Lecture 4-1 Flashcards
What are neutrophils?
-circulating effector cells that are active in early phagocytosis of microbes
What are macrophages?
- circulating effector cells of innate immunity
- phagocytosis and killing of microbes
What are NK cells?
-circulating effector cells of innate immunity that lyse infected cells and activate macrophages
What is C-reactive protein?
- pentraxin
- circulating effector protein
- opsonizes microbes, activates complement cascade
What is mannose-binding lectin (collectin)
- circulating effector protein
- opsonize microbes and activates the lectin complement cascade
What is the complement protein?
- circulating effector protein
- activates leukocytes, kills microbes, opsonizes microbes
What type of response do cytokines TNF, IL-a, and chemokines generate?
inflammatory
What type of response is generated by IFN-alpha/Beta?
resistance to viral infection
What response is activated by IFN-gamma?
macrophage activation
What type of response does IL-12 generate?
stimulates IFN-gamma production and NK and T cells
What type of response does IL-15 generate?
- proliferation of NK cells
What type of response does IL-10 and TGF-beta stimulate?
- helps to control inflammation
What is a PAMP? pathogen associated molecular pattern
- specific motif in non-self Ag that allow the innate immune system to recognize them as threats
What are PRRs? pathogen recognition receptors
-PRRs are responsible for recognizing the PAMPs which are specific to gram (+)(-)
What feature do prokaryotes contain that is unique to them and allows the PMN cells to bind to?
N-formylmethionyl peptide is present and allows the PMN cells to bind and initiate phagocytosis
Which TLR (toll-like receptors) are located intracellularly, within an endosome?
TLR-3,-7,-8,-9
What pathogen does TLR-3 recognize?
dsRNA
- carried on NK cells
- located in endosomes
What pathogen does TLR-7 recognize?
ssRNA
- at endosome
- carried by plasmacytoid DC, NK, B cell, eosinophils
What pathogen does TLR-8 recognize?
ssRNA
- at endosome
- carried by NK cells
What pathogen does TLR-9 recognize?
CpG DNA
- at endosome
- carried by B cells, eosinophils, basophils, plasmacytoid DC
What TLR are located extracellularly?
TLR- 1,2,4,5,6
TLR-1,-2 heterodimer responds to what pathogen?
- lipopeptides, GPI
- at PM
- carried on monocytes, DC, basophils, mast cells
TLR-2 responds to what pathogen?
bacterial peptidoglycan
TLR-4 homodimer responds to what pathogen?
Lipopolysaccharides
- at PM
- carried on macrophages, DC, mast cells, eosinophils
TLR-5 responds to what pathogen?
bacterial flagellin
- at PM
- on cells in the intestinal epithelium
TLR-2,-6 heterodimer responds to what pathogen?
- lipoteichoic acid, zymosan
- at PM
- carried on monocytes, DC, basophils, mast cells
What is the overall product of activating a TLR?
-leads to large activation of NF-kappaB
which is a pro-inflammatory protein
What TLR use MyD88 in order to activate NF-kappaB and interferon response factors (IRF)?
-1,-2,-5,-6,-4,-7,-9
Which TLR use TRIF in order to activate interferon response factor (IRF) and NF-kappaB?
-4,-3
What does activation of the TLR lead to?
- antimicrobial pathway to kill pathogen directly
- induce tissue apoptosis to the host cells
- cause septic shock
- mostly will activate NF-kappaB which produces inflammatory genes
Describe the cascade pathway after a TLR is activated and how the NF-kappaB initiates the production of pro-inflammatory genes.
- the kinase cascade activates IKK by phosphorylation
- IKK binds with NF-kB and allows degradation of inhibitory protein IkB.
- active NF-kB enters the nucleus, activates transcription, and inflammatory genes are synthesized and secreted va the ER
What signaling molecules are largely released by necrotic tissue?
DAMPs, damage associated molecular patterns
What are common DAMPS? damage associated molecular patterns?
- HMGB1
- Uric acid
- HSPs
What does the release of HMGB1 indicate, what does it cause, and where does it bind?
- indicates necrotic tissue
- activates the NF-kB pathway
- Bind to the RAGE receptor on DC
What does the release of uric acid indicate, what does it cause, and where does it bind?
- indicates necrotic tissue
- activates the NF-kB pathway
- this has an unknown receptor on DC
What does the release of HSP indicate, what does it cause and where does it bind?
- indicates necrotic tissue
- induces the NF-kB pathway, release of TNF-alpha and IL-1B, inflammatory genes
- binds to CD91 on DC
What are NLRs used primarily for in the host?
Nucleotide oligomerization domain like receptors
- specialized gorup of intracellular proteins
- regulate the host innate immune response
- activate NF-kB and mitogen activated protein kinase pathways
Overall the NLR (nucleotide oligomerization domain like receptors) have what function?
- regulate the host innate immune response by activating the inflammatory caspases
What is an inflamasome?
- signaling complex of NLR and other proteins that form in response to PAMPs and DAMPs
What enzyme do inflammasomes activate?
caspase-1
What is the function of caspase-1?
- cleave inactive cytoplasmic precursor form of IL-1B and IL-18.
- the cleavage leads to activation of these cytokines and produces and inflammatory response
What response do IL-1B and IL-18 produce?
- pro-inflammatory response
What are the different type of receptors that contribute to form the scavenger receptor (SR) family?
- scavenger receptor class A type I
- scavenger receptor class A type II
- MARCO
What are the three distinct domains on the SRs?
- Cysteine rich domain (absent on TypeII)
- collagen like domain
- alpha-helical coiled coil system (absent in MARCO)
What is the primary purpose of SRs?
- uptake of oxidized lipoproteins
- also bind and uptake bacterial cells with negative charges
Which SRs are expressed on tissue macrohpages and help with recognition of microorganisms?
SR-B and CD 36 whose main function is to eliminate the microbe
TLR-2,-6 has uses a coreceptor to recognize lipoteichoic acid and diacylated lipopeptides. what is that coreceptor?
CD36
What type of bacterial components are SR most likely to bind to?
- negatively charged components
- lipoteichoic acids, nucleic acids, B-glucan, proteins, LPS
What is the primary function of lectin receptors?
- facilitate phagocytosis of microbes
- secrete cytokines to promote adaptive immune response
- contain carbohydrate recognition domain
What will recognize 1) terminal D-mannose, 2) L-fucose, 3) N-acetyl-D-glucosamine sugar?
mannose receptors which is a C-type lectin
What do defensins do to microbes?
-infiltrate and disrupt the function of the microbial membrane
Defensins are activated by what process and are largely located in what area?
- located in epithelial cells, neutrophils, NK cells, CTLs, (cytotoxic T lymphocyte) granule containing leukocytes
- stimulated by cytokines and microbial products
What are antimicrobial peptides largely produced by neutrophils?
- cathelicidins
What effect do cathelicidins have when released?
- toxic to microorganisms
- activate leukocytes
- anti-inflammatory role by blocking inflammasome activation
What are two ways that antimicrobial peptides (cethelicidins) can be activated?
- stimulus from microbe
2. PMN can release antimicrobial peptides in resposne to cytokines
What multiple processes can AMPs produce when released beneath the epidermis?
- promote angiogenesis
- wound repair
- activate TLR-9
- recruit T cells
- degrade mast cell, histamine release–>vasodilation
- block TLR activation
- neutralize proinflammatory gene release from monocytes/macrophages
