Innate Immuno

Question 1

PRR

Answer 1

Pathogen recognition receptors: recognize molecules on pathogens that have a specific molecular pattern (not seen in healthy host)

Question 2

PAMPs (DAMPS)

Answer 2

Pathogen-Associated Molecular Patterns:
recognized molecules on the pathogen (or produced by pathogen)

Damage-Associated Molecular Patterns: patters that arise from “unmasked” or unusual HOST COMPONENTS

Question 3

Where are PRRs located?

Answer 3

Cellular: serum or tissues

1) Cell membrane: sense PAMPS OUTSIDE the cell
2) Endosomal membrane: sense PAMPs that have been endocytosed
3) Cytoplasm: sense PAMPs that have entered cytoplasm

Question 4

What are the two functional outcomes of innate immune response?

Answer 4

1) acute inflammation

2) antiviral resposne

Question 5

TLRs

Answer 5

Toll-like receptors: family of PRRs

• expressed on many cell types
• capable of recognizing a wide variety of PAMPs from different classes of pathogens
• which TLR/combo of TLRs are initially activated has a major role in determining overall response (of initial innate immune response and longer-term responses of cells of adaptive immune response)

Question 6

What happens once PAMP binds to cognate TLR?

Answer 6

Series of molecules are recruited and activated in signal transduction cascade –> activation of TFs in nucleus –> inflammatory/antiviral response

Question 7

What does NF-kB do?

Answer 7

Helps turn on pro-inflammatory responses through the production & secretion of “pro-inflammatory cytokines”

Question 8

Cytokines

Answer 8

secreted proteins with various signaling fxns (mostly immune and inflammatory)

Question 9

What are the key cytokines that mediate inflammation?

Answer 9

TNF (tumor necrosis factor) alpha;
interleukin 1 (IL - 1) Beta;
Interleukin 6

Question 10

Type 1 Interferons

Answer 10

Production and secretion of Type 1 interferons is triggered by activation of IRF family TFs during viral infections

*Crucial to early antiviral defense

Common forms: alpha and beta

Question 11

NLRs

Answer 11

Nod-Like Receptors:
bind PAMPs and DAMPs to initiate intracellular signaling cascade.

Outcome: (one important one) activation of key TFs for inflammatory genes, NF-kB, and activation of pro-inflammatory cytokine IL-1

Location: (various cell types) immune, inflammatory, epithelial barrier cells

Question 12

RIG-I

Answer 12

RNA sensor requires that there be a triphosphate on the 5’ end of the RNA

(Cellular mRNAs have a specially modified “cap” (modified guanine residue) at 5’ end –> do NOT bind RIG-I

Question 13

Lectins

Answer 13

proteins that bind carbohydrates

Question 14

C-lectins

Answer 14

depend on calcium for binding (of carbohydrates)

-Can aid in phagocytosis of microbes and some can also stimulate signaling pathways

Ex: mannose receptor (recognize mannose and several other sugars that are often terminal sugars of human/mammalian proteins

Question 15

Scavenger Receptors

Answer 15

Diverse collection of cell surface receptors; some have broad specificity, including recognition of oxidized lipoproteins.

Mediate phagocytosis of micro-organims

Question 16

FMLP Receptor

Answer 16

(f-Met-Leu-Phe) receptor
responds to N-terminus of bacterial proteins.

*G-coupled protein family

Cellular responses: activation of cells and cytoskeletal and cell surface changes that facilitate chemotaxis toward the course of bacterial infection and entry into infected tissue

Question 17

What are 3 important classes of cellular receptors/ PAMPs & DAMPs sensors?

Answer 17

1) Lectin
2) scavenger receptors
3) FMLP

Question 18

What are the 4 main cells involved in innate immunity?

Answer 18

1) Phagocytes
2) Dendritic Cells
3) NK (Natural killer) cells
4) Mast cells

Question 19

What chemical specifications to Keratinocytes have to help their “outer sentinels” role in immune/defense?

Answer 19

contain large complement of diverse PRRs (including many of the TLRs and some NOD-like receptors)

Question 20

Defensins

Answer 20

class of small peptides; anti-microbial

• have direct antimicrobial toxicity
• can activate cells involved in the inflammatory response

Question 21

Cathelicidins

Answer 21

microbicidal activity (immune activation function)

Question 22

What are the two primary types of phagocytes?

Answer 22

macrophages and neutrophils

Question 23

Macrophages

Answer 23

Arise from circulating blood monocytes that migrate into tissues and undergo differentiation

Fxn: surveillance

Found: healthy CT and all organs (alveolar macrophages in lung; microglia in CNS; Kupffer cells in liver; osteoclasts in bone)

Question 24

How are resident macrophages activated?

Answer 24

several mechanisms:
1) binding of microbes to TLRs or to cell-surface PRRs on macrophages (ie: receptor for the complement)

2) signaling from other activated immune cells (ie: cytokine gamma interferon: IFN-gamma; can be released from NK cells

Upregulation of enzymes (that produce ROS and NO = killing and signaling roles)

Question 25

Neutrophils

Answer 25

60% of white cells in blood (increased during infection)
dominant cells in tissue with acute inflammation
-phagocytose bacteria in circulation or in tissues
-short half life (so not long-lasting defense)

Question 26

Is IFN-gamma at Type I interferon?

Answer 26

NO! Thus it does NOT have a major role in the antiviral response.

Question 27

pDC

Answer 27

have high amounts of TLR7 and 9 in endosomes
-particularly sensitive and respond to viruses

-become Type I IFN factories (Type I IFNs are secreted cytokines)

Question 28

What are the consequences of secreted Type I IFN?

Answer 28

1) Type I IFNs can bind to neighboring cells (paracrine) to induce synthesis of proteins that make cells resistant to viruses)
2) Some cell types of IFN can bind to its interferon receptor on the IFN-producing virus-infected cell (autocrine) –> induce APOPTOSIS
3) stimulate all/most cell types of innate and adaptive immune systems to undergo changes consistent with a stronger short-term and long-term antiviral response

Question 29

What are some of the ways Type I IFNs stimulate all/most cell types of innate and adaptive immune systems to undergo changes consistent with a stronger short-term and long-term antiviral response?

Answer 29

• increased class I MHC/HLA presentation for better presentation of viral antigens
• maturation of dendritic cells and MHC/HLA class II up-regulation for antigen presentation
• stimulation of B cell class switching for production of higher affinity and more effective Abs