infectious
  organism that has been chemically altered to
  destroy its toxic effects
• Includes the antigens that stimulate a primary
  immune response but does not produce the severe
  symptoms of disease.

84

• Vaccine distribution is not equitable worldwide.
  Some of these disease still pose a serious
  threat.
• Typhoid fever Cholera Whooping cough
• Diphtheria Mumps Influenza
• Hepatitis B Bacterial pneumonia Smallpox
• Tetanus Polio Chicken pox
• Measles (rubeola) German measles (rubella)

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Allergic Reactions

• An immune attack against a non-harmful substance
• Similar to normal immune response because
  lymphocytes are sensitized and antibodies may
  bind to antigens.
• Unlike normal response because allergic reactions
  can damage tissues.
• Allergen antigens that trigger allergic
  responses.

86
Delayed-Reaction Allergy

• Result from repeated exposure of the skin to
  certain chemicals commonly household or
  industrial chemicals or some cosmetics.
• Presence of foreign substance activates T cells
  (many of which collect in the skin)
• T cells and macrophages they attract release
  chemical factors which in turn cause eruptions
  and inflammations of the skin (dermatitis)
• Delayed takes 48 hours

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Immediate-Reaction Allergy

• Occurs within minutes after allergen contact
• Inherited tendency to overproduce IgE antibodies
  in response to certain antigens. (IgE normally
  comprises a minute fraction of plasma proteins.)
• During initial exposure
• B cells become sensitized
• IgE attaches to the membranes of widely
  distributed mast cells and basophils.

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• Subsequent exposures to allergen trigger allergic
  reactions and release allergy mediators
  histamine, prostaglandin D2, and leukotrienes.
• Allergy mediators cause severe inflammation
  reaction
• Dilation of blood vessels
• Increased vascular permeability that swells
  tissues (hives, eczema)
• Contraction of bronchial and intestinal smooth
  muscles (asthma, gastric disturbances)
• Increased mucus production (hay fever)

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Anaphylactic Shock

• Severe form of Immediate-Reaction Allergy
• Mast cells release allergy mediators throughout
  the body
• Person may feel inexplicable apprehension, then
  itchy, red hives, vomiting or diarrhea
• Face, tongue, and larynx swell causing breathing
  difficulty. Loss of consciousness and death
  within 5 minutes.
• Treatment injection of epinephrine (adrenalin)
  and sometimes tracheotomy (an incision into the
  windpipe to restore breathing).
• Most often from allergy to penicillin or insect
  stings.
• Fewer than 100 deaths/year due to prompt medical
  attention and avoidance to known allergens.

Link to Video on Allergies
90
Transplantation and Tissue Rejection

• Transplantation of tissues or organ can replace a
  nonfunctional, damaged, or lost body part.
• Ex. Skin, kidney, heart, liver
• Donated organs need to be transplanted quickly
• Heart can last outside body for 3-5 hours.
• Liver can last 10 hours
• Kidney can last 24-48 hours

91
Tissue Rejection Reaction

• The danger the immune system poses to
  transplanted tissue is that the recipients cell
  may recognize the donors tissues as foreign and
  attempt to destroy the transplanted tissue.
• Rejection resembles the cellular immune response
  against a nonself antigen.
• The more antigenic difference between recipient
  and donor tissues, the more rapid and severe the
  rejection reaction.
• Matching donor and recipient tissues can minimize
  rejection reaction (similar to blood typing
  before a transfusion)

92
Immunosuppresive Drugs

• Used to reduce rejection of transplanted tissues
• Interfere with recipients immune response by
  suppressing formation of antibodies or production
  of T cells. Reduces humoral and cellular immune
  responses.
• Can leave recipient unprotected against
  infections.
• Not uncommon for patient to survive transplant
  but die of infection due to weakened immune
  system.

93
Autoimmunity

• Attack against self when immune system fails to
  distinguish self from nonself.
• Producing autoantibodies and cytotoxic T cells
  that attack and damage tissues and organs.
• Example of autoimmune disorders
• Juvenile diabetes
• Rheumatoid arthritis
• Systemic lupis erythematosis

94
Possible Causes of Autoimmunity

• Virus borrows proteins from the host cells
  surface while replicating within human cell and
  incorporates them onto its own surface.
• When immune system learns surface of virus in
  order to destroy it, it also learns to attack
  human cells that normally bear that protein.
• T cells never learned to distinguish self from
  nonself.
• Nonself antigen coincidentally resembles a self
  antigen such as infection by streptococcus
  bacteria that triggers inflammation of heart
  valves.

95
Topics of Interest Immunity Breakdown AIDS
p.382-383

• Infection by the human immunodeficiency virus
  (HIV) which causes Acquired Immune Deficiency
  Syndrome (AIDS)
• Virus attacks lymphocytes by attaching to
  receptors on helper T cells and sending in its
  RNA
• An enzyme called reverse transcriptase
  manufactures viral DNA from the RNA which then
  directs cell activities to make new viral parts.
• Dying T cell can no longer release cytokines or
  stimulate B cells. Eventually bursts releasing
  new HIV particles
• New HIV replicate and overwhelm the immune system.

96

• Common AIDS-related conditions include
• Persistent lymphadenopathy (swollen lymph glands)
• Constant low-grade fever
• Nausea and vomiting
• Fatigue
• Night sweats
• Headaches
• Wasting syndrome (persistent diarrhea, severe
  weight loss, weakness, fever)
• Dementia (confusion apathy, inability to
  concentrate, memory loss, insomnia,
  disorientation, sudden strong emotions)
• Cancers (Kaposi sarcoma, cervical cancer,
  lymphoma, others)
• Opportunistic infections (pneumonia, brain
  infection, diarrhea, spinal meningitis,
  tuberculosis, fungal infections, many others)

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• Three Stages of HIV infection
• Initial symptoms
• Acute stage
• Weakness, recurrent fever, night sweats, swollen
  neck glands, weight loss
• Varies in duration and severity
• Latency period
• Last 5 10 years
• Person feels well although the immune system is
  struggling to contain the growing HIV population
  in the lymph nodes and then in the blood stream
• AIDS
• Opportunistic infections that appear when the
  immune system is compromised.

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• Modes of Transmission
• Requires contact with a body fluid containing
  abundant HIV such as blood or semen.
• Virus has been detected in sweat, tears, and
  saliva but levels are so low that transmission is
  unlikely.
• Whether or not a person becomes infected depends
  on
• Amount of infected fluid contacted
• Site of exposure in the body
• Individuals health

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• Progress
• Three groups of people are providing the clues
  that may lead to conquering HIV infection
• Infected individuals who never develop symptoms
  (long-term nonprogressors). Have a weakened
  strain of HIV that lacks a gene HIV normally uses
  to replicate. Enough of the virus remains to
  alert the immune system to protect against other
  strains. A vaccine might be based on this
  weakened strain.
• People exposed repeatedly who never become
  infected. 1 of population has gene variant that
  protects them from becoming infected by HIV.
  Cells of individuals lack either of two receptor
  molecules that HIV requires to enter cells.
• Infected individuals who apparently become
  uninfected. Several infants infected at birth
  have lost the virus as their immune system
  matured.

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• Research study these groups and use knowledge to
  develop prevention and treatment strategies.

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• Treatment
• Drugs target HIV infection at various stages.
• Block viral replication AZT, ddI, ddC, and 3TC
• Protease inhibitors prevent HIV from processing
  its proteins to a functional size, crippling the
  virus.
• Fusion inhibitors block the binding of HIV to T
  cell surfaces
• Combining drugs can keep viral load low and delay
  symptom onset and progression
• Viral variants emerge that resist the drugs
• Goal is to enable infected people to live normal
  life spans in relatively good health.
• More than 200 drugs available to treat
  AIDS-associated opportunistic infections and
  cancers.

103
Also see

• Clinical Connection Scleroderma p 386
• Genetics Connection Conquering Inherited
  Immunodeficiency p.384-385

104
Clinical Terms Related to the Lymphatic System
and Immunity
105
Allograft
Which tissue can be donated and how is it used?

• Transplantation of tissue from an individual of
  one species to another individual of that species.

Skin Thin top dermis recovered from the donor's
back, causing no disfigurement and allowing for
open casket viewing   Implanted on adults and
children suffering from severe burns, bed sores,
diabetic ulcers and corrective surgical
procedures   Skin implantation decreases pain
significantly, provides a barrier against
infection, regulates the body temperature,
prevents body fluid loss and helps clean the
wound.
Corneal Transplant
106
Orthopedic Meniscus / Humerus / Hemi-Pelvis /
Femur / Tibia / Patellar Tendon / Tibialis Tendon
/ Quadriceps Tendon / Femoral Condoyle / Achilles
Tendon all recovered with prosthetics
replacements and surgical stitching, causing no
disfigurement and allowing for open casket
viewing   Implanted in adults and children for
reconstruction related to trauma, tumors,
degenerative diseases and fractures including
total hip revisions, cervical spinal fusion,
repairs of congenital and traumatic facial
deformity, rotator cuff repair, replacement of
Achilles' tendon and repair of bladder
suspension.
Heart Valves Aortic Valve / Pulmonary Valve /
Mitral Valve / Non-valved Conduit / Pericardial
Patch Material   Implanted in adults and
children to replace damaged heart valves
primarily due to congenital heart defects and
infective endocarditis
107
Peripheral Nerve Peripheral nerves along the
arms and legs when orthopedic and vascular
tissues are recovered with no disfigurement
allowing for open casket viewing   Implanted in
adults and children due to injuries from
collisions, motor vehicle accidents, gun wounds,
fractures, dislocations, lacerations, or some
other form of penetrating trauma including
surgery resulting in major source of disability,
impairing the ability to move muscles or to feel
normal sensations.   Repairs and regenerate
peripheral nerves, beginning with relief and
restoring functionality to patients who suffer
PNS injuries due to trauma or surgery.
Vascular Saphenous Vein / Femoral Vein / Artery
/ Superficial Femoral / Vein Valve / Aortoiliac
Graft recovered from inner leg area with surgical
stitching which causes no disfigurement allowing
for open casket viewing   Implanted to adults
and children to restore circulation in the heart
and extremities as well as for use for dialysis
access.
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Asplenia

• Absence of a spleen

Asplenia refers to the absence ('a-') of normal
spleen function and is associated with some
risks. Asplenia may be congenital (congenital
asplenia), or acquired through surgery
(splenectomy) or through processes that destroy
the spleen, generally through its function to
filter the blood and therefore referred to as
autosplenectomy (eg spherocytosis and sickle-cell
disease). Asplenia increases the risk of
septicaemia from encapsulated bacteria, and can
result in a syndrome known as overwhelming post
splenectomy infection (OPSI) which can kill
within a few hours. In particular patients are at
risk from Pneumococcus, but also Haemophilus
influenzae Meningococcus. To minimise these
risks, antibiotic vaccination protocols have
been established,but are often poorly adhered to
by doctors and patients. The risk to asplenic
patients has been expressed as equivalent for a
child to die in home accident, and for adults
dying in a road traffic accident - so sensible
precautions are needed, but no panic.
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Autograft

• Transplantation of tissue from one part of the
  body to another part of the same body.

Skin Graft following Rattlesnake bite (Click to
read whole story)
110
Immunocompetence

• Ability to produce an immune response to the
  presence of antigens

111
Immunodeficiency

• Inability to produce an immune response

112
Lymphadenectomy

• Surgical removal of lymph nodes

113
Lymphadenopathy

• Enlargement of lymph nodes

114
Lymphadenotomy

• Incision of a lymph node

115
Lymphocytopenia

• Too few lymphocytes in blood

116
Lymphocytosis

• Too many lymphocytes in blood

117
Lymphoma

• Tumor composed of lymphatic tissue

118
Lymphosarcoma

• Cancer within the lymphatic tissue

119
Splenectomy

• Surgical removal of the spleen

120
Splenitis

• Inflammation of the spleen

121
Splenomegaly

• Abnormal enlargement of the spleen

122
Splenotomy

• Incision of the spleen

123
Thymectomy

• Surgical removal of the thymus

124
Thymitis

• Inflammation of the thymus