Innate immune system Flashcards
What are some of the key physical barriers comprising the innate immune system?
- Eyelids protect the eye
- Mucous and cilia in the airways
- Ear wax contains anti-microbials
- Tears and saliva contain antimicrobials and lysozymes
How is the innate immune system present in the gut?
- Low pH (not conducive to the growth of certain bacteria)
- Contains mucous and a microbiome
- Proteases (could attack viral proteins HA and NA)
What species do not have lysozymes in their tears?
Cattle
What is a lysozyme?
An enzyme that attacks peptidoglycan in the cell wall of gram +ve bacteria.
Defensins are another form of anti-microbial, what are they?
- Defensins are small, positively charged proteins effective against viruses (particularly enveloped ones), bacteria and fungi
- Present in the lungs, skin, gut and tears
- Causes pores in the phospholipid bilayer.
How does the innate immune system recognise pathogens?
- Innate cells recognise non-self molecules using pattern recognition receptors
- PRRs recognise PAMPs
Name some examples of non-self molecules.
- LPS, double stranded RNA, flagella
What are the 4 different types of pattern recognition receptor?
- TLR
- NOB-like receptors
- Lectins
- RIG-like receptors
What are the functions of TLR4 and TLR9?
- TLR4 recognises LPS on gram -ve bacteria
- TLR9 recognises Cp6 DNA (can be viral or bacterial)
Where can TLRs be found on innate immune cells?
- Some TLRs occur on the cell surface
- Some TLRs occur within endosomes and are used to recognise nucleic acid structures.
How are pattern recognition receptors activated?
- TLRs dimerize and induce signalling via adapter proteins (TRIF or Myd88)
- TLR initiated signalling activated transcription factors
What is the purpose of these transcription factors?
They mediate the transcription of specific cytokines, such as interferons
When are interferons important?
In an early anti-viral response
What are the 2 different types of interferon?
Alpha IFN
Beta IFN
Where are interferons produced?
Produced by virally infected cells (within hours of infection)
How do interferons lead to the production of anti-viral components?
- They cause inhibition of viral protein translation and block the assembly of viral nucleocapsids
- Cause degradation of dsRNA
- Upregulate MHC class 1 - a molecule presented on the surface of viral infected body cells to help alert the immune system
- Work in a paracrine way
Why are German Shepherds more susceptible to inflammatory bowel disease?
- Because they have polymorphisms in TLR 4 and TLR 5 genes
- Ineffective bacterial detection so risk of disease increases
In what 4 ways does the innate immune system work to kill pathogens? What is it responsible for each pathway?
- Inflammation (acute phase proteins)
- Phagocytosis (macrophages and neutrophils)
- Netosis (neutrophils)
- Killing infected host cells (NK cells)
What are the symptoms of acute inflammation?
- Swelling and redness
- Heat and fever
- Pain
- Loss of function
When is the inflammatory response seen in the absense of infectious disease?
With injury or 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
- Leukotrienes
What 2 substances specifically cause redness and heat?
- IL-1 and TNF alpha
- These lead to vasodilation and increased vascular permeability
- Capillaries come closer to the surface
Which substances cause swelling - how?
- Chemokines
- Cause cellular infiltration at the site of infection + upregulation of adhesion molecules on endothelium
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 all of these acute proteins?
To contribute to opsonisation and thus aid phagocytosis
What is opsonisation?
The coating of a pathogen surface in specific proteins to aid recognition and phagocytosis.
What are C3a, C4a, and C5a proteins responsible for?
C3a = mast cell activation/degranulation
C4a = mast cell activation
C5a = chemotaxis, vasodilation, neutrophil and mast cell activation/ degranulation.
What happens when a bacterium is coated with C3b proteins?
- C3b proteins bind to CR1 receptors on a macrophage
- C5a proteins must bind to C5a receptor on the macrophage and initiate phagocytosis.
What is the destruction complement function?
Polymerisation of terminal proteins forms membrane attack complexes
- These form pores in the cell membrane and can cause cell lysis
What happens during phagocytosis?
- PRRs and other receptors bind to the pathogen
- Transported by phagosomes
- Phagosome fuses with lysosome
- Pathogen destroyed by lysosome products
What is the definition of immune evasion? How does this work?
Definition = the deliberate moderation of a host immune system to benefit the infectious agent
How work =
1) Can prevent phagocytosis
2) Can prevent lysosome fusion
3) Can cause pathogen to escape the endosome.
What are the two key phagocytic cells during inflammation?
Macrophages and neutrophils
What is the additional function of the macrophages?
- Release specific cytokines and chemokines
- This helps to attract other innate and adaptive immune cells to the site
How does a bacterial infection cause inflammation?
- Bacteria triggers macrophages to release cytokines and chemokines
- Vasodilation and increased vascular permeability causes redness, heat and swelling
- Inflammatory cells migrate into the tissue and release inflammatory mediators.
What is the function of neutrophils?
- Kill extracellular bacteria + fungi after activation
- Release antimicrobial nuclear contents
What is netosis?
When neutrophils release extracellular traps (nets) which cause cell death (not apoptosis)
How do natural killer cells distinguish infected from 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 regognised by inhibitory receptors that inhibit signals from activating receptors
How do NK cells destroy infected cells?
- Altered or absent MHC class 1 cannot stimulate the negative signal
- NK cell triggered by signals from activating receptors
- Activated NK cell releases granule contents (causes apoptosis)
