Transcript PowerPoint Presentation to accompany Life: The Science of Biology

Natural Defenses
against Disease
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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 (aka, leukocytes).
Figure 18.1 The Human Lymphatic system
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Animal Defense Systems
• White blood cells are important in defense.
• White blood cells (leukocytes) are clear and have
a nucleus and organelles.
. 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.
Figure 18.2 Blood Cells (Part 2)
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
• 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.
 They shut down transcription and translation
• 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.
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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.
Figure 18.4 Interactions of Cells and Chemical Signals in Inflammation (Part 1)
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.
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 1017
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 don’t 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.
Figure 18.7 Clonal Selection in B 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.
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.
 Before vaccines, tens of millions of people
died each year from infectious diseases
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Specific Defenses: The Immune System
• The body is self 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.
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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 antigenpresenting 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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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.
Figure 18.10 Structure of Immunoglobulins (Part 1)
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 - the majority of serum antibody
 IgM - first antibody made after an infection
 IgA - most abundant antibody made; mucosal
secretions and breast milk
 IgE - parasitic infections; allergies
 IgD - B cell receptor only; not secreted
• The constant regions of IgG antibodies are like
handles that make it easier for a macrophage to
grab and ingest antibody-coated antigens.
Figure 18.11 IgG Antibodies Promote Phagocytosis
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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.
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 virusinfected 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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T Cells Recognize Antigens Bound to MHC
Molecules on APC
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Helper T Cells Provide Permission to B Cells to Secrete
Antibodies Through MHC:Antigen:TCR interactions