Lecture one

Question 1

Name anatomic barriers of the immune system

Answer 1

skin, oral mucosa, respiratory epithelium, intestine

Question 2

name complement proteins and antimicrobial proteins

Answer 2

C3, defensins, RegIIIgamma

Question 3

give examples of innate immune cells

Answer 3

macrophages, granulocytes, natural killer cells

Question 4

give examples of cells of the adaptive immune system?

Answer 4

T cells and B cells

Question 5

Give the four phases of the immune response

Answer 5

inflammatory inducers (ie: LPS, urate crystals, ATP) sensor cells (PRRs on macrophages, dendritic cells, neutrophils), mediators (chemokines and cytokines), target tissues (produce antimicrobial proteins, induce intracellular antiviral proteins, kill infected cells)

Question 6

describe the innate immune response briefly

Answer 6

inflammation, complement activation, phagocytosis and destruction of pathogen

Question 7

give two broad locations of pathogens

Answer 7

intracellular or extracellular

Question 8

how do we protect ourselves against pathogens who’s site of infection is extracellular, in the blood, lymph, interstitial spaces?

Answer 8

via complement activation, phagocytosis, and production of antibodies

Question 9

how do we protect ourselves against pathogens who’s site of infection is extracellular, in the epithelial surfaces?

Answer 9

via antimicrobial peptides, antibodies, specifically IgA

Question 10

How are we protected against pathogens who’s site of infection is in the cytoplasm?

Answer 10

NK cells, cytotoxic T cells (viral/foreign component detected in the cell via NOD receptors or RIG-I or degraded in normal proteasomal recycling, displayed on MHC I)

Question 11

how do we protect ourselves from pathogens who’s site of infection is intracellular in the vesicles?

Answer 11

T cell and NK cell dependent macrophage activation

Question 12

give an example of a pathogen that produces a exotoxin

Answer 12

staphylococcus aureus

Question 13

give an example of a pathogen that produces an endotoxin

Answer 13

E. Coli

Question 14

what effect do chemokines and cytokines released by macrophages when they phagocytose a pathogen have on the site of infcetion?

Answer 14

vasodilation, increased vascular permeability, redness, heat, swelling

Question 15

what do mast cells do

Answer 15

produce histamine, produce chemotactic factors and cytokines

Question 16

which immune cells protect against parasites

Answer 16

eosinophils and basophils

Question 17

describe the microbicidal mechanisms of phagocytes?

Answer 17

the PAMP triggering the phagocyte binds to the GPCR (PRR), GTP binds, turns on and activates enzymes like phosphoinositol-3 kinase that is involved in cytoskeletal reoorganisation in response to chemokines, activates PLC-gamma-2 leading to lysosomal degranulation and phosphorylation of p47phox via activation of PKC, MEK and MAP Kinase systems that oversee the assembly of the NADPH oxidase

Question 18

describe the process of neutrophil NET formation

Answer 18

can occur within 1-2 hrs of neutrophil activation, involves liberation of neutrophil DNA, histones, and granule enxymes into the extracellular space where they can ensnare bacteria, yeast, and other pathogens and killl them in situ

Question 19

name receptors on the surface of macrophages

Answer 19

mannose receptor, Glucan receptor, TLR1:TLR2 heterodimer, scavenger receptor

Question 20

name the chemokines/cytokines secreted by activated macrophages?

Answer 20

TNF, IL-6, IL-8, IL-12

Question 21

Give the functions of TNF, IL-6, IL-8, IL-12

Answer 21

TNF: activates local endothelium, initiates cytokine production, upregulates adhesion molecules
IL-6: triggers production of acute phase proteins in the liver, enhances Ab production by B cells, induces T cell polarisation
IL-12: activation of NK cells; polarisation of T cells to Th cells

Question 22

what is the effector function of NK cells

Answer 22

release lytic granules that kill some virus-infceted cells, results in apoptosis

Question 23

define PAMPs

Answer 23

Pathogen Associated Molecular Patterns that the immune system recognises as foreign.

Question 24

PRRs can be _ or _

Answer 24

soluble or cell associated

Question 25

when does the immune system recognise commensal bacteria as foreign and launch a response?

Answer 25

if the commensal bacteria has migrated and is now in an inappropriate location

Question 26

PRR-PAMP recognition leads to…

Answer 26

direct lysis of pathogen
opsonisation of pathogen followed by phagocytosis
direct phagocytosis via phagocyte associated PRR
enhancement of phagocytic cell function
production of antimicrobial peptides
production of chemokines and cytokines

Question 27

tissue damage elicits an immune response through recognition of which molecules?

Answer 27

Danger associated molecular patterns, DAMPs such as IL-33, HMGB1, IL-1alpha, release of mitochondrial or nuclear DNA into the cytoplasm

Question 28

what happens when a chemokine binds to a GPCR

Answer 28

GPCR associates with G protien, the G protein releases GDP and allows GTP to bind, Gprotein dissociates into alpha and betagamma subunits, Rac/Rho GTPases are activated and stimulate chemotaxis, alpha subunit will cleave GTP and cease signalling when appropriate

Question 29

what does Rac2 do in the phagolysosome

Answer 29

it induces the assembly of NADPH oxidase in the phagolysosome membrane, generating oxygen free radicals, acidification of the phagolysosome due to ion (K+) influx, granule release from granule matrix