Innate Immunity Flashcards
What cytokine causes Th0–>Th1?
IL-12
What cytokine causes Th0–>Th2?
IL-4
What does the complement system do?
- Opsonisation of pathogens
- Forms pores in pathogens via the membrane attack complex
- Pro-inflammatory response due to anaphylatoxins
- Chemotaxis
What do the anaphylatoxins do?
- Vasodilation
- Increased vascular permeability
- Smooth muscle contraction
What are some anaphylatoxins?
C3a, C4a, C5a
Three ways of complement activation?
- Classical
- Alternative
- Mannose binding lectin pathway
Why does complement need to be regulated?
As the anaphylatoxins at high levels and systematically can result in anaphylactic shock
How can complement be regulated?
CD59
Complement factors H and I
How can complement be regulated by CD59?
It can prevent the formation of the MAC
CD59 can also be known as?
MAC inhibitory protein
How do complement factors H and I prevent host cells being targeted?
Complement factor H binds to glycosaminoglycans on the surface of the host cells, recruits complement factor I which can degrade C3b and C4b
Which two parasites can evade complement?
Leishmania
T.cruzi
How does Leishmania evade destruction by complement?
LPG prevents MAC formation
GP63 on the surface converts C3b to iC3b
How does T.cruzi evade destruction by complement?
Uses trans-sialidases to remove sialic acid from host cells and transfers them to the parasite surface= molecular mimicry, placed on mucins
Macrophages can be classically activated through?
IFN-g
Macrophages can be alternatively activated through?
IL-4
Macrophages can be deactivated by?
IL-10
Activated macrophages can produce which signalling molecules?
CXCL8 chemokine
Endogenous pyrogens which induce fever: IL-6, TNF-a, IL1b
Pro-inflammatory TNF-a and IL1b
IL-12
IL-12 produced by macrophages can?
- Activate NK cells
- Cause Th0–>Th1
What does classical activation do to macrophages?
- Causes them to increase their microbicidal activity
- Increased phagocytic activity
- Produce more reactive oxygen and nitrogen species
Alternatively activated macrophages are involved in?
Wound repair
L-arginine is a substrate for?
Nitric oxide production
Production of L-ornithine
L-ornithine can be used to?
Make polyamines
Nutrients for cell growth, repair and proliferation
How can Leishmania survive in macrophages?
Can produce its own arginase or induce the cells to produce arginase
Arginase-1 causes?
L-arginine to become L-ornithine
What is required to transform L-arginine into NO?
iNOS- inducible nitric oxide synthase
Phagolysosome reaches which pH?
~4.5
DC cells also produce which cytokine?
IL-12
Neutrophils survive how long?
6-12 hours
What are TLRs?
Type I integral membrane glycoproteins
TLRs pass through the membrane?
A single time
TLRs are made up of?
Extracellular LRR: Leucine rich repeat
Intracellular cytoplasmic TIR domain
Extracellular part of TLR?
LRR
Leucine Rich Repeat
Intracellular part of TLR?
Cytoplasmic TIR domain
What are TLRs?
Integral transmembrane glycoproteins
TLRs pass through the membrane?
A single time
Extracellular TLRs?
1,2,4,5,6
Intracellular TLRs?
3,7,8,9
TLRs were first identified in?
Drosophila
What is the main difference between TLRs in vertebrates and Drosophila?
Signalling is similar but the TLRs in Drosophila do not directly recognise the PAMPs
The TLRs in vertebrates directly recognise PAMPs
What does inflammation involve?
- Increased vascular permeability
- Increased vascular diameter
- Slowed blood flow
- Expression of receptors on endothelial cells for leukocyte trafficking
Benefits of inflammation?
- Slowed blood flow, increased vascular diameter and increased vascular permeability make leukocyte extravasation much easier
- Increased flow of lymph
What recruits leukocytes to the site of infection?
CXCL8 produced by macrophages
What are the steps of leukocyte trafficking?
1) Rolling: weak interactions involving selectins expressed on endothelial cells
2) Activation of receptors
3) Firm adhesion: expression of integrin LFA-1 on leukocytes which can bind tightly to ICAM-1
4) Transmigration/extravasation occurs
ICAM stands for?
Intracellular adhesion molecule
Dendritic cells are the essential producers of which cytokine?
IL-12
What is the role of DC cells?
Antigen presenting cells
To produce IL-12
IL-12 can lead to?
Classical activation of macrophages
Knocking out the transcription factor Batf3 in mice results in?
The mice lacking certain populations of dendritic cells
In the Batf3 mice when provided with IL-12?
It reverted the phenotype back to the same phenotype as mice without the loss of DC cells
Depleting neutrophils in mice before T.gondii infection?
The mice die
Depleting neutrophils in mice later during T.gondii infection?
The mice do not die
Are neutrophils beneficial at reducing Leishmania infection?
No as Leishmania is able to infect neutrophils and use them as a means of getting into macrophages- trojan horse
What recruits neutrophils during Leishmania infection?
The sandfly bite
NK cells are important during which stage of Plasmodium infection?
During the liver stage
How are NK cells important during the liver stage?
Can kill hepatocytes infected with Plasmodium.
How do NK cells kill infected cells?
Via granzymes and perforin
How are NK cells important during the blood stage of malaria?
ADCC: Antibody dependent cell mediated cytotoxicity. Can recognise the infected cells opsonised with e.g. IgG and can kill them using granzymes and perforin
NK cells can also produce which important cytokine which does what?
IFN-g
Can classically activate macrophages
