Blood and immunity II MFEL1010 - NTNUfolk.ntnu.no/audunfor/7. semester/Medisin... · Blood vessels...
Transcript of Blood and immunity II MFEL1010 - NTNUfolk.ntnu.no/audunfor/7. semester/Medisin... · Blood vessels...
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I:•Functions of the blood•The components of the blood•Blood clotting•Blood groups
II:•The immune system•The immune responses•Disorders of the immune system
•Allergic disease•Autoimmunity•HIV and immunosuppression
Blood and Immunity MFEL1010 2006, Torunn Bruland, IKM, DMF, NTNU
Outline..
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Your immune system
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Each of your cells has a set of 'identity tags' on itssurface, telling your body that it belongs to you.
Science & Society Picture Library
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The structure of the immune system
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Lymphatic tissue and organs
Tonsils
Lymph nodes
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Lymphatic tissue and organs
Spleen
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Lymphatic tissue and organs
Thymus
LM 10x
Trachea
LymphnodesThymusgland
Fat
Heart
Lobule
Thymiccorpuscle
MedullaCortex
Trabecula
Capsule
Trabecula
Lobule
Thymiccorpuscle
MedullaCortex
Bloodvessels
(a) (b)
(c)
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Lymphatic system and immunity
Valves
Fluid
Heart
Blood capillaries
B and Tcells
B and Tcells
Pre-T cells T cells
Red bone marrow
Small intestineThoracic duct
Arterial circulation Venous circulation
(a) Lymphaticcapillary
Lymphaticvessels (b)
Lymph(e)
Lymphatictrunks and ducts
(d)Lymph node
(filters lymph)(c)
Lactealsabsorb fats
(f)
Chyle(g)
Spleen (filters blood)(h)
Bone(i)
Thymus(j)
All lymphatic tissues(k)
B cellsPre-T cells
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When challenged, the immunsystem has many weapons to choose
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I:•Functions of the blood•The components of the blood•Blood clotting•Blood groups
II:•The immune system•The immune responses•Disorders of the immune system
•Allergic disease•Autoimmunity•HIV and immunosuppression
Blood and Immunity MFEL1010 2006, Torunn Bruland, IKM, DMF, NTNU
Outline..
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How does your immune system work?
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Immunity• Ability to resist damage from foreign substances as
microorganisms and harmful chemicals
• Categories– Innate or nonspecific resistance
• Mechanical mechanisms: prevent entry or remove microbes. Skin, tears, saliva, mucous membranes, mucus . Considered the acid mantle
• Chemical mediators: promote phagocytosis and inflammation
• Cells: involved in phagocytosis and production of chemicals
– Adaptive or specific immunity• Specificity: ability to recognize a particular substance• Memory: ability to remember previous encounters with a
particular substance and respond rapidly
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Mechanical mechanisms
• Skin, mucous membranes• Tears, saliva, and urine flush out bacteria• Cilia in respiratory tract• Coughing and sneezing
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Complement
Chemicals of innate immunity
•Surface chemicalsLysozymes
•Histamine•Kinins•Complement•Interferon•Prostaglandiner•Leukotriner•Pyrogener
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Interferons are antiviral proteins produced by cells in response to viral infection
• Prevent viral replication (Viruses use the molecular mechanisms of cells to reproduce themselves).
• Interferons produced by infected cell, but cause neighboring cells to produce antiviral proteins, thus act as a paracrine.
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Innate immunity: Cells
• White blood cells: most important cellular components of immune system. Must be able to move into infected tissues and destroy infection
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A white blood cell engulfing disease-causing bacteria
Phagocytes
Chemotaxis: movement toward the source of chemotactic factors (parts of microbes or chemicals act as chemical signals and attract WBCs)Phagocytosis: endocytosis by neutrophils and macrophages.
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Inflammatory response• Tissue injury regardless of type can cause inflammation• Response initiated by chemical mediators that produce
vasodilation, chemotactic attraction, increased vascular permeability. The latter allows fibrinogen and complement to enter tissue. Fibrinogen converted to fibrin, walls off infected area.
• Types– Local: confined to a specific area of the body. Symptoms are
redness, heat, swelling, pain, loss of function– Systemic: occurs in many parts of the body. Same symptoms as
local, but in addition: • Increase in neutrophil numbers released by red bone
marrow• Fever due to production of pyrogens by various kinds of
cells. Improves performance of immune system.• Widespread increased vascular permeability due to
histamines. Large volume of plasma enters interstitial spaces leading to shock
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Adaptive immunity
Involves the ability to a. recognize, b. respond to, c. remember a particular substance
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Adaptive immunity
• Types
– Humoral or Antibody-mediated: B cells
– Cell-mediated: T cells
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Adaptive immunity
• Stimulants– Antigens: large molecules
• Foreign: not produced by body, introduced from outside. – Bacteria, viruses, other microorganisms that cause
disease– Pollen, animal dander, feces of mites, foods, drugs
cause overreaction of immune system called allergic reaction.
• Self-antigens: produced by body. Used as markers to allow adaptive immune response to differentiate self from non-self.
– Response to self tumor antigens helpful– Response to self-antigens resulting in tissue
destruction: auto immune diseases
– Haptens: small molecules, combine with large proteins and producing an adaptive immune response.
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Origin and development of lymphocytes
Stem cell
Pre-B cell
Pre-T cell B cell
Circulation
Thymus
Pre-T cell
T cell
Red bone marrow
Circulation
B cell
T cell
Lymph nodeCirculation
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Activation of Lymphocytes
1. Lymphocytes must be able to recognize the antigen
2. After recognition, lymphocytes must increase in number to effectively destroy antigen
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Activation of lymphocytes: antigenic determinants
major histocompatibility complex(MHC) molecules attached to plasma membranes. Have variable region that can bind to foreign and self antigens.
Differentantigenicdeterminants
Antigen
Antigen-bindingsite
Variable region
Constant region
Cell interior
Plasma membrane
Cell exterior
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Major Histocompatability Complex (MHC)
• Class I. Found on surface of nucleated cells. In concert with antigens that were produced inside the cell from, for example, digested virus particles. Like displaying a flag saying “Kill me!”MHC-restricted: both MHCI and foreign antigen are displayed together
• Class II. Found on surface of antigen-presenting cells. B-cells, macrophages, monocytes and dendritic cells. Display of MHCII with foreign antigen is like “Rally round the flag”, stimulates other immune system cells to respond to the antigen.
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Antigen processing and MHC class I1. Foreign proteins or self-
proteins within the cytosolare broken down intofragments that are antigens.
2. Antigens are transportedinto the rough endoplasmicreticulum.
3. Antigens combine with MHCclass I molecules.
4. The MHC class I/antigencomplex is transported to theGolgi apparatus, packagedinto a vesicle, andtransported to the plasmamembrane.
5. Foreign antigens combinedwith MHC class I moleculesstimulate cell destruction.
6. Self-antigens combined withMHC class I molecules donot stimulate cell destruction.
Self-antigenSelf-antigen
Foreign antigenForeign antigen
Golgi apparatus
Roughendoplasmicreticulum
Roughendoplasmicreticulum
LumenLumenMembraneMembrane
MHC class ImoleculeMHC class Imolecule
Protein
Protein fragments(antigens)
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Antigen processing and MHC class II
5. The displayed MHC class II/antigen complex can stimulate immune cells.
4. The MHC class II/antigen complex is transported to the plasma membrane.
3. The vesicle containing theprocessed antigen fuses withvesicles produced by the Golgi apparatus that contain MHC class II molecules. Theprocessed antigen and the MHCclass II molecule combine.
2. The antigen is broken down into fragments to form processed antigens.
1. The unprocessed extracellularantigen is ingested byendocytosis and is within avesicle.
ProcessedantigenProcessedantigen
MHC class IImoleculeMHC class IImolecule
Vesicle containingprocessedantigen
Unprocessedantigen
Vesicle containingMHC class IImolecules
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MHC class I
MHC class II
Summary: antigen processingAntigens(protein fragments)
MHC class Imolecule
MHC class I/antigen complex
ProteinMembrane Lumen
Roughendoplasmicreticulum
Golgiapparatus
Normally does notstimulate celldestruction
Self-antigen
MHC class Imolecule
Foreign antigen
Stimulates celldestruction
Vesicle containingMHC class IImolecules
Foreignantigen
Vesicle containingprocessedforeign antigens
MHC class IImolecule
Processedforeign antigen
Stimulates immune cells
MHC class II/antigen complex
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To work effectively, most immune cellsneed the cooperation of their comrades
Sometimes immune cells communicate by direct physicalcontact, sometimes by releasing chemical messengers
30From http://nobelprize.org/medicine/educational/immunity/immune-detail.html
Antigen presentation
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Dendritic Cell and T- cell interacting
Dendritic cells (DC) are key antigen presenting cells
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Costimulation First signalMHCclass II molecule
Processedantigen
T-cellreceptor
Macrophage
HelperT cell
Cytokinereceptor
Costimulation by cytokines
MacrophageMHC class II molecule
Costimulation by surface molecules
B7 CD28
HelperT cell
CD4
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Proliferation of LymphocytesCells from original clones must proliferate before antigen can be attacked effectively
1. Proliferation of helper T cells2. Proliferation of cytotoxic T cells3. Proliferation of B cells
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Proliferation of Helper T Cells
Helper T cellcan be stimulated
to divide againHelper T cell can stimulate B cells or effector T cells
Daughterhelper T cell
Daughterhelper T cell
Helper T cellInterleukin-2 receptor
Interleukin-2
Interleukin-1 receptor
Costimulation
Interleukin-1
CD28CD4B7
T-cell receptorProcessed antigen
MHC class II molecule
Antigen Macrophage
Antigenprocessed
Helper T cell
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Proliferation of Cytotoxic T Cells
DaughterT cell
Target Cell CytotoxicT Cell
CD8
MHC class Imolecule
Processedantigen
T-cellreceptor
Interleukin-2
Helper T cell
DaughterT cell
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Cell-mediated immunity
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A strong immune system can kill cancer cells.
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During the killing process, granules in a T-Cell fuse with the cell membrane and release units of the protein PERFORIN. These combineto form pores in the target cell membrane.
Thereafter fluid and salts enter so that the target celleventually bursts.
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Proliferation of B Cells
DaughterB cell
B cell
Antibodies
Unprocessedantigen
B-cellreceptor
MHCclass IImolecule
Processedantigen
T-cellreceptor
Helper T cell
CD4
Interleukins
DaughterB cell
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40From http://nobelprize.org/medicine/educational/immunity/immune-detail.html
Antibody-mediated immunity
41.Mike Clark, Cambridge University
B-cells make antibodies
Antigen-binding sites
Complement-binding site
Site of binding to macrophages, basophils, and mast cells
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Actions of Antibodies
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INNATE IMMUNITY
ADAPTIVE IMMUNITY
Helper T cell can activate a B cell
Direct effectsagainst antigen
Antibody-mediated immunity Cell-mediated immunity
Plasma cell
Antibodies Cytokines
Memory B cell Memory T Cytotoxic T cell
Responsiblefor adaptive immunity
Lysis of cellsexpressing antigen
B cell proliferatesand differentiates.
Cytotoxic T cell proliferates and differentiates.
Helper T cellcan activate acytotoxic T cell
Cytokines and antibodiesenhance inflammationand phagocytosis.
Helper T cell proliferates andsecretes cytokines.
Macrophage
Antigen
Helper T cell
Helper T cell Helper T cell
B cell Cytotoxic T
Mechanicalmechanisms
Neutrophils, macrophages,basophils, and eosinophils
Chemicalmediators
Inflammation and phagocytosiscause destruction of the antigen.
Interferons preventviral infections.
Macrophage presentsprocessed antigen tohelper T cell(see figure 22.17).
INNATE IMMUNITY
ADAPTIVE IMMUNITY
Helper T cell can activate a B cell
Direct effectsagainst antigen
Antibody-mediated immunity Cell-mediated immunity
Plasma cell
Antibodies Cytokines
Memory B cell Memory T Cytotoxic T cell
Responsiblefor adaptive immunity
Lysis of cellsexpressing antigen
B cell proliferatesand differentiates.
Cytotoxic T cell proliferates and differentiates.
Helper T cellcan activate acytotoxic T cell
Cytokines and antibodiesenhance inflammationand phagocytosis.
Helper T cell proliferates andsecretes cytokines.
Macrophage
Antigen
Helper T cell
Helper T cell Helper T cell
B cell Cytotoxic T
Mechanicalmechanisms
Neutrophils, macrophages,basophils, and eosinophils
Chemicalmediators
Inflammation and phagocytosiscause destruction of the antigen.
Interferons preventviral infections.
Macrophage presentsprocessed antigen tohelper T cell(see figure 22.17).
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Ways to acquire adaptive immunity
Acquired adaptiveimmunity
The individual’s own immune systemis the cause of the immunity.
Active immunityImmunity is transferred from anotherperson or an animal.
Passive immunity
Antigens are introducedthrough naturalexposure.
Antigens are deliberately introducedin a vaccine.
Antibodies from the motherare transferred to her childacross the placenta or in milk.
Antibodies produced byanother person or an animal are injected.
ArtificialNaturalArtificialNatural
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I:•Functions of the blood•The components of the blood•Blood clotting•Blood groups
II:•The immune system•The immune responses•Disorders of the immune system
•Allergic diseases•Autoimmunity•HIV and immunosuppression
Blood and Immunity MFEL1010 2006, Torunn Bruland, IKM, DMF, NTNU
Outline..
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Allergic diseases
The most common types ofallergic diseases occur whenthe immune system respondsto a false alarm
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Autoimmune diseasesWhen the immune system mistakes self tissues for nonself and mounts an inappropriate attack, the result is an autoimmune disease.
482:1Chronic idiopathic thrombo-
cytopenic purpura
2:1Multiple sclerosis
2:1Myasthenia gravis
3:1Scleroderma
4:1Rheumatoid arthritis
7:1Graves' disease/hyperthyroiditis
8:1Chronic active hepatitis
8:1Mixed connective tissue disease
9:1 Primary biliary cirrhosis
9:1 Antiphospholipid syndrome
9:1 Sjogren's syndrome
9:1 Systemic lupus erythematosus
50:1Hashimoto's disease/hypothyroiditis
Female:Male Ratios in Autoimmune Diseases
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EnvelopeRNA
Capsid
Attachment Maturation
Regulatoryprotein
Structural protein
Reverse transcription
DNA
Uncoating
Penetration
Newgenome
Budding
Assembly
EnvelopeRNA
Capsid
Attachment Maturation
Regulatoryprotein
Structural protein
Reverse transcription
DNA
Uncoating
Penetration
Newgenome
Budding
Assembly
HIV infected cells producemassive amounts of virus
New copies of HIV bud from the surface of an infected Helper T cell
HIV attacks and kills crucial immune system cells
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HIV and Aquired immunodeficiencysyndrome (AIDS)
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HAART, or Highly Active Antiretroviral Therapy, is a combination of three or more drugs that target the HIV virus in different ways.
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I:•Functions of the blood•The components of the blood•Blood clotting•Blood groups
II:•The immune system•The immune responses•Disorders of the immune system
•Allergic disease•Autoimmunity•HIV and immunosuppression
Blood and Immunity MFEL1010 2006, Torunn Bruland, IKM, DMF, NTNU
Outline..
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Textbook
Seeley, Stephens, Tate: Essentials of Anatomy and Physiology, 6. edition, ISBN:007110805X. Chapter 11 and 14.
and selected websites
CellsAlive.com: Animations and images of human cells.
http://faculty.ccri.edu/kamontgomery/physiology%20outlines.htmPHYSIOLOGY LECTURE OUTLINES
http://nobelprize.org/medicine/educational/immunity/immune-detail.html
http://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htm
Torunn Bruland, DMF, IKM, [email protected]