Lecture 3&4 early recognition and inflammation

Question 1

___________ cells recognize invading microbes

Answer 1

sentinel cells (guard cells)

Question 2

T/F pathogens grow fast, must be detected and destroyed quickly

Answer 2

TRUE

Question 3

What are the 3 types of sentinel (guard) cells that recognize pathogens

Answer 3

mast cells
macrophages
dendritic cell

Question 4

how do sentinel cells recognize pathogens

Answer 4

they notice alarm signals by using their PRRs

Question 5

what is a PRR

Answer 5

pattern recognition receptors

these identify PAMPs and DAMPs

Question 6

what is a PAMP

Answer 6

Pathogen Associated Molecular Patterns

alarms signals are generated by: invading microorganisms (exogenous signals)

Question 7

what is a DAMP

Answer 7

Damage Associated Molecular Pattern
(sometimes called Alarmins)

alarms signals are generated by: dead or dying host cells

Question 8

DAMPs and PAMPs are identified by _________ present on ___________ cells located throughout the body so that leads to cytokines

Answer 8

PRRs (pattern recognition receptors)
sentinel

Question 9

examples of PAMPs

Answer 9

bacterial lipopolysaccharides
bacterial peptidoglycan
bacterial DNA
Viral nucleic acids

Question 10

Lipopolysaccharides are gram _______

Answer 10

negative

Question 11

peptidoglycan are gram _______

Answer 11

positive

Question 12

some DAMPs are released when cells _____ (intracellular) or generated when _______________ is damaged (extracellular)

Answer 12

die
connective tissue

Question 13

when host cells die what happens to the mitochondria

Answer 13

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

Question 14

list some intracellular DAMPs

Answer 14

HMGB1 (most important)
uric acid
adenosine

Question 15

list some extracellular DAMPs

Answer 15

hyaluronic acid
elastin
collagen derived peptides

**form connective tissue

Question 16

why is HMGB-1 an important DAMP

Answer 16

it affects the epithelium, endothelium, dendritic cells, neutrophils, and macrophages

leads to severe inflammation

Question 17

what are the categories of PRRs

Answer 17

soluble
within vesicles
cytoplasmic
membrane-bound

Question 18

what kind of PRR are TLRs

Answer 18

membrane-bound

Question 19

what are TLRs

Answer 19

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

Question 20

mammals posses _____to____ different functional TLRs. Humans and cattle have TLR__ to TLR___

Answer 20

10 to 12
1 to 10

Question 21

what are the cell surface TLRs and what do they recognize

Answer 21

1,2,4,5,6,11

mainly recognize bacterial/fungal proteins, lipoproteins and LPA

Question 22

what are the intracellular TLRs and what do they recognize

Answer 22

3,7,8,9,10

recognize viral and bacterial nucleic acids

Question 23

why is inflammatory bowl disease so common in German Shepards

Answer 23

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

Question 24

RIG-like receptors are another family of PRRs expressed within the ___________. They recognize __________

Answer 24

cytosol
viral dsRNA

Question 25

NLRs stand for

Answer 25

NOD-like receptors NOD= nucleotide-binding oligomerization domain

Question 26

what happens when a PAMP binds to TLR

Answer 26

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

Question 27

when exposed to infectious agents or their PAMPs, sentinel cells synthesize and secrete 3 major cytokines what are the 3 pro-inflammatory cytokines

Answer 27

TNF-alpha IL-1 IL-6

Question 28

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?

Answer 28

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**

Question 29

tissue reaction that rapidly delivers mediators of host defense to the sites of infection and tissue damage

Answer 29

inflammation

Question 30

what are the 3 essential roles inflammation plays in combating infection

Answer 30

1. deliver additional effector molecules and cells to sites of infection to increase the killing of invading microbes by the front-line macrophages 2. provide a physical barrier presenting the spread of infection 3. promote the repair of injured tissue

Question 31

MAIN PURPOSE of inflammation

Answer 31

focus the immune response to the site of the injury or infection

Question 32

3 steps to the acute inflammatory response

Answer 32

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

Question 33

cardinal signs of inflammation and why these occur

Answer 33

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**

Question 34

autosomal recessive immunodeficiency in holstein

Answer 34

BLAD (bovine leukocyte adhesion deficiency) neutrophil cant get out of vessel to kill of infection

Question 35

what initiates inflammation at the site of infection

Answer 35

response of macrophages to pathogens

Question 36

list of pro-inflammatory mediators

Answer 36

cytokines chemokines vasoactive peptides vasoactive lipids vasoactive amines coagulation system

Question 37

effects of IL-1 on the cells of the body

Answer 37

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

Question 38

effects of TNF-alpha on the cells of the body

Answer 38

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

Question 39

in low quantities of pro-inflammatory cytokines what are the clinical signs

Answer 39

local inflammation macrophage and complement activation

Question 40

in moderate quantities of pro-inflammatory cytokines what are the clinical signs

Answer 40

fever lethargy loss of appetite neutrophilia

Question 41

in high quantities of pro-inflammatory cytokines what are the clinical signs

Answer 41

vasodilation increased vascular permeability acute respiratory distress syndrome

Question 42

septic shock can occur in cows with _____________. Endotoxin from the bacteria induces high quantities of pro-inflammatory _________

Answer 42

gram negative bacterial mastitis cytokines

Question 43

what are the two vasoactive amines

Answer 43

histamine (most important) and serotonin

Question 44

vasoactive peptides C5a and C__ are called ______________, promote histamine release from mast cells. C__ is also a potent attractant for _________________

Answer 44

3a anaphylotoxins 5a neutrophils and monocytes

Question 45

what activates the coagulation system

Answer 45

fluid from the blood vessels leak large quantities of thrombin (clotting enzyme) is generated and fibrin is deposited forming a barrier