The Innate immune system Flashcards
Where is the innate immune system presents?
- present in all plants, invertebrates and vertebrates
What type of memory response does the innate immune system have?
- non-specific with no memory response
What are the steps in the immune system?
- barrier
- identify
- kill
- remember
Describe barriers in the innate immune system?
- physical barriers against invasion
- inhospitable environments
What are examples of innate barriers?
- eyelids
- mucous and cilia in airways
- earwax (antimicrobials)
- gut
- tears and saliva
What does the gut have to aid in the physical barrier?
- low pH (not good for some bacteria)
- mucous
- proteases
- microbiome
What do tears and saliva have to aid in the physical barrier?
- anti-microbials (lysozyme) - not all animals such as cattle
What does lysozyme do to gram positive bacteria?
- attack peptiodo-glycans in gram positive bacteria cell walls exposing the lipid bilayer in the membrane of bacteria
Innate anti-microbials - what are defensins and what do they do?
- small proteins
- electrostatic attraction and the transmembrane electric field bring the defensin into the lipid bilayer
- the defensin peptides then form a pore
Where are defensins present?
- lungs
- skin
- gut
- tears
- other surfaces
What are defensins effective at protecting against?
- viruses
- bacteria
- fungi
What is the innate immune system important in?
- important in early immune responses to pathogens we haven’t seen before
- also helps initiate adaptive immune responses
What does the innate immune system use to recognise pathogens?
- innate cell receptors that recognise specific non-self molecules
= pattern recognition receptors (PRRs)
What are examples of non-self molecules?
- lipopolysaccharide (only in gram-neg bacteria)
- double stranded DNA
What are non-self molecules collectively known as?
- Pathogen-associated molecular patterns (PAMPs)
Name examples of PRRs:
- toll-like receptors
- NOD-like receptors
- lectins (mannose receptor)
- RIG-like receptors
Describe toll-like receptors (TLRs):
- multiple receptors within this family
- recognise a range of PAMPs
What do TLR4 recognise?
- lipopolysaccharides in gram negative bacteria
What do TLR9 receptors recognise?
- unmethylated viral/bacterial DNA
What species are TLRs present in?
- Drosophila
- Horses
- Sheep
- humans
Toll-like receptors can either … or …
- Homodimers
- Heterodimers
Where are TLRs present?
- present on the surface of cells that recognise PAMPs
- some are inside cell in endosomes = specifically the ones that are re -recognising nuclei acids (viruses)
Describe what happens when a PRR is activated by a PAMP?
- TLRs dimerize and induce signalling via adapter proteins
- TLR-initiated signalling activates transcription factors
- These mediate the transcription of specific cytokines such as interferons
What do transcription factors do?
- switch on genes to allow them to be transcribed
What are interferons key in?
- key in early anti-viral response
What are the different types of interferon?
- IFN alpha
- INF beta
What are interferons produced by?
- produced by virally infected cells within hours
Compared to antibodies interferons are not detected until …
- 5-6 days
What do interferons lead to?
- the production of anti-viral components
How do interferons work?
- work in the paracrine way - close to other cells around viral infected cells
What do interferons do?
- upregulate MHC class 1 (showing off viruses to adaptive immune system)
- inhibition of viral protein translation
- degradation of dsRNA
- block assembly of viral nucleocapsids
How do interferons inhibit viral protein translation?
- by slowing down production of capsids, viral proteins involved in attachment, pathways that degrade double stranded DNA, block cellular machinery that assemble viral capsids
What dogs are more susceptible to inflammatory bowl disease?
- German shepherds
Why are German shepherds more susceptible to IBD?
- polymorphisms in TLR4 and TLR5 genes
- making them ineffective at bacterial detection thus increasing disease chance
What are PRRs important in?
- important in identifying pathogens
What can PRRs do?
- recognise conserved PAMPs
- different PRRs interact with different PAMPs (viral, gram-neg, gram-pos, fungal, parasites)
What can differences in PRR and PAMP interactions lead to?
- lead to different immune responses
What different ways does the Innate system kill pathogens?
- inflammation - acute phase proteins
- phagocytosis - macrophages and neutrophils
- netosis - neutrophils
- killing infected host cells - NK cells
Acute inflammation is an immunological response - what are the symptoms?
- swelling and redness
- heat and fever
- pain
- loss of function
Inflammation can also be a seen in what?
- injury and arthritis
What are the 3 types of cytokines released during inflammation?
- TNF alpha
- IL - 1
- IL - 6
What are the 4 other mediators released during inflammation?
- histamine
- chemokines
- prostaglandins and leukotrienes
During inflammation what substances cause redness and heat and what does this lead to?
- IL-1 and TNF alpha
- leads to vasodilation and vascular permeability as capillaries are closer to surface = redness and heat
Which substance causes swelling during inflammation and how does it do this?
- chemokines
- cellular infiltration at site of infection/damage
- upregulation of adhesion molecules on endothelia (IL-1)
What are acute phase responses to acute inflammation?
- pro-inflammatory cytokines lead to upregulation and downregulation of hundreds of proteins
- release of acute-phase proteins from liver
What are the 3 acute phase proteins released from the liver into the blood
- mannan-binding lectin
- C-reactive protein
- complement
What is the function of acute phase proteins?
- to contribute to opsonisation and thus aid in phagocytosis
What is opsonisation?
- coating pathogen surfaces and facilitating recognition and phagocytosis
complement function - Opsonisation:
C3b and C5a proteins increase what?
- increase phagocytosis
What happens when a bacterium is coated with C3b proteins?
- C3b protein bind to CR1 receptors on a macrophage
- C5a proteins must bind to C5a receptor on the macrophage and initiate phagocytosis
What happens when only C3b binds to CR1?
- bacteria are not phagocytosed
What are C3a proteins responsible for?
- mast cell activation/degranulation
What are C4a proteins responsible for?
- mast cell activation
What are C5a proteins responsible for?
- chemotaxis
- vasodilation
- neutrophil and mast cell activation/degranulation
What happens during complement function - destruction?
- polymerization of terminal proteins to form membrane attack complexes which disrupts cell membranes by forming pores which causes cell lysis
- could be due to issues in osmolarity
What happens during phagocytosis?
- PRRs and other receptors bind micro-pathogen
- transported by phagosomes
- fuse with lysosomes
- pathogen destroyed by lysosome products
Describe the enzyme class of phagocytosis?
- lysozyme digests cell walls of some gram-positive bacteria
- acid hydrolyses = break down of ingested microbes
Describe the acidification class of phagocytosis?
- pH = 3.5-4 = bacteriostatic or bactericidal
What is the definition of immune evasion?
deliberate modulation of a host immune system to benefit the infectious agent
How can pathogens evade the innate immune system?
- can prevent phagocytosis (capsules on specific bacteria)
- can prevent lysosome fusion
- can escape endosome (listeria)
What are the two key phagocytic cells during inflammation?
- macrophages
- neutrophils
What is an additional function of macrophages?
- Macrophages will also release specific cytokines and chemokines to attract other innate and adaptive immune cells to the site of infection
What are the phases to phagocytosis?
- activation
- inflammation
- recruitment
How does a bacterial infection cause inflammation?
- bacteria trigger macrophages to release cytokines and chemokines
- vasodilation and increased vascular permeability cause redness, heat and swelling
- inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
What is NETosis?
- cell death to protect other and slow down extracellular pathogens
- NOT apoptosis
During NETosis what do neutrophils do?
- kill extracellular bacteria, fungi after activation
- release nuclear contents - antimicrobials
- neutrophil extracellular traps (NETS)
What are NK cells and what do they do?
- innate cell
- lymphoid lineage
- recognise infected host cells
- not as effective as CD8 t cells
How do natural killer cells distinguish from infected and non-infected cells?
- By MHC class 1 interactions
How is it that NK cells do not kill normal, healthy cells?
- MHC class 1 on normal cell recognised by inhibitory receptors that inhibit signals from activating receptors
How do NK cells destroy infected cells?
- altered or absent MHC class 1 cannot stimulate a negative signal. The NK cell is triggered by signals from activating receptors
- Activated NK cell releases granule contents, inducing apoptosis in the target cell
Abnormal MCH class 1 expression is also observed in what cells?
- cancer cells
