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MCB 2020 > 4.5 Innate Immunity > Flashcards

4.5 Innate Immunity Flashcards

1
Q

What are the three pillars of the innate immune response? Barriers, proteins and cells?

A
  • Fixed and induced defences
  • Barriers (physical, chemical and cellular)
  • Specialised proteins (complement, chemokines, cytokines)
  • Specialised cells (neutrophils, macrophages, NK cells)
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2
Q

How is the innate immune response activated?

A
  • Receptor molecules on cells and in serum recognise PAMPs (activation)
  • Can use specialized cells (NK cells) to detect altered self glycoproteins
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3
Q

What is the role of epithelial cells in innate immunity?

A

More than an important physical barrier, they also produce microbicidal and inhibitory molecules

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4
Q

What are the three specialised plasma factors mediating innate immunity?

A

C reactive protein, Mannose binding lectin, Complement proteins

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5
Q

What does the C-reactive protein do as part of the innate immune system?

A
  • Binds capsule of several bacteria, aids phagocytosis, triggers the complement cascade
  • Acts as soluble pattern recognition receptors
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6
Q

What does mannose binding lectin do as part of the innate immune system?

A
  • Binds mannose residues on pathogens, triggers the complement cascade
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7
Q

What do complement proteins do as part of the innate immune system?

A
  • Pro-enzymes (C1, C2 etc) which are triggered after binding a pathogen to produce a cascade of reactions which generate effector molecules against the pathogen
  • These and others are termed acute phase proteins - rapidly produced in infection (eg CRP, C3, C4)
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8
Q

What does the term complement refer to?

A

The term complement refers to a large group of constitutively produced plasma proteins which interact with pathogens to mark them for killing

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9
Q

How is the complement system activated?

A
  • No matter how the cascade is activated, breakdown of C3 is the critical step in the cascade
  • Complement activation involves an enzyme “cascade”
  • Exist as inactive proenzymes but cleaved products of enzyme cascade are given terms a for smaller fragment as b for larger fragment
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10
Q

What are the stages of complement action?

A
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11
Q

What are the outcomes of the complement cascade?

A
  • migration of phagocytes to site of infection
  • phagocytosis of microorganisms
  • lysis of microorganisms
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12
Q

What three pathways lead to the cleavage of C3 in the complement cascade?

A
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13
Q

What does the cleavage of C3 lead to in the complement cascade?

A
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14
Q

What does this show?

A
  • Release C5b allows recruitment of C6 and 7 and 8
  • Form structure on the membrane which makes a pore and results in lysis
  • Does not occur on the surface of self cells
  • Our own cells have proteins that stop this cascade but microbes do not have defence mechanism
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15
Q

How are these cells divided?

A
  • Bloodstream vs tissues
  • Contains granules they release in response to activation
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16
Q
A
17
Q

Which of these are the PAMPs?

A
18
Q

What are the classes of Pattern Recognition Receptors?

A
  • TLR (toll like receptors) membrane bound on surface or endosome, they recognise RNA and DNA as pathogens unpack and expose nucleic acid
  • NOD (nucleotide binding oligomerisation domain) bind to peptidoglycan
  • RIG (retinoic acid inducible gene), collectins, etc.,
  • Some of these also bind danger associated molecular patterns (DAMPs) which are the rsult of metabolic products or products produced in excess when cell is in distress
19
Q

What are the different outcomes of pattern recognition receptor and PAMP ligation?

A
  • Ligation of soluble receptors such as MBL leads to phagocytosis
  • Ligation of cell bound receptors such as mannose receptor and scavenger receptor leads to phagocytosis
  • Ligation of TLRs and NODs may results in
    • expression of different cell surface receptors
    • production of chemokines and cytokines
    • production of defensins
  • Ligation of RIGs associated with anti-viral immunity
20
Q

What are cytokines?

A
  • a protein secreted by cells that interacts with and affects the behaviour of nearby cell bearing the appropriate receptors
  • Affect multiple functions (regulate innate immunity, adaptive immunity, haematopoiesis and more)
21
Q

What are some types of cytokines?

A

Multiple names – interleukins (IL-), interferons (IFN-), colony stimulating factors (CSF’s) , tumor necrosis factors (TNF’s),

22
Q

What are chemokines?

A

A secreted protein that attracts cells bearing the appropriate receptors

23
Q

What are the two groups of chemokines?

A
  • Two groups of receptors, both of which contain two cysteine molecules
  • CCR
  • CXCR
24
Q

What are the two types of phagocytes?

A

Polymorphonuclear neutrophils

  • most numerous, but short lived cells, found in circulation.

Mononuclear phagocytes (macrophages, monocytes)

  • long lived cells, found in circulation and tissues
25
Q

What is the function of phagocytes?

A
  • Enter an infected site from the circulation, where they:
  • bind , engulf, and kill a wide variety of microbial agents
  • produce immunomodulatory substances, eg. cytokines, chemokines, which regulate the immune response
  • act as a first line defence against infection
26
Q

What sort of receptors do macrophages express?

A

Many different pattern recognition receptors

27
Q

What bioactive products do macrophages express when activated?

A
28
Q

How does inflammation occur?

A
29
Q

How do macrophage and complement proteins induce nuetrophil migration from blood to tissues?

A
30
Q

How does the binding strength compare?

A
31
Q

What are the steps of phagocytosis?

A
32
Q

What are some phagocyte killing mechanisms?

A

Lactoferrin scavenge iron away from the bacteria

33
Q

What are cytotoxic cells?

A
  • Target infected or altered cells, and release granules whose contents are toxic.
  • Natural killer (NK) cells (kill tumour, virus infected cells)
  • Eosinophils (kill antibody coated parasites)
  • Macrophages (release cytotoxic mediators)
34
Q

What are basophils and mast cells?

A
  • Release granules containing inflammatory mediators to augment the action of immune cells,
  • But this increases inflammation and mediates unwanted hypersensitivity reaction such as allergies
35
Q

What is the outcome of the response to microorganism invasion by the innate defences?

A
  • Removal of the invading microorganisms leads to resolution of infection.
  • Persistence and replication of microorganism.
  • because some microorganisms evolved to overcome the defences of the innate immune system - Pathogens
  • Resolution of infection of infections by pathogens requires additional effector mechanisms. These are provided by the more recently evolved Adaptive Immune System.

MCB 2020 (38 decks)

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