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15/05/12 Overview: Recogni3on and Response Immunity
INTERCONNECTEDNESS
REDUCE – REUSE – RECYCLE
•  Pathogens, agents that cause disease, infect a wide range of animals, including humans •  The immune system recognizes foreign bodies and responds with the produc3on of immune cells and proteins •  All animals have innate immunity, a defense ac3ve immediately upon infec3on •  Vertebrates also have adap1ve immunity © 2011 Pearson Education, Inc.
Figure 43.1
•  Innate immunity is present before any exposure to pathogens and is effec3ve from the 3me of birth •  It involves nonspecific responses to pathogens •  Innate immunity consists of external barriers plus internal cellular and chemical defenses © 2011 Pearson Education, Inc.
Figure 43.2
•  Adap3ve immunity, or acquired immunity, develops aJer exposure to agents such as microbes, toxins, or other foreign substances •  It involves a very specific response to pathogens INNATE IMMUNITY
(all animals)
• Recognition of traits shared
by broad ranges of
pathogens, using a small
set of receptors
• Rapid response
ADAPTIVE IMMUNITY
(vertebrates only)
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
• Slower response
Pathogens
(such as bacteria,
fungi, and viruses)
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Natural killer cells
Antimicrobial proteins
Inflammatory response
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic cells defend
against infection in body cells.
© 2011 Pearson Education, Inc.
1 15/05/12 Concept 43.1: In innate immunity, recogni3on and response rely on traits common to groups of pathogens •  Innate immunity is found in all animals and plants •  In vertebrates, innate immunity is a first response to infec3ons and also serves as the founda3on of adap3ve immunity © 2011 Pearson Education, Inc.
Innate Immunity of Invertebrates •  In insects, an exoskeleton made of chi3n forms the first barrier to pathogens •  The diges3ve system is protected by a chi3n-­‐based barrier and lysozyme, an enzyme that breaks down bacterial cell walls •  Hemocytes circulate within hemolymph and carry out phagocytosis, the inges3on and diges3on of foreign substances including bacteria © 2011 Pearson Education, Inc.
Figure 43.3
Pathogen
•  Hemocytes also secrete an3microbial pep3des that disrupt the plasma membranes of fungi and bacteria PHAGOCYTIC
CELL
Vacuole
Lysosome
containing
enzymes
© 2011 Pearson Education, Inc.
Figure 43.4
•  The immune system recognizes bacteria and fungi by structures on their cell walls •  An immune response varies with the class of pathogen encountered © 2011 Pearson Education, Inc.
2 15/05/12 Figure 43.5a
RESULTS
% survival
100
Wild type
RESULTS (part 1)
75
Mutant + drosomycin
50
0
0
24
100
48
72
96
Hours post-infection
120
Fruit fly survival after infection by N. crassa fungi
% survival
100
Wild type
75
Mutant +
defensin
Mutant +
drosomycin
0
0
24
Mutant
48
72
96
Hours post-infection
75
Mutant + drosomycin
50
Mutant
25
0
50
25
Wild type
Mutant + defensin
Mutant
25
% survival
Figure 43.5
0
24
Mutant + defensin
72
48
96
Hours post-infection
120
Fruit fly survival after infection by N. crassa fungi
120
Fruit fly survival after infection by M. luteus bacteria
Figure 43.5b
Innate Immunity of Vertebrates RESULTS (part 2)
% survival
100
Wild type
75
•  The immune system of mammals is the best understood of the vertebrates •  Innate defenses include barrier defenses, phagocytosis, an3microbial pep3des •  Addi3onal defenses are unique to vertebrates: natural killer cells, interferons, and the inflammatory response Mutant +
defensin
50
Mutant +
drosomycin
25
0
0
24
Mutant
72
48
96
Hours post-infection
120
Fruit fly survival after infection by M. luteus bacteria
© 2011 Pearson Education, Inc.
Barrier Defenses •  Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproduc3ve tracts •  Mucus traps and allows for the removal of microbes •  Many body fluids including saliva, mucus, and tears are hos3le to many microbes •  The low pH of skin and the diges3ve system prevents growth of many bacteria © 2011 Pearson Education, Inc.
Cellular Innate Defenses •  Pathogens entering the mammalian body are subject to phagocytosis •  Phagocy3c cells recognize groups of pathogens by TLRs, Toll-­‐like receptors © 2011 Pearson Education, Inc.
3 15/05/12 Figure 43.6
EXTRACELLULAR
FLUID
Lipopolysaccharide
Helper
protein
TLR4
Flagellin
PHAGOCYTIC
CELL
TLR5
•  A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe •  There are different types of phagocy3c cells –  Neutrophils engulf and destroy pathogens –  Macrophages are found throughout the body –  Dendri1c cells s3mulate development of adap3ve immunity –  Eosinophils discharge destruc3ve enzymes VESICLE
CpG DNA
TLR9
TLR3 Innate immune
responses
ds RNA
© 2011 Pearson Education, Inc.
Figure 43.7
Blood
capillary
•  Cellular innate defenses in vertebrates also involve natural killer cells •  These circulate through the body and detect abnormal cells •  They release chemicals leading to cell death (apoptosis), inhibi3ng the spread of virally infected or cancerous cells •  Many cellular innate defenses involve the lympha3c system Interstitial
fluid
Adenoid
Tonsils
Lymphatic
vessels
Thymus
Tissue
cells
Peyer s
patches
(small
intestine)
Appendix
(cecum)
Spleen
Lymphatic
vessel
Lymphatic
vessel
Lymph
nodes
Lymph
node
Masses of
defensive cells
© 2011 Pearson Education, Inc.
An1microbial Pep1des and Proteins •  Pep3des and proteins func3on in innate defense by aZacking pathogens or impeding their reproduc3on •  Interferon proteins provide innate defense, interfering with viruses and helping ac3vate macrophages •  About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflamma3on © 2011 Pearson Education, Inc.
Inflammatory Responses •  The inflammatory response, such as pain and swelling, is brought about by molecules released upon injury of infec3on •  Mast cells, a type of connec3ve 3ssue, release histamine, which triggers blood vessels to dilate and become more permeable •  Ac3vated macrophages and neutrophils release cytokines, signaling molecules that enhance the immune response © 2011 Pearson Education, Inc.
4 15/05/12 Figure 43.8-1
•  Pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged 3ssues Pathogen
Mast
cell
Splinter
Macrophage
Signaling
molecules
Capillary
Neutrophil
Red
blood cells
© 2011 Pearson Education, Inc.
Figure 43.8-2
Pathogen
Mast
cell
Figure 43.8-3
Pathogen
Splinter
Macrophage
Signaling
molecules
Movement
of fluid
Mast
cell
Macrophage
Signaling
molecules
Capillary
Neutrophil
Red
blood cells
Splinter
Capillary
Movement
of fluid
Phagocytosis
Neutrophil
Red
blood cells
Evasion of Innate Immunity by Pathogens •  Inflamma3on can be either local or systemic (throughout the body) •  Fever is a systemic inflammatory response triggered by pyrogens released by macrophages and by toxins from pathogens •  Sep1c shock is a life-­‐threatening condi3on caused by an overwhelming inflammatory response © 2011 Pearson Education, Inc.
•  Some pathogens avoid destruc3on by modifying their surface to prevent recogni3on or by resis3ng breakdown following phagocytosis •  Tuberculosis (TB) is one such disease and kills more than a million people a year © 2011 Pearson Education, Inc.
5 15/05/12 Concept 43.2: In adap3ve immunity, receptors provide pathogen-­‐specific recogni3on •  The adap3ve response relies on two types of lymphocytes, or white blood cells •  Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells © 2011 Pearson Education, Inc.
•  An1gens are substances that can elicit a response from a B or T cell •  Exposure to the pathogen ac3vates B and T cells with an1gen receptors specific for parts of that pathogen •  The small accessible part of an an3gen that binds to an an3gen receptor is called an epitope © 2011 Pearson Education, Inc.
Figure 43.UN01
Antigen
receptors
Mature B cell
•  B cells and T cells have receptor proteins that can bind to foreign molecules •  Each individual lymphocyte is specialized to recognize a specific type of molecule Mature T cell
© 2011 Pearson Education, Inc.
Antigenbinding site
V
C
•  Each B cell an3gen receptor is a Y-­‐shaped molecule with two iden3cal heavy chains and two iden3cal light chains •  The constant regions of the chains vary liZle among B cells, whereas the variable regions differ greatly •  The variable regions provide an3gen specificity B cell
antigen
receptor
C
C
Light
chain
Heavy
chains
B cell
V
Disulfide
bridge
V
Antigenbinding
site
V
An3gen Recogni3on by B Cells and An3bodies Variable
regions
C
Figure 43.9
Constant
regions
Transmembrane
region
Plasma
membrane
Cytoplasm of B cell
© 2011 Pearson Education, Inc.
6 15/05/12 Figure 43.10
•  Binding of a B cell an3gen receptor to an an3gen is an early step in B cell ac3va3on •  This gives rise to cells that secrete a soluble form of the protein called an an1body or immunoglobulin (Ig) •  Secreted an3bodies are similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane Antigen
receptor
Antibody
B cell
Epitope
Antigen
Pathogen
(a) B cell antigen receptors and antibodies
Antibody C
Antibody A
Antibody B
Antigen
(b) Antigen receptor specificity
© 2011 Pearson Education, Inc.
Figure 43.10a
Antigen
receptor
Figure 43.10b
Antibody
Antibody C
Antibody A
Antibody B
B cell
Antigen
Epitope
Antigen
Pathogen
(b) Antigen receptor specificity
(a) B cell antigen receptors and antibodies
Figure 43.11
Antigenbinding
site
An3gen Recogni3on by T Cells •  Each T cell receptor consists of two different polypep3de chains (called α and β) •  The 3ps of the chain form a variable (V) region; the rest is a constant (C) region •  T cell and B cell an3gen receptors are func3onally different T cell
antigen
receptor
V
V
Variable
regions
C
C
Constant
regions
Disulfide
bridge
α chain
Video: T Cell Receptors T cell
Transmembrane
region
β chain
Plasma
membrane
Cytoplasm of T cell
© 2011 Pearson Education, Inc.
7 15/05/12 •  T cells bind to an3gen fragments displayed or presented on a host cell •  These an3gen fragments are bound to cell-­‐surface proteins called MHC molecules •  MHC (major histocompa1bility complex) molecules are host proteins that display the an3gen fragments on the cell surface © 2011 Pearson Education, Inc.
•  In infected cells, MHC molecules bind and transport an3gen fragments to the cell surface, a process called an1gen presenta1on •  A T cell can then bind both the an3gen fragment and the MHC molecule •  This interac3on is necessary for the T cell to par3cipate in the adap3ve immune response © 2011 Pearson Education, Inc.
Figure 43.12
Figure 43.12a
Displayed
antigen
fragment
T cell
Displayed
antigen
fragment
T cell antigen
receptor
MHC
molecule
Antigen
fragment
MHC
molecule
Pathogen
Host cell
T cell
T cell antigen
receptor
Antigen
fragment
(a) Antigen recognition by a T cell
Top view
Antigen
fragment
Pathogen
MHC
molecule
Host cell
(a) Antigen recognition by a T cell
Host cell
(b) A closer look at antigen presentation
Figure 43.12b
B Cell and T Cell Development Top view
Antigen
fragment
MHC
molecule
Host cell
•  The adap3ve immune system has four major characteris3cs –  Diversity of lymphocytes and receptors –  Self-­‐tolerance; lack of reac3vity against an animal s own molecules –  B and T cells proliferate aJer ac3va3on –  Immunological memory (b) A closer look at antigen presentation
© 2011 Pearson Education, Inc.
8 15/05/12 Figure 43.13
Genera1on of B and T Cell Diversity •  By combining variable elements, the immune system assembles a diverse variety of an3gen receptors •  The immunoglobulin (Ig) gene encodes one chain of the B cell receptor •  Many different chains can be produced from the same gene by rearrangement of the DNA •  Rearranged DNA is transcribed and translated and the an3gen receptor formed DNA of
undifferentiated
V37
B cell
V39
V38
J1 J2 J3 J4 J5 Intron
V40
C
1 Recombination deletes DNA between
randomly selected V segment and J segment
DNA of
differentiated
B cell
V37
V39 J5
V38
Intron
C
Functional gene
2 Transcription
pre-mRNA
V39 J5
Intron
C
3 RNA processing
mRNA Cap
V39 J5
C
Poly-A tail
V
V
4 Translation
V
V
C
C
Light-chain polypeptide
V
Variable
region
C
Constant
region
C
C
Antigen receptor
B cell
© 2011 Pearson Education, Inc.
Origin of Self-­‐Tolerance •  An3gen receptors are generated by random rearrangement of DNA •  As lymphocytes mature in bone marrow or the thymus, they are tested for self-­‐reac3vity •  Some B and T cells with receptors specific for the body s own molecules are destroyed by apoptosis, or programmed cell death •  The remainder are rendered nonfunc3onal © 2011 Pearson Education, Inc.
Prolifera1on of B Cells and T Cells •  In the body there are few lymphocytes with an3gen receptors for any par3cular epitope •  In the lymph nodes, an an3gen is exposed to a steady stream of lymphocytes un3l a match is made •  This binding of a mature lymphocyte to an an3gen ini3ates events that ac3vate the lymphocyte © 2011 Pearson Education, Inc.
Figure 43.14
•  Once ac3vated, a B or T cell undergoes mul3ple cell divisions •  This prolifera3on of lymphocytes is called clonal selec1on •  Two types of clones are produced: short-­‐lived ac3vated effector cells that act immediately against the an3gen and long-­‐lived memory cells that can give rise to effector cells if the same an3gen is encountered again B cells that
differ in
antigen
specificity
Antigen
Antigen
receptor
Antibody
Memory cells
Plasma cells
© 2011 Pearson Education, Inc.
9 15/05/12 Figure 43.15
•  Immunological memory is responsible for long-­‐term protec3ons against diseases, due to either a prior infec3on or vaccina3on •  The first exposure to a specific an3gen represents the primary immune response •  During this 3me, selected B and T cells give rise to their effector forms •  In the secondary immune response, memory cells facilitate a faster, more efficient response Antibody concentration
(arbitrary units)
Immunological Memory
Primary immune response Secondary immune response to
to antigen A produces
antigen A produces antibodies to A;
antibodies to A.
primary immune response to antigen
B produces antibodies to B.
104
103
Antibodies
to A
102
101
100
0
7
14
21
28
35
42
49
56
Exposure to
antigens A and B
Exposure
to antigen A
Anima3on: Role of B Cells Antibodies
to B
Time (days)
© 2011 Pearson Education, Inc.
Concept 43.3: Adap3ve immunity defends against infec3on of body fluids and body cells •  Acquired immunity has two branches: the humoral immune response and the cell-­‐mediated immune response •  In the humoral immune response an3bodies help neutralize or eliminate toxins and pathogens in the blood and lymph •  In the cell-­‐mediated immune response specialized T cells destroy affected host cells © 2011 Pearson Education, Inc.
Helper T Cells: A Response to Nearly All An3gens •  A type of T cell called a helper t cell triggers both the humoral and cell-­‐mediated immune responses •  Signals from helper T cells ini3ate produc3on of an3bodies that neutralize pathogens and ac3vate T cells that kill infected cells •  An1gen-­‐presen1ng cells have class I and class II MHC molecules on their surfaces © 2011 Pearson Education, Inc.
Figure 43.16
•  Class II MHC molecules are the basis upon which an3gen-­‐presen3ng cells are recognized •  An3gen receptors on the surface of helper T cells bind to the an3gen and the class II MHC molecule; then signals are exchanged between the two cells •  The helper T cell is ac3vated, proliferates, and forms a clone of helper T cells, which then ac3vate the appropriate B cells Antigenpresenting
cell
Antigen fragment
Pathogen
Class II MHC molecule
Accessory protein
Antigen receptor
1
Helper T cell
Cytokines
+
+
2
Humoral
immunity
B cell
+
3
+
Cellmediated
immunity
Cytotoxic T cell
Anima3on: Helper T Cells © 2011 Pearson Education, Inc.
10 15/05/12 Figure 43.17-1
Cytotoxic T Cells: A Response to Infected Cells •  Cytotoxic T cells are the effector cells in the cell-­‐
mediated immune response •  Cytotoxic T cells recognize fragments of foreign proteins produced by infected cells and possess an accessory protein that binds to class I MHC molecules •  The ac3vated cytotoxic T cell secretes proteins that disrupt the membranes of target cells and trigger apoptosis Cytotoxic T cell
Accessory
protein
Class I MHC
molecule
Antigen
receptor
Infected
cell
Antigen
fragment
1
Anima3on: Cytotoxic T Cells © 2011 Pearson Education, Inc.
Figure 43.17-2
Figure 43.17-3
Cytotoxic T cell
Accessory
protein
Class I MHC
molecule
Infected
cell
1
Cytotoxic T cell
Antigen
receptor
Perforin
Pore
Antigen
fragment
Granzymes
Accessory
protein
Class I MHC
molecule
Antigen
receptor
2
•  The humoral response is characterized by secre3on of an3bodies by B cells Perforin
Pore
Infected
cell
B Cells and An3bodies: A Response to Extracellular Pathogens © 2011 Pearson Education, Inc.
Released
cytotoxic
T cell
Antigen
fragment
1
Dying
infected cell
Granzymes
2
3
Ac1va1on of B Cells •  Ac3va3on of the humoral immune response involves B cells and helper T cells as well as proteins on the surface of pathogens •  In response to cytokines from helper T cells and an an3gen, a B cell proliferates and differen3ates into memory B cells and an3body secre3ng effector cells called plasma cells © 2011 Pearson Education, Inc.
11 15/05/12 Figure 43.18-1
Figure 43.18-2
Antigen-presenting
cell
Class II
MHC
molecule
Antigen
receptor
Antigen-presenting
cell
Pathogen
Antigen
fragment
Class II
MHC
molecule
Accessory
protein
B cell
+
Accessory
protein
Antigen
receptor
Helper T cell
Pathogen
Antigen
fragment
Cytokines
Activated
helper T cell
Helper T cell
1
1
2
Figure 43.18-3
An1body Func1on Antigen-presenting
cell
Class II
MHC
molecule
Antigen
receptor
Pathogen
Antigen
fragment
•  An3bodies do not kill pathogens; instead they mark pathogens for destruc3on •  In neutraliza3on, an3bodies bind to viral surface proteins preven3ng infec3on of a host cell •  An3bodies may also bind to toxins in body fluids and prevent them from entering body cells B cell
Memory B cells
+
Accessory
protein
Cytokines
Activated
helper T cell
Helper T cell
1
2
Plasma cells
3
Secreted
antibodies
© 2011 Pearson Education, Inc.
Figure 43.19
•  In opsoniza3on, an3bodies bind to an3gens on bacteria crea3ng a target for macrophages or neutrophils, triggering phagocytosis •  An3gen-­‐an3body complexes may bind to a complement protein—which triggers a cascade of complement protein ac3va3on •  Ul3mately a membrane aZack complex forms a pore in the membrane of the foreign cell, leading to its lysis Opsonization
Neutralization
Activation of complement system and pore
formation
Complement proteins
Antibody
Virus
Formation of membrane
attack complex
Bacterium
Flow of water
and ions
Pore
Macrophage
Foreign
cell
Antigen
© 2011 Pearson Education, Inc.
12 15/05/12 Figure 43.19a
Figure 43.19b
Neutralization
Opsonization
Antibody
Bacterium
Virus
Macrophage
Figure 43.19c
Activation of complement system and pore
formation
Complement proteins
Formation of membrane
attack complex
Flow of water
and ions
Pore
Foreign
cell
•  B cells can express five different forms (or classes) of immunoglobulin (Ig) with similar an3gen-­‐binding specificity but different heavy chain C regions –  IgD: Membrane bound –  IgM: First soluble class produced –  IgG: Second soluble class; most abundant –  IgA and IgE: Remaining soluble classes Antigen
© 2011 Pearson Education, Inc.
Summary of the Humoral and Cell-­‐
Mediated Immune Responses •  Both the humoral and cell-­‐mediated responses can include primary and secondary immune response •  Memory cells enable the secondary response © 2011 Pearson Education, Inc.
Ac3ve and Passive Immuniza3on •  Ac1ve immunity develops naturally when memory cells form clones in response to an infec3on •  It can also develop following immuniza1on, also called vaccina1on •  In immuniza3on, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory © 2011 Pearson Education, Inc.
13 15/05/12 Figure 43.20
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
+
Engulfed by
•  Passive immunity provides immediate, short-­‐
term protec3on •  It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk •  It can be conferred ar3ficially by injec3ng an3bodies into a nonimmune person Antigenpresenting cell
+
Stimulates
Gives rise to
+
+
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
Defend against intracellular
pathogens and cancer
© 2011 Pearson Education, Inc.
Figure 43.20a
Figure 43.20b
B cell
Humoral (antibody-mediated)
+
immune
response
+
Cytotoxic T cell
Cell-mediated
immune response
Key
Antigen (1st exposure)
+
Engulfed by
Antigenpresenting cell
+
Helper T cell
+
Memory
helper T cells
Stimulates
Gives rise to
+
+
+
+
Antigen (2nd exposure)
Plasma cells
+
B cell
+
Helper T cell
+
Memory B cells
+
Memory
cytotoxic T cells
Active
cytotoxic T cells
Cytotoxic T cell
Secreted
antibodies
Defend against
extracellular
pathogens
Defend against
intracellular
pathogens
and cancer
Figure 43.21
An3bodies as Tools •  An3body specificity and an3gen-­‐an3body binding has been harnessed in research, diagnosis, and therapy •  Polyclonal an3bodies, produced following exposure to a microbial an3gen, are products of many different clones of plasma cells, each specific for a different epitope •  Monoclonal an1bodies are prepared from a single clone of B cells grown in culture Endoplasmic
reticulum of
plasma cell
2 µm
© 2011 Pearson Education, Inc.
14 15/05/12 Immune Rejec3on •  Cells transferred from one person to another can be aZacked by immune defenses •  This complicates blood transfusions or the transplant of 3ssues or organs © 2011 Pearson Education, Inc.
Blood Groups •  An3gens on red blood cells determine whether a person has blood type A (A an3gen), B (B an3gen), AB (both A and B an3gens), or O (neither an3gen) •  An3bodies to nonself blood types exist in the body •  Transfusion with incompa3ble blood leads to destruc3on of the transfused cells •  Recipient-­‐donor combina3ons can be fatal or safe © 2011 Pearson Education, Inc.
Tissue and Organ Transplants •  MHC molecules are different among gene3cally noniden3cal individuals •  Differences in MHC molecules s3mulate rejec3on of 3ssue graJs and organ transplants © 2011 Pearson Education, Inc.
Concept 43.4: Disrup3ons in immune system func3on can elicit or exacerbate disease •  Some pathogens have evolved to diminish the effec3veness of host immune responses © 2011 Pearson Education, Inc.
•  Chances of successful transplanta3on increase if donor and recipient MHC 3ssue types are well matched •  Immunosuppressive drugs facilitate transplanta3on •  Lymphocytes in bone marrow transplants may cause the donor 3ssue to reject the recipient © 2011 Pearson Education, Inc.
Exaggerated, Self-­‐Directed, and Diminished Immune Responses •  If the delicate balance of the immune system is disrupted, effects range from minor to some3mes fatal © 2011 Pearson Education, Inc.
15 15/05/12 Figure 43.22
Allergies •  Allergies are exaggerated (hypersensi3ve) responses to an3gens called allergens •  In localized allergies such as hay fever, IgE an3bodies produced aJer first exposure to an allergen aZach to receptors on mast cells Histamine
IgE
Allergen
Granule
Mast cell
© 2011 Pearson Education, Inc.
Autoimmune Diseases •  The next 3me the allergen enters the body, it binds to mast cell–associated IgE molecules •  Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms •  An acute allergic response can lead to anaphylac3c shock, a life-­‐threatening reac3on, within seconds of allergen exposure © 2011 Pearson Education, Inc.
Figure 43.23
•  In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body •  Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthri3s, insulin-­‐
dependent diabetes mellitus, and mul3ple sclerosis © 2011 Pearson Education, Inc.
Exer1on, Stress, and the Immune System •  Moderate exercise improves immune system func3on •  Psychological stress has been shown to disrupt immune system regula3on by altering the interac3ons of the hormonal, nervous, and immune systems •  Sufficient rest is also important for immunity © 2011 Pearson Education, Inc.
16 15/05/12 Immunodeficiency Diseases •  Inborn immunodeficiency results from hereditary or developmental defects that prevent proper func3oning of innate, humoral, and/or cell-­‐
mediated defenses •  Acquired immunodeficiency develops later in life and results from exposure to chemical and biological agents •  Acquired immunodeficiency syndrome (AIDS) is caused by a virus © 2011 Pearson Education, Inc.
Evolu3onary Adapta3ons of Pathogens That Underlie Immune System Avoidance •  Pathogens have evolved mechanisms to thwart immune responses © 2011 Pearson Education, Inc.
Figure 43.24
An1genic Varia1on Millions of parasites
per mL of blood
•  Through an3genic varia3on, some pathogens are able to change epitope expression and prevent recogni3on •  The human influenza virus mutates rapidly, and new flu vaccines must be made each year •  Human viruses occasionally exchange genes with the viruses of domes3cated animals •  This poses a danger as human immune systems are unable to recognize the new viral strain 1.5
Antibodies to
variant 1
appear
1.0
Variant 1
Antibodies to Antibodies to
variant 2
variant 3
appear
appear
Variant 2
Variant 3
0.5
0
25
26
27
Weeks after infection
28
© 2011 Pearson Education, Inc.
Latency •  Some viruses may remain in a host in an inac3ve state called latency •  Herpes simplex viruses can be present in a human host without causing symptoms ALack on the Immune System: HIV •  Human immunodeficiency virus (HIV) infects helper T cells •  The loss of helper T cells impairs both the humoral and cell-­‐mediated immune responses and leads to AIDS •  HIV eludes the immune system because of an3genic varia3on and an ability to remain latent while integrated into host DNA Anima3on: HIV Reproduc3ve Cycle © 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
17 15/05/12 Helper T cell concentration
(in blood (cells/mm3)
Figure 43.25
Latency
AIDS
Relative anti-HIV antibody
concentration
800
•  People with AIDS are highly suscep3ble to opportunis3c infec3ons and cancers that take advantage of an immune system in collapse •  The spread of HIV is a worldwide problem •  The best approach for slowing this spread is educa3on about prac3ces that transmit the virus Relative HIV
concentration
600
Helper T cell
concentration
400
200
0
0
1
3
7
8
2
4
5
6
Years after untreated infection
9
10
© 2011 Pearson Education, Inc.
Figure 43.26
Cancer and Immunity •  The frequency of certain cancers increases when adap3ve immunity is impaired •  20% of all human cancers involve viruses •  The immune system can act as a defense against viruses that cause cancer and cancer cells that harbor viruses •  In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer © 2011 Pearson Education, Inc.
Figure 43.UN02
Figure 43.UN03
Stem cell
Cell division and
gene rearrangement
Elimination of
self-reactive
B cells
Antigen
Clonal
selection
Formation of
activated cell
populations
Memory B cells
Antibody
Plasma cells
Pathogen
Receptors bind to antigens
18