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Immunity
Dr. Spandana Charles
MD
Immunity
• Resistance to disease
• Immune system
– Two intrinsic systems
• Innate (nonspecific) defense system
• Adaptive (specific) defense system
© 2013 Pearson Education, Inc.
Figure 21.1 Overview of innate and adaptive defenses.
Surface barriers
• Skin
• Mucous membranes
Innate
defenses
Internal defenses
• Phagocytes
• Natural killer cells
• Inflammation
• Antimicrobial proteins
• Fever
Humoral immunity
• B cells
Adaptive
defenses
Cellular immunity
• T cells
© 2013 Pearson Education, Inc.
Surface Barrier
Internal Defenses: Cells and Chemicals
• Necessary if microorganisms invade
deeper tissues
– Phagocytes
– Natural killer (NK) cells
– Antimicrobial proteins (interferons and
complement proteins)
– Fever
– Inflammatory response (macrophages, mast cells,
WBCs, and inflammatory chemicals)
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Phagocytes
• Neutrophils most abundant but die fighting
Become phagocytic on exposure to infectious
material
• Macrophages develop from monocytes – chief
phagocytic cells – robust cells
• Free macrophages wander through tissue spaces, e.g.,
alveolar macrophages
• Fixed macrophages -permanent residents of some
organs; e.g., Kupffer cells (liver) and microglia (brain)
© 2013 Pearson Education, Inc.
Figure 21.2b Phagocytosis.
Phagosome
(phagocytic
vesicle)
Lysosome
Acid
hydrolase
enzymes
1 Phagocyte
adheres to
pathogens or debris.
2 Phagocyte forms
pseudopods that
eventually engulf the
particles, forming a
phagosome.
3 Lysosome fuses
with the phagocytic
vesicle, forming a
phagolysosome.
4 Lysosomal
enzymes digest the
particles, leaving a
residual body.
5 Exocytosis of the
vesicle removes
indigestible and
residual material.
Events of phagocytosis.
© 2013 Pearson Education, Inc.
Slide 1
Inflammatory Response
•
•
•
•
•
•
Triggered whenever body tissues injured
Prevents spread of damaging agents
Disposes of cell debris and pathogens
Alerts adaptive immune system
Sets the stage for repair
Cardinal signs of acute inflammation:
1. Redness
2. Heat
3. Swelling
4. Pain
(Sometimes 5. Impairment of function)
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Figure 21.3 Inflammation: flowchart of events.
Innate defenses
Internal defenses
Initial stimulus
Physiological response
Tissue injury
Release of inflammatory chemicals
(histamine, complement,
kinins, prostaglandins, etc.)
Signs of inflammation
Result
Release of leukocytosisinducing factor
Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Arterioles
dilate
Increased capillary
permeability
Local hyperemia
(increased blood
flow to area)
Capillaries
leak fluid
(exudate formation)
Leaked protein-rich
fluid in tissue spaces
Heat
Redness
Locally increased
temperature increases
metabolic rate of cells
Pain
Attract neutrophils,
monocytes, and
lymphocytes to
area (chemotaxis)
Margination
(leukocytes cling to
capillary walls)
Leaked clotting
proteins form interstitial
clots that wall off area
to prevent injury to
surrounding tissue
Swelling
Possible temporary
impairment of
function
Leukocytes migrate to
injured area
Temporary fibrin
patch forms
scaffolding for repair
Healing
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Diapedesis
(leukocytes pass through
capillary walls)
Phagocytosis of pathogens
and dead tissue cells
(by neutrophils, short-term;
by macrophages, long-term)
Pus may form
Area cleared of debris
Phagocyte Mobilization
• Neutrophils lead; macrophages follow
– As attack continues, monocytes arrive
• 12 hours after leaving bloodstream  macrophages
• These "late-arrivers" replace dying neutrophils and
remain for clean up prior to repair
• If inflammation due to pathogens,
complement activated; adaptive immunity
elements arrive
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Phagocyte Mobilization
• Steps for phagocyte mobilization
1. Leukocytosis: release of neutrophils from bone
marrow in response to leukocytosis-inducing
factors from injured cells
2. Margination: neutrophils cling to walls of
capillaries in inflamed area in response to CAMs
3. Diapedesis of neutrophils
4. Chemotaxis: inflammatory chemicals
(chemotactic agent) promote positive
chemotaxis of neutrophils
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Antimicrobial Proteins
• Interferons (IFNs) and complement
proteins
– Attack microorganisms directly
– Hinder microorganisms' ability to reproduce
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Interferons
• Family of immune modulating proteins
– Have slightly different physiological effects
• Viral-infected cells secrete IFNs (e.g., IFN alpha
and beta) to "warn" neighboring cells
– IFNs enter neighboring cells  produce proteins that
block viral reproduction and degrade viral RNA
– IFN alpha and beta also activate NK cells
• Artificial IFNs used to treat hepatitis C, genital warts,
multiple sclerosis, hairy cell leukemia
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Complement
• Unleashes inflammatory chemicals that
amplify all aspects of inflammatory response
• Kills bacteria and certain other cell types by
cell lysis
• Enhances both innate and adaptive defenses
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Figure 21.6 Complement activation.
Classical pathway
Activated by antibodies
coating target cell
Lectin pathway
Activated by lectins
binding to specific sugars
on microorganism’s surface
Alternative pathway
Activated spontaneously. Lack of
inhibitors on microorganism’s
surface allows process to proceed
Together with other complement
proteins and factors
C3
C3a
C3b
C3b
Opsonization:
Coats pathogen
surfaces, which
enhances phagocytosis
MAC
C5b
MACs form from activated
complement components (C5b
and C6–C9) that insert into the
target cell membrane, creating
pores that can lyse the target cell.
C6
C7
C8
C9
C5a
Enhances inflammation:
Stimulates histamine
release, increases blood
vessel permeability,
attracts phagocytes by
chemotaxis, etc.
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell
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Fever
• Abnormally high body temperature
• Systemic response to invading microorganisms
• Leukocytes and macrophages exposed to
foreign substances secrete pyrogens
• Pyrogens act on body's thermostat in
hypothalamus, raising body temperature
© 2013 Pearson Education, Inc.
Adaptive Immunity
• Immunity against specific antigens
• Is of two types
– Humoral Immunity
– Cell mediated immunity
Cells of the Adaptive Immune System
• Three types of cells
– Two types of lymphocytes
• B lymphocytes (B cells)—Humoral immunity
• T lymphocytes (T cells)—Cell-mediated immunity
– Antigen-presenting cells (APCs)
• Do not respond to specific antigens
• Play essential auxiliary roles in immunity
© 2013 Pearson Education, Inc.
Figure 21.8 Lymphocyte development, maturation, and activation.
Adaptive defenses
Primary lymphoid organs
(red bone marrow and thymus)
Humoral immunity
Cellular immunity
Secondary lymphoid organs
(lymph nodes, spleen, etc.)
Red bone marrow
1 Origin
• Both B and T lymphocyte precursors originate in red
bone marrow.
Lymphocyte
precursors
2 Maturation
• Lymphocyte precursors destined to become T cells migrate
(in blood) to the thymus and mature there.
• B cells mature in the bone marrow.
• During maturation lymphocytes develop immunocompetence
and self-tolerance.
Thymus
Red bone marrow
Antigen
Lymph node
3 Seeding secondary lymphoid organs and circulation
• Immunocompetent but still naive lymphocytes leave the
thymus and bone marrow.
• They “seed” the secondary lymphoid organs and circulate
through blood and lymph.
4 Antigen encounter and activation
• When a lymphocyte’s antigen receptors bind its antigen, that
lymphocyte can be activated.
5 Proliferation and differentiation
• Activated lymphocytes proliferate (multiply) and then
differentiate into effector cells and memory cells.
• Memory cells and effector T cells circulate continuously in
the blood and lymph and throughout the secondary
lymphoid organs.
© 2013 Pearson Education, Inc.
Slide 1
Humoral Immunity
– Antibody-Mediated Immunity
–
Involves production of antibodies against foreign
antigens
– Produced by B cells
– Defense against bacteria, bacterial toxins, and
viruses that circulate freely in body fluids, before
they enter cells
Clonal Selection of B Cells by Antigenic
Stimulation
Clonal Selection:
When a B cell meets an antigen
 it recognizes
 it gets stimulated
 divides into many clones
( plasma cells)
 secrete antibodies
 Each B cell produces antibodies
that will recognize only one
antigenic determinant.
Antibody
5 types:
IgE
IgM
IgG
IgD
IgA
Consequences of Antibody Binding
Figure 21.12 Primary and secondary humoral responses.
Secondary immune response to
antigen A is faster and larger; primary
immune response to antigen B is
similar to that for antigen A.
Antibody titer (antibody concentration)
in plasma (arbitrary units)
Primary immune
response to antigen
A occurs after a delay.
104
103
102
101
AntiBodies
to B
AntiBodies
to A
100
0
7
First exposure
to antigen A
14
21
28
35
42
Second exposure to antigen A;
first exposure to antigen B
Time
(days)
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Education,
Inc.
49
56
Figure 21.13 Active and passive humoral immunity.
Humoral
immunity
Active
Naturally
acquired
Infection;
contact
with
pathogen
Passive
Artificially
acquired
Vaccine;
dead or
attenuated
pathogens
Naturally
acquired
Antibodies
passed from
mother to
fetus via
placenta; or
to infant in
her milk
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Artificially
acquired
Injection of
exogenous
antibodies
(gamma
globulin)
Humoral Immunity
•
Active Humoral Immunity-Vaccines
– Most of dead or attenuated pathogens
– Spare us symptoms of primary response
– Provide antigenic determinants that are
immunogenic and reactive.
• Passive Humoral Immunity-Antibodies are injected
into a person
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Cellular Immunity
• Lymphocytes act against target cell
– Directly – by killing infected cells
– Indirectly – by releasing chemicals that enhance
inflammatory response; or activating other
lymphocytes or macrophages
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T cells
• T cells mature in thymus under negative and
positive selection pressures ("tests")
– Positive selection
• Selects T cells capable of recognizing self-MHC proteins
(MHC restriction); failures destroyed by apoptosis
– Negative selection
• Prompts apoptosis of T cells that bind to self-antigens
displayed by self-MHC
• Ensures self-tolerance
© 2013 Pearson Education, Inc.
Cellular Components of CMI
T cells are key cellular component of immunity
– T cells have an antigen receptor (T cell receptor)
that recognizes & reacts to a specific antigen
– Antigens that stimulate this response are mainly intracellular
– T cell receptor only recognize antigens combined with major
histocompatability (MHC) proteins on the surface of cells.
• MHC Class I: Found on all cells.
• MHC Class II: Found on phagocytes.
– Clonal selection increases number of T cells.
T Cells Only Recognize Antigen Associated with
MHC Molecules on Cell Surfaces
T cells
Helper T cells• Activate macrophages
• Induce formation of cytotoxic T cells
• Stimulate B cells to produce antibodies.
Cytotoxic T cells•
Release protein called perforin which forms a pore in target cell,
causing lysis of infected cells.
• Destroy target cells
Supressor T cells
Inhibit the immune response
Role of Helper Tcells
Organ Transplants
• Four varieties
– Autografts: from one body site to another in same
person
– Isografts: between identical twins
– Allografts: between individuals who are not
identical twins
– Xenografts: from another animal species
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Acquired Immune Deficiency
Syndrome (AIDS)
• Caused by human immunodeficiency virus
(HIV) transmitted via body fluids—blood,
semen, and vaginal secretions
• Attacks the helper T cells- Depresses Cell
mediated Immunity
• HIV enters cell and uses reverse
transcriptase to produce DNA from its viral
RNA
• The DNA copy (a provirus) directs host cell
to make viral RNA and proteins, enabling
virus to reproduce
Autoimmune Diseases
• Immune system loses ability to distinguish
self from foreign
• Production of autoantibodies and
sensitized TC cells that destroy body tissues
• Examples include multiple sclerosis,
myasthenia gravis, Graves' disease, type 1
diabetes mellitus, systemic lupus
erythematosus (SLE), glomerulonephritis,
and rheumatoid arthritis
© 2013 Pearson Education, Inc.
Hypersensitivities
Thank You!