Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MICR3305 > 5 - Induced Responses of Innate Immunity > Flashcards

5 - Induced Responses of Innate Immunity Flashcards

1
Q

The innate immune system recognises microbial elements that are often essential for survival of microbes

A
  • Ensures that the targets of innate immunity cannot be discarded by microbes in an effort to evade recognition by the host
  • Host cell pattern recognition receptors (PRRs) recognise pathogen associated molecular patterns (PAMPs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Examples of target of innate immunity that is indispensable for microbes

A
  • Double stranded viral RNA (essential intermediate in life cycle of viruses)
  • LPS and lipoteichoic acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Cellular locations of pattern recognition receptors of the innate immune system

A

Extracellular, Cytosolic and endosomal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Toll like receptors

A
  • Family of PRRs expressed on many cell types that recognise products of a wide variety of microbes and molecules released by dying cells
  • 9 different functional TLRs in humans (TLR1-TLR9)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Examples of bacterial products that bind to TLRs

A

LPS (gram -‘ve) and lipoteichoic acid (game +’ve)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Examples of nucleic acids that bind to TLRs

A
  • dsRNA
  • ssRNA
  • Unmethylated CpG dinucleotides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is ssRNA distinguished from host/self ssRNA

A

By their location within endosomes and by high guanosine and uridine content

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

End result of TLR recognition of microbial ligands

A
  • Expression of genes whose products are important for inflammatory and antiviral responses
  • Ligand induced TLR dimerisation brings the TIR domains of the cytoplasmic tails of each protein close to one another
  • Leads to recruitment of TIR domain containing adaptor proteins which facilitate the recruitment and activation of various protein kinases
  • Leads to activation of different transcription factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Major transcription factors that are activated by TLR signaling pathways

A
  • Nuclear factor kB(NF-kB)
  • Activation protein 1 (AP-1)
  • Interferon response factor 3 (IRF3)
  • IRF7
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

C type lectin receptors

A

Cellular receptors that recognise carbohydrates on the surface of microbes facilitate the phagocytosis of the microbes and the secretion of cytokines that promote inflammation and subsequent adaptive immune responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where are c type lectin receptors found

A
  • Integral membrane proteins found on the surfaces of macrophages, DCs, and some tissue cells
  • Other lectins are soluble proteins in the blood and extracellular fluids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Types of plasma membrane C type lectins with specificities for different carbohydrates

A
  • Mannose
  • Glucose
  • N-actylglucosamine (GlcNAc)
  • β-glucans
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Inflammatory response

A
  • Bacteria trigger macrophages to release cytokines and chemokines which cause vasodilation
  • Leukocytes move to periphery of blood vessel as a result of increased expression of adhesion molecules by endothelium
  • Leukocytes extravasate at site of infection
  • Neutrophils engulf and kill the microbes
  • Blood clotting occurs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

When do blood monocytes differentiate into tissue macrophages

A
  • During inflammation
  • Monocyte binds adhesion molecules on vascular endothelium near site of infection and receives chemokine signal
  • Monocyte migrates into tissue
  • Monocyte differentiates into macrophage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Adhesion molecules that control immune cell movement

A
  • Selectins
  • Integrins
  • Immunoglobulin superfamily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Selectins

A
  • Bind carbohydrates
  • Initiate leukocyte-endothelial interaction
  • e.g. P selectin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Integrins

A
  • Located on phagocyte
  • Bind to cell adhesion molecules and extracellular matrix
  • Strong adhesion
  • E.g. LFA-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Immunoglobulin superfamily

A
  • Various roles in cell adhesion
  • Ligand for integrins
  • e.g. ICAM-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Multistep process of neutrophils leaving blood and migrating to sites of infection

A
  • Rolling adhesion, tight binding, diapedesis, and migration
  • Binding of a chemokine such as CXCL8 (IL-8) to its receptor on the neutrophil
    triggers activation of integrin LFA-1
  • Inflammatory cytokines such as TNF-⍺ are also necessary to induce expression of adhesion molecules such as ICAM-1,
    ligand for the integrin, on vascular endothelium
  • Tight binding between ICAM-1 and integrin arrests
    rolling and allows neutrophil to squeeze between endothelial cells that form blood vessel wall
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Phagocytosis

A
  • Phagocyte receptors bind to PAMPs and opsonins including antibody molecules and complement proteins
  • Ingested foreign particles are enclosed within phagosome that breaks away from plasma membrane
  • Phagosome fused with lysosome to create phagolysosome that contain antimicrobial molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What antimicrobial molecules do phagolysosomes contain

A
  • Reactive Oxygen Species (ROS)
  • Nitric oxide
  • Proteolytic enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Important cytokines and chemokines secreted by dendritic cells and macrophages in response to bacterial products

A
  • IL-1β
  • IL-6
  • CXCL8 (IL-8)
  • IL-12
  • TNF-⍺
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Local effects of IL-1β

A
  • Activates vascular endothelium
  • Activates lymphocytes
  • Local tissue destruction
  • Increases access of effector cells
24
Q

Systemic effects of IL-1β

A
  • Fever
  • Production of IL-6
25
Q

Local effects of TNF-⍺

A
  • Activates vascular endothelium
  • Increases vascular permeability (leads to increased entry of IgG complement, and cells to tissues and increased fluid drainage to lymph nodes
26
Q

Systemic effects of TNF-⍺

A
  • Fever
  • Mobilisation of metabolites
  • Shock
27
Q

Local effects of IL-6

A
  • lymphocyte activation
  • Increased antibody production
28
Q

Systemic effects of IL-6

A
  • Fever
  • Induces acute phase protein production
29
Q

Local effects of CXCL8

A
  • Chemotactic factor that recruits neutrophils, basophils, and T cells to site of infection
30
Q

Local effects of IL-12

A
  • Activates NK cells
  • Induces the differentiation of CD4 T cells into Th1 cells
31
Q

Excess TNF production

A
  • Leads to sepsis
  • Macrophages activated in liver and spleen secrete TNF-⍺ into bloodstream
  • Systemic edema causing decreased blood volume, leading to collapse of vessels
  • Disseminated intravascular coagulation leading to wasting and multiple organ failure
  • Death
32
Q

Acute phase proteins

A

Produced by hepatocytes in response to cytokines produced by macrophages in the presence of bacteria (e.g. C reative protein and mannose binding lectin)

33
Q

C-reactive protein

A

Binds phosphocholine on bacterial surfaces, acting as an opsonin, and also activating complement

34
Q

Mannose binding lectin

A

Binds mannose residues on bacterial surfaces, acting as an opsonin, and also activating complement

35
Q

What is the major way by which the innate immune system blocks viral infections

A

By inducing the expression of type 1 interferons

36
Q

Type 1 interferons

A
  • Large family of structurally related cytokines that mediate the early innate response to viral infections
  • Most important are IFN-α and IFN-β
37
Q

What produces IFN-α

A

Major source is plasmacytoid DCs but also produced by mononuclear phagocytes

38
Q

What produces IFN-β

A

Many cell types in response to viral infection

39
Q

Outcomes of interferons

A
  • Inhibition of viral protein synthesis
  • Degradation of viral RNA
  • Inhibition of viral gene expression and virion assembly
40
Q

Antiviral response

A
  1. Production of IFN-α, IFN-β, and IL-12 (1-5 days)
  2. NK-cell mediated killing of infected cells (1-6 days)
  3. T-cell mediated killing of infected cells (2-10+ days)
41
Q

NK cells

A
  • Cytotoxic cells that play important roles in innate immune responses, mainly against viruses and intracellular bacteria
  • Innate lymphoid cells (ILCs)
42
Q

How can NK cells be differentiated from T cells

A

As they do not express CD3, (T cell receptor)

43
Q

Why are NK cells referred to as lymphoid cells and not lymphocytes

A

Because they do not express clonally distributed diverse antigen receptors like T lymphocytes

44
Q

Functions of NK cells

A

Kill infected cells and to produce IFN-γ, which activates macrophages to destroy phagocytosed microbes (important for intracellular bacteria)

45
Q

How do NK cells kill other cells

A

Activated NK cells produce perforin, a protein that facilitates the entry of
granzymes into the cytosol of target cells, to initiate a sequence of signalling events that induce apoptosis

46
Q

Activating and inhibitory receptors of NK cells

A
  • Activating receptors recognise ligands on infected and injured cells, stimulating killing activity of NK cells
  • Inhibitory receptors recognise ligands on healthy normal cells, shutting off NK cell activity
47
Q

Antibody dependent cellular cytotoxicity (ADCC)

A
  • Anti-viral function of NK Cells
  • Antibodies bind to virus infected cells
  • NK cells bind to antibodies with CD16 receptor
  • NK cells release cytotoxic granules and antiviral cytokines to kill infected cells
48
Q

Two signal hypothesis of stimulation of adaptive immunity

A
  • Activation of lymphocytes requires two distinct signals
  • First signal is the antigen
  • Second is molecules produced during innate immune responses (e.g. complement, costimulator)
  • Ensures that adaptive response are induced when there is a dangerous infection and not harmless antigens (including self)
49
Q

Examples of two signal hypothesis

A
  • IL-12 stimulates the differentiation of naive CD4+ T cells to the Th1 subset
  • IL-6 promotes the production of antibodies by activated B cells
50
Q

What TLRs detect bacterial lipopeptides

A

TLR1, 2 and 6

51
Q

What TLRs detect bacterial peptidoglycan

A

TLR2

52
Q

What TLRs detect LPS

A

TLR4

53
Q

What TLRs detect bacterial flagellin

A

TLR5

54
Q

What TLRs detect dsDNA

A

TLR3

55
Q

What TLRs detect ssRNA

A

TLR7 and 8

56
Q

What TLRs detect CpG DNA

A

TLR 9

57
Q

TLR structure

A
  • Leucine rich repeat motifs
  • Cysteine rich flanking motif
  • TIR domain

MICR3305 (25 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions