Flashcards in Innate immune system Deck (25):
Innate immune Responses
Interferons --> anti-viral
Stimulate adaptive immunity
Recognise foreign via common molecular motifs
PAMPs - foreign structures
DAMPs - dying cells
What are PAMPs?
Pathogen associated molecular patterns
Highly conserved structures shared by groups of micro-organisms
What is the role of PRR?
Pattern recognition receptors
Expressed on APCs
Triggering activates cell
Types of PRRs
C-type lectin Receptors
Role of Toll-like receptors
Primordial cell surface proteins responsible for host defense
Cell surface = bacterial protein PAMPs
Endosomal = viral - DNA and RNA PAMPs
--> upregulation of cytokines, chemokines and co-stimulatory molecules
Role of TLR-4 in disease?
Binds bacterial LPS
Responsible for shock in gram negative sepsis
What is IRAK4/MyD88 deficiency?
Genetic disease - autosomal recessive
Loss of signalling distal to TLRs and IL-1, IL-18 and IL-33
--> recurrent invasive pyogenic bacterial infections
Role of C-type lectin receptor proteins
Acts as opsonin
--> uptake by macrophages
--> complement activation
Role of NOD-like receptors
Sense PAMPs and DAMPs
Activate caspases --> IL-1beta and IL-18
Role of inflammasomes in gout
Gout = inflammasome mediated disease
Urate crystals ingested by cells --> can't digest --> burst phagosome --> activation of NALP3 inflammasome --> activates caspase 1 --> IL-1 beta --> acute inflammation
Inflammation decreased by anakinra
Colchincine = uncouples urate crystals from inflammasone activations
Role of RIG-1 receptors
Receptors for RNA of viruses
Located in cytoplasm
Release type 1 interferons and inflammatory cytokines
Role of plasmacytoid dendritic cells
Respond to viral infection
--> antiviral state
--> alter cellular processes to decrease viral replication and cause apoptosis of infected cells
--> increase NK cell lysis
--> increased MHC-1 expression
Role of phagocytes
Macrophages --> ingest pathogens --> attract neutrophils
Neutrophils and macrophages --> ingest pathogens --> degrade pathogens in phagosome --> oxidative burst
What is the oxidative burst?
Generation of toxic products which occurs in phagosome with lyzosome
NO2, O2, H2O2, OH, OCl, OBi
What is chronic granulomatous disease?
X linked genetic disease
Loss of gp91 on X chromosome
--> Molecular defect - deficiency of 1 or 4 subunits of NADPH oxidase
--> Loss of respiratory burst in neutrophils necessary for killing intracellular organisms
--> recurrent infection with coagulase negative bacteria and fungi
What is the role of dendritic cells?
In tissues as sentinels
Capture antigens and present it with MHC and co-stimulatory molecules
--> Migrate to LNs and spleen
--> Initiate immune response - stimulate B and Tcells
Role in T cell tolerance
Role of NK cells
Kill virally infected cells
--> recognise by activation of Ab-Dependant cell-mediated cytotoxicity
--> recognise by loss of MHC expression by cells
Kill tumour cells
--> recognise by loss of MHC expression
Release IFN-gamma--> activation of adaptive immune system
How does Ab-dependant cell-mediated cytotoxicity work for NK cells?
NK cells express Fc-gammaR-III - receptor for IgG
IgG binds to viral Ag on surface of infected cells
--> activation of NK cell --> kills infected cell via proforin-granzyme or fas pathway
How does ADCC work for eosinophils?
Eosinophils express Fc-gammaR-1 receptor for IgE
IgE binds to helminths
Eosinophils bind --> induction of degranulation and release of eosinophil toxic proteins
How do NK cells recognize MHC?
Killer inhibitory receptors
If MHC not present - virus infected or tumour cells --> NK cell activation --> cell death
What is the role of MHC Class I?
HLA-A, -B, -C
All cells except RBCs and some neuronal cells
Present intracellular peptides to CD-8 cells - viruses
Allows cytotoxicity by CD-8 cells to eliminate virally infected cells
MHC class I processing pathway?
Production of the protein in the cytosol
--> Proteolytic degradation of proteins by proteasome
--> Transport of peptides from cytosol to endoplasmic reticulum
--> Assembly of peptide-MHC complex in endoplasmic reticulum
--> Transport to cell surface by golgi apparatus
--> surface expression of peptide-MHC complex
What is the role of MHC class II?
HLA-DR, -DP, -DQ
Only on APCs
Present peptides from ingested extracellular antigens to CD-4 cells --> activation of CD-4 cells