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Altered
Spring 09
Immune Responses
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Immunity “a truly amazing constellation of responses to
attacks from outside the body”
• A state of resistance to an agent (the pathogen) that
normally produces an infection
– microorganisms such as bacteria and viruses
– Parasites
– fungus
– Cancer (rids body of altered cells)
• Also recognizes self from non-self
– Cells
– Tissue
– Organs
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Self/non-self recognition
• Achieved by having every cell display a
marker based on the major
histocompatibility complex (MHC).
• Any cell not displaying this marker is
treated as non-self and attacked.
• The process is so effective that undigested
proteins are treated as antigens.
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Normal Immune Response
• Three functions
– Defense
• Specialized cells and structures against invasions by
microorganisms
• Prevents development of infection by attacking foreign
antigens and pathogens
– Homeostasis
• Maintains healthy internal environment
• Damaged or old cellular substances are digested and
removed primarily by the spleen
– Surveillance
• Identifies mutations that continually arise in body but are
normally recognized as foreign cell and destroyed
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Anatomy of the Immune System
Immunity is responsiveness to foreign substances
• Comprised of cells and molecules with
specialized roles
• Defends against invasion and infection
• Major components
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Bone marrow (WBCs leukocytes)
Lymphoid tissue (nodes)
Thymus
Spleen
Tonsils
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Bone Marrow
• Production site of WBC
– Lymphocytes
• generated from stem cells (Undifferentiated cells)
• B lymphocytes (B cells)
– Mature in bone marrow
– Enter Circulation (“B” “Blood”)
– 10%-20%
• T lymphocytes
– Move from bone marrow to (t)hymus (“tissue”) to
mature into several kinds of cells capable of different
functions
– 60%-70%
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White Blood Cell Action
• Participate in both natural and acquired
– Granulocytes (granular leukocytes)
• Fight invasion by mediator release that engulfs
foreign bodies and toxins
– Histamine
– Bradykinin
– Prostaglandins
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Granulocytes
– Neutrophils
• First to arrive at the scene of inflammation
– Eosinophils and Basophils
• increase in number during allergic reactions
and stress response
– Monocytes and macrophages
• Engulfs, ingests, destroys
– Lymphocytes
• B cells and T cells
• Plays major roles in humoral and cell
medicated immune responses
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Lymphoid Organs
• Central (primary)
– Thymus gland
–Differentiation and maturation of T
lymphocytes
–Essential for cell-mediated immune
response
–Gland is large in childhood
–Shrinks to be collection of reticular fibers
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The human lymphoid system has
the following Secondary Organs:
• Peripheral (lymph nodes)at or near
possible portals of entry for pathogens:
• adenoids, tonsils, spleen (located at the upper
left of the abdomen),
• lymph nodes (along the lymphatic vessels with
concentrations in the neck, armpits, abdomen,
and groin)
• Peyer's patches (within the intestines)
• The appendix.
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Lymphoid Organs
– Tonsils (adenoids)- Associated lymphoid
tissues
– Gut- Associated lymphoid tissues
– Genital- Associated lymphoid tissues
– Bronchial- Associated lymphoid tissues
– Skin-Associated lymphoid tissues
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Lymphoid Tissues
• Lymph nodes distributed
throughout body
• Connected by lymph
channels and capillaries
• Removes foreign material
before entering
bloodstream
• Lymph nodes serve as
immune cell proliferation
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Lymphoid Organs
– Spleen (composed of red & white pulp)
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Red-destruction / recycling material
White-T and B lymphocytes
Filters foreign substances from blood
Red pulp-erythrocytes
Macrophages line pulp and sinuses
Major site of blood-borne antigens
If removed, can predispose to life-threatening
septicemia
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Types of Immunity
• Classified as:
– Natural (innate)
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Non-specific response to foreign invasion
Not produced by an immune response
Exists in a person without prior contact with an antigen
Usually species specific
– Acquired
• Active
• Passive
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Physical and Chemical Barriers
• Human body protects itself from invasion by
foreign substances (microorganisms)
• Complex defense system
• Nonspecific protection mechanisms
– Skin
– Cilia
– Coughing and Sneezing
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Physical and Chemical Barriers
• Chemical barriers
– Enzymes in tears
– Saliva enzymes
– Gastric acid secretions
– Mucus
– Sebaceous and sweat
– Phagocytosis by some WBCs
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Inflammatory Response
• Major function of the natural (non-specific or
innate) immune system
• Chemical mediators assist to:
– minimize blood loss
– wall off invading organism
– Activate phagocytes
– Promote formation of fibrous scar tissue
– Regenerate injured tissue
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Inflammatory Response
• Dysfunction when immune component are
inactivated or when they remain active long
after their effects are beneficial
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Immunodeficiencies
• Immune components
– Inactivation
– Impairment
• Disorders of inflammatory component
– Asthma
– “Allergies”
– Arthritis
Persistent inflammatory responses
“foreign rather than self”
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Types of Immunity
• Active Acquired
– Results from invasion
– Development of subsequent antibodies and
sensitized lymphocytes
– With each reinvasion, response to fight off
invader is more rapid and vigorous
– Results from disease or through inoculation of
less virulent antigen
– Takes time to develop but long-lasting
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Types of Immunity
• Passive Acquired
– Implies the host receives antibodies to an antigen
rather than synthesizing them
– May take place naturally through transfer of
immunoglobulins (mommy-baby)
– Artificial occurs through injection with gammaglobulin
– Short lived (host didn’t make it)
– Does not retain memory cells
for the antigen
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Humoral Immunity
• Immunoglobulins
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Composed of amino acids
Essential component in humoral response
IgG- only one that crosses placenta, secondary immunity
IgA- lines Mucous membranes, protects body surfaces
IgM- primary immune response, antibodies to ABO blood
antigens
– IgD- plasma, assists in differentiation of B-lymphocytes
– IgE- plasma, causes symptoms of allergic reactions, assists in
defense of parasitic infections
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Cell- mediated Immunity
• Cytokines
– Immune response involves complex
interactions of T-cells, B-cells, monocytes, and
neutrophils - depends on Cytokines
– Acts as messenger between the cell types
– Instruct cells to alter their proliferation,
differentiation, secretion, or activity
– 60 different ones
– Can have detrimental effects in inflammation,
autoimmunity, and infection
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Cell- mediated Immunity
• Macrophages
– Cytokines attract and activate macrophages in
area for immune response
– Macrophages secrete cytokines which
modulate response
– They release lysosomal enzymes that damage
surrounding tissue
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Haptens
• low molecular weight substances that by
themselves are harmless, however, they can form
complexes with larger molecules called carriers
that are antigenic
• Once antibodies produced, future exposure to
hapten alone can elicit immune response
• Common Haptens
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Dust
Dander
Drugs
Industrial chemicals
• Immune responses to haptens are basis for many
common allergies
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Cell- mediated Immunity
• Immune responses that are initiated through
specific antigen recognition by T cells
• T lymphocytes
– T-cytotoxic
• Attacks antigen on cell membrane and “pours”
cytolytic substance on it
– T-helper
• Positive signal, humoral antibody response, cellmediated immunity
– T-suppressor
• Decreases amount of T-helper cells
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T helper Cells
• Maximizes capabilities of immune system
• They have NO cytotoxic or phagocytic
activity, they do not kill
• Make the antibodies recognize the antigen
by tagging them (cytokines) and get T cells
and B cells activated to attack antigen and
or initiate inflammatory response
• helps signal other cells (like phagocytes) to
do their jobs.
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T-killer cell (cytoxic T cells)
• Differentiated T cells
• Destroys target cells only when specifically
activated by helper T cells.
• Recognize and lyse target cells bearing a
specific foreign antigen, usually by infection
with a virus
• Also function in defense against cancer
cells. Also called cytotoxic T cell, killer T cell.
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Cell- mediated Immunity
• Macrophages
• Natural killer cells (NK)
– Not T and not B
– Large lymphocytes
– Do not require prior sensitization for their
generation
– Involved in the recognition and killing of virusinfected cells, tumor cells, and transplanted grafts
– Has significant role in immune surveillance for
malignant cells
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Cellular Responses (T Cells)
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Transplant rejection
Delayed hypersensitivity (tuberculin reaction)
Graft vs. host disease
Tumor surveillance or destruction
Intracellular infections
Viral, fungal and parasitic infections
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Humoral Responses (B cells)
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Bacterial phagocytosis and lysis
Anaphylaxis
Allergy hay fever and asthma
Immune complex disease
Bacterial and some viral infections
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Complement System
• Circulating plasma proteins (made in liver, activated
when antibody couples with its antigen
• Interact sequentially with one another
• Cascade of events
– Alters cell membranes on which antigen-antibody complex
forms
– Permits fluid to enter cell
– Cell lysis and death
– Attracts macrophages and granulocytes to areas of antigenantibody reactions
– Devours antibody-coated microbes and releases bacterial
agents
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Complement System
• Activation of complement has 3 major
physiologic functions
– Defending body against bacterial infection
– Bridging natural and acquired immunity
– Disposing of immune complexes and
byproducts of inflammation
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Complement-mediated Immune
Responses
Cytolysis
Lysis and destruction of cell membranes of body cells
or pathogens
Iosonization
Targeting of antigen to be easily engulfed and digested
by macrophages, etc.
Chemotaxis
Chemical attraction of neutrophils and phagocytic cells
to the antigen
Anaphylaxis
Activation of mast cells and basophils with
inflammatory mediator release smooth muscle
contraction and increased vascular permeability
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Genetic Engineering
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Evolving technology
Involves use of recombinant DNA
Combine genes of a second organism
Allows for cells and microorganisms to
manufacture proteins, monokines and
lymphkines
• Can alter and enhance immune function
• Gene therapy –replace missing or damaged
gene
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Stem Cells
• Precursor cell that continually replenishes
red and white cells
• Immune system restored with implanted
refurbished stem cells
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Immunoregulation
• Eliminating the inciting antigen that has
stimulated the immune response
• When eliminated (as cascade cools down)
the response goes back to normal level
• Can better control disease by suppressing
areas of immune system that are overactive
• Boosting those areas that are under-active
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Immunity
• Affected by:
– Age
– Predisposition
– CNS function
– Emotional status, Stress
– Medications
– Trauma
– Surgery
– Illness
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Stress and the Immune System
• Stress of any type and duration will effect the
immune system
• Stress causes increased CORTISOL production
• Cortisol decreases production of ANTIBODIES
and other substances released by leukocytes
that stimulate other cells of the immune
system
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Stress and the Immune System
• Cortisol production occurs when
norepinephrine and epinephrine are
released by the SNS (FIGHT or FLIGHT)
• The combined effect of these three
hormones increases the total number of
neutrophils in the circulation
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Stress and the Immune System
• Lymphocyte maturation in the lymph nodes stops
because epinephrine decreases blood flow to the
lymph nodes as it increases blood flow to the
heart, lungs, brain and muscles
• These changes in the immune response brought
on by stress leave the body less capable of
fighting off the effects of injury, disease, and
other stress causes
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Stress Response
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Renin angiotensin aldosterone
mechanism
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Things That Can Go Wrong With the
Immune System
• Disorders of the immune system can be broken
down into four main categories:
• immunodeficiency disorders (primary or acquired)
• autoimmune disorders (in which the body's own
immune system attacks its own tissue as foreign
matter)
• allergic disorders (in which the immune system
overreacts in response to an antigen)
• cancers of the immune system
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Immunity
• The immune response that generates
immunity is also responsible in some
situations for
– Allergies
– Delayed hypersensitivity states
– Autoimmune disease
– And Transplant Rejection.
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