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BSMS 204- Theme 1 > Lecture 3- Innate Immune defences 2 > Flashcards

Lecture 3- Innate Immune defences 2 Flashcards

1
Q

Explain the function of Neutrophils?

A

Neutrophils- phagocytosis, ROS and reactive nitrogen species, antimicrobial peptides and NET

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2
Q

Name the four steps of phagocyte recruitment?

A
  1. Rolling
  2. Activation
  3. Arrest and Adhesion
  4. Migration into cell
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3
Q

What causes the dilation in blood vessels?

A

cytokines

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4
Q

What attracts the monocytes and neutrophils to the site of the infection?

A

chemokines

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5
Q

Which molecules bind integrins on to the leukocytes?

A

ICAM-1 and ICAM-2

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6
Q

What three cells can perform phagocytosis?

A

neutrophils, dendritic cells and macrophages

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7
Q

Define phagocytosis?

A

is the CAPTURE and DIGESTION of foreign particles

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8
Q

What two processes help phagocytosis?

A

Opsonisation

phagocytic RECEPTORS

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9
Q

What initiates the process of receptor mediated process?

A

binding to pathogen

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10
Q

Describe the four steps involved in phagocytosis?

A
  1. macrohphages RECOGNISE microbial receptors
  2. micro-organisms are BOUND by phagocytic receptors on the macrophage surface
  3. Micro-organism are INTERNALISED by receptor mediator endocytosis
  4. fusion of the endosome with a lysosome forms a phagolysosome in which microbes are DEGRADED
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11
Q

Name 6 antimicrobial mechanisms of phagocytes used to destroy infected cells?

A
  1. Acidification (low pH)
  2. ROS (H2O2, superoxide 2)
  3. RNS- NO
  4. Antimicrobial peptides- cathelicidins
  5. enzymes-lysozymes
  6. competitors -lactoferrin
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12
Q

Describe the process of neutrophil extracellular traps (NETs)?

A

Activated neutrophils undergo special death=netosis
During netosis- nuclear CHROMATIN is RELEASED-
TRAPPING microbes-aiding phagocytosis

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13
Q

Name five types of PAMPS (Pathogen-associated molecular pattern molecules)?

A
  1. C-type lectin receptor (CLR)
  2. Toll like receptors (TLR)
  3. NOD like receptor (NLS)
  4. Rig I like receptors (RLR)
  5. Cytosolic DNA sensors (CDS)
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14
Q

How can the innate immunity recognise the PAMPs?

A

PAMPS able to recognise CONSERVED and ESSENTIAL structures

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15
Q

Which types of cells express the c-lectin receptors?

A

Cells that phagocytose GLYCOPROTEINS

Microbes for antigen presentation for T cells

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16
Q

How do CLR bind to carbohydrates?

A

calcium dependent manner

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17
Q

What is the function of:

  1. Type I CLR
  2. Type II CLR
  3. Soluble CLR
A
  1. Type I CLR- antigen uptake
  2. Type II CLR- fungal recognition
  3. Soluble CLR- Include MBL that bind carbohydrates on pathogen surfaces
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18
Q

Describe the structure of TLR?

A

Extracellular- Lucein rich repeats- pathogen binding

Cytosolic- TIR domain

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19
Q

Explain where are all these TLR are located and what is their PAMPs?

A
  • TLR2 and TLR6- Diacyl-lipopeptide
  • TLR1 and TLR2- Triacylipopeptide
  • TLR5- flagellin
  • TLR4- Lipopolysaccharide
  • TL3/TLR10- DsRNA
  • TLR7- ssRNA
  • TLR8- ssRNA
  • TLR9- CpG DNA
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20
Q

What does the TLR signalling induce?

A

production of GENES that function in host defence

21
Q

Name the four possible products of TLR signalling?

A
  1. pro-inflammatory/anti-inflammatory cytokines
  2. chemokines
  3. MHC&co-stimulatory molecules
  4. antimicrobial peptides and complement components
22
Q

What is consequence of MyD88 gain of function mutation?

A

Waldenström macroglobulinemia - B cells make large amount of IgM
Excess bleeding, vision problems and headaches

23
Q

Which TLRs are involved in the following infections?

  1. HIV
  2. Sepsis
  3. TB
A

HIV- TLR8
Sepsis- TLR2 and TLR4
TB- TLR2 and TLR4

24
Q

Which TLRs are involved in the following inflammatory conditions?

  1. SLE
  2. AD
  3. Atherosclerosis
A
  1. SLE- TLR7,8 and 9
  2. AD- TLR2 and TLR4
  3. Atherosclerosis: TLR2 and TLR4
25
Q

Name the use of TLR agonist use?

  1. Infection (which infection and which TLR)
  2. Cancer (which cancer and which TLR)
  3. Allergy (which allergen and which TLR)
A

Infection (which infection and which TLR) GENITAL WARTS AND TLR7

  1. Cancer (which cancer and which TLR)- MELONOMA AND TLR7 Ligand
  2. Allergy (which allergen and which TLR) RAGWEED POLLEN AND TLR9
26
Q

Name the use of TLR antagonists?

A

autoimmunity, sepsis and cancer

27
Q

What does NLR stand for?

A

Nucleotide-binding leucine-rich

28
Q

What are the two major groups of NOD like receptor called?

A

NLRC- (c for caspase recruitment phase)

NLRP (p for Pyrin domain)

29
Q

What are the two examples of NLRCs?

A

NOD1 and NOD2

30
Q

What is the purpose of the leucine rich domain?

A

LR Domain- bind to PEPTIDOGLYCAN which are present on the CELL MEMBRANE of most bacteria

31
Q

What does NOD1 and NOD2 receptor detect and what are these components of?

A

Similar peptidoglycan
NOD1- binds γ-glutamyl diaminopimelic acid (iE-DAP) (Mainly Gm-ve Bacteria)
NOD2: NOD2 binds muramyl dipeptide (both Gm+ve and Gm-ve bacteria)

32
Q

What happens when NOD2 gain function as genetic mutation?

A

early onset SARCIDOSIS- granulomas develop in the organs

33
Q

What happens when NOD2 lose function as genetic mutation?

A

associated with Crohn’s disease-

34
Q

How is NLRP3 activated and what is inflammasome essential for the production of?

A

Activated by= K+ efflux, cellular stress, ATP, ROS and lysosomal damage
Inflammasome is essential for IL-1 and IL-18 secretion

35
Q

How is inflammasome activated and what is the result of this activation?

A

Activated by CELLULAR INFECTION or STRESS- activation leads to the CLEAVAGE of Prol IL1 and Pro IL-18 to allows SECRETION

36
Q

Name the gain of function mutations in NLRP3 and their features?

A

Cryopyrin-Associated Periodic Syndromes (CAPS)- causing over production of IL-1

37
Q

What are the treatment options for the gain of NLRP function mutation?

A

Anakinra- (IL-1RA)

38
Q

Name the two types of RIG-I like receptors?

A

RIG-I

MDA-5

39
Q

What do the RIG I like receptors sense and where is this product made in?

A

Sense cytoplasmic RNA-replication

Intermediate for viruses

40
Q

What do RIG I receptors bind to and what do they recognise?

A

RIG-I> single stranded RNA-containing 5’triphosphate- Flaviviruses (hepatitis C (HCV)
Orthomyxoviruses (Influenza)

41
Q

What does the MDA5 receptors bind to and what do they recognise?

A

MDA5» Long double stranded RNA- Picoviruses

42
Q

Where are the acute phase response proteins produced?

A

Liver

43
Q

What is the acute phase response induced by?

A

cytokines- TNF, IL-6, IL-1

44
Q

What can acute phase response proteins activate and what is the result?

A

complement- result-opsonisation/phagocytosis

45
Q

What does ESR and CRP characteristic of and what do they detect clinically?

A

ESR and CRP= acute phase response»inflammation

46
Q

Explain the functions of Macrophages?

A

Phagocytosis, inflammatory mediators, antigen presentation, ROS and RNS, cytokines and complement proteins

47
Q

Explain the functions of Dendritic cells?

A

Antigen presentation, co-stimulatory signals, ROS, interferons and cytokines

48
Q

Explain the functions of Natural killer cells?

A

Lysis of viral infected cells, Interferon, macrophage activation

BSMS 204- Theme 1 (21 decks)

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