(04) Innate Immunity

Question 1

what is the first line of defence against pathogens? give examples

Answer 1

anatomical and physiological barriers

eg. intact skin, cilliary clearance, low stomach pH, lysozymes in tears / saliva

Question 2

what are the two types of innate immunity?

Answer 2

Cellular
Humoral (or soluble)

Question 3

types of cells involved in cellular innate immunity

Answer 3

Macrophages
Neutrophil

Also:
Eosinophils
Natural killer cells
Dendritic cells
Mast cells

Question 4

elements involved in humoral immunity

Answer 4

complement
LPS Binding Protein
Antimicrobial Peptides
C Reactive protein
Mannose binding lectin

Question 5

describe innate immunity

Answer 5

discrimination between self and non-self
immediate response to pathogen invasion
has no memory

Question 6

name three processes that provide the body with innate immunity

Answer 6

Complement
Myeloid cells and phagocytosis (macrophages + neutrophils)
Pattern Recognition Receptors

Question 7

three types of pathogens

Answer 7

virus
bacteria
protozoa and parasites

Question 8

describe viruses, give examples

Answer 8

intracellular pathogens
the simplest form of life

eg. influenza, polio, smallpox, varicella, HIV

Question 9

describe bacteria and give examples

Answer 9

mostly extracellular pathogens (exists outside cells)
engulfed and destroyed by phagocytic cells

eg. staph, tuberculosis (intracellular), strep, cholera

Question 10

describe protozoa and parasites, give examples

Answer 10

complex multicellular organisms
require direct killing by chemical mediators released by specialist myeloid cells

eg. filarial worm

Question 11

what testing process is used to distinguish types of bacteria?

Answer 11

a Gram stain

Question 12

describe gram positive bacteria

Answer 12

thick peptidoglycan cell wall as defence
requires phagocytosis
resistant to complement MAC lysis

Question 13

describe gram negative bacteria

Answer 13

thin peptidoglycan layer surrounded by outer membrane
can often by lysed directly by complement MAC

Question 14

how do antibiotics work?

Answer 14

stops the ability of the organism to make peptidoglycan (defensive wall in bacteria)

beta-lactam antibiotics eg. penicillin

Question 15

how do antibiotics work?

Answer 15

stops the ability of the organism to make peptidoglycan (defensive wall in bacteria

Question 16

describe the appearance of a neutrophil

Answer 16

three-lobed nuclei and granules

Question 17

what is neutrophil extravasation?

Answer 17

the process by which white blood cells leave the bloodstream and enter tissue to fight infection or injury

Question 18

name the five steps of neutrophil extravasation

Answer 18

Activation
Tethering
Adhesion
Diapadesis
Chemotaxis

Question 19

describe the first step of neutrophil extravasation

Answer 19

activation: chemokines (secreted proteins) from injury / inflammation activated local endothelial cells lining adjacent capillary wall

Question 20

describe the second stage of neutrophil extravasation

Answer 20

tethering: neutrophils slow and tether to the inside capillary wall

Question 21

what is tethering mediated by?

Answer 21

selectins (cell surface lectins mediating adhesion)
sialyl Lewis X (carbohydrate antigen on neutrophils)

Question 22

describe the third step in neutrophil extravasation

Answer 22

adhesion: strong binding between neutrophil integrins and ICAM-1 on the endothelium
neutrophils flatten

Question 23

what is diapadesis

Answer 23

the neutrophil squeezes between endothelial cells into the interstitial space

Question 24

describe the last step in neutrophil extravasation

Answer 24

chemotaxis: neutrophil migrates along CHEMICAL GRADIENT (chemokine gradient) to the site of infection

Question 25

what receptor do neutrophils have on their surfaces to respond to chemoattractants?

Answer 25

Complement receptors (from the complement cascade) neutrophils migrate up the chemoattractant gradient

Question 26

what happens as neutrophils migrate up the chemoattractant gradient?

Answer 26

polymerises actin filaments at their leading edge depolymerising filaments at trailing edge allows neutrophil to migrate

Question 27

define myeloid

Answer 27

having to do with bone marrow

Question 28

what receptors do all myeloid cells have?

Answer 28

complement receptors CR1, 2, 3, 4 CR1 is the main neutrophil receptor, binds to C3b (main component of complement cascade)

Question 29

how do receptors allow neutrophils to destroy organisms?

Answer 29

complement receptors crosslink to initiate phagocytosis causes the neutrophil to engulf the organism

Question 30

define FcR mediated phagocytosis

Answer 30

a specific type of phagocytosis that requires the involvement of antibodies and Fc receptors (antibody mediated phagocytosis) FcR = Fcgamma Receptors

Question 31

describe how phagocytosis is activated via FcR

Answer 31

Antibody (IgM and IgG) bind to bacterial antigens exposes antibody Fc region neutrophil FcR binds multivalent Fc activates phagocytosis

Question 32

name the main phases in phagocytosis

Answer 32

chemotaxis adherence ingestion / fusion --> phagolysosome acidification digestion / killing exocytosis

Question 33

what are virulence factors

Answer 33

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

Question 34

further expand on the ingestion / digestion stages of phagocytosis

Answer 34

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

Question 35

what is molecular pattern recognition?

Answer 35

Pattern Recognition Receptors (PRR) bind complex molecules unique to microbes important innate mechanism

Question 36

what is one type of PRR?

Answer 36

Toll-like receptors (TLR) are a type of Pattern Recognition Receptor TLR are Leucine Rich Repeat (LRR) receptor

Question 37

What are PAMPs?

Answer 37

Pathogen Associated Molecular Patterns these are unique to microbes and are recognised by PRRs structurally complex, evolutionarily stable (doesn't change too much)

Question 38

what is TLR4 the receptor for

Answer 38

lipoplysaccharide (LPS) which is a membrane component of all gram negative bacteria

Question 39

what is lipopolysaccharide?

Answer 39

LPS is a membrane component of all gram negative bacteria, induces powerful response a pyrogen (causes fever) can cause septic shock