Immunology: Animal Defense Systems

1
Immunology Animal Defense Systems
31
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Chapter 31 Immunology Animal Defense Systems

• Key Concepts
• 31.1 Animals Use Innate and Adaptive Mechanisms
  to Defend Themselves against Pathogens
• 31.2 Innate Defenses Are Nonspecific
• 31.3 The Adaptive Immune Response Is Specific

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Chapter 31 Immunology Animal Defense Systems

• Key Concepts
• 31.4 The Adaptive Humoral Immune Response
  Involves Specific Antibodies
• 31.5 The Adaptive Cellular Immune Response
  Involves T Cells and Their Receptors

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Chapter 31 Opening Question

• How can a person survive an infection and be
  resistant to further infection?

5
Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• Animals have various means of defense against
  pathogensagents that cause disease.
• Two general types of defense mechanisms can
  provide immunitythe ability to avoid disease
  when invaded by a pathogen.

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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• Innate immunitynonspecific, used against many
  organisms
• Includes barriers, such as skin and molecules
  toxic to invaders, as first line of defense.
• Second line of innate defenses includes
  phagocytic cells, which ingest foreign cells and
  other particles.
• These defenses may be present all the time or
  activated rapidly.

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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• Adaptive immunity is specific
• Distinguishes between substances produced by self
  and nonself.
• Involves antibody proteins and others that bind
  to and destroy pathogens.
• Slow to develop and long-lasting, found only in
  vertebrate animals.

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Table 31.1 Innate and Adaptive Immune Responses
to an Infection
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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• Mammals have both kinds of defense systemsthey
  work together as a coordinated system.
• The main factors in immunity are specific cells
  and proteins.
• These are produced in the blood and lymphoid
  tissues and circulate throughout the body

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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• White blood cells, or leukocytes, are suspended
  in the blood plasma.
• Two kinds
• Phagocytes (such as macrophages) are large cells
  that engulf pathogens and other substances by
  phagocytosis.
• Lymphocytes, which include B cells and T cells,
  are involved in adaptive immunity

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Figure 31.1 White Blood Cells
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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• Cellcell interactions in the mammalian defense
  system involve four key protein types
• Antibodiesproteins that bind specifically to
  substances identified by the immune system
• Antibodies are produced by B cells.

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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• Major histocompatibility complex (MHC) proteins
  are found in two classes
• MHC I proteins are found on most cell surfaces
• MHC II proteins are found on most immune system
  cells
• MHC proteins are important self-identifying
  labels.

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Concept 31.1 Animals Use Innate and Adaptive
Mechanisms to Defend Themselves against Pathogens

• T cell receptors are integral membrane proteins
  on T cells, recognize and bind nonself molecules
  on other cells
• Cytokines are soluble signaling proteins that
  bind to a cells surface receptors and alter that
  cells behavior

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Concept 31.2 Innate Defenses Are Nonspecific

• Nonspecific defenses are general mechanismsthe
  first line of defense.
• They are genetically programmed and ready to
  go.
• In mammals, they include physical barriers as
  well as cellular and chemical defenses.

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Concept 31.2 Innate Defenses Are Nonspecific

• Skin is a primary nonspecific defense.
• The physical barrier of the skin as well as the
  saltiness of the skin make it hard for bacteria
  to penetrate.
• Normal florathe bacteria and fungi that usually
  live on body surfaces
• They are part of the defense system because they
  compete with pathogens for nutrients and space.

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Figure 31.2 Innate Immunity
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Concept 31.2 Innate Defenses Are Nonspecific

• Mucus is secreted by mucous membranes. Mucus
  traps microorganisms so cilia can remove them.
• Cilia continuously move the mucus plus debris up
  towards nose and mouth.
• Lysozyme, an enzyme that attacks bacterial cell
  walls, is found in tears, nasal mucus, and saliva.

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Concept 31.2 Innate Defenses Are Nonspecific

• Mucous membranes produce defensins, peptides with
  hydrophobic domains that are toxic to many
  pathogens.
• Defensins insert themselves into the plasma
  membrane of the pathogen and make it permeable.
• Harsh conditions in the internal environment,
  such as extreme acidity, can also kill pathogens.

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In-Text Art, Ch. 31, p. 623 (1)
21
Concept 31.2 Innate Defenses Are Nonspecific

• Pathogens that do penetrate surfaces encounter
  more complex nonspecific second defenses
• Activation of defensive cells
• Secretion of defensive proteinscomplement and
  interferon proteins
• Pathogenic cells, viruses, or fragments of
  invaders can be recognized by phagocytes, which
  then ingest them by phagocytosis.

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Concept 31.2 Innate Defenses Are Nonspecific

• Natural killer cellsa type of lymphocyte that
  can detect virus-infected cells and some tumor
  cells
• Can initiate apoptosis in these cells
• Can interact with the specific defense mechanisms
  and lyse cells labeled by antibodies

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Concept 31.2 Innate Defenses Are Nonspecific

• Vertebrate blood has antimicrobial proteins that
  make up the complement system.
• Proteins act in a cascadeeach protein activates
  the next.
• Provide three types of defense
• Attach to microbes and mark them for phagocytes
  to engulf
• Activate inflammation response and attract
  phagocytes to site of infection
• Lyse invading cells

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Concept 31.2 Innate Defenses Are Nonspecific

• Interferons are signaling molecules produced by
  cells infected by a pathogen.
• Interferons increase resistance of neighboring
  cells to the pathogen by
• Binding to receptors on noninfected cell
  membranesstimulate a signaling pathway that
  inhibits viral reproduction
• Stimulating cells to hydrolyze pathogens
  proteins to peptides

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Concept 31.2 Innate Defenses Are Nonspecific

• Inflammation is a coordinated response to
  injuryit isolates damage, recruits cells against
  pathogens, and promotes healing.
• Mast cells are cells adhering to skin and organ
  linings release chemical signals
• Tumor necrosis factorcytokine that kills target
  cells and activates immune cells

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Concept 31.2 Innate Defenses Are Nonspecific

• Prostaglandinsinitiate inflammation in nearby
  tissues, dilate blood vessels and interact with
  nerve endings, increasing sensitivity to pain
• Histamineamino acid derivative that increases
  permeability of blood vessels so white blood
  cells can act on tissues

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Concept 31.2 Innate Defenses Are Nonspecific

• Symptoms of inflammation Redness, swelling,
  heat, pain, result from dilation of blood vessels
  in the area.
• Phagocytes enter the area and engulf pathogens
  and dead cells.
• Cytokines may signal the brain to produce
  fevertoxic to some pathogens.
• Pus is a mixture of leaked fluid and dead cells.
• Platelets appear near a wound to promote healing.

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Concept 31.2 Innate Defenses Are Nonspecific

• The inflammation response may be too strong
• In an allergic reaction, a nonself molecule that
  is normally harmless binds to mast cells, causing
  the release of histamine and subsequent
  inflammation.
• In autoimmune diseases, the immune system fails
  to distinguish between self and nonself, and
  attacks tissues in the organisms own body.
• In sepsis, the inflammation due to a bacterial
  infection does not remain local.

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Figure 31.3 Interactions of Cells and Chemical
Signals Result in Inflammation
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Concept 31.3 The Adaptive Immune Response Is
Specific

• Scientists discovered that a factor that develops
  in blood serum in response to a toxin is an
  example of adaptive immunity that is specific to
  the toxin.
• Passive immunity is the development of immunity
  from antibodies received from another individual.

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Figure 31.4 The Discovery of Specific Immunity
(Part 1)
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Figure 31.4 The Discovery of Specific Immunity
(Part 2)
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Concept 31.3 The Adaptive Immune Response Is
Specific

• Adaptive immunity has four key features
• Specificfocuses on antigens that are present
• Diverseresponds to novel pathogens
• Distinguishes self from nonself, prevents
  destruction of self cells
• Has immunological memory, to respond to a later
  exposure to a pathogen

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Specificitylymphocytes are crucial
• T cell receptors and antibodies bind to specific
  nonself molecules (antigens).
• Specific sites on the antigens are called
  antigenic determinants, or epitopes.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• An antigenic determinant is a specific portion of
  a large molecule.
• A single antigenic molecule can have multiple,
  different antigenic determinants.
• The host responds to an antigens presence with
  highly specific defenses using T cell receptors
  and antibodies.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Diversity
• The immune system must respond to a wide variety
  of pathogens by activating specific lymphocytes
  from a pool.
• Diversity is generated primarily by DNA
  changeschromosomal rearrangements and other
  mutations.
• The adaptive immune system is predevelopedall
  of the machinery available to respond to an
  immense diversity of antigens is already there,
  even before the antigens are encountered.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Antigen binding selects a particular B or T
  cell for proliferation.
• A particular lymphocyte is selected via binding
  and activation, and then it proliferates to
  generate a clonecalled clonal selection for this
  mechanism of producing an immune response.

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Figure 31.5 Clonal Selection in B Cells
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Concept 31.3 The Adaptive Immune Response Is
Specific

• Normally, the body is tolerant of its own
  molecules develops during early B and T cell
  differentiation.
• Clonal deletionAny immature B and T cells that
  show the potential to mount an immune response to
  self antigens undergo apoptosis.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• A failure of clonal deletionautoimmunity.
• In diseases such as systemic lupus erythematosis
  (SLE) or Hashimotos thyroiditis, immune cells
  mount a response against normal tissues.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Immunological memorythe immune system
  remembers a pathogen after the first encounter.
• Primary immune responsewhen antigen is first
  encountered, naïve lymphocytes proliferate to
  produce two types of cells effector and memory
  cells.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Effector cells carry out the attack. Effector B
  cells (plasma cells) secrete antibodies. Effector
  T cells secrete cytokines and other molecules.
• Memory cells are long-lived cells that can divide
  on short notice to produce effector and more
  memory cells.
• Memory B and T cells may survive for decades.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Secondary immune responsewhen antigen is
  encountered again, memory cells proliferate and
  launch an army of plasma cells and effector T
  cells.
• Vaccinations trigger a primary immune response to
  prepare the body for a quicker, secondary
  response, if it encounters the pathogen again.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• The adaptive immune response involves three
  phases
• Recognition phasethe organism discriminates
  between self and nonself to detect a pathogen.
• Activation phasethe recognition event leads to a
  mobilization of cells and molecules to fight the
  invader.
• Effector phasethe mobilized cells and molecules
  destroy the invader.

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Figure 31.6 The Adaptive Immune System (Part 1)
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Figure 31.6 The Adaptive Immune System (Part 2)
47
Concept 31.3 The Adaptive Immune Response Is
Specific

• The three phases can occur in either of two types
  of response the humoral immune response and the
  cellular immune response.
• Humoral immune response involves B cells that
  make antibodies.
• Cytotoxic T (TC) cells are the workhorses of the
  cellular immune response.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• A key event is the exposure or presentation of
  the antigen to the immune system.
• In humoral immunity, this occurs when an antigen
  binds to a B cell that has an antibody specific
  to that antigen.
• In cellular immunity, an antigen is inserted into
  the membrane of an antigen-presenting cell.
• The antigen is recognized by a T-helper (TH)
  cell, with a specific T cell receptor protein.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• Antigen binding readies a B cell for division.
• Antigen fragments bind to the MHC complex and are
  presented on the B cell surface.
• A specific TH cell binds and stimulates the B
  cell to divide and form a clone.
• In the cellular immune response, TH cell binding
  to the antigen-presenting cell causes cytokine
  release.
• Cytokines stimulate TC cells with the same T cell
  receptor to divide.

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Concept 31.3 The Adaptive Immune Response Is
Specific

• The result of activation is the formation of two
  clones of cells
• A clone of B cells that can produce antibodies
  specific for the antigen
• A clone of TC cells that express a T cell
  receptor that can bind to any cell expressing the
  antigen on its surface

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Concept 31.3 The Adaptive Immune Response Is
Specific

• In the effector phase, B clone cells produce
  antibodies that bind to free antigen results in
  inactivation and destruction of the antigen.
• TC clone cells bind to cells bearing the antigen
  and destroy them.

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• B cells are the basis of the humoral immune
  response.
• A naïve B cell expresses a receptor protein
  specific for an antigen on its cell surface.
• The cell is activated by antigen-binding and
  after TH cell stimulation will give rise to
  clones of plasma and memory cells.
• Plasma cells secrete antibodies into the blood
  stream.

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• A B cell can also be stimulated to divide by a TH
  cell binding to the exposed antigen on the B cell
  surface.
• The specific TH cell may come from a clone that
  was activated by the cellular immune response.
• Interaction between B cells and TH cells provides
  a connection between the cellular and humoral
  systems.
• The TH cell bound to the B cell secretes
  cytokines that stimulate the B cell to divide.

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Antibodies, or immunoglobulins, all contain a
  tetramer of four polypeptides.
• In each molecule are two light chains and two
  heavy chains, held together by disulfide bonds.
• Each polypeptide chain has a constant region and
  a variable region.

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Figure 31.7 The Structure of an Immunoglobulin
(Part 1)
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Figure 31.7 The Structure of an Immunoglobulin
(Part 2)
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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• The amino acid sequence of the constant region
  determines the general structure and function
  (the class) of an immunoglobulin.
• The amino acid sequence of the variable region is
  different for each specific immunoglobulinrespons
  ible for antibody specificity.
• Two antigen-binding sites on an immunoglobulin
  are identicalbivalent.

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In-Text Art, Ch. 31, p. 630
59
Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Five classes of immunoglobulins (Ig) differ in
  function and in the type of heavy chain
• IgG is secreted by B cells and constitutes about
  80 percent of circulating antibodies.
• IgD is the cell surface receptor on a B cell.
• IgM is the initial surface and circulating
  antibody released by a B cell.
• IgA protects mucosa on epithelia exposed to the
  environment.
• IgE binds to mast cells and is involved with
  inflammation.

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Each mature B cell can produce only one specific
  antibody with a specific amino acid sequence.
• The B cell genome
• Has a number of different coding regions for each
  domain of an immunoglobulin
• Diversity is generated by putting together
  different combinations of these regions.

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Each gene encoding an immunoglobulin is actually
  a supergene assembled from a cluster of smaller
  genes.
• Every cell has hundreds of immunoglobulin genes
  that could participate in synthesis of both
  variable and constant regions.

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Figure 31.8 Heavy-Chain Genes
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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• During B cell development the genes are cut out
  and rearranged. One gene from each cluster is
  chosen randomly for joining, others are deleted.
• A unique supergene is assembled.
• Resultenormous diversity of specific antibodies.

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Figure 31.9 Heavy-Chain Gene Recombination and
RNA Splicing
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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Each B cell precursor assembles two
  supergenesone for the light chain, one for the
  heavy chain.
• Genes for the light chains are on separate
  chromosomes they are made in a similar way, with
  an equally large amount of diversity possible.

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Other mechanisms for diversity
• When DNA is rearranged, errors can occur during
  recombination, creating new codonsimprecise
  recombination
• Before DNA is rejoined, terminal transferase adds
  nucleotides, creating insertion mutations
• High spontaneous mutation rate

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Concept 31.4 The Adaptive Humoral Immune Response
Involves Specific Antibodies

• Antibodies can act as receptors on the cell
  surface.
• They can also be secreted from B cells into the
  blood
• Some bind to the antigen expressed on surface of
  a pathogen.
• If antigen is free in the bloodstream, antibodies
  may use cross-linking function to form large
  complexes to be destroyed by phagocytes.

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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• Cellular immune response involves two types of
  effector T cells
• T-helper cells (TH)
• Cytotoxic T cells (TC)
• Major histocompatibility proteins (MHC) proteins
  are also involved.

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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• T cells have specific membrane receptorsglycoprot
  eins, with two polypeptide chains.
• Each chain is encoded by a different genehas
  distinct regions with constant and variable amino
  acid sequences.
• T cell receptors can bind a piece or fragment of
  an antigen, on the surface of an
  antigen-presenting cell.

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Figure 31.10 A T Cell Receptor
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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• TH and TC cells respond differently to
  antigen-binding.
• TH binding results in activation of the cellular
  immune response.
• TC binding results in the death of the cell
  carrying the antigen.
• MHC proteins form complexes with antigens on cell
  surfaces and assist with recognition by the T
  cells, so that the appropriate type of T cell
  binds.

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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• MHC proteins are plasma membrane glycoproteins.
  Two types present antigens to T lymphocytes
• Class I MHC proteins are present on the surface
  of every nucleated cell. They present antigens to
  TC cells.
• Class II MHC proteins are on surfaces of
  macrophages, B cells, and dendritic cellspresent
  antigens to TH cells.

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Figure 31.11 Macrophages Are Antigen-Presenting
Cells
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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• People can have very different MHC genotypes due
  to many possible combinations of alleles.
• MHC proteins are self markers.
• For antigen presentation, MHC I and MHC II
  proteins have an antigen binding site, which
  holds a polypeptide fragment.
• T cell receptor recognizes not just the antigenic
  fragment, but the fragment bound to MHC I or II.

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Table 31.2 The Interaction between T Cells and
Antigen-Presenting Cells
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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• Activation of a TC cell results in the production
  of a clone of TC cells with the specific T cell
  receptor.
• These TC cells bind to cells carrying the
  antigenMHC I protein complex.
• When bound, the TC cells do two things to
  eliminate the antigen-carrying cell
• They produce perforin, which lyses the bound
  target cell.
• They stimulate apoptosis in the target cell.

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In-Text Art, Ch. 31, p. 634
78
Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• Regulatory T cells (Tregs) are a third class that
  regulates the immune response.
• Tregs recognize self antigenswhen activated they
  release the cytokine interleukin 10.
• This blocks T cell activation and leads to
  apoptosis of TC and TH cells bound to the same
  antigen.

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Figure 31.12 Tregs and Tolerance
80
Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• The importance of Tregs is mediating tolerance to
  self antigens. Two lines of evidence for role
  of Tregs
• If Tregs are destroyed experimentally in the
  thymus, the immune system mounts strong responses
  to self antigens (autoimmunity).
• A mutation in a gene critical to Treg function
  results in a disease IPEXcauses fatal immune
  responses.

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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• Immune deficiency disorders can be inherited or
  acquired.
• T or B cells may never form, or B cells lose
  their ability to give rise to plasma cellsthe
  affected individual lacks a major line of defense
  against pathogens.
• Acquired immune deficiency syndrome (AIDS)
  results from infection by human immunodeficiency
  virus (HIV).

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Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• HIV initially infects TH cells, macrophages, and
  antigen-presenting dendritic cells.
• At first there is an immune response and TH cells
  are activatedbut are later killed by both HIV
  and by lysis by TC cells.
• Numbers of TH cells decline after infection.
• However, the HIV-infected cells activate the
  humoral immune system and symptoms abate.

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Figure 31.13 The Course of an HIV Infection
84
Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• During the dormant period, people with HIV feel
  fine.
• Eventually more TH cells are destroyed and the
  person is susceptible to opportunistic
  infections
• Kaposis sarcoma, a rare skin cancer caused by a
  herpes virus
• Pneumonia caused by fungus Pneumocystis jirovecii
• Lymphoma tumors caused by Epstein-Barr virus

85
Concept 31.5 The Adaptive Cellular Immune
Response Involves T Cells and Their Receptors

• Drug treatments for HIV are focused on inhibiting
  processes necessary for viral entry, assembly,
  and replication.
• Combinations of such drugs result in long-term
  survival. Unfortunately, like many medical
  treatments, HIV drugs are not available to all
  who need them.

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Answer to Opening Question
Infection is met by the body in one way that
protects it from immediate harm and by another
that produces antibodies to protect against a
future infection. Antibody production is a slower
response, but once in place forms an
immunological memory. Vaccines are an application
of this response.
87
Figure 31.14 Vaccination