Download Ch18_Lecture - Ms. Lee`s Classes @ JICHS

Welcome Back!
Ch. 18-Immune Today
What about this lab due date…
18
Immunology: Gene
Expression and Natural
Defense Systems
18 Immunology: Gene Expression and Natural Defense Systems
• 18.1 What Are the Major Defense Systems of
Animals?
• 18.2 What Are the Characteristics of the Nonspecific
Defenses?
• 18.3 How Does Specific Immunity Develop?
• 18.4 What Is the Humoral Immune Response?
• 18.5 What Is the Cellular Immune Response?
• 18.6 How Do Animals Make So Many Different
Antibodies?
• 18.7 What Happens When the Immune System
Malfunctions?
18.1 What Are the Major Defense Systems of Animals?
Animals have various means of defense
against pathogens—agents that cause
disease.
Defense systems are based on the
recognition of self (one’s own) and
nonself (foreign) molecules.
Photo 18.1 Bacterial plaque in a human mouth. SEM.
18.1 What Are the Major Defense Systems of Animals?
Two general types of defense mechanisms:
Nonspecific defenses, or innate, act rapidly;
include skin, phagocytic cells, and
molecules toxic to invaders.
Specific defenses, or adaptive, are aimed at
specific pathogens,
e.g., antibodies. Slow to develop and
long-lasting.
Photo 18.2 Human skin: Thick surface layer of keratin forms a barrier to pathogens. LM.
18.1 What Are the Major Defense Systems of Animals?
In animals that have both kinds of
defense systems, they work together as
a coordinated system.
Nonspecific defenses are the first line of
defense, and are tremendously
important.
18.1 What Are the Major Defense Systems of Animals?
Lymphoid tissues include thymus, bone
marrow, spleen, and lymph nodes—
essential parts of the defense system.
Blood plasma contains ions, small
molecular solutes, soluble proteins.
Red blood cells stay in the closed
circulatory system. White blood cells
and platelets are also in the lymph.
18.1 What Are the Major Defense Systems of Animals?
Lymph: fluid derived from blood and
other tissues. From tissues, lymph
moves into lymph system vessels.
Lymph vessels join and eventually form
the thoracic duct, which joins the
circulatory system at a vein near the
heart.
Figure 18.1 The Human Lymphatic System
Photo 18.3 Normal human lymph node: pale germinal centers around the periphery. LM.
18.1 What Are the Major Defense Systems of Animals?
Lymph nodes are small, round
structures at many sites along the
lymph vessels.
Lymph nodes contain white blood cells.
As lymph passes through the nodes, it is
filtered and “inspected” for nonself
molecules.
18.1 What Are the Major Defense Systems of Animals?
Red and white blood cells originate from
pluripotent stem cells in the bone
marrow.
These cells constantly divide and can
differentiate into a variety of blood cells.
Figure 18.2 Blood Cells (Part 1)
Figure 18.2 Blood Cells (Part 2)
Figure 18.2 Blood Cells (Part 3)
18.1 What Are the Major Defense Systems of Animals?
White blood cells, leukocytes,
have nuclei; they can leave closed
circulatory system and enter
extracellular spaces if nonself
molecules or cells are present.
The number of white blood cells may
increase in response to pathogens,
providing a clue for detecting infections.
18.1 What Are the Major Defense Systems of Animals?
Two types of white blood cells:
• Granular includes histamine-producing
signaling cells and phagocytes that
engulf foreign cells and debris.
Phagocytes include dendritic cells and
macrophages.
• Lymphocytes participate in specific
defenses—T cells and B cells.
Photo 18.4 Two white blood cells (monocyte, left; neutrophil, right) among red blood cells. LM.
Photo 18.5 Section through a macrophage. TEM.
Photo 18.6 Polymorphonuclear neutrophil ingesting bacteria by phagocytosis. TEM.
18.1 What Are the Major Defense Systems of Animals?
T cells: the immature cells migrate from
the bone marrow to the thymus where
they mature.
B cells leave bone marrow and circulate
in blood and lymph; make antibodies.
Photo 18.7 Lymphocyte (T or B cell) in normal human blood. LM. Wright stain.
18.1 What Are the Major Defense Systems of Animals?
Many proteins are involved in the cell–cell
interactions of the defense system:
• Antibodies are proteins that bind to
substances identified as nonself.
Secreted by B cells.
• T cell receptors are integral membrane proteins,
recognize and bind nonself molecules on other cells.
18.1 What Are the Major Defense Systems of Animals?
Major histocompatibility complex (MHC): on the
surface of most mammalian cells. They are selfidentifying labels.
Cytokines: signal proteins released by T cells,
macrophages, and other cells. Bind to target cells and
alter their activity.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Nonspecific defenses are general
mechanisms; the first line of
defense.
In humans, they include physical barriers,
cellular, and chemical defenses.
Table 18.1 (Part 1)
Table 18.1 (Part 2)
18.2 What Are the Characteristics of the Nonspecific Defenses?
Skin is a primary nonspecific defense.
Bacteria, fungi, and viruses can rarely
penetrate healthy unbroken skin.
Normal flora—the bacteria and fungi
that live on body surfaces without
causing disease. Part of the defense
system because they compete with
pathogens for nutrients and space.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Tears, nasal mucus, and saliva have an enzyme,
lysozyme, that attacks bacterial cell walls.
Mucus in the nose and respiratory tract
traps microorganisms.
Cilia continuously move the mucus
plus debris up towards nose and mouth.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Mucus membranes
produce defensins, peptides with
hydrophobic domains that are toxic
to many pathogens.
18.2 What Are the Characteristics of the Nonspecific Defenses?
If pathogens reach digestive tract:
May be killed by gastric juices
(hydrochloric acid and proteases), or by
bile salts in the small intestine.
Small intestine lining is not normally
penetrated by pathogens.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Vertebrate blood has antimicrobial proteins that make
up the complement system.
The proteins act in a characteristic sequence or
cascade—each protein activates the next.
18.2 What Are the Characteristics of the Nonspecific Defenses?
The complement proteins provide three types of
defense:
• They attach to microbes and mark them for
phagocytes to engulf.
• Activate inflammation response and attract
phagocytes to site of infection.
• Lyse invading cells.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Interferons are antimicrobial proteins produced by cells
that are infected by a virus.
They increase resistance of neighboring cells to the same
or other viruses.
Interferons are glycoproteins that bind to receptors on
noninfected cell membranes; stimulate a signaling
pathway that blocks viral reproduction.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Phagocytes travel freely in the lymph
and circulatory systems, and also move
into tissues.
Foreign cells, viruses, and fragments
become attached to the phagocyte
membrane, and are engulfed.
Defensins inside the phagocyte digest
the foreign material.
Figure 18.3 A Phagocyte and Its Bacterial Prey
18.2 What Are the Characteristics of the Nonspecific Defenses?
Natural killer cells: a type of lymphocyte, detect virusinfected cells, and some cancer cells, and initiate
lysis.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Inflammation is a response to injury.
Cells adhering to skin and organ linings—mast cells—
release histamine, a chemical signal.
Basophils also release histamine.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Symptoms of inflammation: redness, swelling, heat,
pain.
Blood vessels in the area are dilated, induced by
histamine.
The capillaries become “leaky” and plasma moves into
tissues (causes swelling), along with complement
proteins and phagocytes.
Figure 18.4 Interactions of Cells and Chemical Signals Results in Inflammation
Splinter
Skin
Bacteria
introduced
by splinter
Mast cell
Blood
capillary
Damaged tissues attract
mast cells which release
histamine, which diffuses into
the capillaries.
Figure 18.4 Interactions of Cells and Chemical Signals Results in Inflammation
Complement
proteins
Phagocyte
Histamine causes the
capillaries to dilate and
become leaky; complement
proteins leave the
capillaries and attract
phagocytes.
Blood plasma and
phagocytes move
into infected tissue from
the capillaries.
Figure 18.4 Interactions of Cells and Chemical Signals Results in Inflammation
Signaling molecules stimulate
endothelial cell division, healing the
wound.
Dead
phagocyte
Phagocytes engulf
bacteria and dead
cells.
Histamine and complement
signaling cease; phagocytes are no
longer attracted.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Phagocytes (neutrophils and
macrophages) engulf invaders and
dead cells.
They produce cytokines which signal the
brain to produce fever. Increased
temperature inhibits growth of
pathogens.
18.2 What Are the Characteristics of the Nonspecific Defenses?
Cytokines may also stimulate endothelial
cells to make adhesion molecules—
phagocytes bind to these and then pass
through the vessel to the tissue.
18.2 What Are the Characteristics of the Nonspecific Defenses?
The inflammation response may not
remain local.
It can spread throughout the
bloodstream—a condition called sepsis,
which can be lethal.
Pus is a collection of dead cells and
leaked fluids—it is gradually consumed
by macrophages.
18.2 What Are the Characteristics of the Nonspecific Defenses?
An invading pathogen is a signal, and a signal
transduction pathway links the signal and the
response.
The receptor is a membrane protein called toll.
Toll is part of a protein kinase cascade; results in
transcription factors for 40 genes involved in specific
and nonspecific defenses.
18.2 What Are the Characteristics of the Nonspecific Defenses?
The cascade results in the phosphorylation of the
transcription factor NF-κB, which can then enter the
nucleus, and bind to gene promoters.
Figure 18.5 Cell Signaling and Defense
18.3 How Does Specific Immunity Develop?
The specific immune system has four key
traits:
• Specificity
• Diversity—response to a wide variety
of pathogens
• Ability to distinguish self from nonself
• Memory
18.3 How Does Specific Immunity Develop?
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.
text art p. 407
18.3 How Does Specific Immunity Develop?
A large antigen, such as a whole cell, may have many
different antigenic determinants.
Some epitopes evoke a more powerful response—
called immunodominant.
Each T cell and antibody is specific for a
single antigenic determinant.
18.3 How Does Specific Immunity Develop?
Distinguishing self from nonself: The
immune system must be able to
recognize all the body’s own antigenic
determinants, and not attack them.
18.3 How Does Specific Immunity Develop?
Diversity:
The immune system must respond to a
wide variety of pathogens, and each
pathogen may exist in many different
varieties or strains.
Humans can respond specifically to
about 10 million different antigenic
determinants.
18.3 How Does Specific Immunity Develop?
Immunological Memory:
After one response to a pathogen, the
immune system “remembers” the
pathogen and can respond more quickly
and powerfully if that pathogen invades
again.
Vaccination introduces an antigenic
determinant, and the immune system
remembers it.
18.3 How Does Specific Immunity Develop?
Specific immune system has two
types of responses:
• Humoral immune response
• Cellular immune response
18.3 How Does Specific Immunity Develop?
Humoral immune response:
Antibodies react with antigenic
determinants in blood, lymph, and
tissue fluids.
Animals can produce a huge diversity of
antibodies.
18.3 How Does Specific Immunity Develop?
Some antibodies are soluble in blood and
lymph; others are integral membrane
proteins on B cells.
When a pathogen first invades, a B cell
may recognize one of the pathogen’s
antigenic determinants, and bind with it.
This stimulates the B cell to make
multiple copies of the antibody.
18.3 How Does Specific Immunity Develop?
Cellular immune response detects and
destroys virus-infected cells and
mutated cells.
Carried out by T cells in blood, lymph,
and extracellular spaces in tissues.
T cell receptors bind to specific antigenic
determinants, which initiates an immune
response that results in destruction of
the foreign cell.
18.3 How Does Specific Immunity Develop?
Clonal selection:
Diversity is generated by DNA changes
just after B and T cells are formed.
Each B cell is able to produce only one
kind of antibody.
Antigen binding selects a B or T cell for
proliferation—divides to form a clone of
cells.
Figure 18.6 Clonal Selection in B Cells
18.3 How Does Specific Immunity Develop?
An activated lymphocyte produces two
kinds of daughter cells:
• Effector cells carry out the attack.
Effector B cells (plasma cells) secrete
antibodies. Effector T cells secrete
cytokines.
• Memory cells are long-lived cells that
can divide on short notice to produce
effector cells.
18.3 How Does Specific Immunity Develop?
Primary immune response: When
antigen is first encountered, “naïve”
lymphocytes proliferate to produce
clones of effector and memory cells.
Secondary immune response: When
antigen is encountered again, memory
cells proliferate and launch an army of
plasma cells and effector T cells.
18.3 How Does Specific Immunity Develop?
Because of immunological memory,
natural immunity can occur after one
exposure to diseases such as chicken
pox.
Artificial immunity is conferred by
inoculation with an antigen.
18.3 How Does Specific Immunity Develop?
Immunization—inoculation with
antigenic proteins, pathogen fragments,
or other molecular antigens.
Vaccination—inoculation with whole
pathogens that have been modified so
they will not cause the disease.
Both initiate primary immune response,
generating memory cells.
Table 18.2 (Part 1)
Table 18.2 (Part 2)
18.3 How Does Specific Immunity Develop?
Pathogens used for vaccination may be altered by:
• Inactivation—treat with heat or chemicals to kill the
pathogen.
• Attenuation—reduce virulence of a virus by
repeatedly infecting cells with it.
18.3 How Does Specific Immunity Develop?
• Recombinant DNA technology—produce
peptide fragments that bind to lymphocytes,
but don’t have the toxic portion of the protein.
• DNA vaccines—under development, inserting
a gene that encodes an antigen.
18.3 How Does Specific Immunity Develop?
Normally, the body is tolerant of its own molecules—
immunological tolerance. Two mechanisms:
• Clonal deletion: certain immature B and T cells that
show the potential to mount an immune response to
self antigens undergo apoptosis.
18.3 How Does Specific Immunity Develop?
• Clonal anergy: suppression of immune response if a
mature lymphocyte recognizes self antigens.
Before a T cell sends out cytokines, it must also
encounter a second molecule, CD28. Most body cells
lack this signal.
CD28 is a co-stimulatory signal, expressed only on
certain antigen-presenting cells.
Figure 18.7 Immunological Tolerance
18.4 What Is the Humoral Immune Response?
B cells are the basis of the humoral
immune response.
First make an antibody that is expressed
as a receptor protein on the cell surface.
If an antigen binds to the receptor, the B
cell becomes a plasma cell, which
makes antibodies secreted to the blood
stream. Also gives rise to a clone of
plasma and memory cells.
18.4 What Is the Humoral Immune Response?
For B cell to develop into a plasma cell, a
helper T cell (TH) with the same
specificity must also bind to the antigen.
Division and differentiation of the B cell is
stimulated by signals from the TH cell.
As plasma cell develops, ER and
ribosomes increase—for synthesis of
antibody proteins.
Figure 18.8 A Plasma Cell
18.4 What Is the Humoral Immune Response?
Antibodies belong to protein group called
immunoglobulins.
All contain a tetramer of four polypeptides—two light
chains and two heavy chains, held together with
disulfide bridges.
Each polypeptide chain has a variable region and a
constant region.
18.4 What Is the Humoral Immune Response?
Constant region determines the class of antibody—
the function and destination.
Variable regions are specific for each
immunoglobulin—responsible for antibody specificity.
Two antigen-binding sites are identical—bivalent.
Figure 18.9 The Structure of Immunoglobulins (Part 1)
Figure 18.9 The Structure of Immunoglobulins (Part 2)
Table 18.3 (Part 1)
Table 18.3 (Part 2)
18.4 What Is the Humoral Immune Response?
Five classes of antibodies:
IgG—most abundant; soluble; greatest amounts made
during secondary immune response.
Some IgG bind to antigens and then to macrophages,
which engulfs the antigen.
Figure 18.10 IgG Antibodies Promote Phagocytosis
18.4 What Is the Humoral Immune Response?
Monoclonal antibodies are from a clone
of B cells; will have specificity for only
one antigenic determinant.
Polyclonal are from different types of B cells; have
specificity for many antigenic determinants.
18.4 What Is the Humoral Immune Response?
A clone of B cells can be made by fusing a B cell with a
tumor cell—the resulting cell is a hybridoma.
The hybridoma makes monoclonal antibodies and
grows indefinitely in culture.
Figure 18.11 Creating Hybridomas for the Production of Monoclonal Antibodies
18.4 What Is the Humoral Immune Response?
Monoclonal antibodies are used for:
• Immunoassays—detecting small
amounts of molecules in tissue or fluids.
• Immunotherapy—monoclonal
antibodies for antigenic determinants on
cancer cells. Can be coupled with a
radioactive or toxic ligands.
18.4 What Is the Humoral Immune Response?
• Passive immunization—short-lived
monoclonal antibodies are injected into
life threatening situations, where there
is not enough time to allow immune
system to mount its own defense.
18.5 What Is the Cellular Immune Response?
Cellular immune response—mediated
by T cells—directed against any factor
that changes a normal cell into an
abnormal cell.
T cell receptors are glycoproteins, with
two polypeptide chains. The two chains
have different amino acid sequences.
Figure 18.12 A T Cell Receptor
18.5 What Is the Cellular Immune Response?
T cell receptors bind to a piece of an antigen
displayed on the surface of an antigenpresenting cell.
When T cell is activated, it forms a clone and
descendents differentiate into two types of
effectors:
• Cytotoxic T cells (TC) recognize abnormal
cells and kill them by lysis.
• Helper T cells (TH) assist both humoral and
cellular responses.
18.5 What Is the Cellular Immune Response?
Major histocompatibility complex (MHC) proteins:
plasma membrane glycoproteins.
Main role is to present antigens to T cell receptors so
that the T cell can distinguish between self and
nonself.
18.5 What Is the Cellular Immune Response?
Two classes of MHC proteins:
Class I—on surface of every nucleated cell. Bind to
polypeptide fragments, travel to membrane and “present”
the fragments to TC cells. TC cells have a surface protein
CD8 that binds to MHC I.
18.5 What Is the Cellular Immune Response?
Class II—on surfaces of B cells, macrophages, and
other antigen-presenting cells.
When a nonself antigen is ingested, fragments bind to
MHC II and are carried to the membrane and
presented to TH cells. TH cells have a surface
protein CD4 that binds to MHC II.
Figure 18.13 Macrophages Are Antigen-Presenting Cells
18.5 What Is the Cellular Immune Response?
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.
Figure 18.14 The Interaction between T Cells and Antigen-Presenting Cells (Part 1)
Figure 18.14 The Interaction between T Cells and Antigen-Presenting Cells (Part 2)
Figure 18.14 The Interaction between T Cells and Antigen-Presenting Cells (Part 3)
18.5 What Is the Cellular Immune Response?
Humans have three gene loci each for MHC I
and II, all six loci have hundreds of alleles.
Different people have very different genotypes
for these proteins.
Genes for MHC, antibodies, and T cell
receptors may have descended from one
ancestor, and represent a gene “superfamily.”
18.5 What Is the Cellular Immune Response?
Humoral immune response:
Activation phase occurs in lymphoid tissue.
TH cell binds to antigen-presenting
macrophage, produces a clone.
Effector phase—TH cells activate B cells
with the same specificity, to produce
antibodies.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
HUMORAL IMMUNE RESPONSE
ACTIVATION PHASE
Class II MHC
protein
Interleukin-1 (a cytokine)
activates a TH cell.
Antigen
Macrophage
Helper
T cell
(TH)
The antigen is
taken up by
phagocytosis and
degraded in a
lysosome.
A T cell receptor recognizes an
antigenic fragment bound to a
class II MHC protein on the
macrophage.
T cell
receptor
Cytokines released by the
TH cell stimulate
it to proliferate.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
HUMORAL IMMUNE RESPONSE
The TH cell
proliferates
and forms
a clone.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
HUMORAL IMMUNE RESPONSE
EFFECTOR PHASE
Cytokines activate
B cell proliferation.
B cell
TH cell
The binding of antigen to a specific IgM
receptor triggers endocytosis,
degradation, and display of the
processed antigen.
A T cell receptor recognizes an
antigenic fragment bound to a class II
MHC protein on a B cell.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
HUMORAL IMMUNE RESPONSE
Memory cell
B cells proliferate
and differentiate.
Plasma cell
The plasma cell
produces antibodies.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
CELLULAR IMMUNE RESPONSE
ACTIVATION PHASE
Class I MHC
protein
T cell
receptor
Infected
cell
Antigen
A viral protein made in an
infected cell is degraded
into fragments and picked
up by a class I MHC protein.
Cytotoxic
T cell
(TC)
A T cell receptor recognizes
an antigenic fragment bound
to a class I MHC protein on
an infected cell.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
CELLULAR IMMUNE RESPONSE
The TC cell
proliferates
and forms
a clone.
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
CELLULAR IMMUNE RESPONSE
EFFECTOR PHASE
Infected cell
(one of many)
A T cell receptor again recognizes
an antigenic fragment bound to a class I
MHC protein.
The T cell
releases
perforin…
Figure 18.15 Phases of the Humoral and Cellular Immune Responses
CELLULAR IMMUNE RESPONSE
…which lyses
the infected cell before
the viruses can
multiply.
18.5 What Is the Cellular Immune Response?
B cells are also antigen-presenting
cells.
They take up antigens bound to surface
receptors by endocytosis, then display
fragments on MHC II proteins.
A TH cell binds to the displayed complex,
releases cytokines that cause B cell to
produce a clone of plasma cells.
18.5 What Is the Cellular Immune Response?
Cellular immune response:
Activation phase—a virus-infected or
altered cell displays peptide fragments
bound to MHC I. A TC cell binds and is
activated to form a clone.
Effector phase—TC clones recognize
other infected cells, bind to them and
initiate lysis.
18.5 What Is the Cellular Immune Response?
TC cells produce perforin, which lyses
cells.
TC cells also bind to receptor (Fas) on
target cells that initiates apoptosis.
TC cells recognize self MHC proteins
complexed with foreign or altered
fragments.
18.5 What Is the Cellular Immune Response?
TC cells require a second signal for activation—costimulatory signal—when TC first binds to infected
cell, there is additional interactions of TC proteins and
CD28.
Also starts production of an inhibitor to ensure that
response will end. Surface protein CTLA4 binds with
the CD28, blocking the activation of TC cells.
18.5 What Is the Cellular Immune Response?
MHC proteins are important in self-tolerance.
Developing T cells are “tested” in the thymus.
T cells unable to recognize self MHC proteins die
quickly. If a T cell binds to self MHC proteins and the
body’s own antigens, it dies.
18.5 What Is the Cellular Immune Response?
In organ transplants, the tissue from another person
has different MHC proteins and is recognized as
nonself—it is destroyed or “rejected” by the immune
system.
Drugs are used to overcome rejection—cyclosporin
blocks a transcription factor necessary for T cell
development.
18.6 How Do Animals Make So Many Different Antibodies?
As B cells develop, their genomes
become modified so that each mature B
cell can produce only one specific
antibody.
Each gene encoding an immunoglobulin
is actually a supergene assembled from
a cluster of smaller genes.
Every cell has hundreds of genes that
could participate in synthesis of
antibodies.
Figure 18.16 Heavy-Chain Genes
18.6 How Do Animals Make So Many Different Antibodies?
During B cell development, the genes are
cut out and rearranged. One gene is
chosen randomly for joining, others are
deleted.
A unique supergene is assembled.
Result: enormous diversity of specific
antibodies.
Figure 18.17 Heavy-Chain Gene Rearrangement and Splicing (Part 1)
Figure 18.17 Heavy-Chain Gene Rearrangement and Splicing (Part 2)
18.6 How Do Animals Make So Many Different Antibodies?
Genes for the light chains are on
separate chromosomes; they are made
in a similar way, with an equally large
amount of diversity possible.
Light and heavy chain diversity together
yield about 21 billion possibilities.
18.6 How Do Animals Make So Many Different 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
18.6 How Do Animals Make So Many Different Antibodies?
Class switching:
B cells can make only one type of
antibody at a time, but it can change the
class of antibody it makes.
Early B cells produce IgM—receptors
that recognize specific antigenic
determinants.
18.6 How Do Animals Make So Many Different Antibodies?
If B cell becomes a plasma cell, a
deletion occurs in the DNA, resulting in
an antibody with a different constant
region of the heavy chain.
The antibody still has the same variable
regions, and thus the same specificity;
but a different function.
TH cells induce class switching through
cytokine signals.
Figure 18.18 Class Switching
18.7 What Happens When the Immune System Malfunctions?
Allergic reactions occur when the
immune system overreacts or is
hypersensitive to an antigen.
The antigen may not be a danger, but the
immune system produces inflammation
and other symptoms.
Two types: immediate and delayed
hypersensitivity.
Photo 18.11 Eczema, an allergic reaction.
18.7 What Happens When the Immune System Malfunctions?
Immediate hypersensitivity:
When exposed to an allergen, large
amounts of IgE are produced. IgE
constant end binds to mast cells and
basophils—large amounts of histamine
are released.
Histamines produce symptoms such as
inflammation, blood vessel dilation,
difficulty in breathing.
Figure 18.19 An Allergic Reaction (Part 1)
Figure 18.19 An Allergic Reaction (Part 2)
18.7 What Happens When the Immune System Malfunctions?
These reactions can be treated with antihistamines.
Severe allergic reactions can lead to death.
Allergy to pollen can be treated by desensitization—
small amounts of allergen are injected under the skin,
stimulates IgG production, but not IgE production.
18.7 What Happens When the Immune System Malfunctions?
Delayed hypersensitivity:
Begins hours after exposure to the allergen.
The antigen is taken up by antigen-presenting cells
and a T cell response is initiated.
Example: poison ivy rash
18.7 What Happens When the Immune System Malfunctions?
Autoimmunity: clones of B and T cells are produced that are directed
against self antigens. Possible causes:
• Failure of clonal deletion
• Viral infection—if virus has an antigenic determinant that resembles
a self antigen
• Molecular mimicry—self has antigens that resemble nonself and are
recognized by T cells
18.7 What Happens When the Immune System Malfunctions?
Autoimmune diseases tend to “run in families”—
indicating a genetic component.
Genome scans indicate a transcription factor for B
cells, RUNX1, may be involved.
Some alleles for MHC II are strongly associated with
autoimmune diseases.
18.7 What Happens When the Immune System Malfunctions?
Some autoimmune diseases:
• Systemic lupus erythematosis (SLE)—antibodies to
cellular components result in large circulating
antibody-antigen complexes that become stuck in
tissues, causing inflammation.
18.7 What Happens When the Immune System Malfunctions?
• Rheumatoid arthritis—T cell response can not be
shut down, possibly due to low CTLA4 activity.
Results in joint inflammation because of influx of
white blood cells.
• Hashimoto’s thyroiditis—immune cells attack thyroid
secretions.
Photo 18.12 Hands of 50-year-old man with 20-year history of rheumatoid arthritis. X-ray.
18.7 What Happens When the Immune System Malfunctions?
• Insulin-dependent diabetes mellitus
(type I)—occurs most often in children.
Caused by an immune reaction against
cells in the pancreas that make insulin.
18.7 What Happens When the Immune System Malfunctions?
Immune deficiency disorders can be
inherited or acquired.
T or B cells never form, or B cells lose
their ability to become plasma cells.
TH cells (crucial to both humoral and
cellular responses), are the targets of
HIV retrovirus that results in AIDS—
acquired immune deficiency
syndrome.
18.7 What Happens When the Immune System Malfunctions?
HIV can be transmitted by:
• Blood—e.g., needle contamination
• Exposure through broken skin, wounds,
mucus membranes
• Through blood of infected mother to
baby during birth
18.7 What Happens When the Immune System Malfunctions?
HIV initially infects TH cells, macrophages,
and dendritic cells. These cells carry the
virus to the lymph nodes and spleen.
HIV preferentially infects activated TH cells
in the lymph nodes and spleen.
Up to 10 billion viruses are made per day
in the initial phase of infection.
18.7 What Happens When the Immune System Malfunctions?
Symptoms abate as T cells mount an
immune response.
But antibody-complexed viruses can still
infect TH cells—secondary infection.
The rate of secondary infection reaches a
low, steady state level—the set point.
Set point level varies in individuals, and
determines rate of progress of the
disease.
Figure 18.20 The Course of an HIV Infection
18.7 What Happens When the Immune System Malfunctions?
Gradually, TH cells are destroyed, and the
person is susceptible to many infections.
Opportunistic infections:
• Kaposi’s sarcoma, a rare skin cancer
caused by a herpesvirus
• Pneumonia caused by fungus
Pneumocystis carinii
• Lymphoma tumors caused by EpsteinBarr virus
Figure 18.21 Relationship between TH Cell Count and Opportunistic Infections
18.7 What Happens When the Immune System Malfunctions?
HIV is an enveloped retrovirus; the
genome is RNA.
Virally encoded proteins necessary for
infection and replication:
• Membrane glycoproteins gp120 and gp41 attach to
host cell proteins CD4 and a co-receptor.
Figure 18.22 Two Receptors for HIV
18.7 What Happens When the Immune System Malfunctions?
• Reverse transcriptase—catalyzes
synthesis of cDNA from viral RNA.
Lacks proofreading function, which
leads to a pool of mutant viruses.
• Integrase—catalyzes insertion of cDNA into host
chromosome
• Protease—to complete viral proteins
18.7 What Happens When the Immune System Malfunctions?
Treating HIV: develop agents that block
steps in viral life cycle without harming
host cells.
Highly active antiretroviral therapy
(HAART) is a combination of drugs—a
protease inhibitor and two reverse
transcriptase inhibitors.
Many people on HAART develop mutant
strains of HIV.
18.7 What Happens When the Immune System Malfunctions?
New drug combinations are constantly
being developed to combat mutating
strains of HIV.
Researchers are trying to develop
vaccines.
Photo 18.8 Human thymus tissue: lymphocyte lobules; blood vessels in septae. LM, H & E stain.
Photo 18.9 Lymphocytes in cortex of human lymph node tissue. LM, H&E stain.
Photo 18.10 Plasma cell in rat lymph node: extensive RER and large Golgi apparatus. TEM.