Nature of the Immune System

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Nature of the Immune System

• Non-Specific Immunity
• Terry Kotrla, MS, MT(ASCP)BB

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Immunity Very Complex System
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Cellular versus Humoral Immunity

• Cellular - Researchers observed that foreign
  substances were removed by specialized cells in a
  process known as phagocytosis.
• Humoral - Other researchers postulated that
  substances in the blood provided protection from
  microorganisms, humoral immunity.

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Natural versus Acquired Immunity

• Natural immunity born with the ability to
  resist infections by normal bodily functions.
• Acquired immunity requires exposure to a
  pathogen or microbial agent, upon recovery
  lifelong immunity is acquired.

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Natural (Nonspecific , Innate) Immunity

• Non-specific immunity
• First line of defense against infection
• Two mechanisms external and internal

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External

• Composed of structural barriers to keep
  infectious agents out of the body.
• Intact skin
• Cilia
• Physiological factors.

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Physical barriers Intact Skin
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Intact Skin

• Difficult for a pathogen to penetrate,
• Sweat creates high salt conditions.
• Oil layer, fatty acids and acid pH present makes
  an inhospitable environment for microorganisms.
• Normal flora prevent other microorganisms from
  establishing an infection competitive
  exclusion.

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Natural Immunity - Cilia
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Natural Immunity

• Stomach acid (HCl) kills pathogens and sterilizes
  food.
• Mucus lining of lungs traps pathogens and cilia
  move particles out to throat and it is swallowed.
  
• Coughing and sneezing.
• Tears wash away pathogens and have bacteriocidal
  enzymes.
• Flushing action of urine
• Circulating cells and tissue cells
• Wax in ears http//tinyurl.com/27lk4og
• Normal flora prevents growth of opportunistic
  pathogens in mouth, large intestine and
  reproductive system

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Factors Modify Defense Mechanisms

• Age
• Hormones
• Drugs and chemicals
• Malnutrition
• Fatigue and stress
• Genetic determinants

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Nonspecific Immunity Second line of defense

• Inflammatory response - four classic signs are
  redness, swelling, heat and pain.
• Dilation of capillaries (hyperemia) to increase
  blood flow to area
• Chemotaxis - chemicals released which cause
  phagocytic white cells to migrate to the area.
• Increased capillary permeability allowing white
  cells to go to injured area, a process known as
  diapedesis
• Formation of exudate - same composition as plasma
  and it contains antibacterial substances,
  phagocytic cells, and drugs and antibiotics, if
  present.

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Inflammatory Response
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Inflammatory Response
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Phagocytosis

• The following 3 diagrams illustrate the process
  of phagocytosis.
• Be intimately familiar with the process.

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Inflammatory Response
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Second Line of Defense

• If bacteria are not successfully killed locally,
  may further invade the host by way of the
  lymphatics to the regional lymph nodes.
• within lymph nodes the bacteria meet other
  phagocytic cells
• bacteria may overcome these and gain access to
  the bloodstream where they meet circulating
  phagocytes (neutrophils and monocytes).
• may pass through the bloodstream and reach organs
  such as the liver and spleen where they come into
  contact with tissue macrophages.
• although a powerful defense system, this final
  phagocytic barrier may be overcome, with seeding
  of the microorganism to organs such as bone,
  brain, and kidney, terminating in fatal
  septicemia.

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Phagocytosis -MEMORIZE

• Initiation is caused by damage to the tissues,
  either by trauma or as a result of microbial
  multiplication.
• Chemotaxis, attraction of leukocytes or other
  cells by chemicals.
• Opsonization - Opsonization coating a pathogen by
  substances so as to enhance phagocytosis.
• Adherence - firm contact between phagocyte and
  microorganism.
• Engulfment into cytoplasm and enclosed in a
  vacuole.
• Digestion enzymatic contents in vacuole destroy
  the microorganism.
• Number of killing mechanisms operating in the
  vacuoles of phagocytic cells.
• One of the major mechanisms involves hydrogen
  peroxide which, acting along with an
  intracellular enzyme, is rapidly lethal to many
  bacteria.

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Phagocytosis
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Phagocytosis

• http//www.cellsalive.com/ouch.htm
• http//health.howstuffworks.com/adam-200096.htm
• http//tinyurl.com/6oa779

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Cells of the Non-Specific Immune System

• Cells involved in non specific immunity.
• Phagocytic cells
• Mononuclear phagocytes
• Polymorphonuclear phagocytes
• Eosinophils
• Mediator cells
• Basophils and mast cells
• Platelets

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Cells involved in specific immunity

• Lymphocytes
• Plasma cells

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Origin of immune cells

• Origin of all these cell types are from
  pluripotential stem cells found in the bone
  marrow.
• These self replicating cells differentiate into
  two types of "committed" stem cells.
• One group differentiates further and matures to
  become platelets, erythrocytes (red blood cells),
  monocytes or granulocytes.
• Second group produces cells of the lymphoid line
  only.
• The lymphoid line will develop into 2 different
  types, T and B cells, depending upon where they
  complete their maturation, thymus or bone marrow.
• Will be discussed in detail later

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Phagocytic Cells

• Mononuclear phagocytes - include both circulating
  blood monocytes and tissue macrophages found in
  various tissues of the body.
• Arise from bone marrow stem cells
• Not end cells, they may divide.
• Ingest and destroy material such as bacteria,
  damaged host cells or tumor cells (non-specific
  immunity).
• Stay in peripheral blood 70 hours - migrate to
  tissues, double in size, then called tissue
  macrophages.
• Tissue macrophages named according to tissue
  location- liverKupffer cells, brain-microglial
  cells, etc.
• Phagocytosis takes place to a greater degree in
  tissues.

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Monocyte and Tissue Macrophage
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Neutrophils

• Characterized by a large nucleus, 3 - 5 lobes,
  and specific granules in the cytoplasm.
• Arise from bone marrow stem cells.
• They are end cells.
• Primary function is ingestion (phagocytosis).
• Clear body of debris such as dead cells and
  thrombi.
• Able to move into tissues by diapedesis.

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Neutrophils with Ingested Material
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Neutrophil Involved in Phagocytosis
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Eosinophils

• Easily distinguished by the presence of large
  granules in their cytoplasm which appear red when
  stained by routine hematology stains.
• Much less phagocytic than macrophages or
  neutrophils
• Function is far from clear, however the numbers
  increase greatly in certain parasitic diseases
  and allergic diseases.
• Both neutrophils and eosinophils contain
  specific granules, the granules contain various
  enzymes which are released under certain
  circumstances.

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Eosinophil
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Mediator Cells

• Influence the immune response by releasing
  various chemical substances into the circulation.
  
• Have a variety of biological functions
• Increase vascular permeability
• Contract smooth muscle
• Enhance the inflammatory response
• Two types
• basophils/mast cells
• Platelets

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Basophils

• Basophils easily identified due to large numbers
  of bluish-black granules in the cytoplasm.
• The granules are a source of mediators such as
  histamine (vasoactive amine that contracts smooth
  muscle) and heparin.
• Basophils and platelets are found in the
  circulation, mast cells are situated in the
  tissues of skin, lung and GI tract.
• Bind IgE, a type of antibody formed during
  allergic reactions.
• Circulating basophils greatly resemble tissue
  mast cells and it is likely that they are closely
  related in function.
• Basophils exist on a few hours in bloodstream.
• Both of these cells play a role in
  hypersensitivity (allergic) reactions

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Basophil
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Mast cells

• Resemble basophils.
• Fixed in the tissues they are connective tissue
  cells.
• Widely distributed through out the body.
• Long life span, 9-18 months.
• Plays a role in hypersensitivity reactions by
  binding IgE.

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Platelets

• Small non-nucleated cells derived from
  megakaryocytes of the bone marrow.
• Important in blood clotting.
• Contribute to the immunological tissue injury
  occurring in certain types of hypersensitivity
  reactions by releasing histamine and related
  substances which are contained within specialized
  granules in their cytoplasm.

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Megakaryocyte Platelets
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Dendritic Cells

• Primary function is phagocytosis.
• Process antigen material and present it on the
  surface to other cells of the immune system,
  function as antigen-presenting cells.
• Act as messengers between the innate and adaptive
  immunity.
• Classified according to tissue location.
• Found on skin and all major organs.

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Soluble Factors

• Many soluble tissue and serum substances help to
  suppress the grow of or kill microorganisms.
• Interferons - family of proteins which are
  important non-specific defense mechanisms against
  viral infections.
• Transferrin - Bacteria do not thrive well in
  serum that contains low levels of iron but high
  levels of transferrin.
• Complement - a group of proteins that are
  essential for bacterial destruction and plays an
  important role in both non-specific and specific
  immune mechanisms.

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Acute Phase Reactants (Proteins)

• Defined-normal serum constituents that increase
  rapidly because of infection, injury, or trauma
  to tissues.
• Acute-phase proteins are a class of proteins
  whose plasma concentrations increase or decrease
  in response to inflammation.
• This response is called the acute-phase reaction
  .
• In response to injury local inflammatory cells
  (neutrophils, granulocytes and macrophages)
  secrete a number of cytokines into the
  bloodstream, most notable of which are the
  interleukins.
• The liver responds by producing a large number of
  acute-phase reactants.

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C-Reactive Protein

• Increases rapidly within 4-6 hours of infection
  or injury.
• Returns to normal rapidly once condition
  subsides.
• Used to monitor healing and has also increased in
  usefulness in diagnosing Myocardial Infarction.

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Serum Amyloid A

• Major protein secreted during the acute phase of
  inflammation.
• Has several roles, including
• Removes cholesterol from cholesterol-filled
  macrophages at site of injury clean up.
• recruitment of immune cells to inflammatory
  sites, and
• Thought to play a role in cholesterol metabolism
  

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Complement

• A series of serum proteins involved in mediation
  of inflammation but also involved in
• opsonization,
• chemotaxis, and
• cell lysis.

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Alpha-1 Antitrypsin

• Increases during acute inflammation.
• Protects tissues from enzymes of inflammatory
  cells, especially elastase.
• When the lungs do not have enough alpha-1
  antitrypsin, elastase is free to destroy lung
  tissue.
• As a result, the lungs lose some of their ability
  to expand and contract (elasticity). This leads
  to emphysema and sometimes makes breathing
  difficult.

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Haptoglobin

• Binds irreversibly to free hemoglobin to protect
  kidneys from damage and prevent loss of iron by
  urinary excretion.
• Haptoglobin - hemoglobin complex removed by RES,
  mainly spleen.
• Used to monitor hemolysis

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Fibrinogen

• A coagulation factor integral to clot formation
  which serves as a barrier to prevent spread of
  microorganisms further in the body.
• Levels increase with tissue inflammation or
  tissue destruction.
• Thought to play a key role in the inflammatory
  response and development of rheumatoid arthritis.

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Ceruloplasmin

• Principal copper transporting protein in plasma,
  plays a role in iron metabolism and histamine
  regulation.
• Stimulates the immune system to fight infections,
  repair injured tissues and promote healing.
• Depletion found in Wilsons disease, causes the
  body to absorb and retain excessive amounts of
  copper.
• Copper deposits in the liver, brain, kidneys, and
  the eyes.
• The deposits of copper cause tissue damage,
  necrosis (death of the tissues), and scarring,
  which causes decreased functioning of the organs
  affected.
• Liver failure and damage to the central nervous
  system (brain, spinal cord) are the most
  predominant, and the most dangerous, effects of
  the disorder.

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References

• http//www.horton.ednet.ns.ca/staff/Selig/isu/Immu
  nity/Innate.htm
• http//www.metacafe.com/tags/neutrophil/most_popul
  ar/