Basic immunology Flashcards
Lectures -Week 1, day 1, lecture 1 - Innate immunity - Macrophages/granulocytes/dendritic cells -Week 3, day 3, lecture 1 - Developmental aspects - Stem cells & hematopoiesis
What are the differences in innate vs. adaptive immune responses? (6)
- Non-clonal response vs. clonal response
- Immediate response vs. requires time
- Present in all individuals vs. different per individual
- No increase upon re-exposure vs. increased response through memory
- Pattern recognition vs. specific antigen recognition
- Genome-encoded receptors vs. re-arranged receptors
What are the three phagocytic cell types?
- Macrophages
- Immature dendritic cells
- Granulocytes
Are macrophages present in healthy tissues?
Yes, macrophages are important for tissue homeostasis
Are immature DC’s present in healthy tissues?
Yes, immature DC’s are present in tissues for immune surveillance
Are neutrophils present in healthy tissues?
No, neutrophils are not present in healthy tissues
Which two lineages of tissue macrophages can be identified? Where do they originate?
- Embryonic lineages, originating from the foetal liver or yolk sac
- Development from monocytes, originating from the bone marrow
Which receptor is used for self-renewal of tissue macrophages?
IL-34 = M-CSF receptor (monocyte colony stimulating factor)
Do mature dendritic cells phagocytose?
No; as soon as the DC matures it stops phagocytosis and starts presenting antigen
Which three types of neutrophils can be identified?
- Neutrophils
- Eosinophils
- Basophils
Which transcription factor is generally important for the activation of an inflammatory response?
NF-κB
What are the five hallmarks of infection?
- Rubor = redness
- Dolor = pain
- Calor = warmth
- Tumor = swelling
- Functio laesa = loss of function
What are local effects of inflammatory mediators IL-1β, TNF-α & IL-6, secreted by macrophages?
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
What is the trias of systemic inflammation and what are its systemic effects? (5)
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
What happens to a pathogen after phagocytosis?
The phagosome is combined with the endosome, forming the phagolysosome
What are mechanisms used to kill pathogens in the phagolysosome? (5)
- Low pH
- ROS/NO
- Bacteridical proteins (lysozymes, cathepsins)
- Cationic peptides (defensins)
- Nutrient depletion
Activated macrophages can be subdivided into two groups. What are these groups, and what are their general characteristics?
M1 = tissue destruction
M2 = immune regulatory
Which factors induce a M1-macrophage response? (2)
- IFN-γ
- LPS
What kind of Th-response is induced by M1-macrophages? What is this response aimed at?
Th1-response, aimed at killing intracellular pathogens
Which factor induces an M2-macrophage response?
IL-10
What kind of Th-response is induced by M2-macrophages? What is this response aimed at?
Th2-response, aimed at killing and capsulating of parasites
Which subtype of macrophages (M1/M2) is involved in allergy?
M2 -> activates Th2-response that may be involved in allergy
Which subtype of macrophages (M1/M2) can be responsible for tumour promotion, and why?
M2 -> prevents tissue destruction and can in this way prevent immune destruction of tumours
M1 macrophages play a role in resistance to tumours
Which subtype of macrophages (M1/M2) is most often associated with inflammatory disease?
M1 macrophages -> inflammatory type
What are characteristics of immature vs. mature dendritic cells? (3)
- High endocytosis vs. low endocytosis
- Low surface MHCII vs. high surface MHCII
- Low costimulation vs. high costimulation
What are cues that activate DC maturation? (4)
- Danger signals (innate)
- Activated lymphocytes (adaptive)
- Inflammatory cytokines (innate/adaptive)
- Immune complexes (complement or immunoglobulins -> innate/adaptive)
What are semi-mature DC’s? What effect do they induce?
Semi-mature DC’s present a danger signal, but no antigen. This induces anergy.
Which cytokine induces neutrophil production?
IL-17A -> induces production of G-CSF
What are the three killing mechanisms of neutrophils?
- Phagocytosis
- Degranulation
- NET’s (neutrophil extracellular traps)
When do neutrophils reach peak levels in infected tissues?
~6 hours after infection
What is the primary function if eosinophils?
Defence against parasites
What are the three steps of extravasation of leukocytes?
- Rolling adhesion: leukocytes stick to selectins on endothelium
- Tight binding by integrins: cells bind to integrins at the location where the endothelium is most activated
- Diapedesis: gap junctions open and allow cells to follow the chemokine gradient towards the infection
What are the four characteristics of stem cells?
- Self-renewal
- Multilineage differentiation
- Quiescent
- Long-lived
How is self-renewal achieved in stem cells?
Asymmetric division, resulting in a new stem cell and a progenitor cell
What is the main difference between a stem cell and progenitor cell?
Stem cell has the ability to differentiate in multiple lineages, while progenitors can only differentiate into one lineage
What is meant by ‘quiescent’ as a characteristic of stem cells?
A low proliferation rate -> HSC’s = ~once per 6-12 months
What mechanism compensates for the low proliferation rate of stem cells, ensuring that there are enough cells?
Amplification by progenitor cells -> these divide rapidly
What characteristic of stem cells enables a long life?
Low proliferation rate = low mutation rate
What is a stem cell niche?
Specialized micro-environment, allowing self-renewal and regulated differentiation
What are the characteristics of stem cell niches (as determined by Schofield)? (5)
- Defined by anatomic location
- Enables stem cell renewal
- May preserve stem cells by limiting differentiation
- Is limited and size and limits stem cell numbers
- Is capable of reverting daughter cells to the stem cell stage (=controversial)
What is the stem cell niche for haematopoietic stem cells? (in adults)
Trabecular bone
What are (among others) important cell types for the stem cell niche of HSC’s? (3)
Osteoblasts, mesenchymal cells, adipocytes
