Innate Immune system - PRRs Flashcards

Lecture One

1
Q

What is the primary role of the immune system?

A

The immune system provides host defense by distinguishing ‘non-self’ (foreign pathogens) from ‘self’ (host cells) and protecting against both invading pathogens and host-derived “damage” molecules.

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2
Q

What are the four lines of defense in the immune system?

A
  1. Physical barriers (e.g., skin, mucus)
  2. Chemical barriers (e.g., antimicrobial substances)
  3. Innate immune response (quick, non-specific)
  4. Adaptive immune response (slower, specific, with immunological memory)
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3
Q

What are PAMPs and DAMPs, and how do they differ?

A
  • PAMPs (Pathogen-Associated Molecular Patterns) are conserved structures found in pathogens (e.g., Lipopolysaccharides (LPS) in bacteria).
  • DAMPs (Damage-Associated Molecular Patterns) are self-molecules released from damaged or stressed cells, triggering non-infectious inflammatory responses.
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4
Q

What are the four classes of Pattern Recognition Receptors (PRRs)?

A
  1. Toll-like receptors (TLRs)
  2. NOD-like receptors (NLRs)
  3. RIG-I-like receptors (RLRs)
  4. C-type lectin receptors (CLRs)
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5
Q

How do Toll-like receptors (TLRs) function in immune response?

A

TLRs recognize specific molecular patterns not present in healthy conditions, leading to signal transduction that activates immune responses, including the production of pro-inflammatory cytokines.

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6
Q

What is the NLRP3 inflammasome, and what does it do?

A

The NLRP3 inflammasome is a multiprotein complex that activates caspase-1, leading to the production of pro-inflammatory cytokines IL-1β and IL-18, and can trigger a type of cell death called pyroptosis.

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7
Q

What is the innate immune system’s response time compared to the adaptive immune system?

A

The innate immune system responds within minutes, while the adaptive immune system takes hours to respond.

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8
Q

What are the three types of granulocytes in the innate immune system?

A
  1. Neutrophils
  2. Eosinophils
  3. Basophils
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9
Q

What is the function of neutrophils in the innate immune system?

A

Neutrophils are the most important and abundant phagocytic cells that rapidly destroy microorganisms and orchestrate the innate immune response.

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10
Q

What role do eosinophils play in the immune system?

A

Eosinophils release enzymes and toxic proteins to kill parasites, which are too large to be phagocytosed, and contribute to allergic inflammatory responses.

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11
Q

Where do mast cells primarily mature, and what is their function?

A

Mast cells mature in peripheral tissues like the skin, intestine, and airway mucosa, where they release inflammatory mediators, playing a role in allergic reactions.

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12
Q

What are the primary functions of macrophages?

A

Macrophages perform phagocytosis, produce inflammatory mediators, activate other immune cells, and are involved in tissue repair.

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13
Q

How do dendritic cells bridge innate and adaptive immunity?

A

Dendritic cells act as antigen-presenting cells (APCs), processing antigens and presenting them to T cells, thereby linking the innate and adaptive immune systems.

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14
Q

What distinguishes innate lymphoid cells (ILCs) and NK cells from other immune cells?

A

ILCs and NK cells lack antigen-specific receptors, unlike lymphocytes of the adaptive immune system.

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15
Q

What are Pattern Recognition Receptors (PRRs)?

A

PRRs are receptors expressed on immune cells that recognize “danger” signals such as PAMPs and DAMPs, triggering an inflammatory response.

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16
Q

What are PAMPs?

A

Pathogen-Associated Molecular Patterns (PAMPs) are conserved molecular structures found on pathogens, recognized by the immune system as “non-self.”

17
Q

What are DAMPs?

A

Damage-Associated Molecular Patterns (DAMPs) are self-molecules released from damaged or stressed cells, triggering an inflammatory response.

18
Q

Which Toll-like receptor (TLR) recognizes lipopolysaccharides (LPS) from gram-negative bacteria?

A

TLR4 recognizes LPS, a structural component of gram-negative bacteria.

19
Q

What is the role of MyD88 in TLR signaling?

A

MyD88 is an adaptor protein that recruits IRAK kinases, initiating a signaling cascade that leads to the activation of transcription factors like NF-κB.

20
Q

How do TLRs recognize their ligands?

A

TLRs recognize specific molecular patterns associated with pathogens or cellular damage, leading to dimerization and activation of signaling pathways.

21
Q

What happens when TLRs dimerize?

A

Dimerization brings the toll-interleukin-1 receptor (TIR) domains into proximity, allowing the recruitment of adaptor molecules necessary for signal transduction.

22
Q

What is the function of the NLRP3 inflammasome?

A

The NLRP3 inflammasome activates caspase-1, which cleaves pro-inflammatory cytokines IL-1β and IL-18, leading to their activation and secretion.

23
Q

What triggers NLRP3 inflammasome activation?

A

NLRP3 activation is triggered by signals such as reduced intracellular potassium, reactive oxygen species, and extracellular ATP.

24
Q

What is pyroptosis?

A

Pyroptosis is a form of programmed cell death induced by inflammasomes, resulting in cell lysis and the release of pro-inflammatory cytokines.

25
Q

What are the primary components of the innate immune system’s physical and chemical barriers?

A

The skin, saliva, mucus, and antimicrobial substances are key physical and chemical barriers of the innate immune system.

26
Q

What is the function of NK cells in the immune system?

A

NK (Natural Killer) cells are involved in the direct killing of virus-infected cells and tumor cells, and they play a role in regulating immune responses.

27
Q

What are the steps in TLR signal transduction?

A
  1. Recognition of PAMPs/DAMPs
  2. Dimerization and recruitment of adaptor proteins
  3. Formation of signaling scaffold
  4. Activation of transcription factors
  5. Induction of pro-inflammatory cytokines
28
Q

What role does TAK1 play in TLR signaling?

A

TAK1 is a kinase that activates IKK and MAPKs, leading to the activation of transcription factors such as NF-κB and AP-1, which promote inflammatory responses.

29
Q

What are NOD-like receptors (NLRs) and their function?

A

NLRs are cytoplasmic sensors that detect bacterial components and cellular damage, leading to immune activation and inflammasome formation.

30
Q

What is the function of RIG-I-like receptors (RLRs)?

A

RLRs detect viral RNA in the cytoplasm and initiate antiviral immune responses by activating interferon production.

31
Q

What is the role of C-type lectin receptors (CLRs)?

A

CLRs recognize carbohydrate structures on the surface of pathogens, leading to the activation of immune responses, particularly against fungi.

32
Q

What are the four main adaptor molecules involved in TLR signaling?

A
  1. MyD88
  2. TRIF
  3. TRAM
  4. MAL
33
Q

How do NOD1 and NOD2 recognize bacterial peptidoglycan?

A

NOD1 and NOD2 detect specific components of bacterial peptidoglycan within the cytoplasm, triggering immune signaling pathways similar to TLRs.

34
Q

What is the significance of the TIR domain in TLRs?

A

The Toll/Interleukin-1 receptor (TIR) domain is crucial for the initiation of downstream signaling upon ligand binding and receptor dimerization.

35
Q

What is the outcome of NF-κB activation in immune cells?

A

Activation of NF-κB leads to the transcription of genes encoding pro-inflammatory cytokines, chemokines, and other molecules that mediate immune responses.