Innate Immunity Flashcards
What are the primary barriers?
- skin
- ear wax
- mucus
- stomach acid
Define phagocytosis
- the engulfing of pathogens by surrounding it and ingesting it.
List 3 phagocytic cells, what receptor do they express to detect pathogens
- macrophage.
- dendritic cells.
- neutrophils.
- Toll-like receptor (TLR)
What type of receptor are TLR’s? What does it recognise? Why don’t pathogens evolve not to express these? What else can they recognise?
- TLR’s = PRR (pattern recognition receptor).
- They recognise PAMPs (pathogen associated molecular patterns) and DAMPs (danger associated molecular patterns).
- they are essential for pathogen survival.
What type of chemical are TLRs? What amino acid are they rich in?
- type 1 integral membrane glycoproteins.
- they contain leucine rich repeats.
What do TLRs 1 2 and 6 recognise? You can be more specific with 2 (what disease are these molecules associated with)
- lipids.
- TLR 2 - tuberculosis.
What do TLRs 7 8 and 9 recognise?
- nucleic acids.
What does TLR 4 recognise?
- diverse ligands.
Where are TLRs expressed? Immune and non immune cells
- immune cells: macrophage, dendritic cells, B-cells (some T-cells).
- non-immune cells: epithelial cells and fibroblasts.
What does TLR 3 bind?
- ds RNA viruses
Where are TLRs on the cell?
- most are extracellular & bind from the cell membrane.
What are the 2 phagocytes?
- macrophages.
- neutrophils.
Where are neutrophils normally?
- circulating in the blood.
Where are macrophages found?
- circulating in the lymph or in lymph nodes in organs.
Where are dendritic cells found?
- found in tissues such as skin.
- they stimulate adaptive immunity by presenting antigens to t-cells.
Where are eosinophils? What do they provide defense against?
- found on mucus membrane.
- against multicellular invaders.
Where are Natural Killer cells? What do they release and what does this do? What % of leucocytes are NKs?
- lymph nodes and spleen.
- release perforin that breaks down cell membranes.
- 5-10% of leucocytes.
How does the lymphatic system aid phagocytosis?
- some macrophages reside in lymph nodes.
- dendritic cells migrate to lymph nodes after interacting with pathogens to stimulate adaptive immunity.
Describe the 5 steps of phagocytosis
- Chemotaxis: chemicals (microbes, WBC, activated complement system) attract phagocytes to site of damage.
- Adherence: phagocytes attach to the microbe/non-self material as facilitated by bound complement proteins.
- Ingestion: pseudopod (membrane protrusion) extends & surrounds microbe and fuses into a phagosome.
- Digestion: phagosome fuses with lysosome = phagolysosome. enzymes in this break down microbe cell wall, proteins & n-acids & oxidants involved with oxidative burst.
- Killing: microbe degraded, anything left is kept in residual body.
What is a pseudopod?
- a protrusion in the phagocyte membrane which engulfs microbes/non-self cells.
What is a phagosome?
- the vesicle containing microbes/non-self material once the pseudopod has fused around it.
What are interferons?
- proteins released by cells infected by a virus.
- they prevent replication and thus spread of infection.
What is the complement system?
- a process leading to a chemical cascade resulting in lysis of bacteria.
What are Iron binding proteins and how do they work?
- bind to iron which are required by bacterial enzyme action.
- therefore affects bacterial growth.
What is the key component of the complement system?
What is this cleaved into? What are the effects of the cleavage products? Which is largest?
- C3 - activation leads to cleavage.
- cleave products: C3a(small) & C3b(big)
- C3a: stimulates vascular permeability and helps recruit phagocytes.
- C3b: become tagged onto microbial membrane to make it become opsonised.
What are the 3 pathways of activation for C3b? Describe them?
- Classical pathway: IgG or IgM (antibodies) bind to antigens, especially on the surface on pathogen = antigen-antibody complex.
- MB-Lectin pathway: MBL binding to pathogen polysaccharide.
- Alternative (fast): spontaneous C3 cleaving and binding of C3b .
What are the results of activation of complement system?
- 3 end results from any one pathway:
- Inflammation: t-cell attraction = cytokine release = inflammation.
- Opsonisation: antibody FcR and C3-C3R interaction.
- MAC activation and cell lysis. (not for gram negative).
Describe the classical pathway. What is the convertase?
- antibody-antigen complex initiates pathway leading to binding of C1 q,r,s.
- this results in C4-C2 complex being deposited a.k.a. C3 convertase.
- this cleaves C3 into C3a&b.
- C3b binds to C4-C2 complex which activates MAC leading to cell lysis.
- C3a activates and attracts phagocytes.
- C5 cleavage leads to T-cell attraction and cytokine release (inflammation).
- the binding of the complement and or antibody to pathogen increases chance of phagocytosis (opsonisation) due phagocytes having receptors for these -10 fold.
What is MAC made from? What does it do? What type of bacteria is this NOT effective on?
- MAC = membrane attack complex:
- Binding of C3b to C3 convertase = C5 convertase.
- C5 cleaved into C5a (inflammation) & C5b.
- This leads to interaction of C5b-C6-C7 at a second membrane site = deposition of C8 which inserts into the membrane followed by multiple C9 molecules (10-16).
- C9 molecules insert through the membrane, thus lysing the cell.
- not effective on Gram positive bacteria.
Describe the MBL pathway? What is the convertase?
- formation of MBL = resembles C1 complex leads to C4C2 convertase complex being deposited.
- leads to C3 being cleaved into a&b.
- leads to the next steps of the complement system.
Describe the Alternative pathway. What factors are involved? What is the convertase?
- Activated by binding of C3b (from classical or MBL pathway) to the bacterial cell surface.
- C3b binds to serum protein factor B.
- C3b is then cleaved by factor D = C3bBa & C3Bb.
- C3bBb complex = C3 convertase which combines with factor P to become attached to the membrane = very stable.
- This attracts more C3 to be cleaved to start the 3 possible outcomes.
