(04) Innate Immunity Flashcards
what is the first line of defence against pathogens? give examples
anatomical and physiological barriers
eg. intact skin, cilliary clearance, low stomach pH, lysozymes in tears / saliva
what are the two types of innate immunity?
Cellular
Humoral (or soluble)
types of cells involved in cellular innate immunity
Macrophages
Neutrophil
Also:
Eosinophils
Natural killer cells
Dendritic cells
Mast cells
elements involved in humoral immunity
complement
LPS Binding Protein
Antimicrobial Peptides
C Reactive protein
Mannose binding lectin
describe innate immunity
discrimination between self and non-self
immediate response to pathogen invasion
has no memory
name three processes that provide the body with innate immunity
Complement
Myeloid cells and phagocytosis (macrophages + neutrophils)
Pattern Recognition Receptors
three types of pathogens
virus
bacteria
protozoa and parasites
describe viruses, give examples
intracellular pathogens
the simplest form of life
eg. influenza, polio, smallpox, varicella, HIV
describe bacteria and give examples
mostly extracellular pathogens (exists outside cells)
engulfed and destroyed by phagocytic cells
eg. staph, tuberculosis (intracellular), strep, cholera
describe protozoa and parasites, give examples
complex multicellular organisms
require direct killing by chemical mediators released by specialist myeloid cells
eg. filarial worm
what testing process is used to distinguish types of bacteria?
a Gram stain
describe gram positive bacteria
thick peptidoglycan cell wall as defence
requires phagocytosis
resistant to complement MAC lysis
describe gram negative bacteria
thin peptidoglycan layer surrounded by outer membrane
can often by lysed directly by complement MAC
how do antibiotics work?
stops the ability of the organism to make peptidoglycan (defensive wall in bacteria)
beta-lactam antibiotics eg. penicillin
how do antibiotics work?
stops the ability of the organism to make peptidoglycan (defensive wall in bacteria
describe the appearance of a neutrophil
three-lobed nuclei and granules
what is neutrophil extravasation?
the process by which white blood cells leave the bloodstream and enter tissue to fight infection or injury
name the five steps of neutrophil extravasation
Activation
Tethering
Adhesion
Diapadesis
Chemotaxis
describe the first step of neutrophil extravasation
activation: chemokines (secreted proteins) from injury / inflammation activated local endothelial cells lining adjacent capillary wall
describe the second stage of neutrophil extravasation
tethering: neutrophils slow and tether to the inside capillary wall
what is tethering mediated by?
selectins (cell surface lectins mediating adhesion)
sialyl Lewis X (carbohydrate antigen on neutrophils)
describe the third step in neutrophil extravasation
adhesion: strong binding between neutrophil integrins and ICAM-1 on the endothelium
neutrophils flatten
what is diapadesis
the neutrophil squeezes between endothelial cells into the interstitial space
describe the last step in neutrophil extravasation
chemotaxis: neutrophil migrates along CHEMICAL GRADIENT (chemokine gradient) to the site of infection
what receptor do neutrophils have on their surfaces to respond to chemoattractants?
Complement receptors (from the complement cascade)
neutrophils migrate up the chemoattractant gradient
what happens as neutrophils migrate up the chemoattractant gradient?
polymerises actin filaments at their leading edge
depolymerising filaments at trailing edge
allows neutrophil to migrate
define myeloid
having to do with bone marrow
what receptors do all myeloid cells have?
complement receptors CR1, 2, 3, 4
CR1 is the main neutrophil receptor, binds to C3b (main component of complement cascade)
how do receptors allow neutrophils to destroy organisms?
complement receptors crosslink to initiate phagocytosis
causes the neutrophil to engulf the organism
define FcR mediated phagocytosis
a specific type of phagocytosis that requires the involvement of antibodies and Fc receptors
(antibody mediated phagocytosis)
FcR = Fcgamma Receptors
describe how phagocytosis is activated via FcR
Antibody (IgM and IgG) bind to bacterial antigens
exposes antibody Fc region
neutrophil FcR binds multivalent Fc
activates phagocytosis
name the main phases in phagocytosis
chemotaxis
adherence
ingestion / fusion –> phagolysosome
acidification
digestion / killing
exocytosis
what are virulence factors
factors that enhance the ability of an organism to defend itself against innate immunity
generally virulence factors are good at inhibiting one of the steps of phagocytosis
further expand on the ingestion / digestion stages of phagocytosis
bacterium captured by receptors, membrane INVAGINATES into a phagosome
FUSION of phagosome + lysosome –> phagolysosome
ACIDIFICATION as H+ is pumped in
activates proteases + production of superoxides (eg. peroxide H2O2 or hyperchlorous acid HOCl), kills bacteria
EXOCYTOSIS - digested microbe is expelled
what is molecular pattern recognition?
Pattern Recognition Receptors (PRR) bind complex molecules unique to microbes
important innate mechanism
what is one type of PRR?
Toll-like receptors (TLR) are a type of Pattern Recognition Receptor
TLR are Leucine Rich Repeat (LRR) receptor
What are PAMPs?
Pathogen Associated Molecular Patterns
these are unique to microbes and are recognised by PRRs
structurally complex, evolutionarily stable (doesn’t change too much)
what is TLR4 the receptor for
lipoplysaccharide (LPS)
which is a membrane component of all gram negative bacteria
what is lipopolysaccharide?
LPS is a membrane component of all gram negative bacteria, induces powerful response
a pyrogen (causes fever)
can cause septic shock
