L2 - Intracellular immunity (Mtb)

Question 1

What are the pros of an intracellular pathogen?

Answer 1

access to protected environment

Protection from immune response

Protection from bacterial competitors

nutrient rich environment

Question 2

What are the cons of intracellular pathogen?

Answer 2

overcome barriers

resist phagocytosis

resist adaptive immunity

adapt to hostile environment

Question 3

What are the 2 types of intracellular pathogen?

Answer 3

obligate

facultative

Question 4

What is the coherent immune response?

Answer 4

Constant cross communication between cells and tissues of innate and adaptive immune system

Question 5

What are the risk factors for Mtb?

Answer 5

Congregate settings

poverty/unemployment

homelessness

drug abuse

HIV co-infection

immunosuppression (steroid/biologic)

Question 6

What is the pathology of Mtb?

Answer 6

Cachexia
respiratory failure
dissemination
haemoptysis

Question 7

What does Mtb infect?

Answer 7

lung resident phagocytes

Question 8

What does FAP of Mtb do?

Answer 8

engages with macrophages - induces endocytosis

Question 9

What are the antimicrobial activities of the macrophage phagolysosome?

Answer 9

Lactoferrin (deprivation)
defensives (permeable)
hydrolases 
ROS
acidification

Question 10

How does Mtb evade macrophage killing?

Answer 10

arrests phagosome maturation at early stage

no phagolysosome formation

proteins rewire macrophage

Question 11

How do APCs detect Mtb?

Answer 11

APCs express PRRs

PRRs localised in best place to encounter PAMPs

produce antibacterial peptide CATHELICIDIN

TLRs

Question 12

Which TLRs detect Mtb in macrophages?

Answer 12

TLR2 - lipoprotein
TLR4 - LPS
TLR9 - hypomethylated DNA

Question 13

What are the RECEPTORS involved in macrophage activation

Answer 13

MHCI/MHCII
CD40/B7
TNF/IFNg
Fas

Question 14

What are the CYTOKINES involved in macrophage activation?

Answer 14

IL-12
TNF
IL-1
IL-18

Question 15

What are the ANTIMICROBIAL FUNCTIONS involved in macrophage activation?

Answer 15

Toxic oxygen radicals
Lysosomal enzymes
numbers of granules

Question 16

What do macrophages recruit to the site of infection?

Answer 16

NK cells
supply cytokines

positive feedback loop of activation

Question 17

What is the positive feedback loops of NK cell and macrophages?

Answer 17

IFNg activates macrophages

IL-12 activates NK cells

keeps further activating both as more cytokines produced

Question 18

How do macrophages and dendritic cells differ in MHC properties

Answer 18

dendritic MUCH better at loading antigens on MHC molecules

this is ESSENTIAL for APC to activate adaptive immunity

Question 19

How do dendritic cells initiate adaptive immunity?

Answer 19

dendritic detect Mtb in the alveoli

Detect PAMPs

MHC presentation

lymph node - APC scans T cells that recognised MHC

Question 20

What are CD4 protein type cells

Answer 20

T helper cells (Th1)

Question 21

What are CD8+ protein type cells?

Answer 21

Cytotoxic killer cells

Question 22

How do CD4 cells specialise

Answer 22

IFNg, IL-12 = Th1

IL-4 = Th2

Question 23

Why does the Th2 response to M. leprae have severe consequences?

Answer 23

high infectivity

low/absent T-cell responsiveness

Question 24

What is the granuloma?

Answer 24

aggregates of immune cells that surround foci of infected tissues

encased by gunk of necrotic tissue

dynamic

Question 25

How many people manage to effectively clear a granuloma?

Answer 25

70%

granuloma - stale-mate,