Innate Immunity Flashcards
What is first-line immunity?
Skin, mucous membranes, chemicals
What is second-line immunity?
Phagocytosis, complement, interferon, inflammation, fever
What is adaptive immunity?
Lymphocytes and antibodies
What are the three fundamentals of innate immunity?
Protective mechanism that exists before infection
Rapid responses encoded within the germline
Responses are typically identical upon repeat infection
What is inflammation?
Mobilizing bodily defenses at sites of infection
What are the physiological changes the inflammation causes?
Vasodilation
Increase in capillary permeability
Influx of immune cells to affected tissues
What are the four signs of inflammation?
Redness due to vasodilation and increases in blood volume
Heat due to increased blood volume bringing warmth to the area
Edema due to swelling caused by the accumulation of fluid from blood
Pain due to inflammatory mediators that trigger pain responses
How do the dilated capillaries help in immune response?
It helps more immune cells get to the affected area as well as slow down blood flow so that there is more time to contact the wall of the capillary and enter the affected tissue
How did Elie Metchnikoff find evidence for inflammation?
Poked a star-fish larvae with a thorn and observed the rapid localization of cells to the site of injury and the breakdown of the thorn by the cells
First observation of phagocytosis
What are the steps of inflammatory response?
Margination
Diapedesis
Chemotaxis
Phagocytosis
What is margination?
The migration of WBCs to the endothelium of the capillaries
What is diapedesis?
When WBCs squeeze through the epithelial layer
What is chemotaxis?
Attraction to chemokines
What do phagocytes do?
They ingest and destroy microbes via phagocytosis
What are the two processes done by the WBCs?
Chemotaxis = chasing down the microbes
Phagocytosis = eating of the microbes
What are the steps of phagocytosis?
Phagocytes detects and engages the microbe
Microbe engagement initiates cytoskeletal rearrangements that drive phagocytosis
The microbe is internalized in a specialized phagosome
The phagosome fuses with the lysosome to form a phagolysosome
Lysosomal enzymes destroy ingested microbes
Reactive oxygen and nitrogen intermediates destroy microbial proteins, genomes, and walls
What are the steps of macrophage development?
Macrophages arise from undifferentiated stem cells in the bone marrow
Some stem cells differentiate into short-lived monocytes that circulate in the blood
Inflammation recruits monocytes to sites of infection where they differentiate into resident macrophages
Resident macrophages are long-lived professional phagocytes that ingest large amounts of extracellular material
What is an important role of phagocytosis other than eliminating microbes?
Activating neighboring cells through the release of cytokines and chemokines
How are phagocytosed microbes killed?
By reactive oxygen species and NO
What are cytokines?
Secreted proteins that drive immune and inflammatory reactions
What are cytokines produced by during innate immunity?
Macrophages and natural killer cells
What is one effect of cytokines?
Induce proteins in the endothelium that make the endothelium more adherent for passing leukocytes
What are chemokines?
A large family of structurally related, low molecular weight cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood to tissues
What are some examples of PAMPs?
Bacterial lipopolysaccharide
Glycoprotein with terminal mannose residues
Double-stranded RNA
Unmethylated CpG DNA
What is the difference between bacterial and mammalian glycoproteins?
Bacteria tend to have terminal mannose residues while mammalian ones have terminal sialic acid or n-acetylgalactosamine
What is the difference between CpG DNA in bacteria and humans?
Bacteria tend to have unmethylated CpG DNA while humans have methylated CpG DNA
What are the characteristics of pattern recognition receptors (PRRs)?
Detect non-self structures
Ubiquitous either as a circulating molecule or through expression on innate immune cells
Rapidly trigger potent antimicrobial responses
What do PRRs detect?
Conserved, essential microbial features
What do active PRRs drive?
Inflammation
They produce cytokines in response to PAMPs which causes the mobilization of other immune cells
What are toll-like receptors?
PRRs for PAMPs
Which TLRs detect bacterial parasites?
TLR1 + TLR2
Which TLRs detect Gram-positive bacteria and fungi?
TLR2 + TLR6
Which TLRs detect Gram-negative bacteria?
TLR4 + TLR4 (homodimer)
Which TLRs detect flagellated bacteria?
TLR5 + TLR5 (homodimer)
Which TLR detects viral dsRNA?
TLR3
Which TLR detects viral ssRNA?
TLR7 or TLR8
Which TLR detects bacterial DNA elements?
TLR9
What is the difference between TLRs in the membrane and in the endosome?
TLRs on the cell membrane dimerize and TLRs in the endosome are monomers
How might PRRs differ in function?
Some are phagocytic receptors and others are not phagocytic receptors but stimulate the activation of immune cells
Where do PRRs surveil?
On the cell surface, the endosomes, and in the cell cytoplasm
What do PRRs surveil for?
Intact PAMPs, degraded PAMPs, and PAMPs that are never outside of the cell
What cells are PRRs expressed on?
On or in all leukocytes and boundary cells and especially phagocytic cells
Why are pathogens disadvantaged?
They have small genomes and at least some conserved components that are targets of PRRs
What does almost all TLR signaling lead to the production of?
IRFs and/or NF-kappaB which are both transcription factors
What is an IRF?
Interferon response factors which are involved in anti-viral responses
What is NF-kappaB?
A transcription factor that turns on many immune response genes
What are RIG-like receptors?
They include RIG-1 and MDA5 which are related cytoplasmic sensors of viruses
They are found in the cytosol permanently
What is RLR signaling like?
The signaling pathway is similar to TLRs
RLR dependent signaling can amplify TLR signaling
What is the result of PRR signaling?
Production of IFN-1 which augments innate and adaptive immunity
Production of various pro-inflammatory cytokines
Induces many other response genes
What does IFN-1 do?
It tells cells around an infection that there is a pathogen
What are 3 important things about PRR innate immune signaling?
Speed = takes minutes
Economy = limited TLRs can detect a lot of pathogens
Amplification = localized detection leads to large, systematic responses
Why are there many types of, and redundancy in, pattern recognition?
T overcome attempts made by microbes to evade one or more PRRs
Having multiple PRRs that detect the same things enhances the chance that the microbe is detected
Cross-talk in signaling pathways allows for better control over the type or degree of response
