Download Glycolysis

Fig. 6-17
Intermembrane space
Outer
membrane
Free
ribosomes
in the
mitochondrial
matrix
Inner
membrane
Cristae
Matrix
0.1 µm
1
Mitochondria
• Mitochondria are semi‐autonomous
intracellular organelles, which play essential
roles in
– production of ATP,
– generation of reactive oxygen species (ROS),
– regulation of apoptosis,
– conversion of various metabolic intermediates.
2
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Structure of a mitochondrion
3
Mitochondria as dynamic organelles
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Mitochondria as dynamic organelles
Nat. Rev. Mol. Cell Biol
8: 870-879, 2007
5
Mitochondria are dynamic organelles
• Dynamic shape
– The length, shape, size and number of mitochondria
are highly variable.
– They are controlled by fusion and fission.
• Dynamic subcellular distribution
– Mitochondria are actively transported in cells.
– They can have defined subcellular distributions.
• Dynamic internal structure
– The internal structure of mitochondria can change in
response to their physiological state.
6
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Annu. Rev. Biochem. 2007. 76:4.1–4.22
Annu. Rev. Biochem. 2007. 76:4.1–4.22
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8
4
Mitochondrial biogenesis is regulated
by the nuclear genome
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Glucose metabolism in mammalian cells
Nat Rev Cancer 4:891-899, 2004
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5
The Stages of Cellular Respiration: A Preview
• Cellular respiration has three stages:
– Glycolysis (breaks down glucose into two molecules
of pyruvate)
– The citric acid cycle (completes the breakdown of
glucose)
– Oxidative phosphorylation (accounts for most of
the ATP synthesis)
11
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 9-6-1
Electrons
carried
via NADH
Glycolysis
Pyruvate
Glucose
Cytosol
ATP
Substrate-level
phosphorylation
12
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Fig. 9-6-2
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Citric
acid
cycle
Glycolysis
Pyruvate
Glucose
Mitochondrion
Cytosol
ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
13
Fig. 9-6-3
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Citric
acid
cycle
Glycolysis
Pyruvate
Glucose
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
Mitochondrion
Cytosol
ATP
ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
Oxidative
phosphorylation
14
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• The process that generates most of the ATP is
called oxidative phosphorylation because it is
powered by redox reactions
15
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Glycolysis
TCA cycle
16
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Glycolysis
TCA cycle
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Oxidative phosphorylation (OXPHOS)
19
The majority of intracellular ROS production is
derived from the mitochondria
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ATP production by glycolysis and aerobic
respiration
21
The Warburg effect
In 1928 Otto Warburg observed that the ratio of glycolytic rate to oxygen
consumption was higher in cancer cells and embryonic tissues than in normal
differentiated cells. He observed this using manometry, a technique that
monitors pressure changes in enclosed biomass, under conditions where CO2
is absorbed by alkali.
Warburg came to those observations while studying the nature and mode of
action of the respiratory enzyme (cytochrome C oxidase). His work on
cytochrome C oxidase (“respiratory ferment”) was awarded a Nobel prize in
1931.
Otto Warburg
Nobel Prize for Physiology & Medicine 1931
1883 – 1970
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Warburg postulated that mitochondrial damage was
responsible for the increased dependence of cancer
cells on glycolysis
Glycolysis
ATP
Reducing power
Cellular Energy
Cellular Energy
國立交通大學生物科技學系 陳文亮老師
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The Krebs Cycle
Sir Hans Adolf Krebs
Nobel Prize 1953
Medicin and Physiology
1900 – 1981
THE CHEMIOSMOTIC HYPOTHESIS
M
CII
CIV
CIII
CV
CI
Peter Mitchell
Nobel Prize for Chemistry 1978
1920 – 1992
G = RT ln ([H+]cytosol/[H+]matrix) + F  = 2.3 RT (pHmatrix  pHcytosol) + F 
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So all together…….
Stages of tumor development
28
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Tumor formation and progression
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Alterations of energy‐supplying pathways in tumors
• All tumor cell types show an enhanced glycolytic flux; however, not
all have a diminished mitochondrial metabolic capacity.
• Therefore, not all tumor cell types depend exclusively on glycolysis for
ATP supply; some may equally or predominantly rely on oxidative
phosphorylation.
• In consequence, the driving force for the enhanced glycolysis in tumor
cells cannot be an energy deficiency induced only by a damaged
oxidative phosphorylation.
• The accelerated cellular proliferation may also impose an energy
deficiency (as well as a higher demand for glycolytic and Krebs cycle
biosynthetic intermediaries), which can only be covered by an
increased glycolysis together with an unperturbed oxidative
phosphorylation.
FEBS J 274 (2007) 1393–1418
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16
Pasteur effect and Warburg effect
• Pasteur effect
– The absence of oxygen resulted in the inhibition of
oxidative phosphorylation (OXPHOS) and a switch to
glycolysis for ATP generation.
• Warburg effect
– Tumor cells, unlike their normal counterparts, utilize
glycolysis instead of mitochondrial OXPHOS for glucose
metabolism even when in oxygen‐rich conditions.
Curr Opin Cell Biol 18: 598-608, 2006
33
Pasteur effect and Warburg effect in non-invasive
and metastatic breast cancer cell lines
• In both cell lines, glucose
consumption is reduced in the
presence of oxygen — the
Pasteur effect (P).
• MDA-MB-231, the more
aggressive cell line, has much
higher glucose consumption in
the presence of oxygen than the
MCF-7 cells with a non-invasive
phenotype — the Warburg
effect (W).
Nat Rev Cancer 4: 891-899, 2004
34
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Possible mechanisms contributing to decreased mitochondrial respiration and increased glycolysis in cancer cells
Oncogene 25: 4630-4632, 2006
J Bioenerg Biomembr 39:267–274, 2007
•
Tumor microenvironment
– Hypoxia in tumor tissue microenvironment decreases the availability of oxygen for
oxidative phosphorylation, whereas ROS generated in inflammatory tissue environment
may inhibit the redox‐sensitive mitochondrial respiratory chain components. (HIF‐1)
•
Oncogenic signals
– Expression of certain oncogenic molecules such as Ras, Src, c‐myc, Bcr‐Abl, and Akt, as well as defects of tumor suppressor such as p53, can attenuate respiration and/or
enhance glycolysis.
•
nDNA abnormalities
– Mutations in nuclear DNA (nDNA) or aberrant expression of certain nuclear genes may suppress mitochondrial respiratory function and/or the tricarboxylic acid (TCA) cycle, and promote glycolysis. (the loss‐of‐function of fumarate and succinate dehydrogenase;
down‐regulation of ‐F1‐ATPase)
•
mtDNA abnormalities
– Mutations and reduced copy number of mitochondrial DNA (mtDNA) affect the mtDNA‐
encoded respiratory chain components, leading to mitochondrial dysfunction, decreased
ATP generation, and increased ROS generation due to electron leakage from the
respiratory chain.
35
1. Tumor microenvironment- Hypoxia
Nat Rev Cancer 4:891-899, 2004 36
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Nat Rev Cancer 4:891-899, 2004
TiBS 24: 68-72, 1999
(m)
37
Hypoxia induces gene expression
involved in cancer development
Dr. Semenza, 1991– first identified hypoxia-inducible factor 1 (HIF-1), HIF-1
regulates a multiplicity of genes, including all of the glycolytic enzymes.
38
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The upregulation of rate-limiting steps of
glycolysis
TiBS 24: 68-72, 1999
39
Mechanisms and consequences of HIF‐1 activity in cancer cells
Nat Rev Cancer 3, 721-732, 2003
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20
Nat Rev Cancer 3, 721-732, 2003
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Genes that are transcriptionally activated by HIF-1
Hypoxia-inducible factors: central
regulators of the tumor phenotype
Curr Opin Genet Dev 17:71-77, 2007
Nat Rev Cancer 3, 721-732, 2003
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21
Nat Rev Cancer 3, 721-732, 2003
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While HIF-1 stimulates glycolysis, it also actively represses
mitochondrial function and oxygen consumption by inducing
pyruvate dehydrogenase kinase 1 (PDK1).
PDK1 phosphorylates and inhibits pyruvate dehydrogenase
from using pyruvate to fuel the mitochondrial TCA cycle.
44
國立交通大學生物科技學系 陳文亮老師
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The HIF-1 can switch from
mitochondrial respiration to glycolysis
Cell Metabolism 3: 150-151, 2006
Cell Metabolism 3: 177-185, 2006
Cell Metabolism 3: 187-197, 2006
pyruvate dehydrogenase kinase 1 (PDK1)
45
Metabolism in the hypoxic tumour cell
the H+/lactate
monocarboxylate
transporter (MCT4)
An overload in lactic acid contributes to acidosis, a common feature of tumors
Curr Opin Cell Biol 19: 223-229, 2007
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HIF‐1 inhibits mitochondrial biogenesis and cellular respiration in VHL‐deficient renal cell carcinoma by repression of c‐MYC activity
Cancer Cell 11: 407-420, 2007
47
HIF‐1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells
Cell 129: 29-30, 2007
Cell 129: 111-122, 2007
48
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Fig. 6‐25
Microtubule
doublets
ATP
Dynein
protein
(a) Effect of unrestrained dynein movement
ATP
Cross-linking proteins
inside outer doublets
Anchorage
in cell
(b) Effect of cross-linking proteins
1
3
2
(c) Wavelike motion
Fig. 6‐25a
Microtubule
doublets
ATP
Dynein
protein
(a) Effect of unrestrained dynein movement
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Fig. 6‐25b
ATP
Cross-linking proteins
inside outer doublets
Anchorage
in cell
(b) Effect of cross-linking proteins
1
3
2
(c) Wavelike motion
卵丘細胞
獲能
卵周間隙
透明帶
54
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serine/threonine-linked oligosaccharide chains
N-acetylglucosamine
Release of hydrolytic enzymes from the
acrosome is believed to enable the
sperm to penetrate through the zona
pellucida
-1,4-galactosyltransferase
60
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O-linkage to GalNAc
N-linkage to GlcNAc
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Fertilization
• Fertilization brings the haploid nuclei of sperm and
egg together, forming a diploid zygote
• The sperm’s contact with the egg’s surface initiates
metabolic reactions in the egg that trigger the
onset of embryonic development
63
The Acrosomal Reaction
• The acrosomal reaction is triggered when the
sperm meets the egg
• The acrosome at the tip of the sperm releases
hydrolytic enzymes that digest material
surrounding the egg
64
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Fig. 47-3-1
Basal body
(centriole)
Sperm
head
Acrosome
Jelly coat
Sperm-binding
receptors
Vitelline layer
Egg plasma
membrane
65
Fig. 47-3-2
Basal body
(centriole)
Sperm
head
Acrosome
Jelly coat
Sperm-binding
receptors
Hydrolytic enzymes
Vitelline layer
Egg plasma
membrane
66
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Fig. 47-3-3
Sperm
nucleus
Acrosomal
process
Basal body
(centriole)
Sperm
head
Actin
filament
Hydrolytic enzymes
Acrosome
Jelly coat
Vitelline layer
Sperm-binding
receptors
Egg plasma
membrane
67
Fig. 47-3-4
Sperm plasma
membrane
Sperm
nucleus
Acrosomal
process
Basal body
(centriole)
Sperm
head
Actin
filament
Fused
plasma
membranes
Acrosome
Jelly coat
Sperm-binding
receptors
Hydrolytic enzymes
Vitelline layer
Egg plasma
membrane
68
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Fig. 47-3-5
Sperm plasma
membrane
Sperm
nucleus
Fertilization
envelope
Acrosomal
process
Basal body
(centriole)
Sperm
head
Actin
filament
Acrosome
Jelly coat
Sperm-binding
receptors
Cortical
Fused
granule
plasma
membranes
Perivitelline
Hydrolytic enzymes
space
Vitelline layer
Egg plasma
membrane
EGG CYTOPLASM
69
• Gamete contact and/or fusion depolarizes
the egg cell membrane and sets up a fast
block to polyspermy
70
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The Cortical Reaction
• Fusion of egg and sperm also initiates the
cortical reaction
• This reaction induces a rise in Ca2+ that
stimulates cortical granules to release their
contents outside the egg
• These changes cause formation of a
fertilization envelope that functions as a
slow block to polyspermy
71
Fig. 47-4
EXPERIMENT
10 sec after
fertilization
25 sec
35 sec
1 min
10 sec after
fertilization
20 sec
30 sec
500 µm
RESULTS
1 sec before
fertilization
500 µm
CONCLUSION
Point of
sperm
nucleus
entry
Spreading
wave of Ca2+
Fertilization
envelope
72
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Fig. 47-4a
EXPERIMENT
10 sec after
fertilization
25 sec
35 sec
1 min
500 µm
73
Fig. 47-4b
RESULTS
1 sec before
fertilization
10 sec after
fertilization
20 sec
30 sec
500 µm
74
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Fig. 47-4c
CONCLUSION
Point of
sperm
nucleus
entry
Spreading
wave of Ca2+
Fertilization
envelope
75
Upon egg activation by the fertilizing sperm, the egg cortical granules
release N-acetylglucosaminidase into the perivetilline space, which
destroys the GalTase recognition motif on ZP3 and produces the block to
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polyspermic binding
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Activation of the Egg
• The sharp rise in Ca2+ in the egg’s cytosol
increases the rates of cellular respiration and
protein synthesis by the egg cell
• With these rapid changes in metabolism, the
egg is said to be activated
• The sperm nucleus merges with the egg nucleus
and cell division begins
77
phospholipase C
phosphatidylinositol
4,5-bisphosphate
(PIP2)
inositol 1,4,5-trisphosphate
diacylglycerol
78
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Fertilization in Mammals
• Fertilization in mammals and other terrestrial
animals is internal
• In mammalian fertilization, the cortical reaction
modifies the zona pellucida, the extracellular
matrix of the egg, as a slow block to polyspermy
80
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Fig. 47-5
Zona pellucida
Follicle cell
Sperm Cortical
Sperm
nucleus granules
basal body
82
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• In mammals the first cell division occurs 12–
36 hours after sperm binding
• The diploid nucleus forms after this first
division of the zygote
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Human Development Before Implantation
84
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Human Development Before Implantation
85
Human Development Before Implantation
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Human Development Before Implantation
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Human Development Before Implantation
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Human Development Before Implantation
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Human Development Before Implantation
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Human Development Before Implantation
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Human Development Before Implantation
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Human Development Before Implantation
93
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Lymph Transport and Immunity
Outline
• The Lymphatic System
– Lymph Vessels
– Lymphoid Organs
• Nonspecific Defenses
– Barriers
– Inflammatory Response
• Specific Defenses
– Antibodies
– T Cells
• Induced Immunity
– Active versus Passive Immunity
• Immunity Side Effects
– Allergies
– Blood Typing
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The Lymphatic System
• Consists of lymphatic vessels and the
lymphoid organs
– Three main homeostatic functions:
• Lymphatic capillaries take up and return excess fluid to
the bloodstream
• Lacteals receive lipoproteins and transport them to the
bloodstream
• Helps defend body against disease
97
Lymphatic System
98
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The Lymphatic Organs
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Lymphatic System
• One‐way system that begins with lymphatic
capillaries
– Take up fluid that has been diffused from, and not
reabsorbed by, blood capillaries
• Edema ‐ Localized swelling due to accumulation of tissue
fluid
– Lymph flows one way
• From a capillary to ever‐larger lymphatic vessels
• Finally to a lymphatic duct, which enters a subclavian vein
100
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Lymphoid Organs
• Lymph Nodes ‐ Capsule surrounding two
distinct regions, cortex and medulla
– Lymphocytes congregate in cortex when fighting
off a pathogen
– Macrophages concentrated in medulla ‐ cleanse
lymph
– Lymph nodes named for their location
101
Lymphoid Organs
• Tonsils
– Patches of lymphatic tissue located around the
pharynx
– First to encounter pathogens that enter via the
nose and mouth
• Spleen
– Located in upper left region of abdominal cavity
just beneath diaphragm
– Cleanses blood
102
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Lymphoid Organs
• Thymus Gland
– Located along trachea behind the sternum in
upper thoracic cavity
– Produces thymic hormones
• Red Bone Marrow
– Origin for all types of blood cells
– Area of maturation for most white blood cells
103
Immune System
• Nonspecific Defenses
– Barriers to entry serve as mechanical barriers
• Skin
• Mucous membranes lining respiratory, digestive, and
urinary tracts
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Nonspecific Defenses
• Inflammatory Reaction
– Damaged cells and mast cells release histamine and
kinins
– Capillaries dilate and become more permeable
– Enlarged capillaries cause skin to redden
– Swollen area and kinins stimulate free nerve
endings causing pain
105
Inflammatory Reaction
• Neutrophils and monocytes migrate to the site
of injury
– Neutrophils and mast cells phagocytize pathogens
– Monocytes differentiate into macrophages
106
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Inflammatory Response
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Complement System
• A collection of plasma proteins
– Activated when pathogens enter the body
– Complements certain immune responses
• Interferon binds to receptors of non‐infected
cells
– Causes them to prepare for possible attack
– Produce substances that interfere with viral
replication
108
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ct o o t e Co p e e t
System
Against a bacterium
109
Specific Defenses
• An antigen is any foreign substance that
stimulates the immune system to react
– Lymphocytes capable of recognizing antigens
– Have antigen receptors on plasma membrane
– Protein’s shape allow it to combine with a specific
antigen
110
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Specific Defenses
• Immunity primarily the result of
– B lymphocytes
• B cells give rise to plasma cells
• Produce antibodies
– T lymphocytes
• T cells directly attack cells that bear non‐self proteins
111
T Cells
• Requirements for T cell antigen recognition:
– Antigen must be presented by an antigen‐
presenting cell
– Antigen is first linked to a major histocompatibility
complex (MHC) protein in the plasma membrane
– Cytokines ‐ signaling chemicals that stimulate
various immune cells
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Types of T Cells
• Cytotoxic T Cells
– Destroy antigen‐bearing cells
– Contain Perforins
• Helper T Cells
– Regulate immunity by secreting cytokines
113
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
+
Engulfed by
Gives rise to
Antigenpresenting cell
+
Stimulates
+
+
B cell
Helper T cell
+
Cytotoxic T cell
+
Memory
Helper T cells
+
+
+
Antigen (2nd exposure)
Plasma cells
Memory B cells
+
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.
114
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Humoral (antibody-mediated) immune response
Key
+
Antigen (1st exposure)
Stimulates
Gives rise to
Engulfed by
Antigenpresenting cell
+
+
B cell
Helper T cell
+
Memory
Helper T cells
+
+
Antigen (2nd exposure)
Memory
B cells
Plasma cells
+
Secreted
antibodies
Defend against extracellular pathogens
115
Cell-mediated immune response
Key
+
Antigen (1st exposure)
Engulfed by
Antigenpresenting cell
Stimulates
Gives rise to
+
+
Helper T cell
Cytotoxic T cell
+
Memory
Helper T cells
+
+
Antigen (2nd exposure)
+
Active
Cytotoxic T cells
Memory
Cytotoxic T cells
Defend against intracellular pathogens
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Helper T Cells: A Response to Nearly All Antigens
• A surface protein called CD4 binds the class II MHC
molecule
• This binding keeps the helper T cell joined to the
antigen‐presenting cell while activation occurs
• Activated helper T cells secrete cytokines that
stimulate other lymphocytes
117
Antigenpresenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytokines
+
B cell
+
+
+
Cytotoxic T cell
Cell-mediated
immunity
(attack on
infected cells)
118
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Cytotoxic T Cells: A Response to Infected Cells
• Cytotoxic T cells are the effector cells in cell‐mediated
immune response
• Cytotoxic T cells make CD8, a surface protein that
greatly enhances interaction between a target cell and
a cytotoxic T cell
• Binding to a class I MHC complex on an infected cell
activates a cytotoxic T cell and makes it an active killer
• The activated cytotoxic T cell secretes proteins that
destroy the infected target cell
119
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Peptide
antigen
120
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Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Pore
Peptide
antigen
121
Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Dying target cell
Pore
Peptide
antigen
122
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Cell‐mediated Immunity
123
B Cells: A Response to Extracellular Pathogens
• The humoral response is characterized by
secretion of antibodies by B cells
• Activation of B cells is aided by cytokines and
antigen binding to helper T cells
• Clonal selection of B cells generates antibody‐
secreting plasma cells, the effector cells of
humoral immunity
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Bacterium
Antigen-presenting cell
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
+
CD4
Cytokines
Secreted
antibody
molecules
Endoplasmic
reticulum of
plasma cell
Helper T cell
Activated
helper T cell
Clone of memory
B cells
2 µm
125
Antigen-presenting cell
Bacterium
Peptide
antigen
Class II MHC
molecule
TCR
CD4
Helper T cell
126
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Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
+
CD4
Cytokines
Activated
helper T cell
Helper T cell
127
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
+
CD4
Helper T cell
Cytokines
Activated
helper T cell
Secreted
antibody
molecules
Clone of memory
B cells
128
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Fig. 43-14
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells
129
Endoplasmic
reticulum of
plasma cell
2 µm
130
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How many antibody classes do have we?
Antibody Classes
• The five major classes of antibodies,
immunoglobulins, differ in distribution and function
or
• Polyclonal antibodies are the products of many different
clones of B cells following exposure to a microbial
antigen
• Monoclonal antibodies are prepared from a single clone
of B cells grown in culture
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Immunoglobins
• IgG ‐ Main antibody type in circulation
• IgM ‐ Found in circulation Largest antibody
• IgA ‐ Found in secretions
• IgD ‐ Found on surface of immature B cells
• IgE ‐ Found as antigen receptors on basophils in
blood and on mast cells in tissue
133
Fig. 43-20
Class of Immunoglobulin (Antibody)
IgM
(pentamer)
Distribution
Function
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Promotes neutralization and crosslinking of antigens;
very effective in
complement system
activation
Most abundant Ig
class in blood;
also present in
tissue fluids
Promotes opsonization, neutralization,
and cross-linking of
antigens; less effective in activation of
complement system
than IgM
J chain
IgG
(monomer)
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
IgA
(dimer)
J chain
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
Presence in breast
milk confers
passive immunity
on nursing infant
Secretory
component
IgE
(monomer)
Present in blood
at low concentrations
Triggers release from
mast cells and
basophils of histamine and other
chemicals that cause
allergic reactions
IgD
(monomer)
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
Transmembrane
region
134
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135
Fig. 43-20a
Class of Immunoglobulin (Antibody)
IgM
(pentamer)
Distribution
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Function
Promotes neutralization and crosslinking of antigens;
very effective in
complement system
activation
J chain
136
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137
Fig. 43-20b
Class of Immunoglobulin (Antibody)
IgG
(monomer)
Distribution
Most abundant Ig
class in blood;
also present in
tissue fluids
Function
Promotes opsonization, neutralization,
and cross-linking of
antigens; less effective in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
138
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139
The Role of Antibodies in Immunity
• Neutralization occurs when a pathogen can no longer
infect a host because it is bound to an antibody
• Opsonization occurs when antibodies bound to
antigens increase phagocytosis
• Antibodies together with proteins of the complement
system generate a membrane attack complex and cell
lysis
140
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Viral neutralization
Opsonization
Activation of complement system and pore formation
Bacterium
Complement proteins
Virus
Formation of
membrane
attack complex
Flow of water
and ions
Macrophage
Pore
Foreign
cell
141
Fig. 43-20c
Class of Immunoglobulin (Antibody)
IgA
(dimer)
J chain
Secretory
component
Distribution
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Function
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
Presence in breast
milk confers
passive immunity
on nursing infant
142
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143
144
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145
Fig. 43-20d
Class of Immunoglobulin (Antibody)
IgE
(monomer)
Distribution
Present in blood
at low concentrations
Function
Triggers release from
mast cells and
basophils of histamine and other
chemicals that cause
allergic reactions
146
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147
148
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Fig. 43-20e
Class of Immunoglobulin (Antibody)
IgD
(monomer)
Transmembrane
region
Distribution
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Function
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
149
150
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151
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Antibody‐Mediated Immunity
• Clonal selection theory:
– The antigen selects which lymphocyte will
• Undergo clonal expansion, and
• Produce more lymphocytes
– If the same antigen enters the system again
• Memory B cells quickly divide
• Give rise to more lymphocytes capable of quickly
producing antibodies
153
Structure of an Antibody
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Structure of an Antibody
155
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157
158
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Overview of
Nonspecific and Specific Defenses
159
Induced Immunity
• Active Immunity
– Immunization
• Pathogens or pathogen products treated to remove
virulence
• Dependent upon memory B cells & memory T cells
capable of responding to lower doses of antigen
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Active Immunity Due to Immunizations
161
Passive Immunity
• Passive immunity
– Occurs when an individual is given prepared
antibodies (immunoglobins) to combat a disease
• Short‐lived
• Newborns are often passively immune due to mother’s
blood
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Passive Immunity
163
Cytokines and Immunity
• Cytokines
– Signaling molecules produced by lymphocytes,
monocytes, or other cells
– Both interferon and interleukins have been used
as immunotherapeutic drugs
– Enhance the ability of the individual’s T cells (and
B cells) to fight cancer
164
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Production of Monoclonal Antibodies
165
Immunity Side Effects
• Allergies
– Hypersensitivities to substances that ordinarily
would not harm the body
• Immediate Response
– IgE antibodies
• Delayed Response
– Memory T cells
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Immunity Side Effects
• Blood Type Reactions
– ABO blood typing
• Two self antigens ‐ A and B
• If same antigen and its antibody are present in the
blood, agglutination occurs
– Rh blood typing
• People that are Rh+ have Rh factor
• People that are Rh‐ do not have Rh factor
• Rh‐ individuals may produce antibodies to Rh factor if
exposed
167
Blood Transfusions
168
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Hemolytic Disease of the Newborn
169
Immunity Side Effects
• Tissue Rejection
– Antibodies and cytotoxic T cells bring about
destruction of foreign tissues in the body
– Immune system is correctly distinguishing
between self and nonself
• Autoimmune Diseases
– Cytotoxic T cells or antibodies mistakenly attack
the body’s own cells
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Review
• The Lymphatic System
– Lymph Vessels
– Lymphoid Organs
• Nonspecific Defenses
– Barriers
– Inflammatory Response
• Specific Defenses
– Antibodies
– T Cells
• Induced Immunity
– Active versus Passive Immunity
• Immunity Side Effects
– Allergies
– Blood Typing
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