IMM250H1 Study Guide - Final Guide: Innate Immune System, Chemokine, Cytokine

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Published on 8 Mar 2011
School
UTSG
Department
Immunology
Course
IMM250H1
Professor
Lecture FOUR: CELLULAR AND HUMORAL INNATE FACTORS
*recall: actions taken when a pathogen breaks through the barrier
ÆMAMPs released
Ædetection by TLR/Nod proteins/NLR
Æactivates a signal transduction
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Æcontrols cytokine production
ÆDAMPs released
Ædetected by NLRP (a type of NLR)
Æactivates a signal transduction
Æactivates inflammasome
Æcontrols IL-SURGXFWLRQ
*recall: differences between TLRs and NLRs
TLR NLR ± Nod proteins NLR ± NLRPs
Ædetects MAMPs Ædetect MAMPs ± peptidoglycan Ædetects DAMPs -- ROS
Æsignal transduction Æsignal transduction Æsignal transduction
ÆDFWLYDWHV1)%DQG,5) Æ DFWLYDWHV1)% Æactivates the inflammasome
Æleads to cytokine and interferon production Æleads to cytokine production Æproduces Il-
*Æafter the pathogen has been detected, innate immune mediators (cellular and humoral ± secreted) are needed
::cells of the innate immune system kill
::humoral/secreted mediators of the immune system kill and/or protect
innate immune response
Æpathogen with MAMPs damages the epithelium to break through the epithelial barrier
Æupon contact with microorganisms, PRMs DUHWULJJHUHGWRDFWLYDWH1)3,5)DQG&DVSDVHLQIODPPDVRPHDQGLQQDWHLPPXQHPHGLDWRUV± cytokines and
chemokines ± are produced
Æwhich result in inflammation
*cytokine: signalling molecules, enhance the ability of cells to remove pathogens; bring in effector cells that clean up the infection
::interleukins
::tumour necrosis factor alpha 715. = important in inflammatory response
*chemokine: family of chemotactic cytokines that attract other cells with a cytokine gradient to the site of infection
: consist of soluble proteins and peptides that modulate the behaviour of cells at small concentrations
: act locally and systemically
: have pleiotropic effects
::interleukin 8/CXCL8 = calls cells that can phagocytoze bacteria
::monocyte chemotactic peptide 1 (MCP1)
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ÆF\WRNLQHVDQGFKHPRNLQHVDUHDEOHWREULQJLQHIIHFWRUFHOOVRQFHWKH\YHOHIWEORRGYHVVHOV
*endothelial cells: cells that make up the blood vessels
Æendothelial cells under the epithelium are impermeable to cells in the blood stream and plasma
Æcytokines and chemokines cause *vasodilation: cells become more permeable
Ædue to vasodilation, serum can enter into the submucosal space under the epithelium; effector cells are also able to push through the endothelium to reach the
inflammation site
Æwhite blood cells (leukocytes) are brought to the site of infection
::innate system = leukocytes ::adaptive system = lymphocytes (T and B cells)
mechanism of cell migration (tethering & rolling)
Æcytokines activate epithelial cells to express *adhesion molecules: allow tethering of epithelial cells to leukocytes
Æ*selectins: proteins that allow sticking to cells and mediate tethering and rolling.
migration and diapedesis *diapedesis: when leukocytes push through the cell
Æfirm adhesion flattens the cell and allows for migration between the endothelial cells
Æinnate effector cells migrate towards the site of infection by following a chemokine gradient produced by infected epithelial cells
*note: pluripotent hemopoietic stem cells are able to differentiate into every leukocyte in the system; is present in the bone marrow
CELLS OF THE IMMUNE SYSTEM
Name
Immune System & Function
PLURIPOTENT HEMOPOIETIC STEM CELL
::COMMON LYMPHOID PROGENITOR : gives rise to cells of the adaptive immune system
T & B Lymphocytes
- adaptive immune system
natural killer cells (NK)
- both adaptive and innate immune system properties
- adaptive = derived from a common lymphoid progenitor
- innate = can directly kill
PLURIPOTENT HEMOPOIETIC STEM CELL
::MYELOID PROGENITOR : gives rise to cells of the innate immune system
dendritic cell, macrophage, monocyte
- phagocytosis
- antigen presentation
neutrophil, PMN
- phagoytic
- antibacterial
eosinophil
- anti-parasitic
- immunity ± allergy
basophil
- protection of mucosal surfaces
- allergy
mast cell
- protection of musical surfaces
- allergy
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PHAGOCYTES
Type
Function Mechanisms
Other Considerations
monocytes/macrophage
- eat pathogens
- kill pathogens
- help effectuate inflammatory response
- *antigen presentation: present chewed up pieces of
pathogen to T cells
- produces soluble mediators
FDOOHG³monocytes´ in the blood
FDOOHG³macrophages´ in tissue
liver = Kuppfer cells
brain = microglial cells
lung = alveolar macrophage
bone = osteoclast
denritic cells
- resident cells in mucosal tissues (roam around looking for
pathogens)
- sample bacteria via phagocytosis
- are professional antigen presentation cells
- initiates activation of T and B cells
have huge extensions = dendrites
neutrophils
- phagocytic neutrophils respond to epithelial chemokine
interleukin-8 (IL-8 )
- migrate from the blood into the tissue underlying the
infection
- cytoplasm contains granules that are full of toxic products
- after taking up microorganisms, release their granules and
die
- produces *NETs: neutrophil extracellular traps
- as it dies, extrudes its DNA which is stick and traps bacteria
allowing macrophages to clean it up along with the bacteria
first responders to inflammation (main role is to get to
the site of infection and kill microorganisms)
highly sensitive to IL-8 secreted by endothelium cells
also called polymorphonuclear leukocytes (PMNs)
high level in blood
cause a lot of damage to neighbouring tissues
phagocytosis
1) chemotaxis and adherence of microbe to phagocyte
2) ingestion of microbe by phagocyte
3) formation of a *phagosome: phagoctyic vesicle
4) *phagolysosome: fusion of the phagosome with a lysosome
5) phagolysosome undergoes a respiratory burst in which ROS is produced
6) digestion of ingested microbe by enzymes
7) formation of residual body containing indigestible material
8) *poop: discharge of waste materiality of pro-inflammatory cytokines
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