The Innate Immune System Part I – Pattern recognition Flashcards
What is Innate immunity compared to adaptive immunity ?
- It is more popular
- Also evolutionary older than adaptive immunity
Innate immunity is where in our defence ?
It is the frontline of our defences
Innate immunity includes what mechanism and defences ?
Innate immunity includes the basic barrier mechanisms and
simple biochemical defences
What cells does the innate immunity have ?
It includes immune cells (white blood cells) that recognise “general” pathogen molecules
Name some unique features of the innate immune system?
- 1st line of defence
- Present at birth, germline encoded
- Limited number of receptors recognising common patterns on pathogens/diseased tissue
- No memory of prior exposure - same response each time
- Instructs, induces & amplifies adaptive immune response
- Rapid: immediate response by preformed effectors then 48-96 hours for induced innate response
Explain some features of Inflammation ?
- A local response to injury or infection (damage/danger or pathogen)
- Recruitment of immune cells & molecules to kill infection / initiate repair
- Largely co-ordinated by leukocytes & leukocyte traffic
- Normally acute (short term)
Explain Neutrophils ?
- Most abundant white blood cell
- Short lived (hours)
- Dedicated phagocyte
- First line defence at site of infection
1. Degranulation of antimicrobial granule components
2. Neutrophil extracellular traps (NETs)
3. Initiate inflammation by releasing cytokines - Dead/dying neutrophils are a major component of pus (caused by what is known as pyogenic bacteria)
What are neutrophil NETs ?
Chromatin based fibres that trap & kill extracellular microbes
What does neutrophil NETs create ?
- Creates an antimicrobial environment at the inflammatory site
- Acts as a physical barrier contributing to killing of extracellular pathogens
Explain Eosinophils ?
- Characteristic eosin pink staining & bi-lobed nucleus
- Beneficial against parasitic infections
- Damaging part of the allergic response
- Recruited to tissues from blood at sites of inflammation
1. Release of anti-microbial factors
2. Potential to present antigens to T cells
3. Initiate inflammation by releasing cytokines that activate other cells
Explain Basophils ?
- Highly granular, blood circulating leukocyte
- <1% of all leukocytes
- Important in responses to parasites & allergy
- Recruited to sites of inflammation
- Become activated by cross-linking of surface bound antibody
- Activation induces degranulation and inflammatory mediator release
Explain Mast Cells ?
- Found in skin, blood vessels, connective tissue, mucosal tissue
- Large long-lived tissue-residents
- Very important in development of allergies
- Become activated by cross-linking of surface bound receptors with antibodies
1. Activation induces degranulation - histamine, leukotriene & prostaglandin release (vasoactive, smooth muscle contraction)
2. Inflammatory cytokine release, which promotes adaptive Th2 responses
What are Monocytes and it contains ?
- They are the blood precursor to tissue macrophages
- It contains nucleus, lysosome and phagosome
What are Macrophages and it contains ?
- They are specialised for phagocytosis & present antigens to T cells of adaptive immune system
- It contains Pseudopodia, Phagosomes, Lysosome and Phagolysosome
What are Dendritic cell and it contains ?
- They are the dendritic cells are the most potent antigen-presenting cells for T cells of the adaptive immune system
- It contains Phagosomes, Processes and Lysosome
Monocytes are recruited to ?
Tissues from blood at sites of inflammation where they differentiate into macrophages
Macrophages are professional phagocytes recognising & eating germs. What do they release ?
- Release of anti-microbial factors
- Release of pro-inflammatory cytokines
- Antigen presenting cell (APC) capacity
What do Pattern Recognition Receptors (PRR) enable ?
The discrimination between self and non-self
What do PRR recognise ?
PRR recognise simple molecules and molecular patterns specifically
associated with microorganisms known as Pathogen Associated
Molecular Patterns (PAMPs) – i.e., non-self
What can PRR also recognise?
Danger/Damage Associated Molecular Patterns
(DAMPs) - indicator self molecules specifically associated with cellular
infection, damage, stress or malignancy – i.e., self that has been somehow ‘transformed’
What receptors do Innate cells use ?
Pattern Recognition Receptors to recognise pathogens and discriminate from our own healthy cells
What are Pathogen Associated Molecular Patterns (PAMPs) ?
They molecular structures or molecules shared by most pathogenic microorganisms
What are Damage Associated Molecular Patterns (DAMPs) ?
They are molecular structures or molecules commonly found on damaged/necrotic/stressed tissue
How are PAMPs and DAMPs recognised ?
By innate Pattern Recognition Receptors (PRR)
What did Janeway in 1989 predict ?
That activation of the adaptive immune response is controlled by the innate immune system
What did Janeway propose ?
A general theory of innate immune recognition (pattern recognition theory) and suggested the principles of innate control of adaptive immunity
What do the families of innate PRRs function ?
As sensors for pathogen/damage associated molecular patterns (PAMPs/DAMPs)
What are the four different families of Innate PRRs ?
- Toll-like receptors (TLRs)
- C-type lectin receptor (CLR)
- RIG-I-like receptor (RLR)
- NOD-like receptors (NLRs)
Explain Toll-like receptors (TLRs) ?
Family of transmembrane PRR that recognise pathogens and their products. Stimulation on receptor bearing cells produces cytokines that activate immune responses
Explain NOD-like receptors (NLRs) ?
Family of intracellular PRR containing a Nucleotide-oligomerisation domain
(NOD) who detect microbes and cellular stress to induce immune responses
What are on the cell wall of innate cells such as macrophages ?
- Mannose receptors
- Glucan receptor
- Scavenger receptor
Bind cell wall carbohydrates of yeast, bacteria and fungi
What leads to activation of NFkB ?
NOD receptor recognition of bacterial cell-wall components leads to activation of NFkB
What do NLRs also activate ?
They activate the inflammasome
What is Gout a response to ?
It is in response to uric acid crystals to build up in joints
When is Uric acid produced?
Uric acid is a natural product produced when the body breaks down purines found in meat & seafood
What kind of pattern is Uric acid ?
Uric acid is a DAMP which activates the inflammasome
What can also increase the risk of Gout ?
Diuretics, beta blockers, aspirin (when taken regularly) & niacin (for high cholesterol)
What is an auto-inflammatory driven by ?
Innate immune response to deposition of monosodium urate (MSU) crystals in the joint & characterised by a large neutrophil infiltration
What do MSU acts as ?
a DAMP, activating innate immune cells via activation of IL-1 & the inflammasome in macrophages
Explain the steps of autoinflammatory arthritis ?
1) Recognition of MSU by innate immune system
(2) Uptake of MSU by phagocytotic cells
(3) Activation of the NALP3 inflammasome
(4) Release of IL-1β
(5) Endothelial IL-1β receptor type 1 (IL-1R)
(6) Proinflammatory mediators including IL-8 - a potent chemokine for neutrophil recruitment
(7) Neutrophil recruitment into the site
(8) Release of proinflamatory compounds by neutrophils including more IL-1β
