2.1 Detection of pathogens

Question 1

Name the 3 stages of the innate immune function

Answer 1

1) recognition of microbes and damaged cells
2) activation of mechanisms
3) elimination of unwanted substances

Question 2

Explain the role of PRRs

Answer 2

Pattern recognition receptors

They recognize pathogen-associated molecular patterns (PAMPs) and activate other parts of the immune system

Question 3

Compare PAMPs and DAMPs

Answer 3

PAMPs are molecular structures of a pathogen that the pathogen requires for survival

DAMPs are molecular patterns released by injured and necrotic cells that are recognized by leukocytes

Question 4

Name 3 types of PRRs found on different types of immune cells

Answer 4

1) Intracellular (cytosolic)
2) Endosomal (membrane-bound molecules used to tag and induce the complement system)
3) Extracellular

Question 5

Explain the role of Toll like receptors

Answer 5

They recognize pathogens -> found on the plasma membrane and endosome membrane

Activation of these receptors imitates a cascade of events that activate transcription factors

Question 6

What do PRRs trigger? Name 6 of their functions…

OI PAPI

Answer 6

Trigger the innate immune response:

1. initiate opsonization
2. Induce inflammatory mediators
3. induce complement proteins
4. Induce apoptosis
5. Induce phagocytosis
6. Secrete inferno cytokine pro cytokines

Question 7

Name 2 common examples of PRRs

Answer 7

Toll like receptors

Nod like receptors

Question 8

Binding of a bacteria/virus to TLRs initiates a cascade which activates what 3 transcription factors?

Incl the role of each of these

Answer 8

1) NF kappa beta: makes pro-inflammatory cytokines like TNFa (enhances immune response and induces apoptosis) and interleukin (IL-1b and Pro-IL18, enhances immune response through chemotaxis effect)
2) AP=1 adaptor protein causing differentiation, proliferation and apoptosis of cells
3) IRFs: Interferon regulatory factor stimulating the production of type 1 interferon (anti-viral cytokines)

Question 9

Describe what happens when a TLR is activated by a bacteria vs virus? What is the result?

Answer 9

Bacteria:

• activation of NF kapa beta
• This makes proinflammatory cytokines, adhesion molecules and costimulators
• Results in Acute inflammation and stimulation of adaptive immunity

Virus:

• activates IRFs (interferon regulatory factors)
• this stimulates the production of type 1 interferon (antiviral cytokines)
• results in an anti-viral state

Question 10

What are Nod like receptors and where are they found?

List the 3 main types and identify their structural difference

Answer 10

Cytosolic receptors that sense DAMP’s and PAMP’s in the cytoplasm -> they recognise cell walls of pathogens.

All NLRs contain nucleotide oligomerization domain (NOD) but different N-terminal domains

3 main types: NOD-1,2 and NLRP3

Question 11

Describe the function of the 3 main types of NLRs

Answer 11

NOD 1 and 2 activate NF kappa beta

NLPR3 oligomerizes with an adaptor protein and an inactive form of caspase-1 to form an inflammasome. Once formed, the caspase-1 within the inflammasome becomes active and cleaves IL-1b into its active form which recruits leukocytes and induces fever

Question 12

What receptor is responsible for the painful reaction in gout?

Answer 12

NOD like receptors recognize the buildup of uric acid crystals as DAMPs and initiate a cascade producing inflammasomes - leading to inflammation

Question 13

Name 4 other cellular receptors asides from TLRs and NOD like receptors

Answer 13

1) C-type lectin receptors
2) RIG like receptors
3) Cytosolic DNA sensors
4) GPCRs

Question 14

Where are C type lectin receptors expressed and what do they do?

Answer 14

On the PM of macrophages and dendritic cells, they detect fungal glycans and initiate an immune response to fungi

Question 15

Where are RIG like receptors located, what do they detect and what does their activation lead to?

Answer 15

Cytosol of most cells, detect nucleic acids or viruses that replicate in the cytoplasm of most infected cells and induce a cascade leading to the production of type-1 interferons

Question 16

What can cytosolic DNA receptors recognize and induce?

Answer 16

Recognize viral DNA and induce type 1 IFN

Question 17

Where are GPCRs, what do they recognize and stimulate

Answer 17

Neutrophils, macrophages and most leukocytes recognize short bacterial peptides and stimulate a chemotactic response of cells

Question 18

What are the 2 main mechanisms the innate immune response uses to eliminate microbes?

Answer 18

1) Inflammation

2) Anti viral defences

Question 19

Name the 5 basic steps of a typical inflammatory reaction

Answer 19

1) extravascular pathogen recognized by host cells
2) leukocytes and plasma proteins recruited
3) recruited cells are activated and destroy the pathogen
4) reaction is controlled and terminated
5) damage tissue is repaired

Question 20

Describe what happens once viral nucleic acids are recognised

List the 3 main ‘anti-viral’ effects

What is the overall effect?

Answer 20

Viral nucleic acids are recognized by TLRs -> the infected cells or dendritic cells secrete cytokines part of the type 1 interferon family which has 3 effects:

1) Production of RNAase that degrade viral nucleic acids
2) Activate factors that inhibit viral protein synthesis
3) Inhibit viral gene expression and viron assembly

Overall effect is to put the body in an “anti-viral state” where viral replication is inhibited

Question 21

What are the 3 pathways of the complement system?

How are they each activated?

Answer 21

1) Classical: initiated by antigen-antibody complexes
2) Alternative: Initiated by direct binding to a microbe
3) Lectin binding pathway: initiated by binding of the mannose-binding lectin (MBL) to carbohydrates on the surface of pathogens

Question 22

Name the 3 major components of acute inflammation

Answer 22

1) DILATION of small vessels= increased blood flow
2) INCREASED PERMEABILITY (so plasma proteins and leukocytes can leave circulation)
3) EMIGRATION of leukocytes so they accumulate in the area of injury and eliminate the offending agent

Question 23

What happens once any one of the complement system pathways are activated?

Answer 23

Once C3 has split into active C3a and C3b…

C3b is a binding protein and attaches onto bacteria, viruses and fungi: once attached it becomes C3 convertase which activates more C3 proteins (restarting the cycle), therefore it aids in opsonization.

C3a is active: recruits phagocytes to the area, the C3b receptor helps to attach and anchor the phagocytes to the pathogen

C3 convertase becomes a C5 convertase that recruits proteins into making a structure known as membrane attack complex. This punches holes in the pathogen; so fluid rushes in (osmotic lysis) and the pathogen “bleeds out”

In viruses: complement system can grab viruses in circulation and guide them to immune cells

Question 24

Why does activation of the complement system result in inflammation?

Answer 24

C5a and C3a are chemoattractants for leukocytes

Question 25

Explain the role of a second signal

Answer 25

The innate immune system can stimulate the adaptive immune system using second signals, they also help produce the correct type of adaptive immune response i.e., cellular or humoral (ensures lymphocytes don’t respond to harmless non-infectious substances)

*Can also be useful during vaccinations so that a complete immune response is induced

Question 26

What is the compliment system?

What 3 things does its activation aim to achieve?

Answer 26

It is a part of the immune system, activation enhances the ability of antibodies and phagocytic cells to

1) clear microbes and damaged cells from an organism
2) promote inflammation
3) attack the pathogen’s cell membrane

Question 27

3 main functions of the compliment system -> explain each

Answer 27

1) Opsonisation and phagocytosis: C3b coats microbes and promotes binding of microbes to phagocytes by receptors on phagocytes -> allows rapid ingestion and destruction by phagocytes
2) Inflammation: some factors of compliment such as C5 a and C3a are chemoattractants -> promotes leukocyte recruitment (inflammation) at the site of activation
3) Cell lysis: complement activation concludes with the formation of protein complex that inserts into the microbial cell membrane causing either osmotic lysis or apoptosis of the microbe

Question 28

What is the adaptive immune system?

What cell type is involved in the humoral vs cell-mediated components of this response?

Answer 28

This is a specific response that utilises lymphocytes

B lymphocytes: humoral response
T lymphocytes: cell-mediated response

Question 29

How does the innate immune system trigger a humoral response vs a cell-mediated response?

Answer 29

Humoral: a blood borne microbe will activate the compliment system, proteins like C3d attach themselves to microbial surfaces

Cell-Mediated: macrophage identifies a microbe, phagocytosis occurs and macrophage acts as an APC by displaying microbial antigen on its surface

Question 30

How do second signals trigger a humoral response vs a cell-mediated response?

Answer 30

Humoral: recognition of C3b by compliment receptor of B-cells and antigen recognition by B-cells

Cell- mediated: co-stimulator and cytokines work alongside antigen recognition to activate T-cells

Question 31

What is the Adaptive response in humoral vs cell-mediated?

Answer 31

Humoral: proliferation of B-cells

Cell-mediated: proliferation and differentiation of T-cells

Question 32

How is the adaptive immune system stimulated in a vaccination?

Answer 32

Vaccinations require induction of a complete immune response -> adjuvants are used as a “second signal” to stimulate an adaptive immune response