Lecture 3- Innate Immune defences 2 Flashcards
Explain the function of Neutrophils?
Neutrophils- phagocytosis, ROS and reactive nitrogen species, antimicrobial peptides and NET
Name the four steps of phagocyte recruitment?
- Rolling
- Activation
- Arrest and Adhesion
- Migration into cell
What causes the dilation in blood vessels?
cytokines
What attracts the monocytes and neutrophils to the site of the infection?
chemokines
Which molecules bind integrins on to the leukocytes?
ICAM-1 and ICAM-2
What three cells can perform phagocytosis?
neutrophils, dendritic cells and macrophages
Define phagocytosis?
is the CAPTURE and DIGESTION of foreign particles
What two processes help phagocytosis?
Opsonisation
phagocytic RECEPTORS
What initiates the process of receptor mediated process?
binding to pathogen
Describe the four steps involved in phagocytosis?
- macrohphages RECOGNISE microbial receptors
- micro-organisms are BOUND by phagocytic receptors on the macrophage surface
- Micro-organism are INTERNALISED by receptor mediator endocytosis
- fusion of the endosome with a lysosome forms a phagolysosome in which microbes are DEGRADED
Name 6 antimicrobial mechanisms of phagocytes used to destroy infected cells?
- Acidification (low pH)
- ROS (H2O2, superoxide 2)
- RNS- NO
- Antimicrobial peptides- cathelicidins
- enzymes-lysozymes
- competitors -lactoferrin
Describe the process of neutrophil extracellular traps (NETs)?
Activated neutrophils undergo special death=netosis
During netosis- nuclear CHROMATIN is RELEASED-
TRAPPING microbes-aiding phagocytosis
Name five types of PAMPS (Pathogen-associated molecular pattern molecules)?
- C-type lectin receptor (CLR)
- Toll like receptors (TLR)
- NOD like receptor (NLS)
- Rig I like receptors (RLR)
- Cytosolic DNA sensors (CDS)
How can the innate immunity recognise the PAMPs?
PAMPS able to recognise CONSERVED and ESSENTIAL structures
Which types of cells express the c-lectin receptors?
Cells that phagocytose GLYCOPROTEINS
Microbes for antigen presentation for T cells
How do CLR bind to carbohydrates?
calcium dependent manner
What is the function of:
- Type I CLR
- Type II CLR
- Soluble CLR
- Type I CLR- antigen uptake
- Type II CLR- fungal recognition
- Soluble CLR- Include MBL that bind carbohydrates on pathogen surfaces
Describe the structure of TLR?
Extracellular- Lucein rich repeats- pathogen binding
Cytosolic- TIR domain
Explain where are all these TLR are located and what is their PAMPs?
- TLR2 and TLR6- Diacyl-lipopeptide
- TLR1 and TLR2- Triacylipopeptide
- TLR5- flagellin
- TLR4- Lipopolysaccharide
- TL3/TLR10- DsRNA
- TLR7- ssRNA
- TLR8- ssRNA
- TLR9- CpG DNA
What does the TLR signalling induce?
production of GENES that function in host defence
Name the four possible products of TLR signalling?
- pro-inflammatory/anti-inflammatory cytokines
- chemokines
- MHC&co-stimulatory molecules
- antimicrobial peptides and complement components
What is consequence of MyD88 gain of function mutation?
Waldenström macroglobulinemia - B cells make large amount of IgM
Excess bleeding, vision problems and headaches
Which TLRs are involved in the following infections?
- HIV
- Sepsis
- TB
HIV- TLR8
Sepsis- TLR2 and TLR4
TB- TLR2 and TLR4
Which TLRs are involved in the following inflammatory conditions?
- SLE
- AD
- Atherosclerosis
- SLE- TLR7,8 and 9
- AD- TLR2 and TLR4
- Atherosclerosis: TLR2 and TLR4
Name the use of TLR agonist use?
- Infection (which infection and which TLR)
- Cancer (which cancer and which TLR)
- Allergy (which allergen and which TLR)
Infection (which infection and which TLR) GENITAL WARTS AND TLR7
- Cancer (which cancer and which TLR)- MELONOMA AND TLR7 Ligand
- Allergy (which allergen and which TLR) RAGWEED POLLEN AND TLR9
Name the use of TLR antagonists?
autoimmunity, sepsis and cancer
What does NLR stand for?
Nucleotide-binding leucine-rich
What are the two major groups of NOD like receptor called?
NLRC- (c for caspase recruitment phase)
NLRP (p for Pyrin domain)
What are the two examples of NLRCs?
NOD1 and NOD2
What is the purpose of the leucine rich domain?
LR Domain- bind to PEPTIDOGLYCAN which are present on the CELL MEMBRANE of most bacteria
What does NOD1 and NOD2 receptor detect and what are these components of?
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)
What happens when NOD2 gain function as genetic mutation?
early onset SARCIDOSIS- granulomas develop in the organs
What happens when NOD2 lose function as genetic mutation?
associated with Crohn’s disease-
How is NLRP3 activated and what is inflammasome essential for the production of?
Activated by= K+ efflux, cellular stress, ATP, ROS and lysosomal damage
Inflammasome is essential for IL-1 and IL-18 secretion
How is inflammasome activated and what is the result of this activation?
Activated by CELLULAR INFECTION or STRESS- activation leads to the CLEAVAGE of Prol IL1 and Pro IL-18 to allows SECRETION
Name the gain of function mutations in NLRP3 and their features?
Cryopyrin-Associated Periodic Syndromes (CAPS)- causing over production of IL-1
What are the treatment options for the gain of NLRP function mutation?
Anakinra- (IL-1RA)
Name the two types of RIG-I like receptors?
RIG-I
MDA-5
What do the RIG I like receptors sense and where is this product made in?
Sense cytoplasmic RNA-replication
Intermediate for viruses
What do RIG I receptors bind to and what do they recognise?
RIG-I> single stranded RNA-containing 5’triphosphate- Flaviviruses (hepatitis C (HCV)
Orthomyxoviruses (Influenza)
What does the MDA5 receptors bind to and what do they recognise?
MDA5» Long double stranded RNA- Picoviruses
Where are the acute phase response proteins produced?
Liver
What is the acute phase response induced by?
cytokines- TNF, IL-6, IL-1
What can acute phase response proteins activate and what is the result?
complement- result-opsonisation/phagocytosis
What does ESR and CRP characteristic of and what do they detect clinically?
ESR and CRP= acute phase response»inflammation
Explain the functions of Macrophages?
Phagocytosis, inflammatory mediators, antigen presentation, ROS and RNS, cytokines and complement proteins
Explain the functions of Dendritic cells?
Antigen presentation, co-stimulatory signals, ROS, interferons and cytokines
Explain the functions of Natural killer cells?
Lysis of viral infected cells, Interferon, macrophage activation
