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31
Immunology: Animal Defense
Systems
Concept 31.1 Animals Use Innate and Adaptive Mechanisms to
Defend Themselves against Pathogens
Animals have various means of defense
against pathogens—agents that cause
disease.
Two general types of defense mechanisms
can provide immunity—the ability to avoid
disease when invaded by a pathogen.
Concept 31.1 Animals Use Innate and Adaptive Mechanisms to
Defend Themselves against Pathogens
Innate immunity—nonspecific, 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.
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.
Table 31.1 Innate and Adaptive Immune Responses to an Infection
Concept 31.1 Animals Use Innate and Adaptive Mechanisms to
Defend Themselves against Pathogens
Mammals have both kinds of defense
systems—they 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
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
Figure 31.1 White Blood Cells
Concept 31.1 Animals Use Innate and Adaptive Mechanisms to
Defend Themselves against Pathogens
Cell–cell interactions in the mammalian
defense system involve four key protein
types:
• Antibodies—proteins that bind specifically
to substances identified by the immune
system
Antibodies are produced by B cells.
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.
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 cell’s surface receptors and
alter that cell’s behavior
Concept 31.2 Innate Defenses Are Nonspecific
Nonspecific defenses are general
mechanisms—the 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.
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 flora—the 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.
Figure 31.2 Innate Immunity
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.
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.
In-Text Art, Ch. 31, p. 623 (1)
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 proteins—
complement and interferon proteins
Pathogenic cells, viruses, or fragments of
invaders can be recognized by
phagocytes, which then ingest them by
phagocytosis.
Concept 31.2 Innate Defenses Are Nonspecific
Natural killer cells—a 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
Concept 31.2 Innate Defenses Are Nonspecific
Vertebrate blood has antimicrobial proteins
that make up the complement system.
Proteins act in a cascade—each 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
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
membranes—stimulate a signaling
pathway that inhibits viral reproduction
• Stimulating cells to hydrolyze pathogen’s
proteins to peptides
Concept 31.2 Innate Defenses Are Nonspecific
Inflammation is a coordinated response to
injury—it isolates damage, recruits cells
against pathogens, and promotes healing.
Mast cells are cells adhering to skin and
organ linings; release chemical signals:
• Tumor necrosis factor—cytokine that
kills target cells and activates immune
cells
Concept 31.2 Innate Defenses Are Nonspecific
• Prostaglandins—initiate inflammation in
nearby tissues, dilate blood vessels and
interact with nerve endings, increasing
sensitivity to pain
• Histamine—amino acid derivative that
increases permeability of blood vessels so
white blood cells can act on tissues
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
fever—toxic to some pathogens.
Pus is a mixture of leaked fluid and dead
cells.
Platelets appear near a wound to promote
healing.
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
organism’s own body.
• In sepsis, the inflammation due to a
bacterial infection does not remain local.
Figure 31.3 Interactions of Cells and Chemical Signals Result in Inflammation
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.
Figure 31.4 The Discovery of Specific Immunity (Part 1)
Figure 31.4 The Discovery of Specific Immunity (Part 2)
Concept 31.3 The Adaptive Immune Response Is Specific
Adaptive immunity has four key features:
• Specific—focuses on antigens that are
present
• Diverse—responds to novel pathogens
• Distinguishes self from nonself, prevents
destruction of self cells
• Has immunological memory, to respond to
a later exposure to a pathogen
Concept 31.3 The Adaptive Immune Response Is Specific
Specificity—lymphocytes are crucial:
T cell receptors and antibodies bind to
specific nonself molecules (antigens).
Specific sites on the antigens are called
antigenic determinants, or epitopes.
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 antigen’s presence
with highly specific defenses using T cell
receptors and antibodies.
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
changes—chromosomal rearrangements
and other mutations.
The adaptive immune system is
“predeveloped”—all of the machinery
available to respond to an immense
diversity of antigens is already there, even
before the antigens are encountered.
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 clone—called
clonal selection for this mechanism of
producing an immune response.
Figure 31.5 Clonal Selection in B Cells
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 deletion—Any immature B and T
cells that show the potential to mount an
immune response to self antigens undergo
apoptosis.
Concept 31.3 The Adaptive Immune Response Is Specific
A failure of clonal deletion—autoimmunity.
In diseases such as systemic lupus
erythematosis (SLE) or Hashimoto’s
thyroiditis, immune cells mount a response
against normal tissues.
Concept 31.3 The Adaptive Immune Response Is Specific
Immunological memory—the immune
system “remembers” a pathogen after the
first encounter.
Primary immune response—when antigen
is first encountered, “naïve” lymphocytes
proliferate to produce two types of cells—
effector and memory cells.
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.
Concept 31.3 The Adaptive Immune Response Is Specific
Secondary immune response—when
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.
Concept 31.3 The Adaptive Immune Response Is Specific
The adaptive immune response involves
three phases:
• Recognition phase—the organism
discriminates between self and nonself to
detect a pathogen.
• Activation phase—the recognition event
leads to a mobilization of cells and
molecules to fight the invader.
• Effector phase—the mobilized cells and
molecules destroy the invader.
Figure 31.6 The Adaptive Immune System (Part 1)
Figure 31.6 The Adaptive Immune System (Part 2)
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.
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 antigenpresenting cell.
The antigen is recognized by a T-helper
(TH) cell, with a specific T cell receptor
protein.
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.
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
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.
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.
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.
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.
Figure 31.7 The Structure of an Immunoglobulin (Part 1)
Figure 31.7 The Structure of an Immunoglobulin (Part 2)
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
immunoglobulin—responsible for antibody
specificity.
Two antigen-binding sites on an
immunoglobulin are identical—bivalent.
In-Text Art, Ch. 31, p. 630
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.
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.
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.
Figure 31.8 Heavy-Chain Genes
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.
Result—enormous diversity of specific
antibodies.
Figure 31.9 Heavy-Chain Gene Recombination and RNA Splicing
Concept 31.4 The Adaptive Humoral Immune Response Involves
Specific Antibodies
Each B cell precursor assembles two
supergenes—one 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.
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
codons—imprecise recombination
• Before DNA is rejoined, terminal
transferase adds nucleotides, creating
insertion mutations
• High spontaneous mutation rate
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.
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.
Concept 31.5 The Adaptive Cellular Immune Response Involves T
Cells and Their Receptors
T cells have specific membrane receptors—
glycoproteins, with two polypeptide chains.
Each chain is encoded by a different gene—
has 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.
Figure 31.10 A T Cell Receptor
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.
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
cells—present antigens to TH cells.
Figure 31.11 Macrophages Are Antigen-Presenting Cells
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.
Table 31.2 The Interaction between T Cells and Antigen-Presenting Cells
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
antigen–MHC 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.
In-Text Art, Ch. 31, p. 634
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 antigens—when
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.
Figure 31.12 Tregs and Tolerance
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 IPEX—causes
fatal immune responses.
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 cells—
the affected individual lacks a major line of
defense against pathogens.
Acquired immune deficiency syndrome
(AIDS) results from infection by human
immunodeficiency virus (HIV).
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 activated—but 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.
Figure 31.13 The Course of an HIV Infection
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:
• Kaposi’s sarcoma, a rare skin cancer
caused by a herpes virus
• Pneumonia caused by fungus
Pneumocystis jirovecii
• Lymphoma tumors caused by Epstein-Barr
virus
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 longterm survival. Unfortunately, like many
medical treatments, HIV drugs are not
available to all who need them.
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.
Figure 31.14 Vaccination