Innate immune system

Question 1

what are the 2 phases of the innate immune system?

Answer 1

cellular phase (phagocytosis and NKCs)
humoral phase (complement cascade)

Question 2

what are the main components of the cellular phase?

Answer 2

phagocytes (macrophages, neutrophils)
mast cells and basophils
NK cells

Question 3

what is the name for the factors involved in the complement cascade?

Answer 3

serine proteases –> limited proteolysis

Question 4

what are the 4 functions of the complement cascade?

Answer 4

opsonisation of pathogens –> prime them for phagocytosis
attract natural killer cells and neutrophils to site of infection
produce anaphylatoxins
MAC complex –> kill pathogens

Question 5

what are the 3 activation pathways?

Answer 5

classical, alternative, lectin

Question 6

what is the activator in the classical pathway?

Answer 6

antigen-antibody complex

Question 7

which complement factor is activated in the classical pathway?

Answer 7

C1

Question 8

describe the pentamer structure of the antigen-antibody complex

Answer 8

IgM has 5 Fc regions so 5 C1 bind –> close proximity to each other –> trigger classical pathway

Question 9

what bind to mannose on pathogens in the lectin pathway?

Answer 9

mannose-binding-lectin (MBL)

Question 10

what other factors are involved in binding mannose?

Answer 10

MASP1 and MASP2 (MBL associated serine proteases)

Question 11

Which 2 complement factors are activated by the lectin pathway?

Answer 11

C2 and C4

Question 12

how is the alternative pathway activated?

Answer 12

auto-activation of C3 –> C3b = occurs constantly at a very low rate

Question 13

why does contact with bacteria result in the alternative pathway?

Answer 13

C3b binds factor B and properdin on bacterial surface –> activated C3 and C5

Question 14

what are the 2 pivotal points in complement activation?

Answer 14

C3 –> C3b binding to C2a and C4b complex

C5 –> C5b

Question 15

What are C3a, C5a and C4a and what role do they play?

Answer 15

anaphylatoxins
degranulate enodthelial cells, mast cells, phagocytes
smooth muscle contraction + increase vascular permeability

Question 16

Which are chemoattractants?

Answer 16

C5a and C3a –> attract and activate NK cells and neutrophils

Question 17

how does opsonisation work?

Answer 17

C3b is concerted to iC3b on the bacterial surface. iC3b binds to receptors on macrophages so macrophages are attracted to phagocytose the pathogen

Question 18

where are macrophages located?

Answer 18

in tissues: lungs, gut, under skin

Question 19

what are the 3 stages of macrophage activation?

Answer 19

resting, primed, hyperative

Question 20

what do macrophages do in the resting stage?

Answer 20

eliminate apoptotic cells, collect debris from tissue

Question 21

what activates macrophages from the resting to the primed stage?

Answer 21

IFN-y

Question 22

what activate macrophages from the primed to the hyperactive stage?

Answer 22

LPS

Question 23

what do primed macrophages do?

Answer 23

more MHC II expressed, take up larger objects

Question 24

what do hyperative macrophages do?

Answer 24

release cytokines TNF and IL-1
stop proliferating
increased rate of phagocytosis

Question 25

what activates macrophages from the resting to hyperactive state?

Answer 25

IFN-y and LPS (from gram -ve bacteria)

Question 26

what is the lifespan of macrophages?

Answer 26

long lived

Question 27

what does TNF do?

Answer 27

kills virus infected cells, kills tumour cells

Question 28

where do neutrophils reside?

Answer 28

in the blood

Question 29

what happens during the first stage of neutrophil activation?

Answer 29

IL-1 and TNF cause Selectin ligand to bind to selectin | neutrophils roll and slow down

Question 30

what happens during step 2?

Answer 30

C5a and LPS from bacteria in inflamed tissue cause Integrin to bind to ICAM so neutrophil is held in place and stops rolling

Question 31

what is the mechanism called?

Answer 31

double key mechanism --> neutrophil binds to blood vessel wall in inflamed tissue

Question 32

what happens during step 3?

Answer 32

f-Met (the starting AA on a bacterial protein) caused the neutrophil to infiltrate the endothelium

Question 33

what is released from neutrophils?

Answer 33

cytokine TNF

Question 34

what is the lifespan of neutrophils?

Answer 34

short lived, around 5 days

Question 35

which lineage do natural killer cells come from?

Answer 35

lymphoid lineage

Question 36

where do NK cells reside?

Answer 36

bone marrow liver spleen

Question 37

what phrase describes the action of NK cells?

Answer 37

"roll, stop, exit"

Question 38

how do NK cells bind to target cells?

Answer 38

Fas ligand binds to Fas

Question 39

What mechanism prevents NK cells from killing normal healthy cells?

Answer 39

Recognise MHC1 - if expressed inhibitory receptor prevents apoptosis

Question 40

how do NK cells destroy infected cells?

Answer 40

trigger apoptosis by perforin protein injecting granzyme B into the target cell (suicide enzyme) --> triggers apoptosis

Question 41

what are the 2 ways that the complement cascade can kill viruses?

Answer 41

MAC --> pore in wall | opsonisation for phagocytosis

Question 42

how are virus infected cells destroyed?

Answer 42

macrophages --> IL-1 and TNF --> stop virus production by infected cells NK cells --> induce apoptosis of infected cells

Question 43

which 2 cytokines are released by NK cells?

Answer 43

IFN-y and IL-2