test 3: 62 -63 Flashcards
two types of immunity
innate and adaptive
innate immunity happens ___ by action by ___
quickly
phagocytes, dendritic cells, natural killer cells, complement cell
adaptive immunity happens ___ by action of ___
slowly
dedritic, T cells and B cells, Antibodies
autoimmune diseases are usually caused by problems in the ___ immune system
adaptive (long term T and B cells)
auto-inflammatory diseases are usually caused by problems in the ___ immune system
innate (fast acting- phagocytes)
FMF
familial mediterranean fever (type of auto- inflammatory disease caused by problem with the innate immune system.
persistent fever resistent to medications
similar to Familial Shar-Pei fever
___ is a response of vascularized tissues to infection or damaged tissues.
inflammation
2 types of inflammation
acute
chronic
Acute ___ goal is protective response of vascularized tissue and neutralize & eliminate agents
Inflammation
what are some things that can cause acute inflammation?
necrosis
bacteria/viruses
damage
___ (also called hypersensitivity ) are reactions in which the normally protective immune system damages the individual’s own tissues.
Immune reactions
during inflammation blood vessels will ___
vasodilate (get bigger)
What two cells are responsible for inflammation
neutrophils and macrophages
steps of inflammation
vasodilation
increased permeability
endothelial cell activation: important for leukocyte recruitment
redness in inflammation is caused by ___
vasodilation of blood vessels
vasodilation is induced by the chemical mediator ___
histamine
during vasodilation what happens?
histamine triggers endothelial cells to contract allowing spaces for neutrophils to leave blood flow into tissues
this allows for increased vessel diameter and fluid loss
=slower blood flow and increased viscosity
STASIS
STASIS
engorgement of small blood vessels with slowly moving red blood cells
what are some chemical mediators that help with endothelial cells contracting during acute inflammation response
histaime, bradykinin, leukotrienes
The vascular reactions of acute inflammation consist of changes in the ___ and the permeability of vessels, both designed to maximize the movement of plasma proteins and ___ out of the circulation and into the site of infection or injury.
flow of blood
leukocytes
___ is the loss of fluid and increased vessel diameter lead to slower blood flow, concentration of red cells in small vessels, and increased viscosity of the blood.
STASIS
As stasis develops, blood leukocytes, principally neutrophils, accumulate along the vascular endothelium due to damaged tissues expression ___.
adhesion molecules
4 steps of leukocyte getting into tissue
rolling
integrin activation by chemokines
stable adhesion
migration through endothelium
leukocytes are slowed down in the blood stream by ___ binding to ___. This activation will cause endothelial cells in the vessel wall to ___
integrin on leukocyte
selectin in vessel wall
contract
___ chemokine stimulates transmigration of leukocytes in between endothelial cells
PECAM1
leukocytes in tissue are attracted by ___ and then will ___
chemokines
eat (phagocyos) microbes. Eating bad things will trigger the leukocyte to produce cytokines which tigger an even bigger inflammatory response
macrophages that have eaten a microbe will release ___ that triggers ___
cytokines
inflammatory response
___ is the movement along a chemical gradient
chemotaxis
chemotaxis is regulated by chemical mediators such as bacterial products, ___, complement system (C5a) and arachiodonic acid metabolies
cytokines (chemokines, IL-8)
cytokines (____) from macrophages enhance expression of ___ on endothelial cells
TNF1, IL1
selectins (will grab and slow down leukocytes in blood so that it can be pulled out into issue that needs it)
TLR are ___
receptors that act as sensors that trigger inflammatory response
3 main events of chronic inflammation
inflammation and tissue injury
attempts at repair
immune response
causes of chronic inflammation
persistent infection
autoimmunity (attacks itself)
persistent exposure to chemicals
what cells are involved in chronic inflammation
T cell
B cell
macrophage
plasma cells
chronic inflammation will cause ___ formation in the tissues
fibrosis
___ development of fibrous connective tissue in response to injury
fibrosis
Tissue damage induces inflammation, and the amount of damage determines the type of inflammation (___ vs chronic)
acute
•Some tissue damage requires immune responses that favor tissue repair & ___ to maintain organ function
fibrosis
•Damaged epithelial cells release specific cytokines (___) that promote fibrosis
IL-25, IL-33, TSLP
•Autoimmunity: when inflammatory response is inappropriately targeted to __ tissues
host
•Allergies: host reacting ___ against harmless environmental substance
excessively
how to stop acute inflammation
neutrophils are short lived (hours), work and then die. Produce stop signals
macrophages: switch in arachiodonic acid metabolite produced (from leukotrienes to lipoxins). produce anti-inflammatory cytokines. TGT-B, IL-10. Stop TNFa production
To stop acute inflammation macrophages: switch in arachiodonic acid metabolite produced (from ___ to lipoxins). produce anti-inflammatory cytokines such as ___. Stop TNFa production
leukotrienes
TGT-B, IL-10
___ is one of the first amines released during inflammation
histamine
histamine is stored as ___ in mast cells
granules
Histamine is released by cell ___ in response to stimuli
degradation
Histamine functions through ___ types of receptors
4 (H1-4)
cytokines come from ___ cells and act locally: endothelial activation and systemically: fever metabolic abnormalities, hypotension
macrophages, endothelial cells and mast cells
TNFalpha
Tumor Necrosis Factor
cytokine which is a protein
produced by produced by fibroblasts, neutrophils, epithelial cells, smooth muscle cells
mTNF (inactive form) cleaved to active (sTNF)
regulates growth, differentiation, proliferation, apoptosis, inflammatory response
TNFa can induce activation/inflammation or ___
apoptosis
TNFR1 can lead to apoptosis in the cell by __
death domain
TNFa binds to TNFR1
this recuits DISC proteins TRADD,FADD and TRAF2
activates caspase-8
and leads to apoptosis
TNFR2 leads to cell activation by ___
TNFa binds to TNFR2
recruits DISC protein: TRAF2
this binds to NIK (NF-KB) inducing kinase
this activates TNFa gene transcription
NK-KB global activator of inflammatory cytokines (IL6-IL8)
how to target TNFa
infliximab
antibody to bind to TNFa protein and prevent it from binding to cells
feline infectious peritonitis is caused by ___
feline corona virus (FCoV)
feline infectious peritonitis
caused by Feline corona virus 10%
two forms: wet and dry
Risk factors: age, genetics, stress and viral dose
Treatment for FIP
TNF alpha activity neutralizing antibody causes apoptosis
and
antiviral treatment GS4415524
IL-1
cytokines
IL-1 family has a bunch of members: IL-1a and IL-1b are most studied
___ acts locally (associates with plasma membrane of secreted cell).
Widespread expression, even keratinocytes & endothelial cells
IL-1a
___ is secreted & circulates systemically.
Produced by monocytes & macrophages
IL-1B
IL-1 can act on dendritic cells and stimulate
increased cytokine production, upregulation of MHC and co stimulatory molecules
IL-1 acts on macrophages to __
increase cytokine production and phagocytosis
IL-1 acts on neutrophils to ___
increase survival, adhesion, oxidative burst and protease release
IL-1 receptors acts as herterodimer, you can try to prevent this with ___ and ___
antagonist (IL-1Ra)
decoy receptor (IL-1R2)
Familial Mediterranean Fever
recurrent fever syndrome
leukocytes- induced inflammation
-caused by mis-sense mutation in CTD of MEFV gene that produces pyrin protein
pyrin regulates ___ assembly
inflammasome
pyrin binds to ASC to prevent it from binding to pro-caspase 1 and causing inflammation and fever
(pyrin is protein that goes wrong in Familiar Mediterranean Fever syndrome)
pyrin competes with ___ to bind to ASC in the inflammation pathway
procaspase 1
shar-pei dogs have ___ deposits in thickened skin
hyaluronic acid
hyaluronic acid found in folds of sharpei dogs can trigger ___ immune system to stimulate inflammation
innate
for hyaluronic acid, ___ is the rate limiting receptor
HAS2
in shar-pei, ___ receptor is over expressed in dermal fibroblasts
HAS2 → dog has more receptors more hyaluronic acid → inflammation response
the paper on Familial Shar-Pei Fever looked to find gene responsible by __
looked for heterozygosity between shar-pei and other breeds
chromosome 13- showed duplication for the HAS2 gene
paper did not observe a significant correlation between serum HA levels and copy number of shar-pei duplication
SNP(single nucleotide polymorphisms) associated with FSF also correlated with high selective pressure (homozygosity) at the HAS2 gene
