Homeostasis III: The Immune Response

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Homeostasis III The Immune Response

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The Microscopic Threat

• Every Living thing at this moment is surrounded
  by potentially harmful microorganisms.
• Many of these microorganisms have the potential
  not only to destroy cells, but to disrupt entire
  processes in which life depends on.
• Through evolution organisms have developed a wide
  variety of defenses to protect against these
  harmful invaders.

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Non-Specific Defenses

• The bodys first line of defense against harmful
  microorganisms is the outer wrapping of skin and
  mucous membranes.
• The skin is a tough layer of keratin which keeps
  large numbers of microorganisms out as long as
  it is intact.
• The epithelium forms the mucous membrane, which
  is more fragile than skin, but is constantly
  flushed with antimicrobial fluids, such as mucus,
  saliva, and tears.
• The epithelium lines many of the bodys inner
  surfaces, such as the lining of the intestines.
• The acidic environment of the stomach creates an
  inhospitable environment for any ingested
  microorganisms.

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The Inflammatory Response

• When you receive a cut or scrape in the skin, the
  body triggers the inflammatory response
• Cells in the area release histamine and other
  chemicals that increase blood flow to the area.
  Circulating white blood cells are attracted to
  the area by these chemicals and engulf any
  foreign invaders. Blood clots form walling off
  the cut area. The local temperature also
  increases, creating an unfavorable environment
  for organisms. These activities collectively
  constitute the inflammatory response.

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The Bodys defenders

• Both the inflammatory response and immune
  response depend on a variety of types of white
  blood cells.
• All different types of red and white blood cells
  result from the differentiation and division of
  common stem cells in the marrow of long bones.
• The principle cells involved in the inflammatory
  response are granulocytes, circulating white
  blood cells classified by their staining
  properties as neutrophils, eosinophils, or
  basophils.
• Neutrophils make up 50 to 70 percent of all white
  blood cells.

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Neutrophils

• When the first signs of inflammation appear,
  neutrophils begin to stick to the inner surface
  of the endothelium lining the blood vessels.
• They then develop amoeboid projections which
  enable them to push their way between the
  endothelial cells of the capillaries and move
  into the infected tissues.
• When they encounter a foreign microorganism they
  phagocytes them. When inside the cell, lysosomes
  fuse with the phagocytic vacuole and digest the
  microorganism.
• Some microbes, such as encapsulated pneumococcus
  have evolved defense of their own to remain
  virulent against neutrophils.

Human Neutrophils
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Basophils and Eosinophils

• Basophils and eosinophils are phagocytic.
• Basophils are important components of allergic
  reactions.
• Mast cells, which are basophils, play a key role
  in allergic reactions and are found in connective
  tissue.
• The role of eosinophils is still not clear,
  although they are found in increased number
  during infection involving parasites, such as
  worms.

Human basophils
Human Eosinophils
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Monocytes

• Monocytes play a critical role in the
  inflammatory response.
• Monocytes are attracted to the cite of
  inflammation by chemicals released by both
  bacterial and host cells and generally arrive
  later than neutrophils.
• Once they arrive, Monocytes are transformed into
  macrophages.
• Macrophages are large, amoeboid like, and
  phagocytic. They entrap any molecules that
  penetrate the initial defenses.
• They are also important in activating
  lymphocytes.

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Interferons

• Interferons are different from other defensive
  mechanisms in two ways
• They are only active against viruses
• They do not act directly on the invading viruses
  but rather stimulate the bodys own defenses
  against them.

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Interferons

• When a cell is invaded by a virus, it release
  interferon, which interacts with receptor cites
  on near by cells.
• Once these cites have been stimulated, the cells
  produce anti-viral proteins that block the
  translation of viral RNA.
• Only a very few molecules of interferon seem to
  be required to protect the surrounding cells from
  viral infection.
• Interferon molecules also interact with receptors
  on the surface of various types of white blood
  cells, stimulating both the inflammatory and
  immune responses.

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The Immune System

• The specificity of the immune response derives
  from the interactions of two groups of cells
  B-lymphocytes and T-lymphocytes.
• The lymphatic system is the route in which the
  cells of the immune system travel, and also
  captures many of the harmful microorganisms in
  the lymph nodes. Once trapped, white blood cells
  and the lymphocytes can easily attack and destroy
  them.

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B-Lymphocytes and Antibodies

• At any given time 2 trillion B-Lymphocytes are on
  alert in the human body.
• Embedded in the membrane of each B-lymphocyte are
  antibodies with specific three dimensional
  structure.
• When a lymphocyte meets an antigen with a
  structure complimentary to the antibodies on its
  surface, the cell enlarges, its nucleolus swells,
  polysomes form, and an increased synthesis of
  macromolecules begins.

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Plasma Cells

• Plasma cells are one of two types of daughter
  cells that result from the activation of
  B-lymphocytes.
• Plasma cells, in essence, are specialized
  anti-body factories.
• A mature plasma cell can make 3,000 to 30,000
  antibody molecules per second these antibodies
  are released and circulate through the
  bloodstream.

Human Plasma Cells
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Memory Cells

• Memory cells are the second type of cell produced
  by antigen-stimulated B-lymphocytes.
• Memory cells, as well as plasma cells also
  produce antibodies, but differ from them in their
  longevity. (memory cells can last an entire
  lifetime while plasma cells last only a few days)
• Thus when you are infected a second time with a
  pathogen you have already had, memory cells
  immediately being large scale production of
  antibodies, which prevent the pathogen from
  infecting you.
• This source of rapid production of antibodies is
  responsible for the long term immunity to many
  diseases.

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The Action of Antibodies

• Antibodies act against invaders in one of three
  ways
• They may coat the foreign particles and cause
  them to clump together in such a way that they
  can be take up by phagocytic cells.
• They may combine with them in such a way that
  they interfere with some vital activity
• They may themselves, in combination with other
  blood components, collectively known as
  complement, actually lyse and destroy foreign
  cells.

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The structure of Antibodies

• The structure of antibodies was discovered using
  the properties of cancer cells.
• Each antibody is a complex protein consisting of
  two identical light chains and two identical
  heavy chains.
• The light chains have about 214 amino acids and
  the heavy chains have about twice as many.
• Both the light chains and heavy chains have
  constant regions, in which the sequence of amino
  acids is identical from one molecule to the next.

Curtis and Barnes, Biology. Worth Publishers Inc.
1989
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The Clonal Selection theory

• According to the clonal selection theory, each
  individual has a variety of different
  B-lymphocytes, each genetically equipped with the
  capacity to synthesize only one type of antibody,
  which is displayed on its surface.
• According to the clonal Selection theory,
  antibodies are not tailor-made in response to
  an antigen, rather the antibodies displayed by
  the B-lymphocytes like a supplier of all
  different kinds of antibodies.
• The clonal selection model predicted two things
• Only a very small number of lymphocytes would
  respond to a given antigen.
• Any one plasma cell would always form only one
  antibody.

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T-Lymphocytes

• T-lymphocytes are the offspring of
  self-regulating stem cells in the marrow of long
  bones.
• Unlike B-lymphocytes, T-lymphocytes interact with
  other eukaryotic cells -- specifically the bodys
  own cells.
• Three classes of T-lymphocytes are known
• Helper T-cells
• Suppressor T-cells
• Cytotoxic T-cells

T-Lymphocytes
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T-lymphocytes

• In the thymus gland, T-lymphocyte precursors go
  through a complex process of differentiation,
  selection, and maturation.
• Differentiation involves the synthesis of at
  least types of glycoproteins, ultimately
  displayed on the surface of the T-cell.
• The first type of glycoprotein exists in two
  forms T4 and T8
• The second type is the receptor by which the
  T-cell recognizes both the eukaryotic cells of
  the body itself and the foreign antigens
  displayed on those cells.
• The third type is made up of five proteins,
  collectively know as as T3. The function of
  these is still poorly understood.

A T-Cell receptor
Curtis and Barnes, Biology. Worth Publishers Inc.
1989
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The Major Histocompatibility Complex

• The proteins components of glycoprotein antigens
  are coded by a group pf genes known as the Major
  histocompatibility Complex, or MHC.
• The MHC consists of at least 20 different genes,
  and within the human population, each of these
  genes has as many as 8 to 10 alleles.
• Current evidence indicates that there are two
  classes of MHC antigens, known as class 1 and
  class 2.
• Class 1 molecules are found on the cells
  throughout the body and are necessary for
  recognition by Cytotoxic T-cells.
• Class 2 molecules are present only on cells of
  the immune system and identify such cells to each
  other.

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The Functions of T-Lymphocytes

• Cytotoxic T-cells are the simplest T-lymphocytes.
• When a Cytotoxic T-cell encounters such a
  combination of Class 1 MHC antigen and foreign
  antigen to which its receptor can bind, it
  differentiates into active cells that attack and
  lyse the infected cells and into memory cells
  that remain in the circulation indefinitely.
• In addition, the activated Cytotoxic T-cells
  release powerful toxic chemicals, known as
  lymphocytes that attract macrophages and
  stimulate phagocytes. Some of the T-cells
  secrete cytotoxins while others secrete
  interferon.

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Cancer and the Immune Response

• Recent studies have shown that cancer does induce
  an immune response although the cancer cells are
  the bodys own cells.
• This hypothesis suggests that immune responses to
  cancer can even stop the cancer itself,
  suggesting that bolstering the immune system may
  help to better protect the body against cancer.

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Transplants and Transfusions

• Before drugs like cyclosporin were discovered,
  transplants were almost impossible because the
  bodys immune system would see the foreign tissue
  as an invader and attack it as it would foreign
  bacteria.
• Blood transfusions are similar to transplants in
  that they can both invoke an immune response.
• Red Blood cells, unlike nucleated cells, do not
  have MHC antigens on their surface. Instead they
  display unique antigens, coded by an entirely
  different gene, which has three alleles. (A, B,
  and O)
• For blood transfusions to be successful, the two
  blood types of the recipient and donor must
  match.

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The RH Factor

• RH is a antigen on the surface of red blood cells
  similar to the alleles that make up the different
  blood types.
• Like the other surfaces of the red blood cell,
  the RH factor is genetically determined.
• During the birth of an RH-negative mother's first
  RH positive child, fetal red blood cells bearing
  the RH antigen are likely to enter her
  bloodstream. The consequences are the same as
  would occur with a transfusion of RH positive
  blood the mothers immune system produces
  antibodies against the blood cells. These
  antibodies remain in her system and may be
  transferred to fetuses in subsequent pregnancies.
  If the subsequent fetuses are RH positive, the
  antibodies will attack the red blood cells of the
  fetus, destroying them. This reaction can be
  fatal to the baby.

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Disorders of the Immune System

• Autoimmune diseases are diseases in which the
  immune system is caused to make antibodies
  against its own cells.
• Allergies are the immune response to pollen,
  dust, or other substances, such as some foods,
  that are weak antigens to which most people do
  not react.
• When certain individuals are exposed to
  particular antigens, the production of IgE
  antibodies by specific plasma cells is
  stimulated, as well as memory cells. These
  antibodies circulate and attach themselves to the
  mast cells found in connective tissue.
  Subsequent binding of the antigen o these
  attached antibodies triggers the release of
  histamine, which induces an inflammatory
  response.

A human Mast Cell
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AIDS

• AIDS was first identified in 1981, when
  epidemiologists noticed an unusual cases of
  diseases in people that the disease did not
  usually effect.
• This occurrence supported the idea that the
  disease causing these other diseases was an
  immune system repressor.
• The AIDS virus is a retrovirus, which means it
  has a RNA core, and is very complex.
• The virus actually attacks the T-cells in the
  body, destroying them and rendering the victim
  completely susceptible to attack from infections
  that normally would not occur otherwise.
• The Complex system of membranes in the AIDS virus
  makes it very resistant to the immune responses

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The Prospects of AIDS

• The consequences of the AIDS virus are very
  severe and even today death is almost
  unavoidable. Although the widespread use of
  T-cell replenishing drugs has extended the
  survival time with AIDS, death is still very
  likely within about 10 years of the initial
  infection.
• Luckily, the AIDS virus is not contagious like
  many of the viruses we are commonly infected
  with. AIDS is only passed on through the bodily
  fluids of an infected person. The Most common
  ways of transmitting AIDS are through sexual
  intercourse and through the exchange of blood.
• AIDS, like smallpox in another era, is one of the
  great teachers on the subject of immunology.