Week 1: Innate Immunity and Inflammatory Response Flashcards
Why do we have innate defenses?
Innate Immunity may prevent pathogen establishment
Innate Immunity may limit pathogen multiplication
Innate Immunity provides protection from early death during the expansion phase of acquired immune response
Innate Immunity helps to instruct the nature of the aquired immune response generated after infection
What is the complement cascade?
It is a chain reaction of a series of proteins which are enzyme components that is triggered by a pathogen which results in self amplication and results in a large immune response.
What are the 3 pathways for the complement cascade?
Classical Pathway - antigen : antibody pathway
MB-Lectin Pathway - Mannose-binding lectin binds mannose on pathogen surfaces
Alternative Pathway - pathogen surfaces
What pathway do most complement cascade reactions take?
Alternative Pathway
What enzyme does the complement cascade mainly rely on?
C3 convertase
What are complement regulatory proteins?
Self defense proteins to make sure no immune response against body’s own cells
What do mast cells generate?
C5 and c3a bind to receptors on mast cells which degranulate and release chemotactic factors(attracts cells to site of infection) and vascular permeability mediators ( allows cells to move from lumen of vessel to tissue)
How is the membrane attack complex formed in the formation of the complement?
c5b binds c6 and c7 and the c5b67 complex binds to the membrane by c7.
C8 binds to the complex and inserts to the membrane
c9 molecules bind to the complex and polymerize to form around 1-16 molecules of c9 to form a pore in the membrane to form a drill-like structure.
How are pathogens opsonized in the complement system?
Pathogens are opsonized by c3b protein which is then attached onto by the phagocytic receptors.
What are the stages of the acute inflammatory response?
What is the difference between receptors of innate cells (phagocytes) and adaptive immunity (lymphocyte)?
Innate vs Adaptive
Rapid response(hours) vs slow response(days to weeks)
fixed vs variable
constant vs improving
Learn this/keep in mind
Receptors on phagocytes are coupled to x?
x=function
What happens when a pathogen binds on to a receptor on a macrophage?
This causes the release of cytokines and small lipid mediators of inflammation
What are toll like receptors on phagocytes?
They each recognize different signatures produced by different pathogens to induce a specific response to that pathogen. It is a modular approach for linking receptors to function.
What do fungi produce?
Mannan
What do gram negative bacteria produce?
Lipopolysaccharide (LPS)
What do viruses produce?
Double strand RNA
What do protozoa produce?
Glycosylphosphatidylinositol (GPI)
What does each toll like receptor correspond to ?
What are the principle of phagocytosis?
PAMP is attached to pattern recognition receptors > pseudopodia forming a phagosome > granule fusion and killing > release of microbial products
What is the respiratory burst?
The production of toxic oxygen radicals (superoxide and hydrogen peroxide) by the phagocytic cells which attacks the membrane of the pathogen and destroys them.
oxygen radicals may directly damage the microbial membranes and/or activate microbicidal enzymes found in granules.
This happens when the pathogen is engulfed in the phagocyte.
What generates the respiratory burst?
The activation of NADPH oxidase
What are the phagocytic frequencies in blood?
Neutrophils(Polymorphonuclear neutrophils) are:
. rapid responders
Mobilized from Bone marrow
Found in depots in tissue sites
highly phagocytic
produce multiple cytokines
What are neutrophil extracellular traps?
Activated neutrophils catch bacteria using NETs. This is when neutrophils extrude their DNA like a fishing net to trap the pathogens. NETs contain:
chromatid
granule proteins
enzymes to degrade pathogen virulence factors
Blood monocytes can….
Give rise to tissue macrophages
Can differentiate into more long-lived macrophages which are more terminally differentiated.
have distinct characteristics depending on which tissue they migrate to
Relatively long-lived compared to neutrophils so can act as host cells of pathogens that override the macrophage.
Most macrophages arise from non haematopoietic stem precursors
Kupffer cells (Resident liver macrophages) can have:
specific forms and functions in different tissues (inc.homeostasis)
transcription factors and epigenetic mechanisms associated with development
responses to environmental cues
Dendritic cells are …..
phagocytic cells specialized for interacting with lymphocytes
can be sedentary or migratory
are activated during innate immunity
play an important role in initiating immune responses
How do leukocytes egress from blood to the tissue?
Cytokines are produced my macrophages at site of infection
This causes dilation of local small blood vessels
leukocytes move to periphery of blood vessels as a result of increased expression of adhesion molecules
Monocytes bind adhesion molecules on vascular endothelium near sites of infection and monocyte receptor attaches to chemokine
The monocyte then migrates through the gap in the endothelial cells into the surrounding tissues
The monocyte then differentiates into a macrophage and migrates to site of infection.
What are chemokines?
They are a further heterogenous and complex family of small molecular weight chemotactic cytokines known as chemokines. chemokines general function is to induce cell migration.
What happens if the release of cytokines is dysregulated?
Leukocytes will move out of the endothelial cells of the blood vessels into multiple sites of tissues around the body and cause the body to go in shock.
cytokines can be release where else apart from the blood?
synapses
What can be used to reduce inflammation?
Corticosteroids can be used to block cytokine release which therefore reduces inflammation.
How are receptors, phagocytes and cytokines linked?
A specific TLR is linked to a specific response by the phagocytic cell which is linked to a specific cytokine that is released to attract other leukocytes.
Why are t natural killer cells called atypical?
Their receptors are more typical of innate cells rather than lymphocyte cells.
