1. Immunity
Dr. Spandana Charles MD

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Immunity
Resistance to disease
Immune system
Two intrinsic systems
Innate (nonspecific) defense system
Adaptive (specific) defense system
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3. 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
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4. Surface Barrier

5. 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)
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7. Events of phagocytosis.
Figure 21.2b Phagocytosis.
Slide 1
Phagocyte
adheres to
pathogens or debris. 1
Phagocyte forms
pseudopods that
eventually engulf the
particles, forming a
phagosome. 2
Phagosome
(phagocytic
vesicle)
Lysosome
Lysosome fuses
with the phagocytic
vesicle, forming a
phagolysosome. 3
Acid
hydrolase
enzymes
Lysosomal
enzymes digest the
particles, leaving a
residual body. 4
Exocytosis of the
vesicle removes
indigestible and
residual material. 5
Events of phagocytosis.
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8. 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:
Redness
Heat
Swelling
Pain
(Sometimes 5. Impairment of function)
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9. Figure 21.3 Inflammation: flowchart of events.
Innate defenses
Internal defenses
Initial stimulus
Physiological response
Signs of inflammation
Tissue injury
Result
Release of inflammatory chemicals
(histamine, complement,
kinins, prostaglandins, etc.)
Release of leukocytosis-
inducing factor
Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Arterioles
dilate
Increased capillary
permeability
Attract neutrophils,
monocytes, and
lymphocytes to
area (chemotaxis)
Leukocytes migrate to
injured area
Local hyperemia
(increased blood
flow to area)
Capillaries
leak fluid
(exudate formation)
Margination
(leukocytes cling to
capillary walls)
Diapedesis
(leukocytes pass through
capillary walls)
Leaked protein-rich
fluid in tissue spaces
Leaked clotting
proteins form interstitial
clots that wall off area
to prevent injury to
surrounding tissue
Phagocytosis of pathogens
and dead tissue cells
(by neutrophils, short-term;
by macrophages, long-term)
Heat
Redness
Pain
Swelling
Locally increased
temperature increases
metabolic rate of cells
Possible temporary
impairment of
function
Temporary fibrin
patch forms
scaffolding for repair
Pus may form
Area cleared of debris
Healing
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10. 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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11. Phagocyte Mobilization
Steps for phagocyte mobilization
Leukocytosis: release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells
Margination: neutrophils cling to walls of capillaries in inflamed area in response to CAMs
Diapedesis of neutrophils
Chemotaxis: inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils
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12. 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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15. 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
Opsonization:
Coats pathogen
surfaces, which
enhances phagocytosis
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.
Enhances inflammation:
Stimulates histamine
release, increases blood
vessel permeability,
attracts phagocytes by
chemotaxis, etc.
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell C3
C3b
C5b C6 C7 C8 C9
C3a
C5a
MAC
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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
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17. Adaptive Immunity Immunity against specific antigens Is of two types
Humoral Immunity
Cell mediated immunity

18. 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
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19. Figure 21.8 Lymphocyte development, maturation, and activation.
Slide 1
Humoral immunity
Primary lymphoid organs
(red bone marrow and thymus)
Adaptive defenses
Cellular immunity
Secondary lymphoid organs
(lymph nodes, spleen, etc.)
Red bone marrow
Red bone marrow
Origin
• Both B and T lymphocyte precursors originate in red
bone marrow. 1
Lymphocyte
precursors
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. 2
Thymus
Red bone marrow
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. 3
Antigen
Antigen encounter and activation
• When a lymphocyte’s antigen receptors bind its antigen, that
lymphocyte can be activated. 4
Lymph node
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. 5
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20. Humoral Immunity Antibody-Mediated Immunity Produced by B cells
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

21. Clonal Selection of B Cells by Antigenic Stimulation
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.

22. Antibody
5 types: IgE IgM IgG IgD IgA

23. Consequences of Antibody Binding

24. 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.
Primary immune
response to antigen
A occurs after a delay.
104
103
Antibody titer (antibody concentration)
in plasma (arbitrary units)
102
101
Anti-
Bodies
to A
Anti-
Bodies
to B
100 7 14 21 28 35 42 49 56
First exposure
to antigen A
Second exposure to antigen A;
first exposure to antigen B
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Time (days)

25. Figure 21.13 Active and passive humoral immunity.
Naturally
acquired
Infection;
contact
with
pathogen
Artificially
Vaccine;
dead or
attenuated
pathogens
Antibodies
passed from
mother to
fetus via
placenta; or
to infant in
her milk
Injection of
exogenous
antibodies
(gamma
globulin)
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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
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29. 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.

30. T Cells Only Recognize Antigen Associated with MHC Molecules on Cell Surfaces

31. T cells Helper T cells- Cytotoxic T cells- Supressor 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

32. Role of Helper Tcells

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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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34. 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

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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
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36. Hypersensitivities

37. Thank You!