Natural%20Defenses%20against%20Disease

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Natural Defensesagainst Disease
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Natural Defenses against Disease

• Animal Defense Systems
• Nonspecific Defenses
• Specific Defenses The Immune System
• B Cells The Humoral Immune Response
• T Cells The Cellular Immune Response
• The Genetic Basis of Antibody Diversity
• Disorders of the Immune System

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Animal Defense Systems

• Animal defense systems are based on the
  distinction between self and nonself.
• There are two general types of defense
  mechanisms
• Nonspecific defenses, or innate defenses, are
  inherited mechanisms that protect the body from
  many different pathogens.
• Specific defenses are adaptive mechanisms that
  protect against specific targets.

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Animal Defense Systems

• Components of the defense system are distributed
  throughout the body.
• Lymphoid tissues (thymus, bone marrow, spleen,
  lymph nodes) are essential parts of the defense
  system.
• Blood plasma suspends red and white blood cells
  and platelets.
• Red blood cells are found in the closed
  circulatory system.
• White blood cells and platelets are found in the
  closed circulatory system and in the lymphatic
  system.

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Animal Defense Systems

• Lymph consists of fluids that accumulate outside
  of the closed circulatory system in the lymphatic
  system.
• The lymphatic system is a branching system of
  tiny capillaries connecting larger vessels.
• These lymph ducts eventually lead to a large
  lymph duct that connects to a major vein near the
  heart.
• At sites along lymph vessels are small, roundish
  lymph nodes.
• Lymph nodes contain a variety of white blood
  cells.

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Figure 18.1 The Human Lymphatic system
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Animal Defense Systems

• White blood cells are important in defense.
• All blood cells originate from stem cells in the
  bone marrow.
• White blood cells (leukocytes) are clear and have
  a nucleus and organelles.
• Red blood cells are smaller and lose their nuclei
  before they become functional.
• White blood cells can leave the circulatory
  system.
• The number of white blood cells sometimes rises
  in response to invading pathogens.

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Animal Defense Systems

• There are two main groups of white blood cells
  phagocytes and lymphocytes.
• Phagocytes engulf and digest foreign materials.
• Lymphocytes are most abundant. There are two
  types B and T cells.
• T cells migrate from the circulation to the
  thymus, where they mature.
• B cells circulate and also collect in lymph
  vessels, and make antibodies.

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Figure 18.2 Blood Cells (Part 1)
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Figure 18.2 Blood Cells (Part 2)
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Figure 18.2 Blood Cells (Part 3)
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Animal Defense Systems

• Four groups of proteins play key roles in
  defending against disease
• Antibodies, secreted by B cells, bind
  specifically to certain substances.
• T cell receptors are cell surface receptors that
  bind nonself substances on the surface of other
  cells.
• Major histocompatibility complex (MHC) proteins
  are exposed outside cells of mammals. These
  proteins help to distinguish self from nonself.
• Cytokines are soluble signal proteins released by
  T cells. They bind and alter the behavior of
  their target cells.

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Nonspecific Defenses

• The skin acts as a physical barrier to pathogens.
• Bacteria and fungi on the surface of the body
  (normal flora) compete for space and nutrients
  against pathogens.
• Tears, nasal mucus, and saliva contain the enzyme
  lysozyme that attacks the cell walls of many
  bacteria.
• Mucus and cilia in the respiratory system trap
  pathogens and remove them.
• Ingested pathogens can be destroyed by the
  hydrochloric acid and proteases in the stomach.
• In the small intestine, bile salts kill some
  pathogens.

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Nonspecific Defenses

• Vertebrate blood contains about 20 antimicrobial
  complement proteins.
• Complement proteins provide three types of
  defenses
• They attach to microbes, helping phagocytes
  recognize and destroy them.
• They activate the inflammation response and
  attract phagocytes to the site of infection.
• They lyse invading cells.

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Nonspecific Defenses

• Interferons are produced by cells that are
  infected by a virus.
• All interferons are glycoproteins consisting of
  about 160 amino acids.
• They increase resistance of neighboring cells to
  infections by the same or other viruses.
• Each vertebrate species produces at least three
  different interferons.

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Nonspecific Defenses

• Phagocytes ingest pathogens. There are several
  types of phagocytes
• Neutrophils attack pathogens in infected tissue.
• Monocytes mature into macrophages. They live
  longer and consume larger numbers of pathogens
  than do neutrophils. Some roam and others are
  stationary in lymph nodes and lymphoid tissue.
• Eosinophils kill parasites, such as worms, that
  have been coated with antibodies.
• Dendritic cells have highly folded plasma
  membranes that can capture invading pathogens.

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Nonspecific Defenses

• Natural killer cells are a class of nonphagocytic
  white blood cells
• They can initiate the lysis of virus-infected
  cells and some tumor cells.

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Nonspecific Defenses

• The inflammation response is used in dealing with
  infection or tissue damage.
• Mast cells and white blood cells called basophils
  release histamine, which triggers inflammation.
• Histamine causes capillaries to become leaky,
  allowing plasma and phagocytes to escape into the
  tissue.
• Complement proteins and other chemical signals
  attract phagocytes. Neutrophils arrive first,
  then monocytes (which become macrophages).

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Nonspecific Defenses

• The macrophages engulf invaders and debris and
  are responsible for most of the healing.
• They produce several cytokines, which may signal
  the brain to produce a fever.
• Pus, composed of dead cells and leaked fluid, may
  accumulate.

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Figure 18.4 Interactions of Cells and Chemical
Signals in Inflammation (Part 1)
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Figure 18.4 Interactions of Cells and Chemical
Signals in Inflammation (Part 2)
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Nonspecific Defenses

• An invading pathogen is a signal that triggers
  the bodys defense mechanisms.
• A signal transduction pathway acts as the link
  between a signal and the immune response.
• The membrane protein toll is the receptor.
• Toll is part of a protein kinase cascade that
  results in the transcription of at least 40 genes
  involved in both specific and nonspecific
  defenses.
• The signal molecules are made only by microbes.

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Figure 18.5 Cell Signaling and Defense
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Specific Defenses The Immune System

• Four characteristics of the immune system
• 1. Specificity Antigens are organisms or
  molecules that are specifically recognized by T
  cell receptors and antibodies.
• The sites on antigens that the immune system
  recognizes are the antigenic determinants (or
  epitopes).
• Each antigen typically has several different
  antigenic determinants.
• The host creates T cells and/or antibodies that
  are specific to the antigenic determinants.

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Figure 18.6 Each Antibody Matches an Antigenic
Determinant
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Specific Defenses The Immune System

• 2. Diversity
• It is estimated that the human immune system can
  distinguish and respond to 10 million different
  antigenic determinants.
• 3. Distinguishing self from nonself
• Each normal cell in the body bears a tremendous
  number of antigenic determinants. It is crucial
  that the immune system leave these alone.
• 4. Immunological memory
• Once exposed to a pathogen, the immune system
  remembers it and mounts future responses much
  more rapidly.

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Specific Defenses The Immune System

• The immune system has two responses against
  invaders The humoral immune response and the
  cellular immune response.
• The two responses operate in concert and share
  mechanisms.

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Specific Defenses The Immune System

• The humoral immune response involves antibodies
  that recognize antigenic determinants by shape
  and composition.
• Some antibodies are soluble proteins that travel
  free in blood and lymph. Others are integral
  membrane proteins on B cells.
• When a pathogen invades the body, it may be
  detected by and bound by a B cell whose membrane
  antibody fits one of its potential antigenic
  determinants.
• This binding activates the B cell, which makes
  multiple soluble copies of an antibody with the
  same specificity as its membrane antibody.

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Specific Defenses The Immune System

• The cellular immune response is able to detect
  antigens that reside within cells.
• It destroys virus-infected or mutated cells.
• Its main component consists of T cells.
• T cells have T cell receptors that can recognize
  and bind specific antigenic determinants.

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Specific Defenses The Immune System

• Several questions arise that are fundamental to
  understanding the immune system.
• How does the enormous diversity of B cells and T
  cells arise?
• How do B and T cells specific to antigens
  proliferate?
• Why dont antibodies and T cells attack and
  destroy our own bodies?
• How can the memory of postexposure be explained?

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Specific Defenses The Immune System

• Clonal selection explains much of this.
• The healthy body contains a great variety of B
  cells and T cells, each of which is specific for
  only one antigen.
• Normally, the number of any given type of B cell
  present is relatively low.
• When a B cell binds an antigen, the B cell
  divides and differentiates into plasma cells
  (which produce antibodies) and memory cells.
• Thus, the antigen selects and activates a
  particular antibody-producing cell.

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Figure 18.7 Clonal Selection in B Cells
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Specific Defenses The Immune System

• An activated lymphocyte (B cell or T cell)
  produces two types of daughter cells effector
  and memory cells.
• Effector B cells, called plasma cells, produce
  antibodies.
• Effector T cells release cytokines.
• Memory cells live longer and retain the ability
  to divide quickly to produce more effector and
  more memory cells.

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Specific Defenses The Immune System

• When the body encounters an antigen for the first
  time, a primary immune response is activated.
• When the antigen appears again, a secondary
  immune response occurs. This response is much
  more rapid, because of immunological memory.

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Figure 18.8 Immunological Memory
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Specific Defenses The Immune System

• Artificial immunity is acquired by the
  introduction of antigenic determinants into the
  body.
• Vaccination is inoculation with whole pathogens
  that have been modified so they cannot cause
  disease.
• Immunization is inoculation with antigenic
  proteins, pathogen fragments, or other molecular
  antigens.
• Immunization and vaccination initiate a primary
  immune response that generates memory cells
  without making the person ill.

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Specific Defenses The Immune System

• Antigens used for immunization or vaccination
  must be processed so that they will provoke an
  immune response but not cause disease. There are
  three principle ways to do this
• Attenuation involves reducing the toxicity of the
  antigenic molecule or organism.
• Biotechnology can produce antigenic fragments
  that activate lymphocytes but do not have the
  harmful part of the protein toxin.
• DNA vaccines are being developed that will
  introduce a gene encoding an antigen into the
  body.

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Specific Defenses The Immune System

• The body is tolerant of its own molecules, even
  those that would cause an immune response in
  other individuals of the same species.
• Failure to do so results in autoimmune disease.
• This self tolerance is based on two mechanisms
  clonal deletion and clonal anergy.

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Specific Defenses The Immune System

• Clonal deletion eliminates B or T cells from the
  immune system at some point during
  differentiation.
• About 90 percent of all B cells made in the bone
  marrow are removed in this way.
• Any immature B cell in the marrow that could
  mount an immune response against self antigens is
  eliminated.
• The same is true for T cells, but the selection
  occurs in the thymus.
• Elimination is accomplished by means of apoptosis.

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Specific Defenses The Immune System

• Clonal anergy is the suppression of the immune
  response.
• Before a mature T cell mounts an immune response,
  it must recognize both an antigen on a cell and
  another molecule, CD28 (co-stimulatory signal),
  which is not present on most body cells.
• CD28 is present only on certain
  antigen-presenting cells, including macrophages
  and the dendritic cells in the linings of the
  respiratory and digestive tracts.

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Specific Defenses The Immune System

• Immunological tolerance is a poorly understood
  but clearly observable phenomenon.
• Exposing a fetus to an antigen before birth
  provides later tolerance to the antigen.
• Continued exposure is necessary to maintain the
  tolerance.
• Some individuals experience the opposite effect
  they lose tolerance to themselves, which results
  in autoimmune disease.

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B Cells The Humoral Immune Response

• B cells are the basic component of the humoral
  immune system.
• For a B cell to differentiate into a plasma cell,
  it must bind an antigenic determinant.
• A helper T cell (TH) must also bind the same
  determinant as it is presented by an
  antigen-presenting cell.
• Cellular division and differentiation of the B
  cell is stimulated by a signal from the activated
  TH cell.
• Activated B cells become plasma cells and memory
  cells.

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Figure 18.9 A Plasma Cell
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B Cells The Humoral Immune Response

• Antibody molecules are proteins called
  immunoglobulins.
• All are composed of one or more tetramers
  consisting of four polypeptide chains.
• Two identical light chains and two identical
  heavy chains make up the tetrameric units.
• Disulfide bonds hold the chains together.
• Both the light and heavy chains on each peptide
  have variable and constant regions.
• The constant regions are similar among the
  immunoglobulins and determine the class of the
  antibody.

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B Cells The Humoral Immune Response

• The variable regions differ in the amino acid
  sequences at the antigen-binding site and are
  responsible for the diversity of antibody
  specificity.
• The heavy and light chain variable regions align
  and form the binding sites.
• Each tetramer has two identical antigen-binding
  sites, making the antibody bivalent.
• The enormous range of antibody specificities is
  made possible by the recombination of numerous
  versions of coding regions for the variable
  regions.

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Figure 18.10 Structure of Immunoglobulins (Part
1)
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Figure 18.10 Structure of Immunoglobulins (Part
2)
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B Cells The Humoral Immune Response

• The five immunoglobulin classes are based on
  differences in the constant regions of the heavy
  chain.
• IgG molecules make up 80 percent of the total
  immunoglobulin content of the bloodstream.
• They are the primary product of a secondary
  immune response.
• The constant regions of IgG antibodies are like
  handles that make it easier for a macrophage to
  grab and ingest antibody-coated antigens.

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Figure 18.11 IgG Antibodies Promote Phagocytosis
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Table 18.3 Antibody Classes (Part 1)
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Table 18.3 Antibody Classes (Part 2)
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B Cells The Humoral Immune Response

• The normal antibody response is polyclonal
  Because most antigens have more than one
  antigenic determinant, animals injected with a
  single antigen generally produce several
  different antibodies.
• Polyclonal antibodies may have some
  cross-reactivity with other molecules that have
  similar regions within the molecule.

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B Cells The Humoral Immune Response

• A monoclonal antibody is made by a single clonal
  line of B cells and binds to only one antigenic
  determinant.
• Monoclonal antibodies are very useful for
  immunoassays to determine the concentrations of
  other molecules that are present in minute
  amounts.
• Monoclonal antibodies are also used in
  immunotherapy and passive immunization.

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B Cells The Humoral Immune Response

• B cells cannot be cultured. To overcome this
  problem, a cancerous myeloma cell is fused to the
  plasma cell artificially.
• These new cells, called hybridomas, live long and
  produce monoclonal antibodies.

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Figure 18.12 Creating Hybridomas for the
Production of Monoclonal Antibodies (Part 1)
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Figure 18.12 Creating Hybridomas for the
Production of Monoclonal Antibodies (Part 2)
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T Cells The Cellular Immune Response

• T cells, like B cells, possess specific surface
  receptors.
• The genes that code for T cell receptors are
  similar to those for immunoglobulins.
• T cell receptors also have constant and variable
  regions.
• A major difference between antibodies and T cell
  receptors is that T cell receptors bind only to
  an antigenic determinant that is displayed on the
  surface of an antigen-presenting cell.

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Figure 18.13 A T Cell Receptor
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T Cells The Cellular Immune Response

• Activated T cells give rise to two types of
  effector cells.
• Cytotoxic cells, or TC, recognize virus-infected
  cells and kill them by causing them to lyse.
• Helper T cells, or TH cells, assist both the
  cellular and humoral immune systems.
• Activated helper T cells proliferate and
  stimulate both B and TC cells to divide.

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Figure 18.14 Cytotoxic T Cells in Action
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T Cells The Cellular Immune Response

• The major histocompatibility complex (MHC) gene
  products are plasma membrane glycoproteins.
• These molecules are called human leukocyte
  antigens (HLA) in humans and H-2 proteins in
  mice.
• There are three classes of MHC proteins.

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T Cells The Cellular Immune Response

• Class I MHC proteins are present on the surface
  of every nucleated cell in animals.
• When cellular proteins are degraded in the
  proteasome, an MHC I protein may bind a fragment
  and travel to the plasma membrane to present it
  outside on the cells plasma membrane surface.
• TC cells have a surface protein called CD8 that
  recognizes MHC I.

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Figure 18.16 The Interaction between T Cells and
Antigen-Presenting Cells (Part 1)
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Figure 18.16 The Interaction between T Cells and
Antigen-Presenting Cells (Part 2)
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Figure 18.16 The Interaction between T Cells and
Antigen-Presenting Cells (Part 3)
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T Cells The Cellular Immune Response

• Class II MHC proteins are found mostly on the
  surface of B cells, macrophages, and other
  antigen-presenting cells.
• When an antigen is ingested by an
  antigen-presenting cell, it is broken down and
  fragments are presented at the cell surface by
  class II MHC proteins.
• TH cells have CD4 surface proteins that recognize
  MHC II.

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Figure 18.15 Macrophages Are Antigen-Presenting
Cells
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T Cells The Cellular Immune Response

• Class III MHC proteins include some of the
  proteins of the complement system that interact
  with antigenantibody complexes to cause lysis of
  foreign cells.

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T Cells The Cellular Immune Response

• T cells recognize the MHC I or II and then
  inspect the attached fragment.
• There are three different loci for each MHC I and
  for each MHC II.
• The six loci have as many as 100 different
  alleles.
• This is why different individuals generally have
  different MHC genotypes.

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T Cells The Cellular Immune Response

• TH cells bind to an antigen presented to it by an
  antigen-presenting macrophage.
• The then-activated TH cell produces and secretes
  cytokine molecules, which attach to their own
  specific cell membrane receptor proteins.
• The cell can then divide to produce clones
  capable of interacting with B cells.
• These steps, called the activation phase, occur
  in the lymphatic tissues.

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T Cells The Cellular Immune Response

• In the effector stage, an antigen of the same
  sort that was processed by the macrophage binds
  to a specific IgM receptor on the surface of a B
  cell.
• The B cell degrades the antigen and presents a
  piece of processed antigen in a class II MHC
  protein on its cell surface.
• One of the TH cells created in the activation
  stage recognizes the processed antigen and class
  II MHC protein on the surface of the B cell.
• The TH cell releases cytokines, which activate B
  cell proliferation and differentiation into
  plasma cells and memory cells.
• The plasma cells secrete antibodies.

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Figure 18.17 (a) Phases of the Humoral and
Cellular Immune Responses (Part 1)
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Figure 18.17 (a) Phases of the Humoral and
Cellular Immune Responses (Part 2)
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T Cells The Cellular Immune Response

• Like class II MHC molecules, class I MHC
  molecules also present processed antigen to T
  cells.
• Foreign protein fragments are bound by class I
  MHC molecules and carried to the plasma membrane,
  where TC cells can check them.
• If a cell has been infected by a virus, or has
  mutated, it may present protein fragments that
  are not normally found in the body.
• If a TC cell binds to the MHC Iantigen complex,
  the TC cell is activated to proliferate and
  differentiate.

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T Cells The Cellular Immune Response

• In the effector stage, TC cells once again bind
  to the cells bearing MHC Iantigen complex and
  secrete molecules that lyse the cell.
• TC cells can also bind to a specific target cell
  receptor (called Fas).
• This binding initiates apoptosis in the target
  (for example, virus-infected) cell.
• This system helps rid the body of virus-infected
  cells. It also helps to destroy some cancer
  tumors.

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Figure 18.17 (b) Phases of the Humoral and
Cellular Immune Responses (Part 1)
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Figure 18.17 (b) Phases of the Humoral and
Cellular Immune Responses (Part 2)
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T Cells The Cellular Immune Response

• T cells developing in the thymus are tested to
  ensure that they will be functional and will not
  attack normal self antigens.
• Each new T cell must recognize the bodys MHC
  proteins. If it fails to do so, it dies within
  about 3 days.
• If the developing T cell binds to self MHC
  proteins and to one of the bodys own normal
  antigens, it undergoes apoptosis.
• If these T cells were not destroyed they would be
  harmful or lethal to the animal.
• If the T cell survives these tests, it becomes
  either a TC or TH cell.

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T Cells The Cellular Immune Response

• For organ transplants to be successful, MHC
  molecules must match otherwise, these same
  molecules will act as antigens.
• The cellular immune system is responsible for
  rejection.
• Rejection problems can be controlled somewhat by
  treating patients with immunosuppressing drugs
  such as cyclosporin.

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The Genetic Basis of Antibody Diversity

• As B cells develop, their genomes become modified
  until the cell can produce one specific type of
  antibody.
• If we had a different gene for each antibody our
  immune systems are capable of producing, our
  entire genome would be taken up by antibody
  genes.
• Instead, just a small number of genes that can
  recombine to generate multitudes of possibilities
  are responsible for the vast diversity of
  antibodies.

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The Genetic Basis of Antibody Diversity

• Each gene encoding an immunoglobin is in reality
  a supergene assembled from several clusters of
  smaller genes located along part of a chromosome.
  
• During B cell development, these variable regions
  rearrange and join.
• Pieces of DNA are deleted, and DNA segments
  formerly distant from one another are joined
  together.
• Immunoglobulin genes are assembled from randomly
  selected pieces of DNA.

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Figure 18.18 Heavy-Chain Genes
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The Genetic Basis of Antibody Diversity

• Each B cell precursor assembles its own two
  specific antibody genes, one for a heavy chain,
  and the other for a light chain.
• In both humans and mice, the DNA segments coding
  for immunoglobulin heavy chains are on one
  chromosome and those for light chains are on
  another.

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The Genetic Basis of Antibody Diversity

• There are multiple genes coding for each of the
  four kinds of segments in the polypeptide chain
  for the heavy chain in mice 100 V, 30 D, 6 J,
  and 8 C regions.
• Each B cell randomly selects one gene for each of
  the V, D, J, and C regions.
• A similar process occurs for the light chain.
• Theoretically, there are 144,000 x 144,000
  possible combinations of light and heavy chains,
  i.e, 21 billion possibilities.

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Figure 18. Heavy-Chain Gene Rearrangement and
Splicing (Part 1)
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Figure 18. Heavy-Chain Gene Rearrangement and
Splicing (Part 2)
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The Genetic Basis of Antibody Diversity

• Additional diversity is possible because the
  recombinations do not occur at precise segments.
  Imprecise recombinations can create new codons at
  the junctions.
• After DNA fragments are cut out and before they
  are joined, an enzyme, terminal transferase, adds
  some nucleotides to the free end. This adds even
  more variability by causing frame shifts and new
  codons.
• Finally, the relatively high mutation rate in
  immunoglobulin genes leads to even more diversity.

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The Genetic Basis of Antibody Diversity

• B cells make only one class of antibody at a
  time, but class switching can occur. For
  example, the B cell can switch from IgM to IgG.
• The constant region for IgM is coded for by the m
  segment.
• If the cell becomes a plasma cell, another DNA
  splicing event positions the heavy-chain variable
  region next to a constant segment farther down
  the DNA strand, and the m segment is deleted.
• Class switching is triggered and controlled by a
  TH cell via cytokine signals.

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Figure 18.20 Class Switching
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Disorders of the Immune System

• The human immune system can overreact to a dose
  of antigen and produce an inappropriate immune
  response. Allergies are the most familiar
  example.
• Immediate hypersensitivity occurs when too much
  IgE is made.
• If the IgE binds with antigens, mast cells and
  basophils are triggered to release histamine.
• Delayed hypersensitivity does not begin until
  hours after exposure to an antigen and involves
  antigen-presenting cells and T cells.
• The response can activate macrophages and cause
  tissue damage.

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Disorders of the Immune System

• If clonal deletion fails, forbidden clones of B
  and T cells directed against self-antigens are
  sometimes made.
• Examples of autoimmune diseases include
• Systemic lupus erythematosis
• Rheumatoid arthritis
• Multiple sclerosis
• Insulin-dependent (juvenile-onset) diabetes
  mellitus

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Disorders of the Immune System

• HIV (human immunodeficiency virus), which leads
  to AIDS (acquired immune deficiency syndrome),
  causes a depletion of TH cells.
• It can be transmitted through blood or by
  exposure of broken skin or an open wound to the
  body fluids of an infected person.

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Figure 18.21 The Course of an HIV Infection
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Disorders of the Immune System

• HIV uses RNA as its genetic molecule.
• The core of the virus contains two identical
  molecules of RNA and the enzymes reverse
  transcriptase, integrase, and a protease.
• The envelope is derived from the plasma membrane
  of the cell in which the virus grew.
• The envelope has glycoproteins gp120 and gp41
  protruding. These proteins are necessary for the
  targeting of TH cells.
• The virus enters the cell via CD4 membrane
  proteins on TH cells. The gp120 protein binds to
  CD4.

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Disorders of the Immune System

• Once in the cell, reverse transcriptase makes a
  DNA copy (cDNA) of the viral RNA, and cellular
  DNA polymerase makes the complementary strand.
• Reverse transcriptase is error prone this
  elevates the mutation rate and adds to the
  adaptability of the virus.
• The cDNA integrates into the host DNA.

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Disorders of the Immune System

• Viruses are made when the TH cell is activated.
• Transcription of the viral DNA requires host
  transcription factors and a viral protein, Tat.
• The RNA is either spliced and translated or
  unspliced to become the genetic molecule of a new
  virus.
• A viral protease is needed to cleave large viral
  precursor proteins into smaller functional units.
• Viral membrane proteins are synthesized on rough
  ER, and glycosylation occurs within the ER and
  Golgi complex.

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Disorders of the Immune System

• Highly active antiretroviral therapy (HAART) was
  developed in the late 1990s.
• A protease inhibitor obstructs the active site of
  the HIV protease.
• Two reverse transcriptase inhibitors that
  terminate the cDNA molecules prematurely are
  used.
• Unfortunately, 80 percent of patients taking
  HAART develop mutant strains of HIV that are
  resistant.

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Figure 18.22 Relationship Between TH Cell Count
and Opportunistic Infections