Lecture 9 & 10 - Innate Immunity (Pattern Recognition and Signaling)

Question 1

What are pattern recognition receptors?

Answer 1

PRRs are receptors in host cells that recognize pathogen-associated molecular patterns (PAMPs)

Question 2

What are the five main groups of PRRs?

Answer 2

Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), RIG-Like Receptors (RLRs), C-Type Lectin Receptors (CLRs), and Ficolins

Question 3

Why are some TLRs located on the plasma membrane while some are located on endosomes and lysosomes?

Answer 3

The TLRs located on the plasma membrane bind bacteria, parasites, and fungi while the TLRs located on endosomes and lysosomes bind viral proteins, viral dsRNA, viral ssRNA, and bacterial/viral RNA.

Question 4

What are the three main kinds of pathways triggered by TLRs?

Answer 4

NF-κB Transcription Factor Activation, Interferon Regulating Factor (IRF) Pathways, and MAP Kinase Pathway Downstream Transcription Factors (AP-1)

Question 5

What are the two main types of key molecules in signaling cascades?

Answer 5

Adaptor Proteins (MyD88, TRIF) and Transcription Factors (IRF3/7, NF-κB, AP-1)

Question 6

What do most signaling cascades lead to?

Answer 6

Most signaling cascades lead to the activation of a transcription factor which causes a specific gene to be transcribed.

Question 7

What are the general features of signal transduction from ligand-induced receptor dimerization to a functional response?

Answer 7

Ligand-Induced Receptor Dimerization → Recruitment/Activation of Kinases and Adaptors → Second Messenger (Ca²⁺, cAMP, DAG, etc.) → Activation/Nuclear Translocation of Transcription Factors → Changes in Gene Expression → Post-Transcriptional or Post-Translational Modifications → Functional Response

Question 8

Where do transcription factors bind? What do they recruit upon binding?

Answer 8

Transcription factors bind specific sequences on the promotors of target gene. They recruit RNA polymerase.

Question 9

Which type of receptor functions as cytosolic PRRs and recognizes double-stranded RNA?

Answer 9

RLRs

Question 10

What do RLRs activate (through signaling pathways)?

Answer 10

IRFs and NF-κB (Transcription Factors)

Question 11

Which type of receptor functions as cytosolic PRRs and recognizes peptidoglycan from bacterial cell wall?

Answer 11

NLRs

Question 12

Which type of signaling is activated by NLRs?

Answer 12

NF-κB

Question 13

What type of receptor activates the caspase-1 protease? What does caspase-1 do?

Answer 13

NLRs activate the caspase-1 protease. Caspase-1 cleaves IL-1/IL-18 into active forms for release (proinflammatory cytokines). Note, this is a post-translational modification.

Question 14

True or False?:

PRR signaling pathways can lead to modifications like phosphorylation and ubiquitination.

Answer 14

True

Question 15

You are working in a lab that recently made an interesting discovery. You are working with a novel virus that infects macrophages, and have found that this virus can activate the transcription factor NF-κB. However, this NF-κB activation does not occur through any known PRR. Your goal is to try to identify the novel PRR that is triggered by this virus. Where is this novel PRR most likely to be expressed?

• In the Serum
• On an Endosomal Membrane
• On the Cell Surface
• In the Nucleus

Answer 15

On an Endosomal Membrane

Question 16

What are the three main outcomes of PRR signaling?

Answer 16

PRR signaling can lead to pro-inflammatory cytokine production (leading to inflammation (IL-1, IL-6, TNF-α, IL-12) or having potent antiviral effects(Type I IFN)), increased expression of costimulatory molecules (B7.1/CD80, B7.2/CD86 - these provide signal 2 to T-cells in lymphoid tissue), or enhanced migration to regional, secondary lymphoid organs through upregulation of specific adhesion molecules.

Question 17

What do type I IFNs do upon secretion?

Answer 17

Upon secretion, type I IFNs bind to receptors on surrounding cells to trigger signaling cascades leading to the production of cytokines that inhibit translation, induce mRNA degradation, or inhibit virus transcription and assembly.

Question 18

True or False?:

PRR signaling triggers migration and targeting of DCs to lymphoid tissues while decreasing the expression of costimulatory molecules (CD80/CD86).

Answer 18

False

PRR signaling triggers migration and targeting of DCs to lymphoid tissues and increases the expression of costimulatory molecules (CD80/CD86).

Question 19

APCs deliver three kinds of signals to naive T-cells. Which of these three signals are costimulatory molecules involved with?

Answer 19

Survival (2nd)

Question 20

You are a scientist studying a novel virus. You discover that this virus can block TLR3 signaling by preventing the nuclear translocation of the transcription factor IRF3. You decide to further study this virus’s impact on TLR3 signaling. What are you most likely to find in a monocyte infected with this virus?

• Higher Levels of Type I IFN mRNA
• No Activation of Adaptor Proteins
• TLR3 Has Low Affinity to Bind to its Ligand
• High Levels of Activated IRF3 in the Cytoplasm

Answer 20

High Levels of Activated IRF3 in the Cytoplasm

Question 21

What are cytokines?

Answer 21

Cytokines are small heterogenous glycoproteins that provide cellular communication.

Question 22

Cytokines can affect the behaviour of cells via three different mechanisms. What are they and what cells are affected in each?

Answer 22

Cytokines can affect the behaviour of the producing cell (autocrine mechanism), adjacent cells (paracrine mechanism), or distant cells (endocrine mechanism).

Question 23

What is cytokine pleiotropism?

Answer 23

Pleiotropism is when one cytokine is be produced by many different cell types and/or has effects on many different cell types.

Question 24

What is cytokine redundancy?

Answer 24

Redundancy is when different cytokines have the same effect.

Question 25

Activation, proliferation, differentiation, and survival or death of target cells are all functions of which molecules of the immune system?

Answer 25

Cytokines

Question 26

What are the five major groups of cytokines?

Answer 26

Interleukins (IL), Interferons (IFN), Tumour Necrosis Factor (TNF), Hematopeoitins or Growth Factors (varied naming), and Chemokines

Question 27

What is cytokine synergy?

Answer 27

Synergy is when two (or more) cytokines work together to induce an effect.

Question 28

What is cytokine antagonism?

Answer 28

Antagonism is when one cytokine can inactive the effect of another.

Question 29

True or False?:

Pleiotropy, redundancy, synergy, and antagonism all give rise to a complex network of cytokine interactions.

Answer 29

True

Question 30

True or False?:

Immune cells can secrete multiple cytokines, each with different local or systemic effects.

Answer 30

True

Question 31

True or False?:

Cytokines are soluble and found in extracellular fluids.

Answer 31

False

Cytokines are mostly soluble, although some have membrane-bound forms.

Question 32

How is cytokine production regulated?

Answer 32

Cytokine production is tightly regulated transcriptionally (cytokine gene on or off), post-transcriptionally (RNA stability), and post-translationally (some require cleavage).

Question 33

Why is it advantageous for cytokines to induce differentiation of different cell types?

Answer 33

By inducing differentiation of different cell types, cytokines are able to indirectly cause the formation of different cytokines in these differentiated cells that may not be able to be produced in the cell that the differentiating cytokine was produced in.

Question 34

True or False?:

Cell-mediated immunity is mostly directed to extracellular bacteria/pathogens and characterized by predominant B-cell activation and antibody production.

Answer 34

False

Humoral immunity is mostly directed to extracellular bacteria/pathogens and characterized by predominant B-cell activation and antibody production.

Question 35

True or False?:

Humoral immunity is mostly directed to viral infections and intracellular pathogens and is characterized by macrophage activation and cytotoxic T lymphocyte (CTL) activation.

Answer 35

False

Cell-mediated immunity is mostly directed to viral infections and intracellular pathogens and is characterized by macrophage activation and cytotoxic T lymphocyte (CTL) activation.