Innate immunity: Cell migration

Question 1

What do some tlrs do upon ligand protein

Answer 1

Homo or heterodimerize
Then bind pamp = intracellular

Question 2

What does dimerization trigger

Answer 2

Activation of adaptor proteins = myd88 trif
Phosphorylation or sometimes ubiquitination

Question 3

Describe effect of tlrs dimerization - ultimately

Answer 3

Activation of diff tfs
Translocation into nucleus
Expression of diff genes

Question 4

Name 3 effects of prr signalling

Answer 4

Cytokine production
Increased expression of costimulatory molecules
Enhanced migration to regional secondary lymphoid organ

Question 5

Describe cytokine production

Answer 5

Il-1 il-6 Il-18, TNF alpha, il-2= inflammation, pro inflammatory cytokines
Type 1 ifn, ifn alpha, ifn beta = post net antiviral effects
Chemokine production

Question 6

Describe chemokine production

Answer 6

Lead migration of cells to site of infection
Cc chemokines = ccl2 and cxc chemokines = cxcl 8 or Il-8
Different in their location of 2 cysteine residues

Question 7

Describe increased expression of co stimulators molecules

Answer 7

B7.1 (CD80) b7.2 (CD86)
= provide signal 2 to T cells in secondary lymphoid tissue = recall 3 signals needed for T cell activation

Question 8

Describe enhanced migration to regional secondary lymphoid organ

Answer 8

Upregulation of specific adhesion molecules
Or can migrate to site of infection

Question 9

Describe type 1 ifn signalling - process

Answer 9

Has antiviral effects
Ifn secreted upon prr signalling = binds receptors on surrounding cell =
Triggers signalling
More transcription —> these genes inhibit viral replication = can halt/slow virus infection

Question 10

Describe type 1 ifn signalling - effects

Answer 10

Proteins created = inhibit translation, degrade mRNA, inhibit virus transcription and assembly
= effects viral life cycle

Question 11

Describe migration

Answer 11

Enhanced migration to secondary lymphoid organ
Triggered by prr signalling
Targeting of dendritic cells to lymphoid tissue

Question 12

Describe co stimulation

Answer 12

Upregualtion = increase expression
APCs delivers signal to T cells = signal 2 - survival, b7.1 and b7.2 = CD80 and CD86

Question 13

What are chemokine receptors

Answer 13

Ex of G protein coupled receptors
Transducer signals via interactions with gtp/gdp binding G protein
Chemokines bind recpetor = gdp removed and gtp added = leads to signalling

Question 14

Can only one receptor bind to one chemokine

Answer 14

NO
Many receptors can bind to more than one chemokine = several chemokines are able to bind more than one recpetor

Question 15

What do chemokines do

Answer 15

Direct leukocyte migration —> chemotaxis
Signalling through chemokine receptors helps cells move to dif areas

Question 16

How do cells move to diff areas

Answer 16

Chemokines = cause
Change in adhesiveness, changes in cells cytoskeleton, allow migration to take place
Induce movement of leukocytes, up a chemokine concentration gradient, travel to higher conc chemokines

Question 17

Describe answer: You discover that a new virus blocks TLR3 signaling by preventing the nuclear translocation of the IRF3. You decide to further study this virus’ impact on TLR3 signaling. What are you most likely to find in a monocyte infected with this virus?

Answer 17

High levels activated irf3 in cytoplasm
Bc tfs in cytoplasm
Signalling from a prr results in their activation
One tfs activated= translocation to nucleus, but cannot translocate, everything upstream =fine

Question 18

Describe covid and type 1 interferon

Answer 18

3.5% of patients with life threatening covid 19, Had a genetic deficiency = cannot Make type 1 interferon
10% of patients with life threatening covid 19 had neutralizing auto antibodies against type 1 ifn

Question 19

Describe all steps of inflammatory response

Answer 19

1= breach epi layer
2= bacteria enters body
3= resident innate immune cell, prr binds pamp
4=phagocytosis
5=cytokine and chemokines released = inflammation and vasodilation, recruit cells = 4 hallmarks inflammation

Question 20

What is recruited to site of infection

Answer 20

Monocytes

Question 21

Describe whole process of recruiting monocytes

Answer 21

Reunited by adhesion molecules
1= binding of adhesion molecules on endothelial cell and monocyte
2= chemokine binds
Leads to intracellular signalling= can change conformation of adhesion molecules= so binds other adhesion molecule on endothelial cell = anchored now
Then can migrate to tissue

Question 22

Describe adhesion molecules

Answer 22

Diff fams = selectins, integrins, immunoglobulin superfamily
Diff tissue distribution

Question 23

Are all adhesion molecules always expresssed

Answer 23

Nooo
Some expressed at baseline
While others only expressed when infection = upregulated (allows cells to migrate to site of infection)

Question 24

What do leukocytes do

Answer 24

Roll along vascular endothelium
Weak interactions with adhesion molecules

Question 25

Describe recruitment of leukocytes

Answer 25

Monocytes - precursor of macrophages, neutrophils and other leukocytes recruited to site of infection
= casues heat, redness, swelling, edema

Question 26

What happens when severe or chronic inflammtion

Answer 26

Arthritis or loss of function
Inflammation should always be acute

Question 27

Name all migration steps in order

Answer 27

Rolling adhesion
Tight binding = anchoring
Diapedesis
Migration

Question 28

Describe diapedesis

Answer 28

Process by which a cell crosses from the lumen of a vessel between endothelial cells into the surrounding tissue (site of infection)

Question 29

Describe migration

Answer 29

In direction of higher chemokine concentrations