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Combating Disease > The Innate Immune System Part I – Pattern recognition > Flashcards

The Innate Immune System Part I – Pattern recognition Flashcards

1
Q

What is Innate immunity compared to adaptive immunity ?

A
  • It is more popular

- Also evolutionary older than adaptive immunity

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2
Q

Innate immunity is where in our defence ?

A

It is the frontline of our defences

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3
Q

Innate immunity includes what mechanism and defences ?

A

Innate immunity includes the basic barrier mechanisms and

simple biochemical defences

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4
Q

What cells does the innate immunity have ?

A

It includes immune cells (white blood cells) that recognise “general” pathogen molecules

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5
Q

Name some unique features of the innate immune system?

A
  • 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
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6
Q

Explain some features of Inflammation ?

A
  • 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)
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7
Q

Explain Neutrophils ?

A
  • 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)
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8
Q

What are neutrophil NETs ?

A

Chromatin based fibres that trap & kill extracellular microbes

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9
Q

What does neutrophil NETs create ?

A
  • Creates an antimicrobial environment at the inflammatory site
  • Acts as a physical barrier contributing to killing of extracellular pathogens
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10
Q

Explain Eosinophils ?

A
  • 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
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11
Q

Explain Basophils ?

A
  • 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
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12
Q

Explain Mast Cells ?

A
  • 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
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13
Q

What are Monocytes and it contains ?

A
  • They are the blood precursor to tissue macrophages

- It contains nucleus, lysosome and phagosome

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14
Q

What are Macrophages and it contains ?

A
  • They are specialised for phagocytosis & present antigens to T cells of adaptive immune system
  • It contains Pseudopodia, Phagosomes, Lysosome and Phagolysosome
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15
Q

What are Dendritic cell and it contains ?

A
  • 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
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16
Q

Monocytes are recruited to ?

A

Tissues from blood at sites of inflammation where they differentiate into macrophages

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17
Q

Macrophages are professional phagocytes recognising & eating germs. What do they release ?

A
  1. Release of anti-microbial factors
  2. Release of pro-inflammatory cytokines
  3. Antigen presenting cell (APC) capacity
18
Q

What do Pattern Recognition Receptors (PRR) enable ?

A

The discrimination between self and non-self

19
Q

What do PRR recognise ?

A

PRR recognise simple molecules and molecular patterns specifically
associated with microorganisms known as Pathogen Associated
Molecular Patterns (PAMPs) – i.e., non-self

20
Q

What can PRR also recognise?

A

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’

21
Q

What receptors do Innate cells use ?

A

Pattern Recognition Receptors to recognise pathogens and discriminate from our own healthy cells

22
Q

What are Pathogen Associated Molecular Patterns (PAMPs) ?

A

They molecular structures or molecules shared by most pathogenic microorganisms

23
Q

What are Damage Associated Molecular Patterns (DAMPs) ?

A

They are molecular structures or molecules commonly found on damaged/necrotic/stressed tissue

24
Q

How are PAMPs and DAMPs recognised ?

A

By innate Pattern Recognition Receptors (PRR)

25
Q

What did Janeway in 1989 predict ?

A

That activation of the adaptive immune response is controlled by the innate immune system

26
Q

What did Janeway propose ?

A

A general theory of innate immune recognition (pattern recognition theory) and suggested the principles of innate control of adaptive immunity

27
Q

What do the families of innate PRRs function ?

A

As sensors for pathogen/damage associated molecular patterns (PAMPs/DAMPs)

28
Q

What are the four different families of Innate PRRs ?

A
  1. Toll-like receptors (TLRs)
  2. C-type lectin receptor (CLR)
  3. RIG-I-like receptor (RLR)
  4. NOD-like receptors (NLRs)
29
Q

Explain Toll-like receptors (TLRs) ?

A

Family of transmembrane PRR that recognise pathogens and their products. Stimulation on receptor bearing cells produces cytokines that activate immune responses

30
Q

Explain NOD-like receptors (NLRs) ?

A

Family of intracellular PRR containing a Nucleotide-oligomerisation domain
(NOD) who detect microbes and cellular stress to induce immune responses

31
Q

What are on the cell wall of innate cells such as macrophages ?

A
  • Mannose receptors
  • Glucan receptor
  • Scavenger receptor

Bind cell wall carbohydrates of yeast, bacteria and fungi

32
Q

What leads to activation of NFkB ?

A

NOD receptor recognition of bacterial cell-wall components leads to activation of NFkB

33
Q

What do NLRs also activate ?

A

They activate the inflammasome

34
Q

What is Gout a response to ?

A

It is in response to uric acid crystals to build up in joints

35
Q

When is Uric acid produced?

A

Uric acid is a natural product produced when the body breaks down purines found in meat & seafood

36
Q

What kind of pattern is Uric acid ?

A

Uric acid is a DAMP which activates the inflammasome

37
Q

What can also increase the risk of Gout ?

A

Diuretics, beta blockers, aspirin (when taken regularly) & niacin (for high cholesterol)

38
Q

What is an auto-inflammatory driven by ?

A

Innate immune response to deposition of monosodium urate (MSU) crystals in the joint & characterised by a large neutrophil infiltration

39
Q

What do MSU acts as ?

A

a DAMP, activating innate immune cells via activation of IL-1 & the inflammasome in macrophages

40
Q

Explain the steps of autoinflammatory arthritis ?

A

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

Combating Disease (11 decks)

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