topic 6: human physiology topic 6.3 defense against the infectious disease fighting the enemy...
TRANSCRIPT
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Topic 6: Human Physiology
• Topic 6.3
Defense against the infectious disease
Fighting theEnemy Within! phagocytic
leukocyte
lymphocytesattackingcancer cell
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Why an immune system?• Attack from outside
– lots of organisms want you for lunch!– animals are a tasty nutrient- & vitamin-packed meal
• cells are packages of macromolecules• no cell wall
– traded mobility for susceptibility
– animals must defend themselves against invaders • viruses
– HIV, flu, cold, measles, chicken pox, SARS• bacteria
– pneumonia, meningitis, tuberculosis• fungi
– yeast (“Athlete’s foot”…)• protists
– amoeba, Lyme disease, malaria
• Attack from inside– defend against abnormal body cells = cancers
Mmmmm,What’s in your
lunchbox?
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Avenues of attack
• Points of entry– digestive system– respiratory system– urogenital tract– break in skin
• Routes of attack– circulatory system– lymph system
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Lymph system Production & transport of leukocytes
Traps foreign invaders
lymph node
lymph vessels(intertwined amongst blood vessels)
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Lines of defense 1• 1st line: Barriers
– broad, external defense• “walls & moats”
– skin & mucus membranes
• 2nd line: Non-specific patrol– broad, internal defense
• “patrolling soldiers”
– leukocytes = phagocytic WBC• macrophages
• 3rd line: Immune system– specific, acquired immunity
• “elite trained units”
– lymphocytes & antibodies• B cells & T cells
Bacteria & insectsinherit resistance.
Vertebratesacquire immunity!
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Lines of Defense 2
Nonspecific Defense Mechanisms……
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1st line: External defense
• Physical & chemical defenses– non-specific defense
• external barrier– epithelial cells & mucus
membranes • skin• respiratory system• digestive system• uro-genital tract Lining of trachea:
ciliated cells & mucus secreting cells
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1st line: Chemical barriers on epithelium
• Skin & mucous membrane secretions– sweat
• pH 3-5
– tears• washing action
– mucus • traps microbes
– saliva • anti-bacterial = “lick your wounds”
– stomach acid • pH 2
– anti-microbial proteins• lysozyme enzyme
– digests bacterial cell walls
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2nd line: Internal, broad range patrol
leukocytesleukocytes• 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
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Leukocytes: Phagocytic WBCs • Attracted by chemical
signals released by damaged cells – enter infected tissue, engulf & ingest microbes
• lysosomes
• Neutrophils– most abundant WBC (~70%)– ~ 3 day lifespan
• Macrophages– “big eater”, long-lived
• Natural Killer Cells– destroy virus-infected cells
& cancer cells
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Phagocytic and Natural Killer Cells• Neutrophils
60-70% WBCs; engulf and destroy microbes at infected tissue
• Monocytes
5% WBCs; develop into….
• Macrophages
enzymatically destroy microbes
• Eosinophils
1.5% WBCs; destroy large parasitic invaders (blood flukes)
• Natural killer (NK) cells
destroy virus-infected body cells & abnormal cells
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Phagocytes
yeastmacrophage
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• Natural Killer Cells perforate cells– release perforin protein– insert into membrane of target cell– forms pore allowing fluid to
flow into cell– cell ruptures (lysis)
• apoptosis
Destroying cells gone bad!
perforin puncturescell membrane
cell membrane
natural killer cell
cell membrane
virus-infected cell
vesicle
perforin
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Anti-microbial proteins• Complement system
– ~20 proteins circulating in blood plasma– attack bacterial & fungal cells
• form a membrane attack complex• perforate target cell• apoptosis
plasma membrane of invading microbe
complement proteinsform cellular lesion
extracellular fluid
complement proteins
bacterial cell
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Inflammatory response 1• Damage to tissue triggers local
non-specific inflammatory response– release histamines & prostaglandins – capillaries dilate,
more permeable (leaky)• increase blood supply
• delivers WBC, RBC, platelets, clotting factors
• fight pathogens
• clot formation
• accounts for swelling, redness & heat of inflammation & infection
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Inflammatory response 2
Bacteria
Blood vessel
Chemicalalarm signals
Pin or splinterBlood clot
Phagocytes
swelling
• Reaction to tissue damage
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Fever • When a local response is not enough
– systemic response to infection
– activated macrophages release interleukin-1 (IL-1)• triggers hypothalamus in brain to readjust body thermostat to raise
body temperature
– higher temperature helps defense• inhibits bacterial growth
• stimulates phagocytosis
• speeds up repair of tissues
• causes liver & spleen to store iron, reducing blood iron levels
– bacteria need large amounts of iron to grow
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The Inflammatory Response• 1- Tissue injury; release of chemical signals~ • histamine (basophils/mast cells):
causes Step 2...• prostaglandins: increases blood flow & vessel permeability• 2/3- Dilation and increased permeability of capillary~ • chemokines: secreted by blood
vessel endothelial cells mediates phagocytotic migration of WBCs• 4- Phagocytosis of pathogens~ • fever & pyrogens: leukocyte-
released molecules increase body temperature
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• Specific defense – lymphocytes
• B lymphocytes (B cells)• T lymphocytes (T cells)
– antibodies • immunoglobulins
• Responds to…– antigens
• specific pathogens • specific toxins• abnormal body cells
(cancer)
3rd line: Acquired (active) Immunity
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“self” “foreign”
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
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How are cells tagged with antigens• Major histocompatibility (MHC) proteins
– antigen glycoproteins– MHC I – on all nucleated cells– MHC II – on macrophages, B-Ly, activated T-Ly
• MHC proteins constantly carry bits of cellular material from the cytosol to the cell surface– “snapshot” of what is going on inside cell– give the surface of cells a unique label or “fingerprint”
MHC proteinsdisplaying self-antigens
T cell
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Specific Immunity
• Lymphocyctes•pluripotent stem cells...
• B Cells (bone marrow)• T Cells (thymus)
• Antibodies: antigen-binding immunoglobulin, produced by B cells
• Antigen = a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms)
• Antigen receptors = plasma membrane receptors on B and T cells
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What else we’ll study? 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
T
Attack! It’s too late…
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Animals are a tasty nutrient- & vitamin-packed meal !
What’s thepoint?
To defend themselves
against invaders!
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HIV/AIDS - How to protect yourself…
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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
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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 auto-
immune disease
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It’s safe
to Ask Questions!
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Ghost of Lectures past(storage)
T
Did I miss a joke?
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Abnormal immune function• Allergies (anaphylactic shock): hypersensitive responses to environmental
antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine
• Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus
• Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.
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Induction of Immune Responses• Primary immune response: lymphocyte proliferation and
differentiation the 1st time the body is exposed to an antigen
• Plasma cells: antibody-producing effector B-cells
• Secondary immune response: immune response if the individual
is exposed to the same antigen at some later time~ Immunological memory