12: Instrinsic and innate defenses

Question 1

What are the components of the immune system?

Answer 1

Its composed of
- cells (white blood cell, leukocytes)

• tissues (lymphoid organs)

Question 2

What are the layers of the immune system?

Answer 2

Anatomical or Chemical barriers

Epithelial cells joined by tight junctions

Skin: Longitudinal flow of air or fluid ; fatty acids ; antimicrobial peptides

Gut: Longitudinal flow of air or fluid ; low ph, antimicrobial peptides & enzymes

Lungs: movement of mucus by cilia; surfactant & antimicrobial peptides

Eyes/Nose/Oral: Tears nasal cilia, antimicrobial enzymes in tears/saliva ; antimicrobial peptides

Question 3

What type of immunities are there?

Answer 3

Innate immunity: always present in the uninfected cell

(Intrinsic) can be immediate: apoptosis, autophagy, RNA silencing, CRISPER

(Induced): inflammation

Adaptive immunity: tailored to the virus

Question 4

What is apoptosis? Intrinsic

Answer 4

It Is programmed cell death.

Virus-infected cells activate apoptosis as a mechanism of inhibiting viral replication

Macrophages engulf apoptotic bodies and scan for viruses via PRRs

Question 5

What is autophagy? Intrinsic

Answer 5

Autophagy is a process in which a cell gets rid of damaged or redundant cellular components
- cells can use it to destroy viruses
- some viruses can activate or inhibit autophagy pathways

Question 6

What is RNA silencing? Intrinsic

Answer 6

• RNA interference is medicated by silencing RNA and microRNA
• Intrinsic mechanism for viral infection in plants

Question 7

What is induced innate immunity?

Answer 7

Inflammation

Question 8

How does viral infection work in innate immunity?

Answer 8

Recognize viral products and release soluble proteins (cytokines) to start inflammation by:

1. Vasodilation to increase permeability
2. Leukocytes
3. Active antiviral responses (inflammation: redness, swelling, heat and pain)

Question 9

How does the immune system recognize viruses?

Answer 9

Viral products can be:

1) Exogenous antigens:
a. outside the cell (extracellular)

b. inside the cell (In endosome)

2) Endogenous antigens:
Inside the cell (in cytoplasm)

Question 10

Which receptors detect viruses? Pattern Recognition Receptors (PPRs)

Answer 10

Toll-like receptors (TLRs) :
Transmembrane proteins at the plasma membrane or endoscope

Nucleotide-binding oligomerization domain-like receptors (NLR):
Cytoplasmic sensors

AIM2: detects viral and bacterial DNA

RIG-I-like receptors (RLRs);
Cytoplasmic receptors of viral RNA

Question 11

What is the signalling pathway for TLRs?

Answer 11

TLRs detect the viral structures which include ssRNA, dsRNA. nucleotides and protein components of the viral envelope.

Cytoplasm adapter proteins (TRAF6/TRIF and MyD88) are associated with cytoplasmic tails of TLR. These adaptor proteins activate NF-κB pathway to induce the expression of interferon (IFN)-α/β.

Question 12

What is the RIG-1 signalling pathway?

Answer 12

• Retinoic acid-inducible gene detects viral RNA.
• After binding their nucleic acid ligands, RIG-1 signal via an adaptor protein (MAVS) , mitochondrial antiviral signalling protein), which activates NF-κB and enhances gene expression of interferons.

Question 13

What is the cGas/String pathway?

Answer 13

Viral dsDNA in the cytoplasm is detected by cyclic GMP-AMP (cGAMP) synthase (cGAS) which is activated to make cGAMP.

cGAMP activates ER-resident receptor (STING; stimulator of interferon gene)

Activated STING translocates to a perinuclear Golgi compartment to activate NF-κB that induces expression of proinflammatory genes.

Question 14

How do cells react to viral infection? 3 classes of cytokines

Answer 14

• Infected cells secrete soluble proteins (cytokines) that recruit immune cells
• Among cytokines, interferons (IFN) are most important
• IFN-α & IFN-β are mainly produced by infected cells
  
  • resistance to viral replication in cells
  • expression of ligands for receptors on NK cells
    - NK cells to kill-virus infected cells
• IFN-γ is produced by natural killer (NK) cells (cells specialized in killing virus- infected cells)

Question 15

What is the SOS Signal associated with IFN-γ?

Answer 15

• Upon intestinal infection the viral RNA is sensed by RIG-1, which signals to stimulate transcription of type 1 and type 2 IFNS
• IFN-λ is produced by infected intestinal epithelial cells
• IFN-λ binds to IFN-λ receptor (IFNλR) on nearby cells, triggering a downstream signaling pathway to enhance the expression of interferon-stimulated genes (ISGs) coding for antiviral proteins

Question 16

What are natural killer (NK) cells?

Answer 16

• When an epithelium is infected with a virus, the infected cells respond by secreting type 1 IFN.
• NK cells have IFN receptors that activate the NK cells on binding IFN. The activated NK cells kill the virus infected epithelial cells by apoptosis.

Question 17

NK cells and macrophages: mutual activation

Answer 17

1. Macrophages activated by viral infection secrete cytokines that recruit NK cells
2. Nk cell and macrophage conjugate. The synapse delivers IL-15, which with IL-12 activates the NK cells
3. NK cells proliferate and differentiate into effector NK cells secreting IFN Y
4. IFN-y binds its receptor to the macrophage which increases phagocytosis + cytokine secretion