Lecture 6 Flashcards
(30 cards)
What are the Clinical symptoms of inflammation?
Redness
Dilatation of small blood vessels and increased blood flow
Heat
Dilatation of small blood vessels and increased blood flow
Swelling
Accumulation of fluid and inflammatory cells in the extravascular space
Pain
Stretching and distortion of tissues by inflammatory fluid
Release of pain-inducing inflammatory mediators
Loss of function
Swelling and pain inhibit movement
cytokines
A diverse collection of soluble proteins and peptides that modulate the behaviour of cells at nanomolar to picomolar concentrations
Act both locally and systemically
Have highly pleiotropic effects
The activities of cytokines and chemokines often overlap with other cytokines and chemokines
In the innate immune response the principal sources of cytokines are….
(slide 7)
macrophages, mast cells, and dendritic cells that have been activated by the recognition of microbes.
What are some thing that an activated macrophage will secrete?
IL-1 IL-6 TNF-alpha IL-8 (CXCL8) IL-12
What pathway is up-regulated in an activated macrophage?
NF-kB pathway is activated leading to the production of these proinflammatory cytokines.
NF-kappa B
increase the amount of transcription of genere for :
IL-1 IL-6 TNF-alpha IL-8 (CXCL8) IL-12
The Major Proinflammatory Cytokines:
TNF, IL-1, and IL-6
The local effects of proinflammatory cytokines act to activate the local endothelium and subsequent recruitment of leukocytes. What are the steps?
Vasodilation- marginalization of leukocytes
Activation of endothelium- adhesion molecules make it sticky
Increased endothelial permeability- give space for leukocytes to traverse (diapedesis or extravasation)
Systemic Effects of Inflammatory Cytokines take place in which tissues?
LIver
Bone Marrow/Endothelium
Hypothalmus
Fat,Muscle
Pyrogens
IL-1 (MAIN!!)
IL-6
TNF-alpha
Pathogens (or pathogen products) that induce fever generally do so through inducing the production of these cytokines
endogenous pyrogens
Cytokines are called endogenous pyrogens because they originate inside of the body.
exogenous pyrogens
The bacterial products that induce fever are called exogenous pyrogens, because they originate outside of the body
wHY RAISE TEMP?
An elevated temperature slows pathogen growth. In addition, at higher temps. the body is thought to more actively sequester iron, which also limits bacterial growth.
iRON SEQUESTRATION (slide 11)
elevating temps in body will cause the body to store away iron. this is good bc it limits bacterial growth
IL-6 main role =
induce the production of Acute Phase proteins
Where are Acute Phase proteins secreted from?
LIver in response to inflammatroy cytokines
What are some key Acute Phase proteins?
Mannose-binding lectin (MBL): recognizes microbial carbohydrates, and can coat microbes for phagocytosis or activate the lectin complement pathway.
C-reactive protein: binds to phosphorylcholine on microbes and coats the microbes for phagocytosis by macrophages, which express a receptor for CRP. CRP can also trigger the classical complement pathway.
C-reactive protein= can check the level of this in the blood/serum to see if you are having inflame response
Acts as an Opsonin!!
Why are Excessive amounts of inflammatory cytokines released systemically extremely dangerous?
(slide 13)
Septic Shock:
The early clinical and
pathologic manifestations of septic shock are caused by very high levels of TNFa produced in response to a systemic bacterial infection.
Gram (-) bacteria will cause Sepsis
dec blood volume, collapse of vessels, organ failure
a major chemotactic factor for neutrophils
IL-8
IL-8 will signal the leukocytes to change the formation of their integrins and it will change from a low affinitiy state and then go to a HIGH AFFINITY CELLS- and this makes it go from rolling to firm adhesion, and then they will be able to go thru the endothelium (transmigration thru the tissue)
IL-12
slide 17
made by activated- macrophages and dendritic cells
So important cytokine bc is a link between the innate and the adaptive immunity
Activates NK cells–which make Interferon gamma (IFN-GAMMA) which causes the macrophages hulk out
induces CD4 T cells to differentiate into Th1 cells
The major innate cytokines produced in response to viral infection are ….
Type I Interferons (IFN)
Type I Interferons (IFN) is made of…..
Interferon-alpha (IFN-α)
Interferon-beta (IFN-β)
What is the function of IFN?
Secreted by virally infected cells and various leukocytes
Act to protect surrounding cells from becoming infected
IFN-gamma
this is secreted by the NK cells once marcophage secrete IL-12
what is the role of RIG-1 in a viral infection
slide 19
Important in the cytoplasm-
Host cells are alerted to the presence of a viral infection by the recognition of viral PAMPs (here dsRNA), by pattern recognition receptors, such as RIG-1.
Activate IRF
stimulate the production of type I interferons IFN-α and IFN-β
