Immune System I

Question 1

Which cytokine mediator activates macrophages and which two cells produce this?

Answer 1

IFN-Y

Produced by T-cells and NK cells

Question 2

Name five cytokines secreted by activated macrophages?

Answer 2

IL-1B
TNF-a
IL-6
CXCL-8
IL-12

Question 3

Describe four things that IL-1B does?

Answer 3

Activates vascular endothelium
Activates lymphocytes
Local tissue destruction
Increases access for effector cells
(systemically = fever and production of IL-6)

Question 4

Describe three things that TNF-a does?

Answer 4

Activates vascular endothelium
Increases vascular permeability - leading to entry of IgG and complement and cells (neutrophils, NK-cells) to tissues
Increases drainage to lymphoid tissue
(systemically - fever and shock)

Question 5

Describe two things that IL-6 does?

Answer 5

Lymphocyte activation
Increased antibody production
(systemically -fever and acute phase protein production)

Question 6

Describe what CXCL-8 does?

Answer 6

Chemotactic factor - recruits basophils, neutrophils, T-cells to site of infection

Question 7

Describe what IL-12 does?

Answer 7

Activates NK-cells and induces the conversion of CD4 T-cells into Th1 T-cells

Question 8

Once activated alongside cytokine secretion what are the other features of macrophages?

Answer 8

Up-regulation of MHC and co-stimulatory molecules CD80 and CD86
Capillary cell-adhesion molecule expression
Activation of complement cascade

Question 9

Describe NK cells?

Answer 9

Bone marrow derived
Kill tumour cells and virally infected cells directly
Secrete IFN-Y - activating macrophages (they secrete TNF-a and IL-12 which further activates NK cells)

Question 10

Describe neutrophils?

Answer 10

Bone marrow derived (5 day lifespan)
Professional killer cells (No APC)
Attracted to site of infection by TNF-a

Question 11

Describe dendritic cells? (5)

Answer 11

Bone marrow derived
Resting state - (low levels of MHC expression and low levels of CD80 and CD86)
Activated by IFN-Y or (pathogen-TLR) stimulation
Migrate to lymph node to find cognate TCR - live in lymph node for 1 week

Question 12

How do CD4 T-cells activate macrophages?

Answer 12

Via CD40.L(T-cell) and CD40 interaction with focal secretion of IFN-Y to get the macrophages into hyper-activation state

Question 13

What are the actions of IFN-Y and TNF-a on the macrophage?

Answer 13

Induce the production of NO and superoxide ions by the macrophage = important for causing the destruction of ingested pathogens

Question 14

Name three Ag presenting cells?

Answer 14

1. Dendritic cells (recruitment of monocytes as they die - proportional response)
2. Macrophages (activated T-cells need constant reassurance at the site of infection or they apotose or become resting
3. Activated B-cells (BCR has high affinity for Ag and therefore if little Ag around it can concentrate them all very quickly)

Question 15

What are the two ways of immune cessation?

Answer 15

Intrinsic = Failure/cessation of survival signals
Extrinsic = Activation of death receptors (FAS-FAS.L)
Both work via apoptosis

Question 16

Describe negative selection?

Answer 16

Naive progenitor T-cells rearrange the blocks that make up their TCR (random VDJ recombination) and this leads to TCRs with differing affinities to SELF-Ag. If affinity Ag too high = termination

Question 17

Where does T-cell and B-cell negative selection occur?

Answer 17

T-cells - Thymic medulla

B-cells - Bone marrow

Question 18

Describe FOXP3?

Answer 18

T-reg cell - in regulates the immune response and keeps equilibrium when there are no danger signals/inflammation about
(Once danger signals = Inhibition of FOXP3 T-reg cells)

Question 19

Describe peripheral tolerance?

Answer 19

Induction of peripheral T-cell ANERGY by dendritic cells/T-reg cells OR peripheral DELETION of SELF-reactive T-cells

Question 20

Describe the two different types of T-reg cells and name any cytokines that play a role in differentiation?

Answer 20

1. Natural = Thymic derived (nTreg)

2. Induced = Within the periphery from CD4 T-cells (iTreg) via IL-2/RA/TGF-B

Question 21

Describe the three ways in which T-reg cells work?

Answer 21

1. Cell-cell mediated contact inhibition
2. Secrete inhibitory cytokines (prevent activation of effector T-cells)
3. Secrete metabolites (prevent activation of effector T-cells)

Question 22

Describe the four mechanisms of self-tolerance failure?

Answer 22

1. Down regulation of T-reg cells (immunosupression/IPEX)
2. Failure of central tolerance (AIRE)
3. Molecular mimicry (Guillan-Barre/Rheumatic fever)
4. Chronic APC stimulation

Question 23

Name and describe the condition commonly associated with central tolerance loss?

Answer 23

AIRE deficiency
AIRE gene drives negative selection within the thymus surrounding tissue restricted Ag - therefore with deficiency = organ-specific autoimmunity
Pts can develop chronic mucotaneous candidiasis (Ab against IL-17)

Question 24

What is APECED?

Answer 24

Autoimmune polyendocrinopathy cadidiasis ectodermal dystrophy -

1. Hypothyroidism
2. Candidiasis
3. Adrenal insufficiency

Question 25

Name and describe a condition commonly associated with peripheral tolerance loss - naming five associated features?

Answer 25

IPEX syndrome (immune-dysregulation-enteropathy-X-linked) (develops in early days of life)
Absence of CD4CD25(bright) T-reg cells due to mutations in FOXP3
= eczema, enteropathy, DM, haemolytic anaemia, neutropenia