Natural Defenses against Disease

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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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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

• 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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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 virus enters the cell via cell membrane
  proteins on TH cells.

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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.