Lecture 3&4 early recognition and inflammation Flashcards
___________ cells recognize invading microbes
sentinel cells (guard cells)
T/F pathogens grow fast, must be detected and destroyed quickly
TRUE
What are the 3 types of sentinel (guard) cells that recognize pathogens
mast cells
macrophages
dendritic cell
how do sentinel cells recognize pathogens
they notice alarm signals by using their PRRs
what is a PRR
pattern recognition receptors
these identify PAMPs and DAMPs
what is a PAMP
Pathogen Associated Molecular Patterns
alarms signals are generated by: invading microorganisms (exogenous signals)
what is a DAMP
Damage Associated Molecular Pattern
(sometimes called Alarmins)
alarms signals are generated by: dead or dying host cells
DAMPs and PAMPs are identified by _________ present on ___________ cells located throughout the body so that leads to cytokines
PRRs (pattern recognition receptors)
sentinel
examples of PAMPs
bacterial lipopolysaccharides
bacterial peptidoglycan
bacterial DNA
Viral nucleic acids
Lipopolysaccharides are gram _______
negative
peptidoglycan are gram _______
positive
some DAMPs are released when cells _____ (intracellular) or generated when _______________ is damaged (extracellular)
die
connective tissue
when host cells die what happens to the mitochondria
may be recognized as the bacteria they once were
mitochondria were originally sing celled and its DNA is un-methylated so it presents as bacterial DNA
list some intracellular DAMPs
HMGB1 (most important)
uric acid
adenosine
list some extracellular DAMPs
hyaluronic acid
elastin
collagen derived peptides
**form connective tissue
why is HMGB-1 an important DAMP
it affects the epithelium, endothelium, dendritic cells, neutrophils, and macrophages
leads to severe inflammation
what are the categories of PRRs
soluble
within vesicles
cytoplasmic
membrane-bound
what kind of PRR are TLRs
membrane-bound
what are TLRs
Toll-like receptors; transmembrane glycoprotein receptors present on many different cell types including sentinel cells
most important PRRs
play a critical role in microbial sensing by recognizing viruses, fungi, and bacteria
located on cell surface to recognize extracellular invaders OR located in cell to recognize intracellular invaders
mammals posses _____to____ different functional TLRs. Humans and cattle have TLR__ to TLR___
10 to 12
1 to 10
what are the cell surface TLRs and what do they recognize
1,2,4,5,6,11
mainly recognize bacterial/fungal proteins, lipoproteins and LPA
what are the intracellular TLRs and what do they recognize
3,7,8,9,10
recognize viral and bacterial nucleic acids
why is inflammatory bowl disease so common in German Shepards
they have several single-nucleotide polymorphisms (SNPs) in the TLR4 and TLR5 genes
this suggest that their TLR4 and 5 have reduced the ability to defend against bacterial invasion resulting in predisposition to intestinal infections
RIG-like receptors are another family of PRRs expressed within the ___________. They recognize __________
cytosol
viral dsRNA
NLRs stand for
NOD-like receptors
NOD= nucleotide-binding oligomerization domain
what happens when a PAMP binds to TLR
TLR4 recognizes LPS (lipopolysaccharide= type of PAMP)
signal that PAMP and TLR have binded travels through sentinel cell
transcriptional factors get turned on
caspase-1 is then activated which turns cytokines on, leading to cytokines being released resulting in inflammation
when exposed to infectious agents or their PAMPs, sentinel cells synthesize and secrete 3 major cytokines
what are the 3 pro-inflammatory cytokines
TNF-alpha
IL-1
IL-6
sentinel cells trigger the release of cytokines (TNF-alpha, IL-1, and IL-6) leading to inflammation
How do these cytokines effect the hypothalamus, liver and bone marrow?
hypothalamus: fever, anorexia, sleepiness, depression
liver: iron sequestration (bacteria require iron to survive)
bone marrow: increased white cell production
smooth muscle: break down amino acid chains to get energy
natures way to make you stay home while you’re sick
tissue reaction that rapidly delivers mediators of host defense to the sites of infection and tissue damage
inflammation
what are the 3 essential roles inflammation plays in combating infection
- deliver additional effector molecules and cells to sites of infection to increase the killing of invading microbes by the front-line macrophages
- provide a physical barrier presenting the spread of infection
- promote the repair of injured tissue
MAIN PURPOSE of inflammation
focus the immune response to the site of the injury or infection
3 steps to the acute inflammatory response
surface wound introduces bacteria which activate resident effector cells to secrete cytokines
vasodilation and increased vascular permeability allow fluid, protein and inflammatory cells to leave blood and enter tissue
the infected tissue becomes inflamed, causing redness, heat, swelling and pain as leukocytes destroy microbes clear damaged cells and promote more inflammation/repair
cardinal signs of inflammation and why these occur
redness: increased blood flow to area of injury
heat: increased blood flow and action of pyrogens (fever-inducing agents)
swelling: due to increased extravascular fluid and phagocyte infiltration to damaged area
pain: local tissue destruction and irritation of sensory nerve receptors
if whole organ/tissue is involved– loss of function may occur
autosomal recessive immunodeficiency in holstein
BLAD (bovine leukocyte adhesion deficiency)
neutrophil cant get out of vessel to kill of infection
what initiates inflammation at the site of infection
response of macrophages to pathogens
list of pro-inflammatory mediators
cytokines
chemokines
vasoactive peptides
vasoactive lipids
vasoactive amines
coagulation system
effects of IL-1 on the cells of the body
macrophages see pathogen and produce IL-1
effects metabolism, blood flow, cell growth, leukocytes, kills cells, promotes inflammation
most important: affects the brain causing drowsiness, loss of appetite, and fever
effects of TNF-alpha on the cells of the body
macrophage/monocyte/T cells/ mast cells notice pathogen and produce TNF-alpha
TNF-alpha activates cells. promotes inflammation, enhances collagen synthesis, bone reabsorption but kills tumor cells
in low quantities of pro-inflammatory cytokines what are the clinical signs
local inflammation
macrophage and complement activation
in moderate quantities of pro-inflammatory cytokines what are the clinical signs
fever
lethargy
loss of appetite
neutrophilia
in high quantities of pro-inflammatory cytokines what are the clinical signs
vasodilation
increased vascular permeability
acute respiratory distress syndrome
septic shock can occur in cows with _____________. Endotoxin from the bacteria induces high quantities of pro-inflammatory _________
gram negative bacterial mastitis
cytokines
what are the two vasoactive amines
histamine (most important) and serotonin
vasoactive peptides C5a and C__ are called ______________, promote histamine release from mast cells. C__ is also a potent attractant for _________________
3a
anaphylotoxins
5a
neutrophils and monocytes
what activates the coagulation system
fluid from the blood vessels leak
large quantities of thrombin (clotting enzyme) is generated and fibrin is deposited forming a barrier
