Lecture 4

Question 1

What do Pattern recognition receptors do

Answer 1

They recognise things common to microbes (MAMPs and DAMPs)

Question 2

Features of microbe-associated molecular patterns

Answer 2

-They’re shared by many microbes
-They’re distinct from “self”
-They’re critical for survival/ function of pathogens
-Conserved

Question 3

What are damaged-associated molecular patterns

Answer 3

They’re alarm signals from the body’s own cells.
Host components released during injury (cancer, heart attack and cell damage)

Question 4

Examples of MAMPs in bacteria

Answer 4

Bacteria:
(-VE): Lipopolysaccharides
(+VE): Lipotechoic acid
Flagellins
Unmethylated CpG in DNA
N-formylated proteins

Question 5

Examples of MAMPs in fungi

Answer 5

Chitin
Beta-glucans

Question 6

Examples of MAMPs in viruses

Answer 6

dsRNA

Question 7

Examples of MAMPs in protozoa

Answer 7

GPI-linked proteins
Mannose-rich glycans

Question 8

Examples of DAMPs

Answer 8

-Fragments of extracellular matrix proteins (e.g. fibronectin)
-Exposed phosphatidylserine (component of lipid bilayer found inside)
-Mitochondrial components
-Uric acid (build up with excess purines caused by stress)
-DNA

Question 9

What are the classes of Pattern recognition receptors

Answer 9

-Soluble receptors (found in the tissue, e.g. Mannose binding lectin)
-Cytoplasmic receptors (found in the cytosol e.g. NOD-like receptors)
-Membrane receptors (e.g. lectin receptors, chemotactic receptors and Toll-like receptors)

Question 10

What does MAMP binding lead to in membrane receptors

Answer 10

It may initiate phagocytosis, chemotaxis or signalling.

For example, macrophage mannose receptor, CD14.

Question 11

What do chemotactic receptors recognise

Answer 11

Chemoattractants. For example, F-met-leu-phe receptor recognise N-formylated polypeptides produced by bacteria

Question 12

What do Toll-like receptors do

Answer 12

They’re sensors that signal the presence of microbial components.

Question 13

The stages of toll-like receptor binding

Answer 13

1. The macrophage expressed receptors for many bacterial constituents
2. Bacteria binding to macrophage receptors initiates the release of cytokines and small lipid mediators of inflammation
3. Macrophages engulf and digest bacteria to which they bind

Question 14

Features of Toll like receptors

Answer 14

• Ancient pathogen recognition systems
  -10 in humans, each recognising distinct MAMPs
  -They can be found on the cell surface or endosome

Question 15

PAMP for TL1

Answer 15

Lipopeptides

Question 16

PAMP for TLR2

Answer 16

Glycolipids

Question 17

PAMP for TLR3

Answer 17

dsRNA

Question 18

PAMP for TLR4

Answer 18

LPS

Question 19

PAMP for TLR5

Answer 19

Flagellin

Question 20

PAMP for TLR9

Answer 20

unmethylated CpG

Question 21

What’s the structure for TLR3

Answer 21

-Horseshoe shape formed by leucine-rich repeats. The inner surface has a Beta-sheet structure and forms the ligand binding domain.

The horseshoe bit recognises MAMP

Question 22

What are NOD-like receptors

Answer 22

They’re a large group of cytoplasmic receptors that recognise bacterial components (e.g. peptidoglycan flagellin)

Question 23

What do NOD-like receptors do

Answer 23

They signal expression of pro-inflammatory cytokines

They trigger the assembly of inflammasomes (cytokines that induce inflammation)

Question 24

Whats the structure of NOD-like receptors

Answer 24

They’re structurally similar to proteins found in plants (nucleotide-binding oligomerization domains)

Question 25

What are RIG-I-like receptors

Answer 25

They're viral sensors that detect viral RNA produced within host cells. They signal expression of interferons

Question 26

What do macrophages/mast cells release

Answer 26

-Inflammatory mediators that increase blood flow and vascular permeability -Chemoattractants that attract phagocytes into tissues -Cytokines which are Small proteins that induce other cells to help deal with the infection

Question 27

What are the four classic signs of inflammation and what are they caused by

Answer 27

Redness, swelling, heat and pain -Release of inflammatory mediators -Dilation of local blood vessels -Increased permeability and blood flow -Immune cell migration into inflammatory site

Question 28

Examples of inflammatory mediators

Answer 28

-Lipid mediators e.g. prostaglandins (stimulate dilation of blood vessels) -Vasoactive amines e.g. histamine (chemicals that cause dilation of blood vessels) -Chemoattractants e.g. Fmet-leu-phe (help phagocytes move into tissues) -complement proteins e.g. C5A -Cytokines e.g. TNF

Question 29

What is acute inflammation

Answer 29

Beneficial in dealing with infection/ injury (comes on rapidly but goes down rapidly)

Question 30

What is chronic inflammation

Answer 30

It's caused by chronic infection e.g. TB or other conditions e.g. autoimmune disease. It can be damaging

Question 31

What are cytokines crucial for

Answer 31

They control the immune responses in innate and adaptive immunity. They regulate immune responses by changing cell behaviour or gene expression

Question 32

Features of cytokines

Answer 32

They're small proteins They're known as the hormones of the immune response (trigger changes in the body) Most act locally They can be produced by many cell types in response to immune activation They act on cells bearing specific cytokine receptors The expression of cytokines and their receptors is tightly regulated to prevent damage to own body's tissues

Question 33

IL-1 family

Answer 33

Most produced as inactive precursors that must be cleaved by inflammasomes. They're important in inflammation

Question 34

Haematopoietin (cytokine)

Answer 34

Includes factors involved in leukocyte differentiation e.g. gm-csf but also IL-2, IL-4, IL-6

Question 35

Interferons (cytokines)

Answer 35

They're involved in responses to viruses

Question 36

TNF family (cytokines)

Answer 36

TNF alpha (many are transmembrane proteins that are shed and important in inflammation. These are very toxic

Question 37

Chemokines (cytokines)

Answer 37

Involved in cell movement (e.g. IL-8)

Question 38

Type 1 interferons

Answer 38

-Many cell types make type 1 interferons after viral infection and induce expression of interferon stimulated genes

Question 39

Type 2 interferons

Answer 39

Including IFN-gamma modulates immune responses. They're made by neutrophils, NK cell and T cells They play a primary role in adaptive immunity Increases expression of MHC1 and MHC2 IFN-gamma made by T helper cells activated macrophages in response to intracellular pathogens