Innate immunity Flashcards
What are the functions of the innate immune system?
- Provides physical and chemical defense at epithelial barriers to block microbial entry
- Initial reaction to microbes to prevent, control or eliminate infection
- Stimulate adaptive immune system
- Eliminates damaged cells and initiates tissue repair
What is the response time of the innate immune system?
Of the adaptive immune system?
Minutes to hours
Days
Physical and Chemical Barriers
- Barrier of eyes
- Barrier of respiratory tract
- Barrier of skin
- Barrier of GU tact
- Barrier of GI tract
- Lysozyme
- Mucus, cilia, macrophages in alveloli
- Antimicrobial secretion
- Acidity of urine, lysozyme
- Stomach acidity, bile, mucus, normal flora
What are defensins?
Different categories of small peptides that are produced by epithelial cells, neutrophils, and NK cells. Most are constitutively expressed, but some are upregulated by cytokine expression. They are secreted in a pro-protein form that is cleaved by trypsin to the active form. When active, they create a pore in the membrane of the bacteria causing leakage and cell death.
What is Cathelicidin?
A precursor protein that has 2 domains and is cleaved into 2 peptides to become active. It is produced by epithelial cells, neutrophils and macrophages. Its expression is upregulated by cytokine response. It is directly toxic to microbes by destroying the lipid membrane.
PAMPS
- What does it stand for?
- What are they?
- What do they recognize?
DAMPS
- What does it stand for?
- What is it?
- What does it recognize?
What is a pattern recognition receptor?
Where are they mostly expressed?
What occurs once they bind to their liagands?
Molecule that recognizes PAMPs and DAMPs
Expressed at surface of cell, cytosol and endosome of macrophages, NK cells, DCs, epithelial cells
Stimulation of cytokines, inflammation, adaptive immune response, repair
Toll-Like Receptors
- These are a subtype of what family of receptors?
- What are their ligands?
- Describe their structure.
- PRRs
- PAMPs and DAMPs
- They are membrane spanning and their extracellular region is shaped like a hook and consists of leucine-rich repeat motifs
Describe the response in the cell once ligand binds to TLR.
Nod Like Receptors
- Where are these located in the cell?
- What are their ligands?
- What phsyiologic response do they promote?
- Describe the structure of a tpical nod like receptor.
- Cytosol
- DAMPs and PAMPs in cytosol
- Inflammation
- C-terminal leucine rich region that senses ligand, central nucleotide-binding oligomerization domain (NOD) that promotes oligomerization, N-terminal region that is the effector domain responsible for recruiting a signaling complex
Describe the process of activation of the NOD like receptor NLRP-3 and formation of the inflammasome.
Binding of ligands / presence of signaling molecules are sensed by leucine rich binding domain of NLRP3. Promotes assembly of receptor with adaptor and procaspase 1 to form inflammasome. Inflammasome cleaves procaspase 1 to caspase 1 (active) and that cleaves Pro-interleukin 1B to interleukin 1B, which is secreted from the cell and enduces accute inflammation.
Other PRRs
- Location and ligand for C-type lectin receptor
- Locationa nd ligand fro RIG-like receptor (RLR)
- Location and ligand for Cytosolic DNA sensors (CDS)
- What responses do they illicit?
- plasma membrane, microbial polysaccharide
- cytosol, viral RNA
- cytosol, microbial DNA
- Production of cytokines/chemokines, immune cell recruitment, inflammation, stimulation of adaptive immunity, tissue repair
Describe the process of Dendritic cell maturation.
What are the 2 main subdivisions of receptors on the surface of NK cells?
Activating –> when inhibitory receptor is absent and an activating ligand binds to the stimulatory receptor on NK cell, the NK cell responds by inducing death of the target cell
Inhibitory –> inhibitory receptor is present and both activating and inhibitory receptors are bound by ligand –> inhibitory suppresses activation and does not result in killing of target cell
What are 2 means by which natural killer cells kill infected cells?
1) Perforin - It is a membrane perforating protein that creates an injection site for the natural killer cell to introduce its granules directly into the cell inducing apoptosis.
2) Activation of Fas ligand pathway (Tumor necrosis factor)
How do natural killer cells kill phagocytosed microbes?
Macrophages that have engulfed microbes express IL-12, which is recognized by the NK cell and leads to production of interferon gamma by NK cell, which is then secreted and enters the macrophage killing the microbes but not the macrophage.
Describe the process of microbes entering a macrophage/neutrophil, what happens once they’re inside the cell, and the process of those cells generating a respiratory burst.
Microbes are bound by receptors on the surface of the macrophage. When enough receptors bind the membrane begins to “zip up” and form a pocket. The pocket is then internalized via endocytosis and the phagosome is fused with a lysosome to form a phagolysosome. Binding of PAMPs/DAMPs from microbe to TLRs on the macrophage membrane trigger production of Nitric Oxide (NO) and also stimulate production of reactive oxygen species (ROS) by oxidation of NADPH (NADPH + O2 –> NADP+ + O2-). O2- that is produced then reacts with H2O2 to produce HOCL (bleach), which is toxic to the microbe. These ROS along with NO are pumped into the lysosome and result in death and degradation of the microbe.
Interferons
Explain how interferons are antivirals.
What receptors do they increase the expression of?
What immune cells do they stimulate?
Dendritic cells produce interferons, which bind to receptors on cell surfaces. Interferons induce enzymes that block viral replication by inhibiting viral protein synthesis, activating RNAases to degrade viral RNA, and inhibiting viral gene expression and virion assembly.
MHC class I
NK and CD8+ T cells
Lymphocytes need 2 signals in order to fully respond. What are those 2 signals?
