detecting and responding to pathogens

Question 1

define virulence factors

Answer 1

microbial factors that cause disease

Question 2

define pathogenesis

Answer 2

refers to the development of a disease and encompasses the entire process from initial exposure to the pathogen to the manifestation of symptoms and disease progression

Question 3

what are the 4 main stages of pathogenesis?

Answer 3

• exposure
• adhesion
• invasion
• infection

Question 4

what are the routes which transmission can occur through?

Answer 4

• airborne
• contact
• food-bourne
• vector-bourne

Question 5

name the PAMP receptors.

Answer 5

• toll-like receptors
• RIG-I like receptors
• NOD-like receptors
• C-type lectins

Question 6

give some examples of DAMPS.

Answer 6

dna
rna
extracellular atp
hylauronic acid
glucose
fibrinogen
fibronectin
heat shock proteins
uric acid
silica
alum
nanoparticles
UVB
mutations

Question 7

outline some examples of PAMPS.

Question 8

how do PAMPS bind to receptors

Answer 8

• there is no lock and key method because there are just too many pamps
• there is a master key receptor
• they bind and move shape to mould around the different PAMPS
• meaning receptors can bind to multiple pamps

Question 9

what are host defence peptides, where are they found and what is their role?

Answer 9

• antimicrobial peptides
• theyre secreted into the fluid which lines epithelia

can be internalised by bacteria, targeting destruction on internal organelles
- can bind and cause compliment cascade causing lysis
- can target bacteria for destruction by other cells eg macrophages like opsonisation
- can bind to machinery eg hydrogen ion channels, disrupting

Question 9

what is CRP an example of?

Answer 9

• PRR
  _ react with C-polysacharide of pneumococci
• activates compliment and promotes phagocytosis

Question 10

what are lectins and collectins

Answer 10

• carbohydrate-containing proteins that bind carbohydrate or lipids in microbe walls
• activate compliment, improve phagocytosis
• mannose binding lectin
• surfacant proteins A and D

Question 11

what are the 2 groups of TLR?

Answer 11

• extracellular
  recognise bacteria, viruses and our own proteins
• intracellular
  recognise rna and dna - predominantle viral species inside the cell

Question 12

what is the mechanism of TLRs and what are the functions as a result of them?

Answer 12

• triggers intracellular signalling pathway leading to the production of cytokines, chemokines and antimicrobial peptides

functions:
- hsot defence by amplifying APC and cytokine production
- tissue repair - responds to damps for tissue healing and injury

Question 13

name the different C-type lectin receptors

Answer 13

type 1 - antigen uptake
type 2 - includes the dectin subtype 1 and 2 which are anti-fungal
soluble - mannose-binding lectin

Question 14

name the 2 extracellular, membrane bound receptors PRRs

Answer 14

• TLR
• C-type lectin

Question 15

outline RIG-I receptors

Answer 15

• detect cytoplasmic viral RNA in the early stages of antiviral immunity

Question 16

outline NOD-like receptors

Answer 16

• sit within cytoplasm
• recognise pathogens and damage

functions:
- activate inflammasomes
- pathogen/damage sensing
- antigen presenting
- inflammatory signallling inhibitors

Question 17

outline the intracellular PRRS

Answer 17

NOD-like
RIG-I

Question 18

outline what happens during PRR intracellular signalling

Answer 18

• pamps and damps bind to prrs
• signalling complex adaptor proteins
• transcription factors
• inflammatory and / or antiviral responce

Question 19

name the responses associated with the binding of pamps and damps

Answer 19

• inflammatory responces - innate and adaptive immunity
• antiviral responce

Question 20

outline what happens during the mechanism of the binding of pamps and prrs

Answer 20

• IFRa release IFNa and IFNB which bind to IFNa receptor
• this:
• induces resistance to viral replication by activating genes that cause the destruction of mrna and inhibits the translation of viral
• increases MHC-I expression and antigen presentation of viral proteins
• facilitates recognition and susceptibility to cytoxic t cells

Question 21

what is the damage chain reaction and use it to explain how damps and associated responces can be dangerous

Answer 21

• illustrates that when damps are released, causing pro-inflammatory mediator release, this can lead to the further release of damps which are associated with cancers, inflammation sidorders and autoimmune disorders

Question 22

whats the cytokine storm and how is it dangerou s

Answer 22

• profound increase in cytokine and chemokine and interferons
• causes severe inflammation and tissue damage
• role in sepsis, influenza, coviv ect
  can be induced from:
• genetic makeup of host
• inflammaging

Question 23

which 2 PRR families contain the predominant receptors that detect SARS-CoV-2?

Answer 23

TLR
Rig-I

Question 24

which 2 cytokines are primarily responsible for the anti-viral response to covid-19?

Answer 24

interferon alpha interferon beta

Question 25

define immunomodulation

Answer 25

Immunomodulation refers to the alteration of the immune system's activity to either enhance or suppress its response. It is a broad concept that encompasses natural processes as well as therapeutic interventions aimed at maintaining immune homeostasis, treating diseases, or improving vaccine responses.

Question 26

what are the 2 main stratagies of immunomodulation?

Answer 26

Two main strategies of immunomodulation: Agonists (enhance TLR signalling): adjuvant effect (used with a primary treatment) promoting protective responses e.g. vaccines immune stimulators e.g. in cancer treatment Modify adaptive immune response: bias Th and Treg responses side-effects: potentially enhance inflammation Antagonists (inhibit TLR signalling): block binding of ligands or protein-ligand complexes to receptors / interfere with intracellular adaptor molecules of common signalling pathways sepsis syndromes, COVID-19, inflammation, arthritis, etc side-effects: potentially allow pathogen outgrowth, mutation, etc