human immune response · immune system . internal defense: ... which cell type is part of the...
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Human Immune Response
Part 1: innate immunity
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Our bodies are under constant
attack from pathogens
• A pathogen is an organism that can cause
disease
• Pathogens include:
– Bacteria
– Viruses
– Protists
– Fungi
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nucleic acid
capsid
envelope
Review: VIRUSES
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cell wall
plasma membrane
cytoplasm
circular DNA
Review: BACTERIA
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There are two types of
responses to pathogens INNATE IMMUNITY
• Non-specific: doesn’t
distinguish one infectious agent from another
• Rapid response to pathogens
• Is present before any exposure to pathogens
• Is effective from the time
of birth
ACQUIRED IMMUNITY (AKA Adaptive response)
• Specific response to a
particular antigen
• Slower response to pathogens
• Requires previous exposure to the pathogen
• Built over a life time of exposure to pathogens
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Two types of Innate Immunity
“First Line of Defense”
External defenses
– Skin
– Mucous membranes
– Chemical secretions
“Second Line of Defense”
Internal defenses
– Phagocytic cells
– Natural killer cells
– Antimicrobial proteins
– Inflammation
– Fever
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External Defense: Skin
• Cannot normally be penetrated by bacteria and viruses
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Secretions from sebaceous and sweat glands keep the skin in a pH range of 3 to 5 (acidic) which kills most microbes
External Defense: Skin
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Line digestive,
respiratory, and
genitourinary tracts
Trap microbes and
particles
External Defense:
Mucous Membranes
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• In the trachea, ciliated epithelial cells sweep out mucus and trapped microbes
• Prevents these from entering the lungs
• Swallowing exposes them to the acidic environment of the stomach
External Defense:
Mucous Membranes
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• Microbial colonization is also inhibited by saliva, tears, and mucus secretions
• All of these secretions contain antimicrobial proteins
External Defense:
Chemical Secretions
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• An example is lysozyme, an
enzyme that digests the cell walls of
many bacteria.
External Defense:
Chemical Secretions
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Two types of Innate Immunity
“First Line of Defense”
External defenses
– Skin
– Mucous membranes
– Chemical secretions
“Second Line of Defense”
Internal defenses
– Phagocytic cells
– Natural killer cells
– Antimicrobial proteins
– Inflammation
– Fever
Link to video clip
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Internal Defense:
Phagocytic cells
White blood cells (leukocyctes) that ingest
invading organisms
3m
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Internal Defense:
Phagocytic cells
Three types:
1. Macrophages
2. Esinophils
3. Neutrophils
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Internal Defense:
Phagocytic cells Macrophages
– Large, long-lived phagocytes
– Cells extend long pseudopodia, engulf the microbe into a vacuole which fuses with a lysosome.
– Some microbes have outer capsules to which macrophages cannot attach
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Link to animation
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Internal Defense:
Phagocytic cells
Esinophils
– Help fight large parasitic
invaders
– Position themselves
alongside the parasite
and discharge
destructive enzymes
through exocytosis
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Internal Defense:
Phagocytic cells
Neutrophils
• Most abundant white
blood cell
• Recruit and activate
other cells of the
immune system
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Internal Defense:
Phagocytic cells Neutrophils
• Have three strategies for directly attacking micro-organisms
– phagocytosis (ingestion)
– release of anti-microbial proteins
– generation of neutrophil extra cellular traps (NETs)
Link to video clip
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Internal Defense:
Natural Killer Cells
• Do not attack microbes directly
• They destroy infected cells (typically those infected with viruses)
• Also attack abnormal body cells that could become cancerous
• They attack the cell’s membrane and cause the cell to lyse Link to video clip
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Internal Defense:
Antimicrobial Proteins
• A variety of proteins that attack microbes
directly or impede microbe reproduction
• Example: Lysozyme
• Example: Interferons
– Secreted by virus-infected cells
– Do not benefit the infected cell but induce
neighboring cells to produce chemicals that
inhibit viral reproduction
Link to website
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Internal Defense:
Inflammation • Tissue damage leads to a localized
inflammatory response
– Could be injury
– Could be invasion by microbes
• Capillaries respond by:
– Increased dilation
– Increased permeability
– Enhanced delivery of clotting elements
– Enhanced migration of phagocytic cells
• Leads to increased redness, heat, and swelling
Link to video clip
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Major events in the local inflammatory response
Pathogen Pin
Macrophage
Chemical signals
Capillary
Phagocytic cells
Red blood cell
Blood
clotting
elements
Blood clot
Phagocytosis
Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
2
Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
1 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
3 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the site, and the
tissue heals.
4
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Internal Defense:
Fever • If damage or infection is
severe, a widespread non-specific response may occur
• Increased body temperature
• Inhibits growth of some microbes
• Facilitates phagocytosis
• Speeds up repair of tissue
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Two types of Innate Immunity
“First Line of Defense”
External defenses
– Skin
– Mucous membranes
– Chemical secretions
“Second Line of Defense”
Internal defenses
– Phagocytic cells
– Natural killer cells
– Antimicrobial proteins
– Inflammation
– Fever
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6.3.1 Define pathogen.
6.3.3 Outline the role of skin and
mucous membranes in defense
against pathogens.
6.3.4 Outline how phagocytic
leucocytes ingest pathogens in
the blood and in body tissues.
Assessment Statements
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Which of the following is NOT a "first
line of defense" in the immune
response?
A. Fever
B. Skin
C. Mucous membranes
D. Lysozyme
E. Tears
F. Saliva
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Which of the following is NOT a cell
of the innate immune system?
A. Natural killer
B. Macrophage
C. Neutrophil
D. T cell
E. Esinophil
F. Skin
A
B
C
D
E
F
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Which cell type is part of the innate
immune system?
A. Lymphocyte
B. Leukocyte A
B
C
D
E
F
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pH of the skin is:
A. Basic
B. Acidic
A
B
C
D
E
F
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Which of the following cells acts by
killing cells that have been infected
by a virus?
A. Skin
B. Neutrophil
C. Macrophage
D. Lymphocyte
E. Esinophil
F. Natural Killer
A
B
C
D
E
F
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Which molecule disrupts the viral
life cycle by preventing the
replication of DNA in infected cells?
A. Lysozyme
B. Interferons
C. Phagocytol
D. NETs
A
B
C
D
E
F
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Review
• “Second line defenses”
• Pathogen
• Acquired
• Virus
• Skin
• Phagocytic cells
• Natural killer cells
• Antimicrobial proteins
• Inflammation
• Fever
• Macrophages
• Esinophils
• Neutrophils
• Interferons
• Bacteria
• Innate
• “First line defenses”
• Mucous membrane
• Sebaceous gland
• Sweat gland
• Cilia
• Trachea
• Lysozyme
• Leukocyte
• Pseudopodia
• Lysosome
• Exocytosis
• NETs
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Human Immune Response
Part 2: acquired immunity
aka adaptive immunity
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Acquired Immunity
• The “third line of defense”
• The key cells of the third line of defense are
lymphocytes • B cells
• T Cells
• Lymphocytes recognize and respond to
specific microbes and the molecules on the
foreign cells membrane (antigens)
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• Antigens include:
Potentially damaging
microbes and
their toxins.
Substances such as pollen
and flea and dust mite feces.
Blood cell surface proteins.
The surface proteins of
transplanted tissues and
organs.
Photo
: E
II
Mallow pollen SEM.
Many pollens are antigens
The feces of fleas and mites
are antigenic in some people
Antigens
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• Lymphocytes originate
from pleuropotent stem
cells in the bone marrow or liver of a developing fetus
– If they migrate to the
thymus to mature, they
become T cells
– If they stay in the bone
marrow to mature, they
become B cells
Lymphocytes
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• B and T cells have
antigen receptors
– A single B or T cells
has about 100,000
receptors, all with
exactly the same
specificity
How do B and T cells
recognize antigens?
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– There is an
enormous variety of
B and T cells in the
body, each with
different specificity
– This allows
response to millions
of potential
pathogens
How do B and T cells
recognize antigens?
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While B cells and T cells are developing, their antigen
receptors are tested for potential self-reactivity
• “Will I attack cells of my own body?
– If YES: rendered non-functional or destroyed
by apoptosis
• This leaves only lymphocytes that react to
foreign substances
• Autoimmune diseases result when this
self-reactivity check malfunctions
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How do T and B cells differ?
• B cells: HUMORAL IMMUNE RESPONSE
• T cells: CELL MEDIATED IMMUNE RESPONSE
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HUMORAL IMMUNE RESPONSE
“challenge and response” • The immune system needs to "challenged" by
a disease
• The immune system “responds” by producing
a clone of "B" cells which produce large
amounts of antibodies to fight and eliminate
the pathogen.
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B cells: HUMORAL IMMUNE RESPONSE
1.Antigen floating in the blood binds to
receptor on B cell surface
2.B cell divides into two cell types:
• Plasma B cells:
• Memory B cells:
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HUMORAL IMMUNE RESPONSE
Plasma B cells
• Secrete antibodies
into the blood
immediately
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HUMORAL IMMUNE RESPONSE
Plasma B cells
• Antibodies are
proteins that attach to
specific pathogen
antigens
– Tip of antibodies
become specialized for
specific antigens
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Antibody Molecule
antigen binding sites
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HUMORAL IMMUNE RESPONSE
Plasma B cells
• The antibody / antigen
complex makes the
microbe easier targets
for phagocytes
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Inactivation of Antigens Clumping particulate
antigens
Solid antigens such as
bacteria are stuck together in
clumps.
Bacterial cell
Neutralization
Antibodies bind to viral
binding sites and coat
bacterial toxins.
Virus Toxin
Antibody
Enhances Phagocytosis
Macrophage
Bacteria
Soluble antigens are stuck
together to form
precipitates.
Precipitation of
soluble antigens
Soluble
antigens
Antibodies
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Free antigens directly activate
B
Cell
Gives
rise
to
Plasma
B Cells
Memory
B Cells
Secrete
antibodies
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HUMORAL IMMUNE RESPONSE
Memory B cells • Memory B cells:
– Long-lived cells bearing receptors for the same
specific antigen
– Eventually, a few cells give rise to thousands of
new cells—all clones of the original and all specific
to original invading antigen
– Memory cells will continue to divide and create
antibodies for the rest of the life of the organism
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1. A blood stem cell undergoes differentiation and
genetic rearrangement to produce:
2. immature lymphocytes with many different
antigen receptors. Those that bind to:
3. antigens from the body's own tissues are
destroyed, while the rest mature into:
4. inactive lymphocytes. Most of these will never
encounter a matching:
5. foreign antigen, but those that do are activated
and produce
6. many clones of themselves!
Division of antigen specific B
cells is called
CLONAL SELECTION
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B Cells
antibodies
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Activation of B Cells by
Antigen
antigen
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Clonal Selection
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Clonal Selection
plasma cells memory cells
antibodies
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T cells: CELL MEDIATED IMMUNE RESPONSE
– A viral infected cell exposes the antigen on its own
cell surface, to say… ”I’ve been infected…kill me”
– “Helper T cell” binds to the antigen exposed on the
surface of an infected cell
– “Helper T cells” release chemicals called cytokines
that activate macrophages, natural killer cells, and
“killer T cells”
– These cells respond by destroying the infected cell
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The rate of the immune response is different
depending on if the body has “seen” the antigen
before
• If it’s the first exposure:
– About 10 to 17 days required for peak
plasma B cell response
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The rate of the immune response is different
depending on if the body has “seen” the antigen
before
• Second (and subsequent) exposure:
– Response is faster (2 to 7 days)
– Magnitude is greater
– Duration is longer
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Types of
Acquired
Immunity
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Naturally Acquired Immunity
Naturally Acquired
Active
Antigens enter the body
naturally, as when:
• Microbes cause the person
to catch the disease.
• There is a sub-clinical infection
(one that produces no evident
symptoms).
The body produces specialized
lymphocytes and antibodies.
Passive
Antibodies pass from the mother
to the fetus via the placenta
during pregnancy or to her infant
through her milk.
The infant's body does not produce
any antibodies of its own.
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Artificially Acquired Immunity
Active
Antigens (weakened or dead
microbes or their fragments) are
introduced in vaccines.
The body produces and
specialized lymphocytes and
antibodies.
Passive
Preformed antibodies in an
immune serum are introduced
into the body by injection
(e.g. anti-venom used to
treat snake bites).
The body does not produce
any antibodies.
Artificially Acquired
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A summary of innate and acquired immunity
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic lymphocytes)
Invading
microbes
(pathogens)
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Assessment Statements
6.3.5 Distinguish between antigens and antibodies.
6.3.6 Explain antibody production.
11.1.2 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity.
11.1.3 Define active and passive immunity.
11.1.4 Explain antibody production.
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Immune Technologies
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Monoclonal Antibodies
• A monoclonal antibody is an
artificially produced antibody
for a specific antigen.
• Monoclonal antibodies are
useful for 3 reasons:
– They are totally uniform (i.e. clones).
– They can be produced in large quantities.
– They are highly specific.
Monoclonal antibodies
chemically linked to a
fluorescent dye to detect the
presence of gonorrhea
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Monoclonal Antibody Production
• Stimulate the production of B-cells
in mice by injecting them with the
antigen.
• These B-cells produce an
antibody against the antigen.
• B-cells isolated and fused with
immortal tumor cells.
• Immortal cells cultured indefinitely
in a suitable growing medium.
• Antibodies isolated via protein
chromatography
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Diagnostic Uses of
Monoclonal Antibodies • Monoclonal antibodies have many
diagnostic uses:
Detecting the presence of pathogens such as Chlamidia and
streptococcal bacteria, distinguishing between Herpesvirus I and II, and diagnosing AIDS.
Measuring protein, toxin, or drug levels in serum.
Blood and tissue typing.
Detection of antibiotic
residues in milk.
Detecting pregnancy.
Direct treatment of disease (i.e. rabies)
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Dipstick
Antibody moves
by capillary action
Antibodies
tagged
with blue
latex
HCG bound to
free antibody
HCG in the urine of a pregnant women binds to
the color-labeled antibodies. The antibodies
then travel up the dipstick by capillary action.
How Pregnancy Tests Work The test area of the dipstick contains two types of antibodies: free monoclonal antibodies and capture monoclonal antibodies, bound to the substrate in the test window (arrowed).
Immobilized
capture antibodies
Colored latex in
test window
The HCG-antibody complexes are bound by
capture antibodies. The labeled antibodies
create a coloured line in the test window.
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Assessment Statement
11.1.5 Describe the production of
monoclonal antibodies and their
use in diagnosis and in treatment.
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Vaccination
• Vaccination is the purposeful
administration of antigenic material to
produce immunity to a disease.
– live but weakened forms of pathogens
– killed or inactivated forms of pathogens
– purified material such as proteins
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Vaccination
• The vaccine stimulates clonal selection
and development of memory cells, but
without developing the disease symptoms.
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Vaccination
• If an infection of the disease occurs
naturally after vaccination, the body reacts
as if it is the second exposure to the
disease
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Vaccination
• Vaccination is generally considered to be
the most effective and cost-effective
method of preventing infectious diseases.
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Vaccination
BENEFITS
• Eradication of disease
from a population (i.e. small
pox)
• Reduced death from
disease (i.e. measles)
• Reduced disabilities from
disease (i.e. polio)
• Decreased loss of work
days due to disease (i.e. flu)
DANGERS
• Vaccine immunity less
effective than natural
immunity
• Side effects of vaccination
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Assessment Statements
11.1.6 Explain the principle of vaccination.
11.1.7 Discuss the benefits and dangers
of vaccination.
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Antibiotics
Antibiotics are substances that kills
bacteria or inhibits its growth
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Antibiotic Action
Antibiotics block metabolic pathways
and structures found in bacteria
– the bacterial cell wall
– bacterial ribosomes
– enzymes that are specific to bacteria
Viruses can’t do metabolism, so they
aren’t effected by antibiotics
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Assessment Statement
6.3.2 Explain why antibiotics are effective
against bacteria but not against
viruses.