Lecture 4 Flashcards

1
Q

What do Pattern recognition receptors do

A

They recognise things common to microbes (MAMPs and DAMPs)

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2
Q

Features of microbe-associated molecular patterns

A

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

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3
Q

What are damaged-associated molecular patterns

A

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

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4
Q

Examples of MAMPs in bacteria

A

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

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5
Q

Examples of MAMPs in fungi

A

Chitin
Beta-glucans

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6
Q

Examples of MAMPs in viruses

A

dsRNA

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7
Q

Examples of MAMPs in protozoa

A

GPI-linked proteins
Mannose-rich glycans

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8
Q

Examples of DAMPs

A

-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

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9
Q

What are the classes of Pattern recognition receptors

A

-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)

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10
Q

What does MAMP binding lead to in membrane receptors

A

It may initiate phagocytosis, chemotaxis or signalling.

For example, macrophage mannose receptor, CD14.

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11
Q

What do chemotactic receptors recognise

A

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

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12
Q

What do Toll-like receptors do

A

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

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13
Q

The stages of toll-like receptor binding

A
  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
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14
Q

Features of Toll like receptors

A
  • Ancient pathogen recognition systems
    -10 in humans, each recognising distinct MAMPs
    -They can be found on the cell surface or endosome
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15
Q

PAMP for TL1

A

Lipopeptides

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16
Q

PAMP for TLR2

A

Glycolipids

17
Q

PAMP for TLR3

A

dsRNA

18
Q

PAMP for TLR4

A

LPS

19
Q

PAMP for TLR5

A

Flagellin

20
Q

PAMP for TLR9

A

unmethylated CpG

21
Q

What’s the structure for TLR3

A

-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

22
Q

What are NOD-like receptors

A

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

23
Q

What do NOD-like receptors do

A

They signal expression of pro-inflammatory cytokines

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

24
Q

Whats the structure of NOD-like receptors

A

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

25
Q

What are RIG-I-like receptors

A

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

26
Q

What do macrophages/mast cells release

A

-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

27
Q

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

A

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

28
Q

Examples of inflammatory mediators

A

-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

29
Q

What is acute inflammation

A

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

30
Q

What is chronic inflammation

A

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

31
Q

What are cytokines crucial for

A

They control the immune responses in innate and adaptive immunity.

They regulate immune responses by changing cell behaviour or gene expression

32
Q

Features of cytokines

A

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

33
Q

IL-1 family

A

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

34
Q

Haematopoietin (cytokine)

A

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

35
Q

Interferons (cytokines)

A

They’re involved in responses to viruses

36
Q

TNF family (cytokines)

A

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

37
Q

Chemokines (cytokines)

A

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

38
Q

Type 1 interferons

A

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

39
Q

Type 2 interferons

A

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