Basic immunology

Question 1

What are the differences in innate vs. adaptive immune responses? (6)

Answer 1

1. Non-clonal response vs. clonal response
2. Immediate response vs. requires time
3. Present in all individuals vs. different per individual
4. No increase upon re-exposure vs. increased response through memory
5. Pattern recognition vs. specific antigen recognition
6. Genome-encoded receptors vs. re-arranged receptors

Question 2

What are the three phagocytic cell types?

Answer 2

1. Macrophages
2. Immature dendritic cells
3. Granulocytes

Question 3

Are macrophages present in healthy tissues?

Answer 3

Yes, macrophages are important for tissue homeostasis

Question 4

Are immature DC’s present in healthy tissues?

Answer 4

Yes, immature DC’s are present in tissues for immune surveillance

Question 5

Are neutrophils present in healthy tissues?

Answer 5

No, neutrophils are not present in healthy tissues

Question 6

Which two lineages of tissue macrophages can be identified? Where do they originate?

Answer 6

1. Embryonic lineages, originating from the foetal liver or yolk sac
2. Development from monocytes, originating from the bone marrow

Question 7

Which receptor is used for self-renewal of tissue macrophages?

Answer 7

IL-34 = M-CSF receptor (monocyte colony stimulating factor)

Question 8

Do mature dendritic cells phagocytose?

Answer 8

No; as soon as the DC matures it stops phagocytosis and starts presenting antigen

Question 9

Which three types of neutrophils can be identified?

Answer 9

1. Neutrophils
2. Eosinophils
3. Basophils

Question 10

Which transcription factor is generally important for the activation of an inflammatory response?

Answer 10

NF-κB

Question 11

What are the five hallmarks of infection?

Answer 11

1. Rubor = redness
2. Dolor = pain
3. Calor = warmth
4. Tumor = swelling
5. Functio laesa = loss of function

Question 12

What are local effects of inflammatory mediators IL-1β, TNF-α & IL-6, secreted by macrophages?

Answer 12

IL-1β = activates vascular endothelium -> increases access of effector cells
TNF-α = activates vascular endothelium, increases vascular permeability -> increased entry of IgG, complement and effector cells
IL-6 = activation of lymphocytes

Question 13

What is the trias of systemic inflammation and what are its systemic effects? (5)

Answer 13

Trias = IL-1β, TNF-α & IL-6
Systemic effects:
1. Liver: production of acute phase proteins (complement, coagulation, etc.) -> higher complement activation & opsonization
2. Bone marrow: neutrophil mobilization -> phagocytosis
3. Hypothalamus: increased body temperature -> decreased viral & bacterial replication + increased antigen processing
4. Fat & muscle: increased body temperature -> decreased viral & bacterial replication + increased antigen processing
5. Dendritic cells: TNF-α stimulates migration to lymph nodes -> activation of adaptive immune response

Question 14

What happens to a pathogen after phagocytosis?

Answer 14

The phagosome is combined with the endosome, forming the phagolysosome

Question 15

What are mechanisms used to kill pathogens in the phagolysosome? (5)

Answer 15

1. Low pH
2. ROS/NO
3. Bacteridical proteins (lysozymes, cathepsins)
4. Cationic peptides (defensins)
5. Nutrient depletion

Question 16

Activated macrophages can be subdivided into two groups. What are these groups, and what are their general characteristics?

Answer 16

M1 = tissue destruction
M2 = immune regulatory

Question 17

Which factors induce a M1-macrophage response? (2)

Answer 17

1. IFN-γ
2. LPS

Question 18

What kind of Th-response is induced by M1-macrophages? What is this response aimed at?

Answer 18

Th1-response, aimed at killing intracellular pathogens

Question 19

Which factor induces an M2-macrophage response?

Answer 19

IL-10

Question 20

What kind of Th-response is induced by M2-macrophages? What is this response aimed at?

Answer 20

Th2-response, aimed at killing and capsulating of parasites

Question 21

Which subtype of macrophages (M1/M2) is involved in allergy?

Answer 21

M2 -> activates Th2-response that may be involved in allergy

Question 22

Which subtype of macrophages (M1/M2) can be responsible for tumour promotion, and why?

Answer 22

M2 -> prevents tissue destruction and can in this way prevent immune destruction of tumours
M1 macrophages play a role in resistance to tumours

Question 23

Which subtype of macrophages (M1/M2) is most often associated with inflammatory disease?

Answer 23

M1 macrophages -> inflammatory type

Question 24

What are characteristics of immature vs. mature dendritic cells? (3)

Answer 24

1. High endocytosis vs. low endocytosis
2. Low surface MHCII vs. high surface MHCII
3. Low costimulation vs. high costimulation

Question 25

What are cues that activate DC maturation? (4)

Answer 25

1. Danger signals (innate) 2. Activated lymphocytes (adaptive) 3. Inflammatory cytokines (innate/adaptive) 4. Immune complexes (complement or immunoglobulins -> innate/adaptive)

Question 26

What are semi-mature DC's? What effect do they induce?

Answer 26

Semi-mature DC's present a danger signal, but no antigen. This induces anergy.

Question 27

Which cytokine induces neutrophil production?

Answer 27

IL-17A -> induces production of G-CSF

Question 28

What are the three killing mechanisms of neutrophils?

Answer 28

1. Phagocytosis 2. Degranulation 3. NET's (neutrophil extracellular traps)

Question 29

When do neutrophils reach peak levels in infected tissues?

Answer 29

~6 hours after infection

Question 30

What is the primary function if eosinophils?

Answer 30

Defence against parasites

Question 31

What are the three steps of extravasation of leukocytes?

Answer 31

1. Rolling adhesion: leukocytes stick to selectins on endothelium 2. Tight binding by integrins: cells bind to integrins at the location where the endothelium is most activated 3. Diapedesis: gap junctions open and allow cells to follow the chemokine gradient towards the infection

Question 32

What are the four characteristics of stem cells?

Answer 32

1. Self-renewal 2. Multilineage differentiation 3. Quiescent 4. Long-lived

Question 33

How is self-renewal achieved in stem cells?

Answer 33

Asymmetric division, resulting in a new stem cell and a progenitor cell

Question 34

What is the main difference between a stem cell and progenitor cell?

Answer 34

Stem cell has the ability to differentiate in multiple lineages, while progenitors can only differentiate into one lineage

Question 35

What is meant by 'quiescent' as a characteristic of stem cells?

Answer 35

A low proliferation rate -> HSC's = ~once per 6-12 months

Question 36

What mechanism compensates for the low proliferation rate of stem cells, ensuring that there are enough cells?

Answer 36

Amplification by progenitor cells -> these divide rapidly

Question 37

What characteristic of stem cells enables a long life?

Answer 37

Low proliferation rate = low mutation rate

Question 38

What is a stem cell niche?

Answer 38

Specialized micro-environment, allowing self-renewal and regulated differentiation

Question 39

What are the characteristics of stem cell niches (as determined by Schofield)? (5)

Answer 39

1. Defined by anatomic location 2. Enables stem cell renewal 3. May preserve stem cells by limiting differentiation 4. Is limited and size and limits stem cell numbers 5. Is capable of reverting daughter cells to the stem cell stage (=controversial)

Question 40

What is the stem cell niche for haematopoietic stem cells? (in adults)

Answer 40

Trabecular bone

Question 41

What are (among others) important cell types for the stem cell niche of HSC's? (3)

Answer 41

Osteoblasts, mesenchymal cells, adipocytes