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Chapter 43
The Immune System
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Overview: Reconnaissance (inspection), Recognition,
and Response
• An animal must defend itself
– From the many dangerous pathogens it may
encounter in the environment or abnormal cells
that might develop into cancer
• Two major kinds of defense have evolved that
counter these threats
– Innate immunity and acquired immunity
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• Innate immunity
– Is present before any exposure to pathogens
and is effective from the time of birth
– Involves nonspecific responses to pathogens
Figure 43.1; a macrophage
ingesting a yeast cell.
3m
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Innate immune system
•
nonspecific defense: it does not distinguish
between infective agents.
•
External consisting of epithelial tissue that
cover skin and mucus membranes
•
Internal it get trigered by chemical signals
and involves macrophages and other
phagocytic ells.
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• Acquired immunity, also called adaptive immunity
– Develops only after exposure to inducing agents
such as microbes, toxins, or other foreign
substances
– Involves a very specific response to pathogens
– The recognition involves WBC called lymphocytes
that produces the humoral (B cells secreting
antibodies) and the cellular (T cells such as
cytotoxic cells that directly kill the microbe).
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A summary of innate and acquired immunity
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Skin
Internal defenses
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Invading
microbes
(pathogens)
Figure 43.2
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ACQUIRED IMMUNITY
Slower responses to
specific microbes
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
• Concept 43.1: Innate immunity provides broad
defenses against infection
• A pathogen that successfully breaks through an
animal’s external defenses
– Soon encounters several innate cellular and
chemical mechanisms that impede its attack
on the body
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External Defenses
• Intact skin and mucous membranes
– Form physical barriers that bar the entry of
microorganisms and viruses
• Certain cells of the mucous membranes
produce mucus
– A viscous fluid that traps microbes and other
particles such as in lungs.
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• In the trachea, ciliated epithelial cells
– Sweep mucus and any entrapped microbes
upward, preventing the microbes from entering
the lungs
10m
Figure 43.3
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• Secretions of the skin and mucous membranes
– Provide an environment that is often hostile to
microbes
• Secretions from the skin
– Give the skin a pH between 3 and 5, which is acidic
enough to prevent colonization of many microbes
– Also include proteins such as lysozyme, an enzyme
that digests the cell walls of many bacteria
• Stomach acidity; kills many bacteria ingested with
food, however, some pathogens survive this acidity
such as Hepatitis A virus.
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Internal Cellular and Chemical Defenses
• Internal cellular defenses
– Depend mainly on phagocytosis
• Phagocytes, types of white blood cells
– Ingest invading microorganisms
– Initiate the inflammatory response and produce
antimicrobial proteins
– None phagocytic cells are called natural killers
that play a role in the innate immunity
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Phagocytic Cells
• Phagocytes attach to their prey via surface receptors
– And engulf them, forming a vacuole that fuses with a
lysosome
Pseudopodia
1
surround
microbes.
Microbes
2 Microbes
are engulfed
into cell.
MACROPHAGE
Vacuole
containing
microbes
forms.
3
Vacuole
Lysosome
containing
enzymes
4 Vacuole
and lysosome
fuse.
Toxic
5
compounds
and lysosomal
enzymes
destroy microbes.
Microbial
debris is
released by
exocytosis.
6
Figure 43.4
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•
When engulfing any bacteria or virus, the
engulfed mateial fuses with lysozymes which
kills by two ways;
•
Generates toxic forms of oxygen as the super
oxide anion and nitric oxide.
•
Lysosomal enzymes including lysozyme that
digests the engulfed material.
•
However some pathoges has systems to evade
these enzymes or they are naturally resistant to
such lysosome as the TB pathogen
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Four Types of Phagocytic Cells
•
Neutrophils; comprise 60-70% of total
WBCs.
–
Attracted by chemical signals, they enter
infected tissue by amoeboid movement. So
they are atracted by chemotaxis
–
Only live for few days as they destroy
themselves when destroying pathogens.
•
Macrophages; a specific type of phagocyte
–
Can be found migrating through the body
–
Can be found in various organs of the
lymphatic system and comprise about 5% of
WBC.
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Macrophages
•
–
Long lived phagocytosis
–
Most wander through interstitial fluid engulfing
bacteria, viruses and cell debris by means of
extending pseudopodia that can attach to
polysaccharides in the bacterial or viral surface.
–
Some reside permanently in organs and connective
tissues.
Eosinophils; have lower phagocytic activity and are
crucial against intracellular parasites such as
schistosoma mansoni by secreting enzymes damaging
the parasite.
•
Dendritic cells; can ingest microbes but their
major role to stimulate development of acquired
immunity.
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The lymphatic system
• Plays an active role in defending the body from pathogens
1 Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
Interstitial
fluid
Adenoid
Lymphatic
capillary
Tonsil
Lymphatic vessels
4
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
Lymph
nodes
Blood
capillary
Spleen
Tissue
Peyer’s patches
cells
(small intestine)
Appendix
Figure 43.5
Lymphatic
vessels
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Fluid inside the
2
lymphatic
capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
Lymph
node
Lymphatic
vessel
Within lymph nodes,
microbes
and foreign
3
particles present in
the circulating lymph
encounter macrophages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
Masses of
lymphocytes and
macrophages
Antimicrobial Proteins
• Numerous proteins function in innate defense
– By attacking microbes directly or by impeding
their reproduction such as lysozymes.
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Complement System
• About 30 proteins make up the complement system
– Which can cause lysis of invading cells and help trigger
inflammation.
– The presence of invading microbes triggers a cascade of
reactions leads to lysis of invaders
– In absence of infection these proteins will be inactive
• Interferons; produced by viral infected cells
– Provide innate defense against viruses and help activate
macrophages
– There are two types of interferons; Α and β
– Some other lymphocytes produce γ interferon that activates
macrophages to produce defensins, another
antibmicrobial protein that kills wide range of bacteria.
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Inflammatory Response
•
•
A localized inflammatory response occurs
when there is a damage in a tissue due to
physical injury or entry of microorganisms.
–
dilation of small vessels near the injury
increases blood flow to the area (causes
redness).
–
The dilated vessels become more permeable
allowing fluids and antimicrobial proteins to
move into surrounding tissues resulting in
localized edema.
Certain chemical signals are important in
initiating inflammatory response:
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–
Histamine is released from injured circulating
basophils and mast cells in the connective tissue.
Histamine increase dialtion thus increase
permiability of nearby capillaries.
–
Prostaglandins also released from white blood cells
and damaged cells. These promote blood flow to the
injured area and enhances the migration of
phagocytic cells from blood into the injury site.
–
This increased blood flow delivers clotting elements
that help block the spread of pathogens and begin
the repair process.
–
Phagocytes are attracted to the damaged tissues by
several chemical signals including small proteins
called Chemokines.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•
–
Neutrophils arrive first, followed by monocytes which
develop into phagocytes.
–
Neutrophils eliminate pathogens and then die.
–
Macrophages destroy pathogens and clean up the
remains of damaged tissues.
In sever infections, e.g. meningitis,
•
the bone marrow may be stimulated to release
more neutrophils by molecules emitted by
injured cells and several fold leukocytes will be
produced within hours.
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–
A fever may develop in response to toxins released
by pathogens, or due to pyrogens released by
certain leukocytes. The pyrogens sets the body
thermostat at higher temperature.
–
Moderate fever inhibits the growth of some
microorganisms and also facilitate phagocytosis and
speed up tissue repair. However, sever fever is
dangerous
–
Certain pathogenes can induce an overwhelming
immune response causing what is called septic
shock that is characterized by high fever and low
blood pressure.
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Major events in the local inflammatory response
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1
Chemical signals released 2
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
Fluid, antimicrobial proteins,3
and clotting elements move
from the blood to the site.
Clotting begins.
Figure 43.6
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4
Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
Neutrophils and macrophage
phagocytose pathogens and
cell debris at the site, and the
tissue heals.
Natural Killer Cells
• Natural killer (NK) cells
– Patrol the body and attack virus-infected body
cells and cancer cells
– it is attached to a virus or a cancers cell due to
surface receptors on them.
– The attachment trigger the release of ceratin
chemicals that cause apoptosis in the cells
they attack
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Invertebrate Immune Mechanisms
• Many invertebrates defend themselves from
infection
– By many of the same mechanisms in the
vertebrate innate response
– Fruit fly have similar mechanism to
vertebrates, they contain hemocytes as
equavlent to blood.
– Invertbrates lacks lymphocytes, thus they
depend heavily on innate immune mechanisms
to defend themselves against invaders.
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• Concept 43.2: In acquired immunity, lymphocytes
provide specific defenses against infection
• Acquired immunity
– Is the body’s second major kind of defense
– Involves the activity of lymphocytes
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The Antigen Concept
• An antigen is any foreign moleculethat is specifically
recognized by lymphocytes and elicits a response
from them
• A lymphocyte actually recognizes and binds to just a
small, accessible portion of the antigen called an
epitope or an antigenic determinant (4-5 a.a).
Antigenbinding
sites
Antibody A
Antigen
Antibody B
Antibody C
Figure 43.7
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Epitopes
(antigenic
determinants)
Antigen Recognition by Lymphocytes
• The vertebrate body is populated by two main
types of lymphocytes
– B lymphocytes (B cells) and T lymphocytes
(T cells) which circulate through the blood
– B and T cells recognize antigens by means of
antigen specific receptors in their plasma
membranes.
• The plasma membranes of both B cells
and T cells have about 100,000 antigen receptors
that all recognize the same epitope
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B Cell Receptors for Antigens
• B cell receptors bind to specific, intact antigens
– Are often called membrane antibodies or membrane
immunoglobulins and are similar to secreted antibodies
Antigenbinding
site
Antigenbinding site
Disulfide
bridge
Variable
regions
Light
chain
C C
Heavy chains
B cell
Plasma
membrane
Cytoplasm of B cell
(a)
Figure 43.8a
Constant
regions
Transmembrane
region
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
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T Cell Receptors for Antigens and the Role of the MHC
• Each T cell receptor consists of two different
polypeptide chains
AntigenBinding site
Variable
regions
Constant
regions
V
V
C
C
Transmembrane
region
Plasma
membrane
a chain
b chain
Disulfide bridge
Cytoplasm of T cell
Figure 43.8b
(b) A T cell receptor consists of one
a chain and one b chain linked by
a disulfide bridge.
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T cell
• T cells bind to small fragments of antigens
– That are bound to normal cell-surface proteins
called MHC molecules
• MHC molecules
– Are encoded by a family of genes called the
major histocompatibility complex
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• Infected cells produce MHC molecules inside the
cell and while they are being exported to cell
surface, they bind a fragment of protein from
antigens and will present it on the surface. This
process is called antigen presentation
• A nearby T cell
– Can then detect the antigen fragment displayed
on the cell’s surface and will elicit the production
of a clone of T- cells that are specific for this
particular peptide.
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• Depending on their source
– Peptide antigens are handled by different
classes of MHC molecules
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Class I MHC molecules
• Found on almost all nucleated cells of the body
– Display peptide antigens to cytotoxic T cells
– Infected and cancerous cells display such peptide
antigens.
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Class I MHC molecules
Infected cell
11
Antigen
fragment
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
1
Class I MHC
molecule
2
T cell
receptor
Figure 43.9a
(a) Cytotoxic T cell
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2
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
Class II MHC molecules
• Located mainly on dendritic cells, macrophages,
and B cells (Antigen presenting cells, APC).
– Bind peptides derived from foreign materials that
have been internalized by phagocytosis.
– Display antigens to helper T cells
– Humans have large number of different MHC
alleles in human population.
– Any two people (except identical twins) are very
unlikely to have same set of MHC molecules.
– MHC provides fingerprint of each individual
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Class II MHC molecules
Microbe
Antigenpresenting
cell
1
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Antigen
fragment
Class II MHC
molecule
2
1 T cell
receptor
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
2
Helper T cell
(b)
Figure 43.9b
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Lymphocyte Development
• Lymphocytes
– Arise from pluripotent stem cells in the bone marrow
• Newly formed lymphocytes are all alike
– But they later develop into B cells or T cells, depending
on where they continue their maturation.
• There are three events in the life of a lymphocyte
– First 2 events are;Lymphocyte maturation of B or T
– Third event is the lymphocyte encounter with an antigen
that leads to its activation, proliferation and
differentiation, a process called clonal selection.
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Development and Differentiation of lymphocyte
Bone marrow
Lymphoid
stem cell
Thymus
T cell
B cell
Both circulate in
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
Figure 43.10
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Generation of Lymphocyte Diversity by Gene
Rearrangement
• B and T lymphocytes recognize specific epitopes on
antigens via their antigen receptors.
• A single B or T cell has about 100,000 or these receptors.
• The variable region at the tip of each antigen receptor chain
(antigen binding site) forms this diversity.
• The sequence of a.a. in these regions varies from cell to cell,
thus it is estimated that each individual has as many as 1
million different B cells and 10 million T-cells each respond to
different antigen.
• Early in development, random, permanent gene
rearrangement Forms functional genes encoding the different
B or T cell antigen receptor chains.
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Immunoglobulin gene rearrangement
V4–V39
DNA of
undifferentiated
B cell
V2
V1
V40
V3
J1 J2 J3 J4 J5 Intron
C
1 Deletion of DNA between a V segment
and J segment and joining of the segments
DNA of differentiated
B cell
V1
V3 J5 Intron
V2
C
2 Transcription of resulting permanently rearranged,
functional gene
pre-mRNA
V3 J5 Intron
3
mRNA Cap
V3 J 5
C
RNA processing (removal of intron; addition of cap
and poly (A) tail)
C
Poly (A)
4 Translation
Light-chain polypeptide
Figure 43.11
V
C
Variable Constant
region
region
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B cell receptor
B cell
Summary of the immunoglobulin gene rearrangement
• Immunglobulin light chain gene contains a series of 40
variable gene segments separated by long stretch of DNA from
the 5 Joining (J) gene segments.
• Down stream of the J segments there is an intron and an exon
(C) that codes for the constant region.
• Early in development, a set of enzymes called recombinase
links one V gene to a J segment eliminating the long stretch of
DNA and forming one exon
• Recombinase acts randomly thus it could join any of the V gene
segments to the J segments i.e 200 combinations with only one
combination/cell.
• Once this combination takes place, the gene can be transcribed
mRNA processed and translated to a light chain with both
variable and constant regions.
• The light chain produced will randomly combine with a heavy
chain that was made in the same way.
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Testing and Removal of Self-Reactive Lymphocytes
• As B and T cells are maturing in the bone and
thymus
– Their antigen receptors are tested for possible
self-reactivity
• Lymphocytes bearing receptors for antigens
already present in the body
– Are destroyed by apoptosis or rendered
nonfunctional
• The immune system exhibits the critical feature
of self-tolerance.
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Clonal Selection of Lymphocytes
–
Binding of antigen to a mature lymphocyte
induces the lymphocyte’s proliferation and
differentiation, a process called clonal
selection.
–
Clonal selection generates;
•
a clone of short-lived activated effector cells
•
a clone of long-lived memory cells
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Clonal selection of B cells
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen molecules
bind to the antigen
receptors of only one
of the three B cells
shown.
Antigen
receptor
The selected B cell
proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating cells
develop into long-lived
memory cells that can
respond rapidly upon
subsequent exposure
to the same antigen.
Some proliferating
cells develop into
short-lived plasma
cells that secrete
antibodies specific
for the antigen.
Antibody
molecules
Clone of memory cells
Figure 43.12
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Clone of plasma cells
– The nature and function of the effector cell
depends on whether the lymphocyte selected is a
helper T cell, a cytotoxic T cell or a B cell.
– The other clone consist of memory cells that live
long and bear receptors for specific for same
inducing antigen.
– So the clonal selection can be defined as this;
each antigen by binding to specific receptor,
selectively activates a tiny fraction of cells from
the body’s diverse pool of lymphocytes that is
dedicated to destroy the antigen.
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Primary Immune Response
– Is the proliferation of lymphocytes to form
effecter cells specific to an antigen during the
body’s first exposure to the antigen.
– There is 10-17 days lag period between initial
exposure and maximum production of effecter
cells. Mainly IgM
– The lympnocytes selected by the antigen are
differentiated into B and T cells during the lag
period.
– Activated B cells give rise to effecter cells
called plasma cells which secrete antibodies
(humoral response).
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Secondary immune response
• Memory cells facilitate a faster, more efficient
response that takes 2-7 days. IgG mainly
1 Day 1: First
exposure to
antigen A
2 Primary
response to
antigen A
produces antibodies to A
3 Day 28:
Second exposure
to antigen A; first
exposure to
antigen B
4 Secondary response to antigen A produces antibodies
to A; primary response to antigen B produces antibodies to B
Antibody concentration
(arbitrary units)
104
103
102
Antibodies
to A
Antibodies
to B
101
100
0
Figure 43.13
7
14
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21
28
35
Time (days)
42
49
56
• Secondary response leads to the production of
very high amount of antibodies that have more
affinity than the antibodies produced in the primary
response.
• The immunes system capacity to generate
secondary immune response is called
Immmunological memory
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• Concept 43.3: Humoral and cell-mediated
immunity defend against different types of
threats
• Acquired immunity includes two branches
– The humoral immune response involves the
activation and clonal selection of B cells,
resulting in the production of secreted
antibodies
– The cell-mediated immune response involves
the activation and clonal selection of cytotoxic
T cells
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An overview of the acquired immune response
Cell-mediated immune response
Humoral immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate
Activate
Activate
B cell
Gives rise to
Plasma
cells
Figure 43.14
Memory
B cells
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
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Secreted
cytokines
activate
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Helper T Cells: A Response to Nearly All Antigens
• Helper T cells produce CD4, a surface protein
– That enhances their binding to class II MHC molecule–
antigen complexes on antigen-presenting cells
• When helper T-cell encounters a class II MHC moleculeantigen complex, TH proliferates and differentiate into a
clone of activated TH and memory TH.
• Class II MHC molecules found mainly on dendritic cells, B
cells and Macrophages. \
• Dendritic cells are particularly effective in triggering primary
immune response.
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• Activated helper T cells
– Secrete several different cytokines that
stimulate other lymphocytes thereby promoting
cell mediated and humoral response.
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The role of helper T cells in acquired immunity
1 After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR (T-cell receptor) with the aid of
CD4. This interaction promotes secretion of cytokines by the dendritic cell.
Cytotoxic T cell
Peptide antigen
Dendritic
cell
Class II MHC
molecule
Bacterium
Helper T cell
Cell-mediated
immunity
(attack on
infected cells)
TCR
2
3
1 CD4
Dendritic
cell
Cytokines
2
Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHC–antigen complex.
Figure 43.15
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B cell
3 The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytotoxic T Cells: A Response to Infected Cells and
Cancer Cells
• Cytotoxic T cells make CD8
– A surface protein that greatly enhances the
interaction between a target cell and a
cytotoxic T cell
– The role of class I MHC molecules and the
CD8 is similar to that for class II MHC and CD4
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• Cytotoxic T cells
– Bind to viral infected cells , cancer cells, and
transplanted tissues
• Binding to a class I MHC complex on an
infected body cell
– Activates a cytotoxic T cell and differentiates it
into an active killer
– Nearby helper T cells secrete cytokines that
promote this activation.
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The activated cytotoxic T cell secretes proteins
• that destroy the infected target cell and present its
fragments to circulating antibodies for long immunity.
1 A specific cytotoxic T cell binds to a
2 The activated T cell releases perforin
class I MHC–antigen complex on a
molecules, which form pores in the
target cell via its TCR with the aid of
target cell membrane, and proteolytic
CD8. This interaction, along with
enzymes (granzymes), which enter the
cytokines from helper T cells, leads to
target cell by endocytosis.
the activation of the cytotoxic cell.
Cytotoxic T cell
3 The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.
Released
cytotoxic
T cell
Perforin
Cancer
cell
Granzymes
1 TCR
Class I MHC
molecule
Target
cell
3
CD8
2
Apoptotic
target cell
Pore
Peptide
antigen
Figure 43.16
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Cytotoxic
T cell
• Cancerous cells also display class I MHC
moleules on their surface.
• These are abnormal thus are recognized by
cytotoxic T-cells which destroys them and
presenting them to curculating antibodies.
• Some cancerous cells minimize their production of
class I MHC molecules to avoid body’s immune
system.
• In this case NK cells which are part of non-specific
immune system will kill these cells.
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B Cells: A Response to Extracellular Pathogens
• Antigens that elicit a humoral response are
typically proteins and polysaccharides present on
surface of bacteria or from pollens or transplanted
tissues.
• Activation of B cells is aided by cytokines and
antigen binding to helper T cells
• Upon stimulation, active B cells proliferate and
differentiate into a clone of antibody secreting
plasma cells and a clone of memory cells. This is
called the clonal selection of B-cells.
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• When an antigen binds to a receptor on surface of B
cells, cells takes in a few molecules from the fragmented
molecule by endocytosis.
• Cell presents these antigen fragments to HT which will
guarantee a direct binding between HT and the B-cell
which is necessary for their activation.
• Antigens that induce antibody production only with
assistance of HT are called T-dependent antigens.
• Some other antigens can evoke B-cell response without
involvment of TH such polysaccharides and flagellar
antibodies of bacterial are called T-independent antigens.
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1 After a macrophage engulfs and degrades
a bacterium, it displays a peptide antigen
complexed with a class II MHC molecule.
A helper T cell that recognizes the displayed
complex is activated with the aid of cytokines
secreted from the macrophage, forming a
clone of activated helper T cells (not shown).
2
3 The activated B cell proliferates
A B cell that has taken up and degraded the
same bacterium displays class II MHC–peptide
and differentiates into memory
antigen complexes. An activated helper T cell
B cells and antibody-secreting
bearing receptors specific for the displayed
plasma cells. The secreted
antigen binds to the B cell. This interaction,
antibodies are specific for the
with the aid of cytokines from the T cell,
same bacterial antigen that
activates the B cell.
initiated the response.
Bacterium
Macrophage
Peptide
antigen
Class II
MHC
molecule
B cell
2
3
1
TCR
Clone of plasma cells
Endoplasmic
reticulum of
plasma cell
CD4
Cytokines
Helper T cell
Secreted antibody
molecules
Activated
helper T cell
Figure 43.17
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Clone of memory
B cells
Antibody Classes
• The five major classes of antibodies, or
immunoglobulins
– Differ in their distributions and functions within
the body
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The five classes of immunoglobulins
IgM
(pentamer)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
J chain
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
IgG
(monomer)
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
IgA
(dimer)
Secretory
component
J chain
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
IgE
(monomer)
IgD
(monomer)
Figure 43.18
Transmembrane
region
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Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
Antibody-Mediated Disposal of Antigens
• The binding of antibodies to antigens Is also the basis of
several antigen disposal mechanisms.
–
The simplest of these is viral neutralization (Ab binds the
virus, thus making it unable to inter the cell).
– Ab binds to pathogens thus coating its surface. This
process called oposnization.
– Opsonization leads to elimination of microbes by
phagocytosis and complement-mediated lysis
– Ab mediated clumping of pathogens is another
mechanism. IgM is the best to do this.
– Antibodies could also precipitate soluble antigens thus
making them available for phagocytosis.
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Antibody-mediated mechanisms of antigen disposal
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Complement
proteins
Bacteria
Virus
Soluble
antigens
Bacterium
Activation of complement system
and pore formation
MAC
Pore
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Figure 43.19 Macrophage
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Active and Passive Immunization
• Active immunity
– Develops naturally in response to an infection
– Can also develop following immunization, often
called vaccination
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• In immunization
– A nonpathogenic form of a microbe or part of a
microbe elicits an immune response to an
immunological memory for that microbe
– Developed by Edward Jenner in 1796. Later
become the savor of hundreds of millions of
people all over the world.
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• Passive immunity, which provides immediate,
short-term protection
– Is conferred naturally when IgG crosses the
placenta from mother to fetus or when IgA
passes from mother to infant in breast milk
– Can be conferred artificially by injecting
antibodies into a nonimmune person
– Example; people bitten by rabid dogs get
passive immunity to keep virus at bay and
active to develop person’s own immune
system.
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• Concept 43.4: The immune system’s ability to
distinguish self from non-self limits tissue
transplantation
• The immune system
– Can wage war against cells from other
individuals
• Transplanted tissues
– Are usually destroyed by the recipient’s
immune system
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Blood Groups and Transfusions
• Certain antigens (glycoproteins) on red blood
cells
– Determine whether a person has type A, B,
AB, or O blood
– Type A contains antigen A on its surface
– Type B contain antigen B on in its surface
– Type AB contains antigens A and B on its
surface
– Type O contains NO antigens on its surface
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• Antibodies to nonself blood types
– Already exist in the body!!!! How can some
thing like that happen?
– These antibodies might have arise in response
to normal bacterial inhibitants of the body that
have epitopes very similar to blood group
antigens.
• Transfusion with incompatible blood
– Leads to destruction of the transfused cells
due to the presence of the preexisting
antibodies against different blood gropus.
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Recipient-donor combinations; Can be fatal or safe
Table 43.1
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• Antibodies against blood groups are always IgMs. This is
a blessing as these does not cross the placenta, thus does
not destroy the fetus even when his/her blood does not
match the mothers.
• Another red blood cell antigen, the Rh factor
– Creates difficulties when an Rh-negative mother
carries successive Rh-positive fetuses
– Rh negative persons do not have Rh antigens
– Rh negative mothers with negative fetus creates No
problem
– Rh negative mothers with positive fetus will have a
reaction that destroys fetus
– Rh positive mothers with +ve or –ve fetus does not
create a problem
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Tissue and Organ Transplants
• MHC molecules
– Are responsible for stimulating the rejection of
tissue grafts and organ transplants
– The polymorphism of MHC molecules
garantees that no two people have the same
set of MHC molecules
– To prevent rejection of grafts, donors and
recipients must have similar (as much as
possible) MHC, and immunosuppressive drugs
are to be used.
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• In bone marrow transplantation, the immune
system of recepients will be wiped out completely
by radiation to kill both normal and abonromal
cancerous cells.
• The fear here is that the donors cells will react
against the host, therefore, it is necessary to have
two people with matched MHC molecules as
possible.
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• Concept 43.5: Exaggerated, self-directed, or
diminished immune responses can cause
disease
• If the delicate balance of the immune system is
disrupted
– The effects on the individual can range from
minor such as allergy to often fatal
consequences of serious autoimmune
diseases and immunodeficiency diseases.
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Allergies
• Allergies are exaggerated (hypersensitive)
responses
– To certain antigens called allergens
– Most common allergies involve IgE class
antibodies
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• In localized allergies such as hay fever
– IgE antibodies produced after first exposure to
an allergen attach to receptors on mast cells
• The next time the allergen enters the body
– It binds to mast cell–associated IgE molecules
• The mast cells then release histamine and
other mediators
– That cause vascular changes and typical
symptoms of allergy. Figure 43-20.
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The allergic response
IgE
Histamine
Allergen
1
3
2
Granule
Mast cell
1
IgE antibodies produced in
response to initial exposure
to an allergen bind to
receptors or mast cells.
3
2
On subsequent exposure to the
same allergen, IgE molecules
attached to a mast cell recognize and bind the allergen.
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Figure 43.20
Degranulation of the cell,
triggered by cross-linking of
adjacent IgE molecules,
releases histamine and other
chemicals, leading to allergy
symptoms.
• An acute allergic response sometimes leads to
anaphylactic shock
– A whole-body, life-threatening reaction that can occur
within seconds of exposure to an allergen
– Anaphylactic shock develops when a widespread mast
cell degranulation triggers abrupt dilation of peripheral
blood vessels.
– Allergic to bee venom or penicillin or even peanuts or
fishcan lead to such anaphylactic shock in people who
are extremely allergic to such substances.
– People with such type of allergy carry syringes with
epinephrine hormone that counteracts such allergy.
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Autoimmune Diseases
• In individuals with autoimmune diseases
– The immune system loses tolerance for self
and turns against certain molecules of the
body
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Other examples of autoimmune diseases include
– Systemic lupus erythematosus where the
immune system generates antibodies against a wide
range of self molecules including histones and DNA
released by normal breakdown of body cells. This
disease is characterized by skin rashes (butterfly shape
on the face), fever, arthritis and kidney disfunction.
– Multiple sclerosis is the most common chronic
disease in developed countries; in this disease T cells
infiltrate the CNS and destroy myelin sheath that
surrounds some neurons.
– Insulin-dependent diabetes where the insulin
producting beta cells of the pancreas are the target of the
cytotoxic T cells
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Rheumatoid arthritis
– Is an autoimmune disease that leads to
damage and painful inflammation of the
cartilage and bone of joints
Figure 43.21
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Immunodeficiency Diseases
• An inborn or primary immunodeficiency
– Results from hereditary or congenital defects
that prevent proper functioning of innate,
humoral, and/or cell-mediated defenses
– Defects of IgA and complement system leads to
such a disorder.
– People with this disease are susceptible to
infectious disease and cancers .
– Some people will have defected humoral and
cellular immune systems leading to severe
combined immunodeficiency disease (SCID).
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• In one type of SCID, a deficency of the enzyme
adenosine deaminase leads to accumulation of
substances that are toxic to both B and T cells.
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• An acquired or secondary immunodeficiency
– Range from temporary states to chronic
diseases
– Results from exposure to various chemical and
biological agents
– Drugs used to suppress immune system after
tissue transplantation
– Certain cancers such as Hodgkin’s disease
damages the lymphatic system thus suppress
the immune system.
– Viruses such as HIV suppresses the immune
system
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Stress and the Immune System
• Growing evidence shows
– That physical and emotional stress can harm
immunity
– Nearly 2000 years ago Greek physician Galen
recorded that people suffering from depression
are more likely to develop cancer…How?
– Hormones secreted during stress affect the
numbers of WBC and may sppress the immune
system in other ways.
– Some neurotransmitters secreted when we are
happy may enhance immunity.
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Acquired Immunodeficiency Syndrome (AIDS)
• People with AIDS
– Are highly susceptible to opportunistic
infections and cancers that take advantage of
their collapsed immune system.
– Example Pneumocystis carinii a ubiquitous
fungus cause severe pneumonia in people with
AIDS but cant cause any disease in healthy.
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• Because AIDS arises from the loss of helper T cells
– Both humoral and cell-mediated immune responses
are impaired.
– HIV inters cells by using three proteins that participate
in normal immune response.
– The main receptor is the CD4 molecules, virus also
infects other cells such as macrophages and brain
cells.
– In addition to CD4, HIV requires a second protein a coreceptor. One of these is called fusin that present on
all cells infected by HIV.
– Other co-receptor is found only on macrophages and
helper T cell.
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• A T cell infected with HIV; newly made virus
particles (gray) are seen budingfrom the surface of
the T cell in this colorized SEM.
Figure 43.22
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1µm
• The spread of HIV
– Has become a worldwide problem
– Transfer of HIV requires the transfer of body
fluids containing infected cells.
• The best approach for slowing the spread of
HIV
– Is educating people about the practices that
transmit the virus.
– Illegal sex and drugs are among the issues
that need to be stressed upon in this context.
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End Of Chapter
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