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
What are the primary components of the innate immune system's physical and chemical barriers?
The skin, saliva, mucus, and antimicrobial substances are key physical and chemical barriers of the innate immune system.
26
What is the function of NK cells in the immune system?
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
What are the steps in TLR signal transduction?
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
What role does TAK1 play in TLR signaling?
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
What are NOD-like receptors (NLRs) and their function?
NLRs are cytoplasmic sensors that detect bacterial components and cellular damage, leading to immune activation and inflammasome formation.
30
What is the function of RIG-I-like receptors (RLRs)?
RLRs detect viral RNA in the cytoplasm and initiate antiviral immune responses by activating interferon production.
31
What is the role of C-type lectin receptors (CLRs)?
CLRs recognize carbohydrate structures on the surface of pathogens, leading to the activation of immune responses, particularly against fungi.
32
What are the four main adaptor molecules involved in TLR signaling?
1. MyD88 2. TRIF 3. TRAM 4. MAL
33
How do NOD1 and NOD2 recognize bacterial peptidoglycan?
NOD1 and NOD2 detect specific components of bacterial peptidoglycan within the cytoplasm, triggering immune signaling pathways similar to TLRs.
34
What is the significance of the TIR domain in TLRs?
The Toll/Interleukin-1 receptor (TIR) domain is crucial for the initiation of downstream signaling upon ligand binding and receptor dimerization.
35
What is the outcome of NF-κB activation in immune cells?
Activation of NF-κB leads to the transcription of genes encoding pro-inflammatory cytokines, chemokines, and other molecules that mediate immune responses.