Transcript The potential “bad guys”

The Immune Wars
Part I
General types of immunity
Innate (aka non-specific)
inborn
pattern recognition
Adaptive (aka specific, acquired)
“learned” through exposure
exquisite specificity
Chapter 15 Innate Immunity
Preview
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First line of defense
Cells
Sensor system
Phagocytosis
Inflammation
First-line Defenses
Physical barrier
Antimicrobial chemicals
Normal flora
Physical Barriers
Skin
•Sheets of tightly packed cells
•Outermost layers are embedded with keratin (dry)
•Cells continually slough off
•Perspiration (salty)
•Normal flora
Physical Barriers
Mucous Membranes
•Single layer of cells
•Layer of mucus (traps particles, including microbes)
•Often a mechanism to propel the mucus toward exit
•(ex. mucociliary escalator, peristalsis)
Antimicrobial Chemicals
•Lysozyme
•Transferrin, lactoferrin
•Gastric acid
The Cells of the Immune System
Cell Communication
Surface receptors - “eyes, ears”
Cytokines - chemical messengers; proteins released by
cells that affect the behavior of other cells; “voice”
Cell Communication
Surface receptors - “eyes, ears”
Cytokines - chemical messengers; proteins released by cells that
effect the behavior of other cells; “voice”
Adhesion molecules - “hands”
Sensor Systems
Toll-like receptors - surface receptors that allow cells to “see”
molecules that signify the presence of microorganisms or viruses
pattern recognition
Sensor Systems
Toll-like receptors - surface receptors that allow cells to “see”
molecules that signify the presence of microorganisms or viruses
pattern recognition
Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3  C3a + C3b
C5  C5a + C5b
“prepare for eating”
Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3  C3a + C3b
C5  C5a + C5b
Alternative Complement Systems
Sensor Systems
The complement system - series of proteins that, when activated, result in
destruction/removal of foreign material; cascade reaction
C3  C3a + C3b
C5  C5a + C5b
Sensor Systems
Recognition of long double-stranded RNA
Signifies to a cell that it is infected with a virus
infected cell produces interferon
Apoptosis = programmed
cell death
Phagocytosis
Macrophages
Neutrophils (polymorphonuclear leukocytes, PMNs, polys)
Process of phagocytosis
Chemotaxis
Recognition and attachment
•opsonins
Engulfment (ingestion)
•phagosome
Fusion of the phagosome with lysosomes
(forms a phagolysosome)
Destruction and digestion
Exocytosis
•Specialized attributes of macrophages
Fixed in tissue or routinely wander
Clean up infection
Long-lived (months)
Can become activated
•Specialized attributes of neutrophils
First to migrate to site of infection
Short-lived (days)
Always have tremendous killing power
•Specialized attributes of macrophages
Fixed in tissue or routinely wander
Clean up infection
Long-lived (months)
Can become activated
•Specialized attributes of neutrophils
First to migrate to site of infection
Short-lived (days)
Always have tremendous killing power
Inflammation
Redness, pain, swelling, heat
Purpose:
Contain a site of damage
Localize the response
Restore tissue function
Factors that initiate the inflammatory response
Microbial cell products detected by toll-like receptors
Microbial surfaces (trigger the complement cascade)
Tissue damage
The Inflammatory Process
•Pro-inflammatory cytokines
released
•Dilation of small blood vessels
 increased blood flow to the area
•Leakage of fluids from vessels
•Adherence of phagocytic cells to
endothelial cells
•Diapedesis
Apoptosis - programmed cell
death; does not trigger
inflammation
Other responses
Interferon
Fever
 metabolic rate;  response to invaders
elevates temperature above optimum growth temperature of
invader
Immune Wars
Adaptive Immunity
Chapter16 Adaptive Immunity
Preview
• Characteristics of adaptive immunity
• Lymphatic system
• Humoral immunity
– Antibody structure, function, classification,
production (B cell activation)
• Cellular immunity
– T cell activation, function
Strategy of the Adaptive Immune
Response
Characteristics of adaptive immunity
•Memory
•Specificity
•“Self” vs. non-self …..or harmless vs. danger
“self” vs. dangerous non-self
Antigen - Material to which an immune system mounts a response
Development of the Response
Effect
step 1  step 2  step 3              finale
Strategy of the Adaptive Immune Response
lymphocytes
Strategy of the Adaptive Immune Response
Extracellular antigens
•Most bacteria
•Toxins
•Viral particles
aka cell-mediated
immunity (CMI)
Intracellular antigens
•Viruses (inside a cell)
•Intracellular bacteria
•(Cancer cells)
Strategy of the Adaptive Immune Response
Strategy of the Adaptive Immune Response
Strategy of the Adaptive Immune Response
Strategy of the Adaptive Immune Response
Strategy of the Adaptive Immune Response
Anatomy of the Lymphoid
System
Lymphatic vessels
Secondary
Collect fluids,
lymphoid
WBCs from
organs
the tissues
Where lymphocytes “hang out” to
encounter antigens
•Lymph nodes
Anatomy of the Lymphoid
System
Lymphatic vessels
Secondary lymphoid organs
Where lymphocytes “hang out” to
encounter antigens
•Lymph nodes
•Spleen
•Mucosal-associated lymphoid tissue
•Peyer’s patches; M cells sample
material in the intestine
P
M
lumen
Anatomy of the Lymphoid
System
Lymphatic vessels
Secondary lymphoid organs
Where lymphocytes “hang out” to
encounter antigens
•Lymph nodes
•Spleen
•Mucosal-associated lymphoid tissue
•Peyer’s patches; M cells sample
material in the intestine
•Skin-associated lymphoid tissue
Primary lymphoid organs
Where lymphocytes develop
•Bone marrow
•Thymus
The Nature of Antigens
• Proteins
• Molecules w/ repeating identical subunits (ex. polysaccharides)
Epitopes/antigenic determinants
10-20 amino acids
“antigenic”
T helper cell dependent
T helper cell independent
The Nature of Antibodies
Magic bullet: bind antigen with high specificity
Basic structure: Y-shaped molecule
•Fab regions - antigen-binding regions
•Fc region - “red flag” region
The Nature of Antibodies
Structure and properties of antibodies
Basic structure: Y-shaped molecule
200 a.a.
450 a.a.
•Fab regions - antigen-binding regions
•Fc region - “red flag” region
•four protein chains - two heavy chains (H); two light chains (L)
•variable region
•constant region
Immunoglobulin Classes (isotypes)
Immunoglobulins = antibodies
Protective outcomes of antigenantibody binding
Protective outcomes of antigenantibody binding
Protective outcomes of antigenantibody binding
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Naïve lymphocytes have a receptor, but
have not “seen” antigen
BCRs are membranebound antibodies
~1/2 billion naïve B cells, recognizing ~ 100 million different epitopes!
Those that recognize “self” are eliminated during lymphocyte development
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Activated lymphocytes - able
to proliferate; have received
confirmatory signals
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Activated lymphocytes - able
to proliferate; have received
confirmatory signals
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Activated lymphocytes - able
to proliferate; have received
confirmatory signals
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Effector lymphocytes endowed with specific
protective attributes (plasma
cells = effector B cells)
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Effector lymphocytes endowed with specific
protective attributes (plasma
cells = effector B cells)
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
Memory lymphocytes long-lived; ready to
become effector cells
Clonal Selection and Expansion of Lymphocytes
Basic principles are true for
both B and T cells
•Naïve
•Activated
•Effector
•Memory
Requires confirmatory
signals (“second opinion”)
from another cell type
B Lymphocytes and the Antibody
Response (T-dependent antigens)
•Most common type of response; primarily protein antigens
•Requires assistance of T-helper cells (TH cells)
B Cell Activation
•B cell processes/presents antigen to TH cell for “inspection” in order to gain
second opinion
B Cell Activation
•B cell processes/presents antigen to TH cell for “inspection” in order to gain
second opinion
B Cell Activation
•B cell processes/presents antigen to TH cell for “inspection” in order to gain
second opinion
•If a TH cell recognizes a fragment being presented, it delivers cytokines that
activate the B cell
B Cell Activation
•B cell processes/presents antigen to TH cell for “inspection” in order to gain
second opinion
•If a TH cell recognizes a fragment being presented, it delivers cytokines that
activate the B cell
•If no TH cell recognizes antigen, the B cell becomes unresponsive
B Cell Activation
•B cell processes/presents antigen to TH cell for “inspection” in order to gain
second opinion
Characteristics of the Primary Response
Affinity maturation
•Naïve
•Activated
•Effector
•Memory
Characteristics of the Primary Response
Affinity maturation - mutation fine tunes the fit
Characteristics of the Primary Response
Affinity maturation - mutation fine tunes the fit
Class switching - IgM  IgG (or IgA or IgE)
Characteristics of the Primary Response
Affinity maturation - mutation fine tunes the fit
Class switching - IgM  IgG (or IgA or IgE)
Formation of memory cells - cells have undergone affinity maturation and
class switching
Characteristics of the Primary Response
Affinity maturation
Class switching
Formation of memory cells
Secondary response
Characteristics of the Secondary Response
Swifter response, primarily IgG in
blood/tissues (due to memory cells)
(mucosal response is IgA)
More effective response (due to affinity maturation)
Continued fine-tuning
Characteristics of the Secondary Response
Swifter response, primarily IgG in
blood/tissues (due to memory cells)
(mucosal response is IgA)
More effective response (due to affinity maturation)
Continued fine-tuning
General Characteristics of T Cells
(regulatory T cells)
Two general categories of T cells:
General Characteristics of T Cells
T-cell receptor - recognizes antigen “presented” by another cell
Antigen is presented by major histocompatibility complex (MHC) molecules
General Characteristics of T Cells
T-cell receptor - recognizes antigen “presented” by another cell
Antigen is presented by major histocompatibility complex (MHC) molecules
Effector T cell delivers signals to the presenting cell
General Characteristics of T Cells
CD = cluster of differentiation
•CD8+ T cell
•CD4+ T cell
Activation of T Cells
The role of dendritic cells scouts
Activation of T Cells
The role of dendritic cells
In the tissues: antigen-capturing
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
Activation of T Cells
The role of dendritic cells
In the tissues: antigen-capturing
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Activates
naïve T cell
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Naïve T cell
becomes
unresponsive
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
Activation of T Cells
The role of dendritic cells
In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by
BOTH MHC Class I AND MHC Class II molecules
In the tissues: antigen-capturing
Activates
naïve T cell
Migrate to secondary lymphoid
organs
Co-stimulatory molecules expressed
when “danger” is sensed
Functions of TC (CD8+) Cells
•Recognizes antigen presented by Major
Histocompatibility Complex (MHC) Class I
•Found on all nucleated cells
• Endogenous proteins (i.e. made
by the cell) are presented
•Induces apoptosis in “corrupt” self cells (ex. virallyinfected)
• Secretes cytokines; some increase surveillance of
neighboring cells (MHC Class I expression)
Functions of TH (CD4+) Cells
“Helps” other cells (operations commander); produces various cytokines that
activate presenting cell and direct other cells
Recognizes antigen presented by Major Histocompatibility Complex (MHC)
Class II
Exogenous proteins (i.e. those that have been taken up by the cell) are presented
Found on antigen-presenting cells (macrophages, B cells….and dendritic cells)
Functions of TH (CD4+) Cells
Functions of TH (CD4+) Cells
B cell activation (B cell as the APC)
Antigen represents material that the B cell’s receptor has recognized
Functions of TH (CD4+) Cells
B cell activation (B cell as the APC)
Antigen represents material that the B cell’s receptor has recognized
TH cell directs cytokines to that B cell,
activating it/enabling it to:
•Multiply and differentiate to form
antibody-secreting plasma cells
•Produce memory cells
•Undergo class switching
Note: T-independent antigens (generally
polysaccharides) can activate B cells without
T cell help; IgM only, no memory
Children < 2 yo have weak response
Functions of TH (CD4+) Cells
B cell activation ( B cell as the APC)
Antigen represents material that the B cell’s receptor has recognized
TH cell directs cytokines to that B cell,
activating it/enabling it to:
•Multiply and differentiate to form
antibody-secreting plasma cells
•Produce memory cells
•Undergo class switching
Note: T-independent antigens (generally
polysaccharides) can activate B cells without
T cell help; IgM only, no memory
Children < 2 yo have weak response
Functions of TH (CD4+) Cells
Macrophage activation (macrophage as the APC)
Presented peptides are parts of material that the phagocyte has engulfed
TH cell:
•directs cytokines to that macrophage (activating it)
•secretes cytokines that stimulate activated T-cytotoxic cells
B Lymphocytes and the Antibody
Response (T-independent antigens)
Primarily polysaccharide antigens; also LPS of Gram-negatives
Multiple evenly-spaced identical epitopes
No memory cells formed
No class switching (therefore IgM only)
Immature immune systems (children <2 years of age) respond poorly
capsular polysaccharides - ex. Haemophilus influenzae
The Big Picture
Presented step-by-step
Peripheral Tissues
Primary Lymphoid Organs
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Peripheral Tissues
Primary Lymphoid Organs
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Naive B cells
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
Naive B cells
Virus
Infected "self" cell
(harbors antigen
within the cell)
Macrophage (engulf and destroy
invaders; limited killing powers)
Extracellular
antigen
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TCcells
Naive B cells
TH cells
Virus
Memory
helper T
cells
Infected "self" cell
(harbors antigen
within the cell)
Memory
cytotoxic
T cells
Macrophage (engulf and destroy
invaders; limited killing powers)
Extracellular
antigen
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TCcells
Naive B cells
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TH cells
Virus
Memory
helper T
cells
Infected "self" cell
(harbors antigen
within the cell)
Memory
cytotoxic
T cells
Memory
B cells
Plasma cells
secrete antibodies.
Macrophage (engulf and destroy
invaders; limited killing powers)
Extracellular
antigen
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TCcells
Naive B cells
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TH cells
Virus
Memory
helper T
cells
Infected "self" cell
(harbors antigen
within the cell)
Memory
cytotoxic
T cells
Memory
B cells
Plasma cells
secrete antibodies.
Macrophage (engulf and destroy
invaders; limited killing powers)
Extracellular
antigen
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Naive B cells
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TCcells
TH cells
Virus
Memory
helper T
cells
Memory
cytotoxic
T cells
Infected "self" cell
(harbors antigen
within the cell)
Memory
B cells
Plasma cells
secrete antibodies.
TH cells activate macrophages that
present antigen via MHC class II
molecules; also produce cytokines that
orchestrate other responses.
Macrophage (engulf and destroy
invaders; limited killing powers)
Activated macrophage (engulf and
destroy invaders; enhanced killing powers)
Extracellular
antigen
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Naive B cells
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TCcells
TH cells
Virus
TC cells induce apoptosis in
infected "self" cells; also
produce cytokines that cause
neighboring cells to become
more vigilant against
intracellular pathogens.
Infected "self" cell
(harbors antigen
within the cell)
Memory
helper T
cells
Memory
cytotoxic
T cells
Memory
B cells
Plasma cells
secrete antibodies.
TH cells activate macrophages that
present antigen via MHC class II
molecules; also produce cytokines that
orchestrate other responses.
Macrophage (engulf and destroy
invaders; limited killing powers)
Activated macrophage (engulf and
destroy invaders; enhanced killing powers)
Extracellular
antigen
Peripheral Tissues
Primary Lymphoid Organs
After gathering antigen in periphery,
dendritic cells bring it to naive T cells in
the secondary lymphoid organs;
co-stimulatory molecules are expressed if
antigen represents microbial invasion or
tissue damage. Antigens are presented
by both MHC class I and MHC class II
molecules, activating both cytotoxic T
cells and helper T cells.
Immature T cells
(thymus marrow)
Immature B cells
(bone marrow)
Secondary lymphoid
organs
Naive cytotoxic Naive-helper
T cells (CD8)
T cells (CD4)
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
Dendritic cells
(gather antigen
for presentation
to naive T cells)
Naive B cells
Activation,
proliferation,
differentiation to
form effector cells
and memory cells
TCcells
TH cells
Virus
TC cells induce apoptosis in
infected "self" cells; also
produce cytokines that cause
neighboring cells to become
more vigilant against
intracellular pathogens.
Infected "self" cell
(harbors antigen
within the cell)
Memory
helper T
cells
Memory
cytotoxic
T cells
Memory
B cells
Plasma cells
secrete antibodies.
TH cells activate macrophages that
present antigen via MHC class II
molecules; also produce cytokines that
orchestrate other responses.
Macrophage (engulf and destroy
invaders; limited killing powers)
Activated macrophage (engulf and
destroy invaders; enhanced killing powers)
Extracellular
antigen
Table 1
Non-specific Immunity
Specific Immunity
Response is antigenindependent
Response is antigen-dependent
There is immediate maximal
response
There is a lag time between
exposure and maximal
response
Antigen-specific
Not antigen-specific
Exposure results in no
immunologic memory
Exposure results in
immunologic memory