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8/9/2019 Disturbances in Inflammatory and Immunologic Function
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DisturbancesIN
Inflammatory andImmunologicFUNCTIONING
by:
Joanne T. Tolentino, RN
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Overview of Immune System
• Central and Peripheral Lymphoid SystemPrimary
Secondary
• Immune Function
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• Defenses
A. Innate Immunity
Barriers
Defensive cells Chemical defenses
B. Adaptive Immunity Cell mediated immunity
Antibody mediated immunity
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• Types of Immunity1. Active immunity
2. Passive immunity
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We all get sick sometimes...but then we
get better.
What happens when we get sick?
Why do we get better?
THE IMMUNE SYSTEM
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Immune/ Lymphatic
System
A collection of cells and proteinsthat works together to protect
the body from harmful/infectious micro organisms
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Parts of Lymphatic System
• Lymph—the tissue fluid that enters lymph
capillaries
• Lymph Vessels are found in most tissue
spaces; collect tissue fluid and proteins
• Lymphatic tissue consists mainly of
lymphocytes
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• The immune system is localized
in several parts of the body –immune cells develop in the
primary organs - bone
marrow and thymus
–immune responses occur in
the secondary organs
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Primary Lymphatic Organs
• Thymus –
glandular organnear the heart –
where T cells
learn their jobs
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• Bone marrow – blood-producing tissue
located inside certain
bones
– blood stem cells give rise
to all of the different types
of blood cells
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Secondary Lymphatic Organs
• Lymph Nodes—encapsulated masses of
lymphatic tissue
• Lymph Nodules—small unencapsulated
masses of lymphatic tissue
• Spleen—located in the upper left
abdominal quadrant behind the stomach
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Adenoid
Tonsil
Lymphnodes
Spleen
Peyer’s patches(small intestine)
Appendix
Lymphaticvessels Lymph
nodeMasses of defensive cells
Bloodcapillary
Lymphatic
vessel
Tissue
cells
Interstitial fluid
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Immunity
may be defined as the ability to
destroy pathogens or other
foreign material and to preventfurther cases of certain
infectious diseases.
YOUR ACTIVE IMMUNE
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YOUR ACTIVE IMMUNE
DEFENSES
Innate Immunity- invariant (generalized)
- early, limited specificity- the first line of defense
Adaptive Immunity- variable (custom)
- later, highly specific
- ‘‘remembers’’ infection
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INNATE IMMUNITY
Recognition of traitsshared by broad rangesof pathogens, using asmall set of receptors
•
•Rapid response
• Recognition of traitsspecific to particular pathogens, using a vastarray of receptors
•Slower response
ACQUIRED IMMUNITY
Pathogens(microorganisms
and viruses)
Barrier defenses:SkinMucous membranesSecretions
Internal defenses:
Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells
Humoral response:Antibodies defend againstinfection in body fluids.
Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.
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INNATE IMMUNITY
Innate immunity consists of:
• Barriers
• Defensive cells
• Chemical defenses
When you were born, you brought with you several
mechanisms to prevent illness. This type of immunityis also called nonspecific immunity.
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INNATE IMMUNITY
Barriers
• Physical
– skin – hair
– mucous
• Chemical
– sweat – tears
– saliva
– stomach acid
– urine
INNATE IMMUNITY
Barriers
• Physical
– skin – hair
– mucous
• Chemical
– sweat – tears
– saliva
– stomach acid
– urine
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Defensive cells
• Phagocytes—macrophages, neutrophils,
eosinophils
• Langerhans cells and other dendritic cells
• Natural killer cells
• Basophils and mast cells
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Macrophages engulf pathogens and dead cell remains
Neutrophils release chemicals that kill nearby bacteria• pus = neutrophils, tissue cells and dead
pathogens
Phagocytic cells include:
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Phagocyte migration
Neutrophils and macrophages recognize
chemicals produced by bacteria in a cut or
scratch and migrate "toward the smell".
CELLS alive!
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Macrophages
• WBCs that ingest bacteria, viruses, deadcells, dust
• most circulate in the blood, lymph andextracellular fluid
• Macrophages, both fixed and wandering,
have receptors for the pathogens humans arelikely to encounter
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Macrophage and E. coli
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Macrophage ingesting yeast
This human macrophage, like the neutrophil, is a
professional "phagocyte" or eating cell (phago="eating",
cyte = "cell"). Here, it envelops cells of a yeast, Candida
albicans. After ingestion, the white cell must kill the
organisms by some means, such as the oxidative burst.
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Neutrophils
• WBCs – are phagocytic, like
macrophages
• neutrophils also release toxic chemicals
that destroy everything in the area,
including the neutrophils themselves
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Neutrophil phagocytosing S. pyogenes,
the cause of strep throat
Human neutrophils are WBCs that arrive quickly at the site of a bacterial infection and whose primary function is to eat and
kill bacteria. This neutrophil ingesting Streptococcus
pyogenes was imaged in gray scale with phase contrast optics
and colorized.
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Neutrophil killing yeast
One way that neutrophils kill is by producing an anti-
bacterial compound called “superoxide anion“, a processcalled oxidative burst. Here, an amoeboid human
neutrophil senses, moves toward and ingests an ovoid
yeast. In the next two panels, oxidation can be seen by
using a dye, and is colorized here.
YEAST →
NEUTROPHIL
↓
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•Langerhans cells and other dendritic cells—activate lymphocytes
• Natural killer cells—destroy foreign cells by
rupturing their cell membranes
• Basophils and mast cells—produce
histamine and leukotrienes (inflammation)
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Chemical defenses
• Interferon blocks viral reproduction
• Complement proteins lyse foreign cells,attract WBCs, & contribute to inflammation
• Inflammation
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Types of Inflammation
• Acute inflammation
• Chronic inflammation
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Acute Inflammation
• the early (almost immediate) response
to injury
• It is nonspecific and may be evoked by
any injury short of one that is immediately
fatal.
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The Inflammatory Response
The cardinal signs of inflammation
Heat (calor )
redness (rubor )
swelling (tumor )
pain (dolor )loss of function (functio laesa)
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The manifestation of acute
inflammation can be dividedinto two categories:
•vascular response
•cellular responses
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Vascular Responseimmediate vascular changes that occur
(vasodilation and increased capillary permeability)
Three Patterns of Response
1. immediate transient response
2. immediate sustained response
3. delayed hemodynamic response
Vascular and Surrounding Tissues at Steady
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Vascular and Surrounding Tissues at SteadyState
InflammationInflammation
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InflammationInflammation
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The Cellular Stage
•marked by movement of phagocytic white blood
cells (leukocytes) into the area of injury.
• two types of leukocytes participate in the acute
inflammatory response—the granulocytes and
monocytes.
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The sequence of events in the cellular
response to inflammation includes:
(1) pavementing
(2) emigration(3) chemotaxis
(4) phagocytosis
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Phagocytosis involves three
distinct steps:
(1) adherence plus opsonization
(2) Engulfment
(3) intracellular killing
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PhagocytosisPhagocytosis
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PhagocytosisPhagocytosis
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Inflammatory Mediators
•Histamine
•Plasma Proteases
•Prostaglandins
•Leukotrienes
•Platelet-Activating Factor
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Chronic Inflammation
is self perpetuating and may last for weeks,months, or even years
it may develop during a recurrent or progressive
acute inflammatory process
characterized by an infiltration by mononuclear
cells (macrophages) and lymphocytes
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Healing of a skin wound by primary
and secondary intention
(A) The inflammatory phase
(B) The proliferative phase
(C) Remodeling stage
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• Your mom’s antibodies were effective for
just a short time at birth, but your innate
immune system can be activatedquickly. It is always your first line of
defense during an infection, but it can’t
always eliminate the germ.
• When this happens, your body initiates afocused attack against the specific
pathogen that is causing the infection.
This attack may lead to long-term
protection against that pathogen.• This type of immunity is called adaptive
immunity, the customized second line
of defense.
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• Acquired immunity, or adaptiveimmunity, develops after exposure to
agents such as microbes, toxins, or other
foreign substances• It involves a very specific response to
pathogens
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Acquired Immunity: An Overview • 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
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RESPONSEForeign invaders - viruses, bacteria, allergens, toxins
and parasites - constantly bombard our body.
The response to this assault is a carefully orchestrated and
controlled interaction between immune cells with the ultimate
goal to eliminate the invader by pathogen-specific mechanisms.
↓ ↓ ↓
↓
↓ ↓
Antigen Recognition by
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Antigen Recognition by
Lymphocytes
• An antigen is any foreign molecule to
which a lymphocyte responds• A single B cell or T cell has about
100,000 identical antigen receptors
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Antigen-
bindingsite
Antigen-
binding site
Antigen-
bindingsite
Disulfidebridge
Variableregions
Constantregions
Transmembraneregion
Plasmamembrane
Light
chain
Heavy chains
T cell
α chain β chain
Disulfide bridge
Cytoplasm of T cell
(b) T cell receptor
Cytoplasm of B cell
) B cell receptor
B cell
V
V
C
C
V
V
C C C C
VV
Antigen- Antigen-
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gbindingsite
binding site
Disulfidebridge
Variableregions
Constantregions
Transmembraneregion
Plasmamembrane
Light
chain
Heavy chains
Cytoplasm of B cell
a) B cell receptor
B cell
V
V
C
C
V V
C C
Antigen-
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bindingsite
Variableregions
Constantregions
Transmembraneregion
Plasmamembrane
T cell
α chain β chain
Disulfide bridge
Cytoplasm of T cell
(b) T cell receptor
C C
VV
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•All antigen receptors on a singlelymphocyte recognize the same epitope,
or antigenic determinant , on an antigen
• B cells give rise to plasma cells, which
secrete proteins called antibodies or
immunoglobulins
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Antigen-binding sites
Antigen-bindingsites
Epitopes(antigenicdeterminants)
Antigen
Antibody B
Antibody CAntibody A
CC C
V
V
V
V
C
The Antigen Receptors of B Cells and
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The Antigen Receptors of B Cells and
Cells
• B cell receptors bind to specific, intact antigens
• The B cell receptor consists of two identical heavy
chains and two identical light chains
• The tips of the chains form a constant (C) region,
and each chain contains a variable (V) region, so
named because its amino acid sequence variesextensively from one B cell to another
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• Secreted antibodies, or immunoglobulins, are structurally
similar to B cell receptors but lack transmembraneregions that anchor receptors in the plasma membrane
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•Each T cell receptor consists of twodifferent polypeptide chains
• The tips of the chain form a variable (V)
region; the rest is a constant (C) region• T cells can bind to an antigen that is free
or on the surface of a pathogen
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• T cells bind to antigen fragments presented on a host
cell
• These antigen fragments are bound to cell-surface
proteins called MHC molecules
• MHC molecules are so named because they areencoded by a family of genes called the major
histocompatibility complex
The Role of the MHC
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The Role of the MHC
• In infected cells, MHC molecules bind and
transport antigen fragments to the cell surface, a
process called antigen presentation
• A nearby T cell can then detect the antigenfragment displayed on the cell’s surface
• Depending on their source, peptide antigens arehandled by different classes of MHC molecules
Fig. 43-11
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Antigen
Top view: binding surfaceexposed to antigen receptors
Plasmamembrane of infected cell
Antigenlass I MHColecule
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• Class I MHC molecules are found on almost
all nucleated cells of the body
• They display peptide antigens to cytotoxic Tcells
Fig. 43-12
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fected cell
ntigenragment
lass I MHColecule
celleceptor
a)
Antigen
associateswith MHCmolecule
T cellrecognizescombination
Cytotoxic T cell (b) Helper T cell
T cellreceptor
Class II MHCmolecule
Antigenfragment
Antigen-presenting
cell
Microbe
1
11
2
22
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• Class II MHC molecules are located mainly on dendritic cells,
macrophages, and B cells
• Dendritic cells, macrophages, and B cells are antigen-presenting
cells that display antigens to cytotoxic T cells and helper T cells
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Lymphocyte Development
• The acquired immune system has three
important properties:
– Receptor diversity – A lack of reactivity against host cells
– Immunological memory
G ti f L h t Di it b G
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Generation of Lymphocyte Diversity by Gene
Rearrangement
• Differences in the variable region account for
specificity of antigen receptors
• The immunoglobulin (Ig ) gene encodes one chain of the B cell receptor
• Many different chains can be produced from the
same Ig chain gene by rearrangement of the DNA
• Rearranged DNA is transcribed and translated and
the antigen receptor formed
Fig. 43-13DNA of undifferentiated B cell
V V V V J J J J CJ I t
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1
DNA of differentiated B cell
pre-mRNA
mRNA
Light-chain polypeptide
Variableregion
Constantregion
Translation
B cell
B cell receptor
RNA processing
Transcription
DNA deleted between randomly selected V and J
segments
Functional gene
V 37 V 38 V 39 V 40 J 1 J 2 J 3 J 4 C J 5 Intron
V 37 V 38 V 39 C J 5 Intron
V 39 C J 5 Intron
V 39 C J 5 Poly-A tailCap
C V
VV
VV
C C
C C
2
3
4
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Origin of Self-Tolerance
• Antigen receptors are generated by randomrearrangement of DNA
• As lymphocytes mature in bone marrow or thethymus, they are tested for self-reactivity
• Lymphocytes with receptors specific for the body’s
own molecules are destroyed by apoptosis, or
rendered nonfunctional
Amplifying Lymphocytes by Clonal
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p y g y p y y
Selection
• In the body there are few lymphocytes with antigenreceptors for any particular epitope
• The binding of a mature lymphocyte to an antigen
induces the lymphocyte to divide rapidly
• This proliferation of lymphocytes is called clonal
selection
• Two types of clones are produced: short-livedactivated effector cells and long-lived memory
cells
Fig. 43-14Antigen molecules
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B cells thatdiffer inantigen
specificity
Antibodymolecules
Antigenreceptor
Clone of memory cells Clone of plasma cells
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• The first exposure to a specific antigen represents the
primary immune response
• During this time, effector B cells called plasma cells are
generated, and T cells are activated to their effector forms
• In the secondary immune response, memory cells
facilitate a faster, more efficient response
Secondary immune response toantigen A produces antibodies to A;
Primary immune responseto antigen A produces
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Antibodiesto A
Antibodiesto B
g p ;
primary immune response to antigen
B produces antibodies to B.
g p
antibodies to A.
Antibody
con
centrat io
n
(arbitraryunit
s)
Exposureto antigen A
Exposure toantigens A and B
Time (days)
104
103
102
101
100
0 7 14 21 28 35 42 49 56
Acquired immunity defends against
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infection of body cells and fluids
• Acquired immunity has two branches: the humoralimmune response and the cell-mediated immuneresponse
• Humoral immune response involves activationand clonal selection of B cells, resulting inproduction of secreted antibodies
•Cell-mediated immune response involvesactivation and clonal selection of cytotoxic T cells
• Helper T cells aid both responses
Fig. 43-16Humoral (antibody-mediated) immune response Cell-mediated immune response
Key
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B cell
Plasma cells
Key
Stimulates
Gives rise to
+
+
++
+
+
+Memory B cells
Antigen (1st exposure)
Engulfed by
Antigen-
presenting cell
Memory
Helper T cells
Helper T cell Cytotoxic T cell
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Antigen (2nd exposure)
Secreted
antibodies
Defend against extra cellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.
Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.
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Key Antigen (1st exposure)
Humoral (antibody-mediated) immune response
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Stimulates
Gives rise to
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MemoryHelper T cells
Antigen-presenting cell
Helper T cell
Engulfed by
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Defend against extracellular pathogens
Memory
B cells
Antigen (2nd exposure)
Plasma cells
B cell
Secretedantibodies
Cell-mediated immune response
Antigen (1st exposure) Key
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Defend against intracellular pathogens
ActiveCytotoxic T cells
MemoryCytotoxic T cells
MemoryHelper T cells
Antigen-presenting cell
Antigen (2nd exposure)
Helper T cell
Engulfed by
g ( p )
Cytotoxic T cell
Stimulates
Gives rise to
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Helper T Cells: A Response to
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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
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Antigen-presentingcell
Peptide antigen
Cell-mediated
immunity
(attack on
infected cells)
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Humoral
immunity
(secretion of
antibodies by
plasma cells) Cytotoxic T cell
Cytokines
B cell
Bacterium
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Cytotoxic T Cells: A Response
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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 celland a cytotoxic T cell
• Binding to a class I MHC complex on an infectedcell activates a cytotoxic T cell and makes it an
active killer
• The activated cytotoxic T cell secretes proteinsthat destroy the infected target cell
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Cytotoxic T cell
Perforin
Granzymes
TCRCD8
ass I MHClecule
rgetll
Peptideantigen
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Cytotoxic T cell
Perforin
Granzymes
TCRCD8
ass I MHClecule
rgetll
Peptideantigen
Pore
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Cytotoxic T cell
Perforin
Granzymes
TCRCD8
ass I MHClecule
rgetll
Peptideantigen
Pore
Released cytotoxic T cell
Dying target cell
B Cells: A Response to
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p
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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ntigen-presenting cell Bacterium
Peptide
antigen
ass II MHC
lecule
TCR CD4
Helper T cell
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ntigen-presenting cell Bacterium
Peptide
antigen
ass II MHC
lecule
TCR CD4
Helper T cell
B cell
Activated
helper T cell
Cytokines
+
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ntigen-presenting cell Bacterium
Peptide
antigen
ass II MHC
lecule
TCR CD4
Helper T cell
B cell
Activated
helper T cell
Cytokines
+ Secreted
antibodymolecules
Clone of memory
B cells
Clone of plasma cells
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tigen-presenting cell
Endoplasmicreticulum of plasma cell
Secretedantibodymolecules
Bacterium
B cellPeptideantigen
ass II MHClecule
TCR CD4
Helper T cellActivated
helper T cell
Cytokines
Clone of memory
B cells
Clone of plasma cells
2 µm
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Antibody Classes
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Antibody Classes
• The five major classes of antibodies, or immunoglobulins, differ in distribution and function
• Polyclonal antibodies are the products of manydifferent 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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Distribution FunctionClass of Immuno-
globulin (Antibody)
IgG
(monomer)
Most abundant Igclass in blood;also present intissue fluids
Promotes opsoniza-tion, neutralization,and cross-linking of antigens; less effec-
tive in activation of complement systemthan IgM
Only Ig class that
crosses placenta,thus conferringpassive immunityon fetus
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Distribution FunctionClass of Immuno-
globulin (Antibody)
IgA
(dimer)
J chain
Secretory
component
Present insecretions suchas tears, saliva,mucus, andbreast milk
Provides localizeddefense of mucousmembranes bycross-linking andneutralization of antigens
Presence in breast
milk conferspassive immunityon nursing infant
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DistributionClass of Immuno-
globulin (Antibody)
IgM
(pentamer)
J chain
First Ig classproduced after initial exposure toantigen; then itsconcentration inthe blood declines
Promotes neutraliza-tion and cross-linking of antigens;very effective incomplement systemactivation
Function
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Distribution FunctionClass of Immuno-
globulin (Antibody)
IgE
(monomer)
Present in blood
at low concen-trations
Triggers release from
mast cells andbasophils of hista-mine and other chemicals that causeallergic reactions
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Distribution FunctionClass of Immuno-globulin (Antibody)
IgD
(monomer)
Trans-membraneregion
Present primarilyon surface of
B cells that havenot been exposedto antigens
Acts as antigenreceptor in the
antigen-stimulatedproliferation anddifferentiation of B cells (clonalselection)
The Role of Antibodies in
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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
Viral neutralization
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Virus
Fig. 43-21b
Opsonization
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Bacterium
Macrophage
Activation of complement system and pore formation
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Complement proteins
Formation of
membrane
attack complex
Flow of water and ions
Pore
Foreign
cell
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Viral neutralization
Virus
Opsonization
Bacterium
Macrophage
Activation of complement system and pore formation
Complement proteins
Formation of
membrane
attack complex
Flow of water
and ions
Pore
Foreign
cell
Active and Passive
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Immunization
• Active immunity develops naturally in response to an
infection
• It can also develop following immunization, also calledvaccination
• In immunization, a nonpathogenic form of a microbe or
part of a microbe elicits an immune response to an
immunological memory
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• Passive immunity provides immediate, short-
term protection
• 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 artificially by injecting
antibodies into a nonimmune person
Fig. 43-22
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How does an immune
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How does an immune
response end?
•The immune response will end when the antigen that caused the response is no longer present
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Induction of an immune response to infection
requires several days or weeks
What can you do while you’re waiting???????
• Temporary protection against infection can beestablished by giving pre-formed antibody
THE IMMUNE SYSTEM IN
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THE IMMUNE SYSTEM IN
HEALTH AND DISEASE
How does your everyday life affectyour immune system?
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Exercise and stress
• exercise has been shown to boost the immune response – moderate exercise increases the immune response in all age
groups
– intensive exercise can stress the immune system
• lack of sleep and exhaustion decrease immune function
• psychological stress has also been found to decrease
immune function
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Diet
• a well-balanced diet is essential for good immune
system health
– fats are very important in the production of WBCs, cytokines
and natural killer cells – selenium, zinc, and copper are required in small amounts,
which you get if you eat a balanced diet
– vitamin E has been shown to boost antibody production in
the elderly
– vitamin B6aids in antibody synthesis
• but mega-dosing can be harmful, too!
Environment
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Environment
• Chemicals
– dioxin
– pesticides
– solvents
• Sunlight
• Medication
• Viruses
• Bacteria
• Food
Exposure to certain things in their environment may
activate the immune systems of some people
Gender and the immune
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Gender and the immune
system
• women respond to antigens more strongly than men
• estrogen may affect the development or function of
immune cells
• may explain why more women develop autoimmune
diseases