2.1 Detection of pathogens Flashcards
Name the 3 stages of the innate immune function
1) recognition of microbes and damaged cells
2) activation of mechanisms
3) elimination of unwanted substances
Explain the role of PRRs
Pattern recognition receptors
They recognize pathogen-associated molecular patterns (PAMPs) and activate other parts of the immune system
Compare PAMPs and DAMPs
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
Name 3 types of PRRs found on different types of immune cells
1) Intracellular (cytosolic)
2) Endosomal (membrane-bound molecules used to tag and induce the complement system)
3) Extracellular
Explain the role of Toll like receptors
They recognize pathogens -> found on the plasma membrane and endosome membrane
Activation of these receptors imitates a cascade of events that activate transcription factors
What do PRRs trigger? Name 6 of their functions…
OI PAPI
Trigger the innate immune response:
- initiate opsonization
- Induce inflammatory mediators
- induce complement proteins
- Induce apoptosis
- Induce phagocytosis
- Secrete inferno cytokine pro cytokines
Name 2 common examples of PRRs
Toll like receptors
Nod like receptors
Binding of a bacteria/virus to TLRs initiates a cascade which activates what 3 transcription factors?
Incl the role of each of these
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)
Describe what happens when a TLR is activated by a bacteria vs virus? What is the result?
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
What are Nod like receptors and where are they found?
List the 3 main types and identify their structural difference
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
Describe the function of the 3 main types of NLRs
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
What receptor is responsible for the painful reaction in gout?
NOD like receptors recognize the buildup of uric acid crystals as DAMPs and initiate a cascade producing inflammasomes - leading to inflammation
Name 4 other cellular receptors asides from TLRs and NOD like receptors
1) C-type lectin receptors
2) RIG like receptors
3) Cytosolic DNA sensors
4) GPCRs
Where are C type lectin receptors expressed and what do they do?
On the PM of macrophages and dendritic cells, they detect fungal glycans and initiate an immune response to fungi
Where are RIG like receptors located, what do they detect and what does their activation lead to?
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
What can cytosolic DNA receptors recognize and induce?
Recognize viral DNA and induce type 1 IFN
Where are GPCRs, what do they recognize and stimulate
Neutrophils, macrophages and most leukocytes recognize short bacterial peptides and stimulate a chemotactic response of cells
What are the 2 main mechanisms the innate immune response uses to eliminate microbes?
1) Inflammation
2) Anti viral defences
Name the 5 basic steps of a typical inflammatory reaction
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
Describe what happens once viral nucleic acids are recognised
List the 3 main ‘anti-viral’ effects
What is the overall effect?
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
What are the 3 pathways of the complement system?
How are they each activated?
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
Name the 3 major components of acute inflammation
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
What happens once any one of the complement system pathways are activated?
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
Why does activation of the complement system result in inflammation?
C5a and C3a are chemoattractants for leukocytes
Explain the role of a second signal
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
What is the compliment system?
What 3 things does its activation aim to achieve?
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
3 main functions of the compliment system -> explain each
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
What is the adaptive immune system?
What cell type is involved in the humoral vs cell-mediated components of this response?
This is a specific response that utilises lymphocytes
B lymphocytes: humoral response
T lymphocytes: cell-mediated response
How does the innate immune system trigger a humoral response vs a cell-mediated response?
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
How do second signals trigger a humoral response vs a cell-mediated response?
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
What is the Adaptive response in humoral vs cell-mediated?
Humoral: proliferation of B-cells
Cell-mediated: proliferation and differentiation of T-cells
How is the adaptive immune system stimulated in a vaccination?
Vaccinations require induction of a complete immune response -> adjuvants are used as a “second signal” to stimulate an adaptive immune response
