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Flashcards in Innate immune system Deck (25):

Innate immune Responses

Interferons --> anti-viral

Stimulate adaptive immunity


Innate receptors

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

Bind PAMPs
Expressed on APCs
Triggering activates cell

Germline encoded
Limited diversity


Types of PRRs

Toll-like receptors
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

Universal Antibody

Acts as opsonin
--> uptake by macrophages
--> complement activation


Role of NOD-like receptors

Sense PAMPs and DAMPs

Form inflammasomes
Activate caspases --> IL-1beta and IL-18
--> inflammation


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

Release interferons
--> 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

Ingest pathogens
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

Bind MHC
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?


Only on APCs

Present peptides from ingested extracellular antigens to CD-4 cells --> activation of CD-4 cells


MHC class II processing pathway?

Uptake of extracellular proteins into endosome
--> processing of internalized proteins in endosomal-lysomal vesicles
--> MHC produced in ER and transported to endosome via golgi apparatus
--> Peptide-MHC complex formation
--> surface expression of peptide-MHC complex