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Chapter 43
The Immune System
Reconnaissance, Recognition, and Response
PowerPoint TextEdit Art Slides for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Copyright © 2005 PearsonEducation, Inc. publishing as Benjamin Cummings
Two major kinds of defense that counter the threats.
zInnate immunity:
•present before any e xposure to pathogens and is
effecti ve from the time of birth
-quickly recognizing
-nonspecific
zAcquired immunity (adaptive immunity):
•develops only after e xposure to inducing agents
-specific
-slow (~ 10-14 D)
-achieved by lymphocyte s
1
Overview of vertebrate defenses against bacteria,
viruses, and other pathogens
second line
first line
third line
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
- nonspecif ic
External def enses
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal def enses
Skin
Mucous membranes
Antimicrobial proteins
Phagocytic cells
Secretions
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
External defenses (first line)
1. The skin:
-Largest organ of the body
-Makes up about 16% of body weight, Avg.
surface area ~1.8 m2
-Epidermis, dermis and subcutis (fat)
epider mis
(waterpoof barrier)
dermis
sweat glands
sebaceous (oil) glands
2
External defenses (first line)
2. Mucous membranes
-mucus, a viscous fluid that traps microbes and other particles.
-microvilli (cilia), sweep mucus and any entrapped microbes
(Goblet10μm
cells the trachea)
External defenses (first line)
3. Secretions
eg. mucus, saliva, and tears
z Functions:
•constantly bathe the surfaces to avoid microbial
colonization
• create acidic environments
eg. skin, stomach
So me pathogens would survive (hepatitis A virus)
• contains antimicrobial proteins.
eg. lysozy me: digests the cell walls of many bacteria
3
Internal defenses (second-line)
1 Pseudopodia surround
microbes (recognized by
receptors)
1. Phagocytosis
Microbes
2 Microbes are engul fed
into cell.
MACROPHAGE
Vacuole containing
3
microbes
forms.
Vacuole
Lysosome
containing
enzymes
Vacuole and lysosome
4
fus e.
5 Toxic compounds and
lysosomal enzymes destroy
microbes.
6 Microbial debris is
releas ed by exocytosis.
Internal defenses (second-line)
Lysosome
H+ Na+
-Found in both plant and animal cells,
-Produced from the Golgi apparatus by budding.
-Stabilizes the low pH4.8 by pumping in protons (H+) from the cytosol (pH7).
Destroyed mechanisms in the lysosomes
1. nitric oxide and other toxic forms of oxygen
-poison the engulfed microbes.
2. enzymes (only wok in low pH)
-lysozyme, w hich digests the cell w alls of many bacteria
-Lipase, w hich digests lipids,
-Carbohydrases, w hich digest carbohydrates (e.g., sugars),
-Proteases, w hich digest proteins,
-Nucleases, w hich digest nucleic acids.
4
Internal defenses (second-line)
z Introduction of Phagocytic Cells : (leukocytes)
-neutrophils
most abundant, about 60–70% of all WBC
life span: ~ few days.
self–destruct in the process of phagocytosis
-macrophages
develop from monocyte s, ~5% of circulating WB C.
migrat ed
reside permanently,
eg. in the spleen, lymph nodes
3μ m
Internal defenses (second-line)
lymphatic system
1 Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
Interstitial
fluid
Lymphatic
capillary
2 Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
Adenoid
Tonsil
Lymph
nodes
Blood
capillary
Spleen
Peyer’s patches
(small intestine)
Tissue
cells
Lymphatic
vessel
Appendix
Lymphatic
vessels
Lymph
node
Masses of
lymphocytes and
macrophages
5
Internal defenses (second-line)
Eosinophils 嗜“伊紅”血球 (readily stained w ith eosin)
-low phagocytic activity
-defense against multicellular parasitic invaders eg. blood fluke血蛭)
-discharge destructive enzymes rather than engulfing
Dendritic cells
-ingest microbes like macrophages do
-primary role is to stimulate the development of
acquired immunity. (learn later)
Internal defenses (second-line)
Antimicrobial Proteins
•com plement system
contains~30 serum proteins
-triggered by some surface markers of microbes and lyse them
-trigger inflammation or play a role in acquired defense
•Interferon: defense against viral infections
interferon (α and β)
secreted by virus –infected body cells and induce neighboring uninfected cells to produce substances that inhibit viral reproduction.
interferon (γ)
secreted by some ly mphocytes
-activate macrophages, enhancing their phagocytic ability.
•defensins
secreted by activated macrophages (and neutrophils)
Mechanis m: Cationic. Chemotactic. Stabilize clotting ……
6
Internal defenses (second-line)
Inflammatory Response ( Figure 43.6)
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1 Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
2 Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
3 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
4 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the sit e, and the
tissue heals.
Step1: dilation and sw elling triggered by chemical signals
Histam ine: secreted by mast cells found in connective tissues.
Æ triggering dilation and increased per meability of nearby capillar ies
prostaglandins: secreted by activated macrophages and other cells
Æ promote blood flow to the injured site.
Internal defenses (second-line)
Inflammatory Response ( Figure 43.6)
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1 Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
2 Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
3 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
4 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the sit e, and the
tissue heals.
Step 2: deliver clotting elements and antimicrobial proteins
Blood clotting: block the enter ing and the spread of microbes
Antim icrobial proteins (complements, defensins…)
Ælyse microbes, promote the release of histamine, stabilize the clotting…
7
Internal defenses (second-line)
Inflammatory Response ( Figure 43.6)
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1 Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
2 Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
3 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
4 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the sit e, and the
tissue heals.
Step 3: chemotaxis
chem okines : secreted from blood vessel endothelial and other cells
near a site of injury or infection.
Æ direct the migration of the phagocytes (neutrophils and macrophages)
Internal defenses (second-line)
Inflammatory Response ( Figure 43.6)
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1 Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
2 Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
3 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
4 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the sit e, and the
tissue heals.
Step 4: phagocytosis
•Neutrophils and macrophages phagocytose pathogens and cell debris
•Bring signals for acquired immunity
8
Inflammatory Response
zInjured cells put out a call fo r reinforcements and signal amplification
Î Swelling and fever
• Local inflammation
Fasten the cleaning process of infection
• Systemic inflammation: caused by a severe infection
eg. meningitis (腦膜炎) or appendicitis
Æ the number of WBC increase severalfold within hours
Æ high fever
eg. Septic shock:
Æ very high fever and low blood pressure
Æ a co mmon cause of death after surgery or bacteria infect ion
Internal defenses (second-line)
z Natural killer (NK) cells
Target to virus–infected body cells and cancer cells by
their surface receptors.
NK cells release chemicals that lead to the death of the
stricken cell by apoptosis
z Cell surface markers recognized by NK cells
•Oligosaccaride
•MHC (major histocompatibility complex)
9
major histocompatibility complex (MHC)
• Discovery: fro m the phenomena of skin graft rejection
• Function: carry s mall peptide to provide a biochemical fingerprint
Class I MHC molecules
Class II MHC molecules
- on almost all nucleated cells
phagocytes, eg: dendritic cells, macrophages
(身份証)
(懸賞公告)
Protein
vesicle
proteosome
lysosome
Peptide
Peptide
ER
ER
Express yourself or die: peptides, MHC molecules, and NK cells.
Science. 1995 Feb 17;267(5200):978-9.
normal cell Ænot kille d
oligosaccaride
conjugate
self MHC
class I
triggering
receptor
NK
+
foreign cell Æ kille d
foreign peptide
NK
+
inhibitory
receptor
self peptide
foreign MHC
class I
mutant (cancer) cell Æ kille d
NK
virus-infecte d cell Æ kille d
+
NK
+
viral peptide
10
Acquired immunity (third-line)
z Lymphocytes provide specific defenses induced by
(1) Direct contact with microbes
(2) Signals from active innate defenses cause lymphocytes
to join the fight.
first line
second line
third line
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
- nonspecif ic
Phagocyte
signals
External def enses
Skin
Mucous membranes
Secretions
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal def enses
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
zAntigens
Antigens:
Molecules that was recognized by lymphocytes and
elicits a response
zEpitope (antigenic determinant):
A small portion where a lymphocyte actually recognizes and
binds
Antigenbinding
sites
Antibody A
Epitopes
(antigenic
determinants)
Antigen
Antibody B
Antibody C
Figure 43.7 Epitopes
11
Lymphocytes (B cells and T cells)
The vertebrate body is populated by two types of lymphocytes:
-- B lymphocytes (B cells) and T lymphocytes (T cells)
receptor
receptor
Antigens
zA single B or T cell bears about 100,000 antigen receptors
zAll the receptors on a single cell are identical
Lymphocytes (B cells and T cells)
Difference 1: receptor conformation
2H2LÆ2 Ag binding sites
V
V
Antigenbinding site
V
C
C
Light
chain
Disulfide
bridge
C C
Heavy chains
B cell
Antigenbinding
site
V
Antigenbinding
site
1α1βÆ1 Ag binding site
Variable
regions
Constant
regions
Transmembrane
region
V V
C C
Plasma
β chain
membrane α chain
Disulfide bridge
membrane immunoglobulins
(a) A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
sev eral disulf ide bridges.
T cell
(b) A T cell receptor consists of one
α chain and one β chain linked by
a disulfide bridge.
Figure 43.8
12
Difference 2: antigen recognition
z B cell receptors recognize an intact antigen in its
native state
zT cell receptors recognize small Ag fragments that are
bound to MHC presented by Ag presenting cells.
MHC
Ag
Ag
ER
Why antigen presentation??
z Easier to kill virus-infected cells before virus
amplification than to kill individual virus particles
Why MHC needed??
zDuel-specificity model
Tcr
MHC
13
Two types of MHC molecules
(antigen–presenting cells)
(all nucleated cells)
mainly dendritic cells, macrophages, and B cells
Infected cell
Antigenpresenting
cell
Microbe
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Antigen
fragment
1
Class I MHC
molecule
Antigen
fragment
1
Class II MHC
molecule
T cell
receptor
2
2
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
T cell
receptor
Helper T cell
(a)
Cytotoxic T cell
(b)
Figure 43.9
Cytotoxic T cell
MHC II
CD4
Tcr
Ag
MHC I
phagocytes
CD8
Tcr
Ag
nucleated cells
Helper T cell
zCluster of differentiation (CD) markers, CD8 and CD4, help
the selection of MHC molecules
Cytotoxic T cell (CD4 -/CD8 +) Æ MHC class I
Hel perT cell (CD4 +/CD8 -) Æ MHC class II
help
for
two
14
Overview of lymphocyte development
z Lymphocytes originate from pluripotent stem
cells in the bone marrow
Bone marrow
Thymus
Ly mphoid
stem cell
B cell
T cell
Blood, lymph, and lymphoid tissues
(ly mph nodes, spleen, and others)
Lymphocyte development
•It is estimated that each person has ~ 1 million different B
cells and 10 million different T cells
Three key events in the life of a lymphocyte
1. Generation of Diversity by Gene Rearrangement
2. Testing and Removal of Self–Reactive Lymphocytes
3. Clonal Selection of Lymphocytes
Induced by encountered antigens
15
1. Generation of Lym phocyte Diversity by Gene Rearrangement
eg. immunoglobulin (Ig) genes
V –V
4
DNA of
undifferentiated
B cell
V1
V2
39
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
V2
V3 J5 Intron
recomb inases
C
2 Transcription of res ulting permanentl y rearranged,
functional gene
pre-mRNA
V3 J5 Intron
C
3 RNA processing (removal of intron; addition of cap
and poly (A) tail)
mRNA Cap
V3 J5
C
Poly (A)
4 Translation
Light-chain polypeptide
V
V
C
Variable Constant
region region
C
B cell receptor
B cell
2. Testing and Removal of Self–
Self–Reactive Lymphocytes
z The rearrangements of antigen receptor genes are random,
which may generate receptors against self antigens.
Î Failure of selection can lead to autoimmune diseases
z B cells and T cells are maturing and are tested for
potential self–reactivity in the bone marrow, thymus,
and even lymphoid organs
Î Lymphocytes with self-targeting receptors will be
destroyed
16
Clonal selection of B cells
(antigen–driven cloning of lymphocytes )
Antigen molecul es
B cells that
differ in
antigen
specificity
Antigen
receptor
Some proliferating cells
develop into long-lived
Antibody
memory cells that can
molecules
respond rapidl y upon
subsequent exposure
to the same antigen. Long-lived memory cells
Short-lived effector cells
Some proliferating
cells develop into
short-lived plas ma
cells that secrete
antibodies specific
for the antigen.
secondary immune response (2-7D)
The specificity of immunological memory
•Antibodies produced in the secondary response tend to have greater
affin ity than those secreted in the primary response.
1 Day 1: First
exposure to
antigen A
3 Day 28:
2 Primar y
Second exposure
response to
to antigen A; first
antigen A
exposure to
produces antiantigen B
bodies to A
4 Secondar y response to antigen A produces antibodies
to A; primar y response to antigen B produces antibodies to B
Antibody concentration
(arbitrary units)
104
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
14
21
28
35
Time (days)
42
49
56
17
An overview of the acquired immune response
Cell-mediated immune response
Humoral immune respo nse
First exposure to antigen
Helper T cell
Intact antige ns
Antigens displayed
Antigens engulfed and
displayed by dendritic cells by infected cells
Activate
Activate
B cell
Gives rise to
Gives rise to
Plas ma
cells
Helper
T cell
Activate
Secreted
cytokines
activate
Memory
B cells
Active and
me mory
helper
T cells
Secrete antibodies that defend a gainst
patho gens a nd toxins in extracellular fluid
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
•re cognize peptide
antigens displayed
on phagocytes
• in turn stimulates
the activation of
nearby B cells and
cytotoxic T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and trans planted t iss ues
The central role of helper T cells
18
The central role of helper T cells immune responses
Dendritic cells
effective in presenting antigens to naive helper T
cells in p rimary immune response
Cytotoxic T cell
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
Helper T cell
Cell-mediated
immunity
(attack on
infected cells)
T CR
2
3
Humoral
immunity
(secretion of
antibodies by
plasma cells)
1 CD4
Dendritic
cell
Cytokines
3 T he cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Macrophages
3μ m
B cell
effective in presenting antigens to memory helper
T cells in secondary immune response
Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells
•Cytokines secreted from nearby helper T cells promote cytotoxic T cells to
release perforins and proteolytic enzy mes (granzymes).
Cytotoxic T cell
Released
cytotoxic
T cell
Perforin
Cancer
cell
Granzymes
1 T CR
Class I MHC
molecule
T arget
cell
3
CD8
2
Apoptotic
target cell
Pore
Peptide
antigen
Cytotoxic
T cell
•Certain cancers and viruses actively reduce the number of
class I MHC molecu les on affected cells, help ing them
escape detection by cytotoxic T cells.
19
Express yourself or die: peptides, MHC molecules, and NK cells.
Science. 1995 Feb 17;267(5200):978-9.
normal cell Ænot kille d
oligosaccaride
conjugate
mutant (cancer) cell Æ kille d
triggering
receptor
NK
self MHC
class I
+
NK
+
inhibitory
receptor
self peptide
virus-infecte d cell Æ kille d
foreign cell Æ kille d
NK
foreign MHC
class I
+
NK
+
viral peptide
foreign peptide
B Cells: A Response to Extracellular Pathogens
Bacterium
Macrophage
Peptide
antigen
Class II
MHC
molecule
B cell
2
1
T CR
3
Clone of plasma cells
Secreted antibody
molecules
Endoplasmic
reticulum of
plasma cell
CD4
Cytokines
Helper T cell
Activated
helper T cell
Clone of memory
B cells
•Each plasma cell secretes an estimated 2,000 antibody
molecules per second over the cell’s 4– to 5–day life span.
20
The five classes of immunoglobulins (antibodies)
IgM
(pentam er)
First Ig class prod uced after i niti al exp osur e to
antig en; then its co ncentr ation i n the bl oo d dec lin es
J chain
IgG
(monom er)
Promotes n eutral izati on a nd a ggl utin ation of
antig ens; very effective i n comp lem ent activati on
(see Figu re 43.1 9)
Most abun da nt Ig class in b loo d; also p rese nt in
tissue flui ds
Only Ig class that crosses plac enta, thus co nferri ng
passiv e immu nity on fetus
Promotes o pson izati on, ne utral izatio n, and a gg luti natio n
of antige ns; less effective in com plem ent activ ation th an
IgM (see Figur e 43.1 9)
IgA
(dimer)
Secretory
compo ne nt
Present i n secreti ons suc h as tears, sal iva, mucus,
and br east milk
J chain
Provid es loc al ized d efens e of muco us membr anes by
agg lutin atio n an d neutr aliz atio n of antig ens (se e
Figure 4 3.19)
Presenc e in br east milk c onfers p assiv e immu nity on
nursi ng i nfant
IgE
(monomer)
IgD
(monom er)
Transmem bran e
regi on
Triggers r ele ase from mast cel ls an d bas oph ils of
histami ne a nd oth er chem ical s that cause a ll ergic
reactio ns (see Fi gure 4 3.20)
Present pr imari ly on surf ace of na ive B cel ls that have
not bee n exp ose d to antig ens
Acts as antige n rece ptor in a ntig en-stim ulate d
prol iferati on an d differe ntiati on of B cel ls (clo nal
selecti on)
Four antibodyantibody- mediated mechanisms of antigen disposal
21
Antibody-- mediated mechanisms of antigen disposal
Antibody
Binding of antibod ies to antigens
inactivates antigens by
Viral neutralization
Agglutination of
(blocks binding to host)
antigen-bearing particles,
and opsonization (increases
such as microbes
phagocytosis)
Precipitation of
soluble antigens
Complement
proteins
Bacteria
Virus
Activation of complement system
and pore formation
MAC
Pore
Soluble
antigens
Bacterium
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
Positive immune feedback
antibodies promote phagocytosis,
enables A PC to present antigens
and stimulate helper T cells, w hich
in turn stimulate the very B cells.
Activate complement proteins
To generate a m em brane attack
com plex (MAC) that forms a pore
in the membrane.
Applications of immunology
z Blood Groups and Transfusions
•Blood types: A, B, AB, O
A-antigen individuals naturally have antibodies against the B antigen,
even if they have never been exposed to type B blood!
Q: w here are the antibodies from ??
•Explanation
The antibodies arise in response to bacterial inhabitants of the
body that have epitopes very similar to blood group antigens.
Polysaccharides
on bacteria
Y
anti-A
Y
A-type person
bone marrow
Y
Y
Y
Y Y
Y YY
Y
anti-B Ab
anti-B
22
Blood Groups That Can and Cannot Be Safely Combine d in Transfusion
Transfusion
Type AB: “universal recipient”
Type O: “universal donor”
z Epitopes: polysaccharides.
Î No memory cells are generated.
Î Antibodies are always IgM. IgM does not cross the placenta
Difference between T–
T– dependent and T–
T– independent antigens
zT–dependent antigens:
Antigens that induce antibody production by B cells with
assistance from helper T cells
zT–independent antigens
Antigens evoke a B cell response without involvement of
helper T cells.
eg. polysaccharides of many bacterial capsules
proteins that make up bacterial flagella
-generates no memory B cells
23
Blood Group that can induce IgG and memory response
z Rh factor
a protein antigen
allows immune responses to induce IgG and memory cells
•Rh(+): contain Rh factor
•Rh( ): lacks the Rh factor, will induce anti-Rh antibody
A potentially dangerous situation
Rh( ) mother carries a Rh(+) child
Î Rh IgG antibodies can cross the placenta and destroy fetus red blood cells
Strategy:
Î mother is injected with anti–Rh antibodies around the seventh
month of pregnancy and again just after delivering
Problems during Tissue and Organ Transplants
z Major histocompatibility complex (MHC)
Î No two people have identical MHC, except identical
twins and “clones”
Strategy:
The recipient takes medicines that suppress immune responses
z Bone marrow transplant
Strategy:
The recipients are treated with irradiation to eliminate their own
bone marro w cells, including any abnormal cells.
Side effect
New donated lymphocytes will react against the recipient
z New hope Î stem cells and clone
24
Autoimmune Diseases
Immune system turns against certain molecules of the body
Systemic lupus erythematosus (lupus)
•Self-antibodies against a wide range of self mo lecules, including
histones and DNA released by the normal breakdown of body cells.
Î skin rashes, fever, arthritis, and kidney dysfunction.
•1 million sufferers in the U.S.
•Strikes women nine times more often than men
Butterfly rash of lupus
Damaged kidney (left) caused by immunoglobulin deposits (right)
Autoimmune Diseases
z rheumatoid arthritis 類風濕性關節炎
Self-antibodies target to the cartilage and bone of joints
rheumatoid arthritis
25
z Inborn (Primary) Immunodeficiencies
•An immunodeficiency disease caused by a genetic or
developmental defect in the immune system
•Treatment: bone marrow transplant
z Acquired (Secondary) Immunodeficiencies
•Immune dysfunction develops later in life following exposure
to various chemical and biological agents
•AIDS (acquired immunodeficiency syndrome ): caused by a virus
•Certain cancers that damage the lymphatic system.
•Drugs used to fight autoimmune diseases or to prevent
the rejection of a transplant
z Human Immunodeficiency Virus (HIV
( HIV))
a retrovirus (reverse–transcribed, integrated, production of new virus)
z HIV infected mechanism
Use three proteins that participate in normal
immune responses.
1. CD4 mo lecule on the helper T cells
2. co–receptor 1: chemokine receptor
fusin (CXCR4)
Æ on all the cell types infected by HIV
3. co–receptor 2: chemokine receptor CCR5
Æ only on macrophages and helper T cells
Partially defective CCR5 confers
increased HIV Resistance
26
Death of the helper T cells:
-damaging effects of virus reproduction,
-both infected and uninfected cells may undergo inappropriately timed
apoptosis triggered by the virus.
1µm
Figure 43.22 A T cell infected with HIV
27