Transcript IMMUNE SYSTEM

IMMUNE SYSTEM
FOR STUDENT COPY
Key attributes of immune system
• 4 attributes that characterize the
immune system as a whole
– specificity
• antigen-antibody specificity
– diversity
• react to millions of antigens
– memory
• rapid 2° response
– ability to distinguish self vs. non-self
• maturation & training process to reduce autoimmune disease
Immune System
• must be able to identify nonself from self
• detection determined by molecular
recognition of receptor & cell-identity
markers molecules
Innate Immunity
• nonspecific defense that is active
immediately upon infection
• found in all animals & plants
• includes:
– outer covering
• skin
– chemical secretions
• @ openings to interior of body
– Mucous membranes
– Sweat glands
Innate Immunity
• defenses that body naturally has:
– Skin
– Secretions
– Phagocytes
– Natural killer cells
Barrier Defenses
• epithelial tissues block entry of many
pathogens
– skin
– mucous membranes
• line organs that have opening to outside of
body
• mucus: viscous fluid that blocks microbes &
other particles
• saliva, tears have “washing” action keeping
microbes from colonizing
Barrier Defenses
• cellular secretions
– lysozyme kills by breaking down cell walls
– saliva, tears dilute & prevent colonization
– sweat pH 3 – 4
– stomach pH 2
Adaptive Immunity
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found only in vertebrates
very specific
aka acquired immune response
activated after innate responses &
develops more slowly
2nd line: Internal, broad range patrol
• Innate, general defense
– rapid response
• Patrolling cells & proteins
– attack invaders that penetrate
body’s outer
barriers
• leukocytes
– phagocytic white blood cells
• complement system
– anti-microbial proteins
• inflammatory response
leukocytes
Internal Innate Defenses
1. phagocytes
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cells that can detect fungi & bacteria
then engulf them
Types of Phagocytic Cells(#4)
1. Neutrophils
– circulate in blood
– attracted by signals sent from infected cells
2. Macrophages
– larger cells migrate thru tissues or reside
permanently in organs/tissues likely to have
invaders
Types of Phagocytic Cells
3. Dendritic cells
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mainly found in tissues with contact to
outside (skin)
– stimulate adaptive immunity after engulfing
pathogen
4. Eosinophils
– found beneath mucous membranes
– low phagocytic activity
– speciality: able to defend against parasitic worms
 secrete enzymes
Neutrophils
60 to70 % of all WBCs
Active phagocytes
Number increases rapidly
during short term or acute
infections
Eosinophils
2 to 4 % of all WBCs
Increase during allergy attacks
React to parasitic worms
Inactivate some inflammatory
chemicals
Lymphocytes
20 to 25 % of all
WBCs
Provides Immunity
(eg. Killer T-Cell)
Produces antibodies
Nucleus fills most of
the cell
Inflammatory Response
• innate immune defense triggered by
physical injury or infection of tissue
involving the release of substances that
promote swelling, enhance the infiltration
of WBCs, & aid in tissue repair &
destruction of invading pathogens
Inflammatory Response
Histamine
• 1 of inflammatory signaling molecules
• stored in granules of mast cells (in CT)
Fever: Abnormally High Body
Temperature
• Hypothalamus normally set at 37°C.
• Gram-negative endotoxin cause phagocytes to
release interleukin–1 (IL–1).
• Hypothalamus releases prostaglandins that
reset the hypothalamus to a high temperature.
• Body increases rate of metabolism and shivering
which raise temperature.
• When IL–1 is eliminated, body temperature falls
(crisis).
Fever
• Advantages
– Increase transferrins
– Increase IL–1 activity
• Disadvantages
– Tachycardia
– Acidosis
– Dehydration
Some Pathogens Evade Innate
Immunity
• Bacteria:
– some have outer capsule that interferes with
recognition & phagocytosis
– Streptococcus pneumoniae
Natural Killer Cells
• circulate thru body detecting abnl surface
proteins of cells infected with virus or
cancer cells
• on detection  secrete chemicals that kill
affected cell
Destroying cells gone bad!
• Natural Killer Cells perforate cells
– release perforin protein
– insert into membrane of target cell
– forms pore allowing fluid to
flow into cell
natural killer cell
– cell ruptures (lysis)
• apoptosis
perforin
perforin
punctures
cell membrane
vesicle
cell
membrane
cell
membrane
virus-infected cell
Anti-microbial proteins
• Complement system
– ~20 proteins circulating in blood plasma
– attack bacterial & fungal cells
• form a membrane attack complex
• perforate target cell
• apoptosis
extracellular fluid
– cell lysis
complement proteins
form cellular lesion
plasma membrane of invading
microbe
complement proteins
bacterial cell
3rd line: Acquired (active) Immunity
• Specific defense
– lymphocytes
• B lymphocytes (B cells)
• T lymphocytes (T cells)
– antibodies
• immunoglobulins
• Responds to…
– antigens
• specific pathogens
• specific toxins
• abnormal body cells
(cancer)
4 Major Characteristics of Acquired
Immunity
1. immense diversity of lymphocytes &
receptors
– enables immune system to detect
pathogens never before encountered
2. adaptive immunity normally has
“self” tolerance
– arises as B cell matures
4 Major Characteristics of Adaptive
Immunity
3. cell proliferation triggered by activation
greatly increases the # of B and T cells
4. there is a stronger & more rapid response
to agn previously encountered
– immunological memory occurs after mature
lymphocyte encounters & binds to a specific
agn
How are invaders recognized: antigens
• Antigens
– proteins that serve as cellular name tags
• foreign antigens cause response from WBCs
– viruses, bacteria, protozoa, parasitic worms, fungi, toxins
– non-pathogens: pollen & transplanted tissue
• B cells & T cells respond to different antigens
– B cells recognize intact antigens
• pathogens in blood & lymph
– T cells recognize antigen fragments
• pathogens which have already infected cells
“self”
“foreign”
Thymus
• organ in thoracic cavity
• some new lymphocytes travel from
bone marrow  thymus & are
“taught” how to respond in immune
attack  mature into T cells
Lymphocytes
• B cells
– mature in bone marrow
– humoral response system
• “humors” = body fluids
• produce antibodies
• T cells
– mature in thymus
– cellular response system
• Learn to distinguish
“self” from “non-self”
antigens during maturation
– if they react to “self” antigens,
they are destroyed during maturation
bone marrow
B cells
• Humoral response = “in fluid”
– defense against attackers circulating
freely in blood & lymph
• Specific response
– produce specific antibodies
against specific antigen
• Types of B cells
• plasma cells
– immediate production of antibodies
– rapid response, short term release
• memory cells
– long term immunity
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• Proteins that bind to a specific antigen
• “this is foreign…gotcha!”
antigenbinding site on
antibody
antigen
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– tagging “handcuffs”
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• millions of antibodies respond to millions of foreign
antigens
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– multi-chain proteins produced by B cells
– binding region matches molecular shape of antigens
– each antibody is unique & specific
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Antibodies
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variable
binding region
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each B cell
has ~100,000
antigen receptors
Structure of antibodies
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antigen-binding site
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light
chain
B cell
membrane
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variable region
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light
chain
heavy
chains
light chains
antigen-binding
site
heavy chains
antigen-binding
site
How antibodies work
invading pathogens
tagged with antibodies
macrophage
eating tagged invaders
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B Cell Activation
• starts when agn binds to a B cell agn
receptor
• ends with B cell secreting soluble form of
its agn receptor = antibody (aby) or
immunoglobulin (Ig)
• abys have same “Y” shaped organization as
the B cell agn receptor
10 to 17 days for full response
B cell immune response
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clone
1000s of clone cells
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recognition
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release antibodies
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plasma cells
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“reserves”
captured
invaders
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B cells + antibodies
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memory cells
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invader
(foreign antigen)
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tested by
B cells
(in blood & lymph)
Humoral Immunity
B-Cells
• Long Term Memory
• B-Cells make antibodies which trigger a TCell reaction to kill the invader
• Vaccines, Chicken Pox, Viral
Infections
Humoral
Immunity
(Go animation)
Types of Antibodies
• IgG
– major immunoglobulin in extra vascular spaces
– crosses placenta
• IgA
– in secretions
• IgM
– 1st immunoglobulin to be made by fetus
– very good at clumping microorganisms
Types of Antibodies
• IgD
– mostly found on B cell surfaces
• IgE
– involved in allergic reactions
– levels rise in helminthic parasitic infections
(worms)
Antibody Function
• do not kill pathogens
• bind to agns  inactivation or destruction
Immunological Memory
• gives individual long term protection from
an infection or vaccination
• Primary Immune Response
– produces effector cells from a clone of
lymphocytes
– peaks 10 -17 days after initial exposure
1° vs 2° response to disease
• Memory B cells allow a rapid, amplified response
with future exposure to pathogen
Humoral Immune Response
• occurs in blood &
lymph
• abys neutralize or
eliminate toxins &
pathogen in blood or
lymph
• includes a primary &
secondary immune
response
Cell-Mediated Immune Response
• specialized T cells
destroy infected host
cells
• includes primary &
secondary immune
responses
Vaccinations
• Immune system exposed
to harmless version of pathogen
– triggers active immunity
– stimulates immune system to produce
antibodies to invader
– rapid response if
future exposure
• Most successful
against viral diseases
Jonas Salk
April 12, 1955
• Developed first vaccine
– against polio
• attacks motor neurons
Albert Sabin
1962
oral vaccine
1914 – 1995
Passive Immunity
• Obtaining antibodies from another
individual
• Maternal immunity
– antibodies pass from mother to baby across
placenta or in mother’s milk
– critical role of breastfeeding in infant health
• mother is creating antibodies against pathogens
baby is being exposed to
• Injection
– injection of antibodies
– short-term immunity
Artificial Active Immunity
• Immunizations: introduce agns to body 
abys develop giving immunity to person
receiving vaccination
• Jenner: took cowpox virus to induce
adaptive immunity against small pox
(closely related viruses)
Small Pox Vaccination
Tissue & Organ Transplants
• MHC molecules stimulate the immune
response that  rejection
• MHC molecules have many alleles and any
1 individual has many that vary in shape &
charge
• for most transplant recipients there will be
some MHC molecules seen as foreign
Moon Face
Graft Versus Host Rejection
• seen in bone marrow transplants
• recipient’s bone marrow radiated b/4 to
get rid of abnl cells  also wipes out their
immune system
• lymphocytes in donor’s marrow react to
“foreign” recipients tissues and cells
Allergic Response
• agn attaches to IgE
abys on mast cells
• when cross linked 
release of histamine 
typical allergic
symptoms of itchy eyes,
sneezing, runny nose,
teary eyes, smooth
muscle contraction 
constriction of airways
What if the attacker gets past the
B cells in the blood & actually
infects some of your cells?
You need trained assassins to kill
off these infected cells!
T
Attack
of the
Killer T cells!
2007-2008
T cells
• Cell-mediated response
– immune response to infected cells
• viruses, bacteria & parasites (pathogens) within
cells
– defense against “non-self” cells
• cancer & transplant cells
• Types of T cells
– helper T cells
• alerts immune system
– killer (cytotoxic) T cells
• attack infected body cells
How do T cells know a cell is infected?
• Infected cells digest pathogens & MHC
proteins bind & carry pieces to cell surface
– antigen presenting cells (APC)
– alerts Helper T cells
infected
cell
WANTED
MHC proteins displaying
foreign antigens
T cell
T cell
antigen receptors
Cytotoxic T Cells
• in cell-mediated immune response
• role: effector cells
– synthesize toxic gene products that kill
infected cells
• activated by signaling molecules from
helper T cells + interaction with APC
T Cell response
infected cell
killer
T cell
helper
T cell
helper
T cell
helper
T cell
interleukin 1
or
activated
macrophage
activate
killer T cells
stimulate
B cells &
antibodies
helper
T cell
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helper
T cell
Attack of the Killer T cells
• Destroys infected body cells
– binds to target cell
– secretes perforin protein
• punctures cell membrane of infected cell
Killer T cell
binds to
infected cell
Killer T cell
vesicle
cell
membrane
infected cell
destroyed
perforin
punctures
cell membrane
target cell
cell
membrane
HIV & AIDS
• Human Immunodeficiency Virus
– virus infects helper T cells
– helper T cells don’t activate rest of immune
system: T cells & B cells
• also destroy T cells
• Acquired ImmunoDeficiency Syndrome
– infections by opportunistic
diseases
– death usually from other
infections
• pneumonia, cancer
How to protect yourself…
Immune system malfunctions
• Auto-immune diseases
– immune system attacks own molecules & cells
• lupus
– antibodies against many molecules released by normal
breakdown of cells
• rheumatoid arthritis
– antibodies causing damage to cartilage & bone
• diabetes
– beta-islet cells of pancreas attacked & destroyed
• multiple sclerosis
– T cells attack myelin sheath of brain & spinal cord nerves
• Allergies
– over-reaction to environmental antigens
• allergens = proteins on pollen, dust mites, in animal saliva
• stimulates release of histamine
Allergies
• exaggerated hypersensitivity reactions to
allergens: agn that triggers exaggerated
immune response
• most involve aby of IgE class
• example:
– hayfever
• agn on surface of pollen grains
Autoimmune Diseases
• Immune system reacts to some molecules
of self
Stress & the Immune System
• psychological stress disrupts immune
system by altering interplay of the nervous
system endocrine system & immune
system
• rest important for immunity
– adults with < 7 hrs sleep/nite : 3x more likely
to get sick when exposed to cold virus as those
who average 8 hrs sleep/nite
Lymphatic System
• network of vessels that connect lymphatic
tissues thru out body
– ECF  lymph vessels  lymph nodes 
lymph vessels  venous drainage
• some macrophages in lymph nodes
Lymphatic System