Apr 22, 2013 ... Web Page: theory.bio.uu.nl/immbio. (check regularly for updates). • Book: The
Immune System by Peter Parham. • Teachers: Bontrop, de Boer, ...
4/22/13
ImmunoBiology 2013
Form of the course
• Coordinator: Can Keşmir (
[email protected]) Kruyt, Z509 • Web Page: theory.bio.uu.nl/immbio (check regularly for updates)
• Book: The Immune System by Peter Parham • Teachers: Bontrop, de Boer, de Haard, Klarenbeek,
Borghans and Kesmir, together with a number of TAs and quest lecturers.
• Overlaps with: Cancer and AIDS • ComputaUonal part:
• Lectures • Werkcolleges/Computer Exercises (in groups of 2 or 3) • Experimental work (PracUca, further seperaUon in groups A and B) • ArUcle discussions
– TheoreUcal Ecology/ComputaUonal Biology/Genome Biology 1
2
Volunteers for student lecture? (Bonus)
Assessment • Exam: 40% • Two wri\en reports
• You can choose one of the chapters 3-‐14 (or part of it) • You will prepare a lecture of 20 minutes • Slides/Figures of the corresponding chapter will be available • Please email me at least two days beforehand
– 25%: About one of the computer exercise/ werkcollege (there are 8 all together) – 20%: Experimental work and follow-‐up data analysis
• ArUcle presentaUons and discussions (15%)
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Chapter 1
Chapter 1 & 2:
Elements of the Immune System and their Roles in Defense
• Immunology is the study of physiological mechanisms that h
umans and other animals use to defend their bodies from invasion by other organisms
Elements of the Immune System and their Roles in Defense The innate immune system
• The hosts invests heavily in cells dedicated to defense, which collecUvely form the Immune system
5 © Garland Science 2009
Greatest triumph of Immunology: VaccinaUon or ImmunizaUon
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Immune cells
• In Asia people were immunized with small amounts of virus to induce protecUve immunity • Method was introduced in Western Europe in 1721 by Lady Montagu • Edward Jenner introduced in 1796 a safer method by inoculaUon with cowpox virus • Jenner called this method vaccinaUon ager the mild disease (vaccinia) produced by cowpox 7
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Innate and adapUve immunity are complimentary
EvoluUon of the immune system
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Chapter 1
Elements of the Immune System and their Roles in Defense
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Creepies and Crawlies a) b) c) d) e) f) g) h) i) j) k) l)
Chapter 1
HIV-‐1 Influenza virus Staphylococcus aureus Streptococcus pyogenes Salmonella enteri5dis Mycobacterium tuberculosis Listeria monocytogenes Pneumocys5s carinii Epidermophyton floccosum Candida albicans Trypanosoma brucei Schistosoma mansoni
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Elements of the Immune System and their Roles in Defense
Skin and mucosal surfaces form barriers against infecUon
Strong barriers to infecUon provided by the skin, hair and nails are colored blue. More vulnerable mucosal membranes are colored red
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Chapter 1
Elements of the Immune System and their Roles in Defense
Immune defense involves recogniUon of pathogens followed by their destrucUon
Not all microorganisms are pathogens. Numerous commensal ones inhabit healthy human bodies
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Immune cells
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What do we learn from this exercise?
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Chapter 2
Chapter 2
Innate Immunity
Innate immune receptors disUnguish features of microbial structure
Innate Immunity
Toll-‐like receptors sense the presence of infecUon
TLR are transmembrane proteins with a Toll-‐interleukin receptor (TIR) signalling domain on the cytoplamic side of the membrane and a horse shoe shaped sensor domain on the other side
• LecUns: recognizes carbohydrates that are not found in human body (mannose, glucan) • Scavenger: Ligands that are posiUvely charged (ogen Gram-‐posiUve bacteria) • CR3 and CR4: LPS
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AcUvaUon of resident macrophages induces inflammaUon at sites of infecUon
ProtecUon and danger: Macrophages
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TNF-‐α released by macrophages induces protecUon at the local level but can lead to a catastrophe when released systemically 26
Neutrophils are dedicated phagocytes that are summoned to sites of infecUon
40-‐75% of leukocytes are neutrophils
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A small wound made in the ventral tail fin of a 4-‐day-‐old zebrafish larva results in recruitment of fluorescently tagged neutrophils (red) to the wound site within minutes, where they persist for several hours, providing a miniature model of the human wound inflammatory response. Hydrogen peroxide is implicated as the earliest signal recruiUng neutrophils to the wound. 28 MarUn & Feng, Nature 2009.
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Neutrophils express receptors for many bacterial and fungal consUtuents
Chapter 2
Innate Immunity
Neutrophils die young! Macrophages live longer….
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Chapter 2
Innate Immunity
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Chapter 1
Elements of the Immune System and their Roles in Defense
The adapUve immune response adds to an ongoing innate immune response
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Chapter 1
Elements of the Immune System and their Roles in Defense
Most lymphocytes are present in specialized lymphoid Ussues
CirculaUng lymphocytes meet lymph-‐borne pathogens in draining lymph nodes
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Architecture of the lymp node, the place where blood-‐borne lymphocytes respond to lymph-‐borne pathogens
Clonal selecUon of lymphocytes by a pathogen (adapUve response)
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Chapter 1
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Chapter 1
Elements of the Immune System and their Roles in Defense
AdapUve immune responses generally give rise to long-‐lived immunological memory and protecUve immunity
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Elements of the Immune System and their Roles in Defense
Spleen provides adapUve immunity to blood infecUons
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Chapter 1
Other components of the innate immune system
Elements of the Immune System and their Roles in Defense
Most lymphoid Ussue is associated with the gut
• NK Cells • Complement
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Chapter 2
Chapter 2
Innate Immunity NK cells provide an early defense against intracellular infecUons
Innate Immunity NK-‐cell receptors differ in the ligands they bind and the signals they generate
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NK cell receptors disUnguish unhealthy cells from healthy cells
NK cells regulate other immune responses
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Modeling NK cell regula5on within hosts and host-‐pathogen co-‐evolu5on in popula5ons
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Complement System • Ancient defence mechanism (>1.000 Myears) • Involves 30 large mulU-‐domain plasma proteins and cell-‐surface receptors • Two-‐edged sword: – Clearance of pathogens – Host Ussue damage
• When pathological: therapies needed to control (down-‐regulate or acUvate) complement responses • Interested? Check out Piet Gros’ group h\p://www.crystal.chem.uu.nl/~gros/ complement.html
Paola Carillo-‐Bustamante Lecture: 3rd of May 47
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Most important: C3
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Beginning of the cascade: alternaUve pathway
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C3b bound pathogens are taken in and removed faster from the system
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Protec5on of host cells from Complement responses
Other complement proteins in acUon
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CD59 prevents membrane a\ack complex formaUon on human cells
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