1: Intro / Hematopoesis 🏁

Question 1

Name 3 major steps (history) for vaccination developement and a disease that was most severe without vaccination

Answer 1

China, 100 b.c.
transfer of pox crust

Turkey, beginning of 18th century
Lady Montagu: pox pus vaccination

End of 19th century
Developement of vaccines and vaccination programmes

Most severe disease
Diptheria killed almost every 2nd child

Question 2

Name 5 general differences between innate and adaptive immunity and 2 components for each

Answer 2

Developement
- I: early in evolution (plants, animals)
- A: vertebrates only

Presense
- I: present before infection
- A: adapt to infection

Time
- I: hours
- A: first slow, fast only during memory response

Memory
- I: no memory
- A: memory

Recognition
- I: unspecific limitited recognition of PAMPs
- A: specific unlimited recognition of epitopes

Examples
- I: complement system, phagocytes
- A: B and T cell lymphocytes, antibodies

Question 3

Here are 5 antigen subgroups:
Infection, harmless stimuli, transplant, self tissue and tumor

What happens with/without antigen response for each group?

Answer 3

Infection
Response leads to protective immunity, otherwise chronic infection

harmless stimuli
Response leads to allergy

transplant
Response leads to rejection of transplant

self tissue
Response leads to autoimmune diseases

Tumor
Response helps limiting tumor growth

Question 4

Exam question

Content of blood based on 10.000 blood cells

Answer 4

Adults have 5-6 litres of blood containing blood plasm and blood cells, for 10.000 blood cells we observe:

erythrocytes
95% -> 9500 cells

Platelets
4,7% -> 470 cells

leucocytes
0,15 % -> 15 cells

30% lymphocytes -> 4-5
66% granulocytes -> 10
4% monocytes -> 0-1 cells

Question 5

Name 2 different classes of phagocytes (+ subclasses in %)

Answer 5

Granulocytes
Neutrophil: >90%,
Eosinophil: 2-5%,
Basophil: 0,1-1%,
Monocytes
differentiate into DCs and macrophages: AG-presentation and phagocytosis

Question 6

Name lymphcyte classes of the innate and adaptive immune system (+% and function)

Answer 6

Innate
- 10% NK cells for cell killing (CD16,CD56)

Adaptive
- 60% T cells (CD3) for immune regulation ( CD4+ T helper cells) and cell killing (CD+ T cytotoxic cells)
- 20-50% B cells (CD19) for antibody matuation and secretion from plasma cells

Question 7

Sites (+when?) of hematopoiesis

Answer 7

before birth
yolk sac -> liver/spleen -> bone marrow

after birth
bone marrow, slowly replacement of active (red) marrow by inactive (fatty) tissue, but expansion can occur during increases need for cell production

Question 8

Draw a chart for all hematopoetic lineages and their subclasses after differentiation

Answer 8

Question 9

How do stem cells divide? Shortly explain how they differentiate into mature cells (steps)

Answer 9

Stem cells can divide asymmetrically (1 stem cell and 1 differentiated cell)

This makes self renewal + differentiation possible at the same time

Differentiation steps
- multipotent progenitors
- oligopotent progenitors (e.g. common lymphoid progenitorm, common myeloid progenitor
- commited progenitor
- mature cells

Question 10

How to identify blood cell types?

Answer 10

Surface markers (CD) measurable by flow cytometry or confocal microscopy

Question 11

Regulation of hematopoesis
- 2 extracellular factor classes
- 5 specific examples and function of 2 of them

Answer 11

classes
- growth factors for proliferation and self renewal
- differentiation factors

Examples
Erythropoietin (erythropoiesis)
Thrombopoietin (platelets, megakarypoiesis)
IL-3 (basophils)
Il-7(lymphoid progenitor)
colony stimulating factors like macrophage CSF or granulocyte-macrophage CSF

Question 12

EPO
Regulation of EPO as a growth factor

Answer 12

First of all, Free Vuskovic!

EPO is a systemically regulated factor with a negative feedback mechanism: EPO leads to more RBC mass that strenghtens oxygen production, once oxygen is high enough, low/no EPO production

Question 13

In addition to EPO as a systemically regulated growth factor there are … that provide …

Answer 13

There are microenviromental niches
that provide distinct cytokine milieus supporting differentition into various hematopoetic lineages locally

Question 14

Name 2 microenviromental niches in the bone marrow and explain their factors and function

Answer 14

Stromal cells
Cell-cell contacts and secretion of cytokines that are needed for certain steps in differentiation

Osteoblasts
Factors for osteoblast also influence hematopoiesis (BMP differentiation, PTH for self renewal)

Question 15

Lymphocyte developement
receptor domains / chains
how is varibaility achieved

Answer 15

receptor domains
- constant region that determines the antibody class and antibody effector function for B cells or CD4/CD8 cell binding for T cells
- variable region that binds antigen
- 2 heavy + 2 light chains

Variability
there is no whole gene for the receptors / antibody -> gene segments
Somatic mutation: Rearrangement of genes for receptor / antibody

Question 16

Name 3 different mechanism on how to remove self reactive lymphcytes

Answer 16

deletion
pyhsical removal (e.g. apoptosis)

anergy
weaker signal that results in paralysis of function

Receptor editing
alteration of specificity via rearrangement

Question 17

Name 2 microenviromental niches for B and T cell differentiation

Answer 17

• SDF-1 and reticular stromal cell for Pre-Pro B lymphcytes to differentiate
• IL-7 and stromal cell for Pro-B lymphcyte to differentiate

Question 18

Master transcription factors
Activation
Function
3 specific examples

Answer 18

Activation
other extracellular differentiation factors induce expression of master transcription factors inside the cell

Function
Due to activation of other transcription factors that finally determine the lineage of cell it leads to lineage commitment, if master transcription factor is knocked out, cells can re-differentiate

Examples
Pax5: B cells
E4BP4 + Id2: NK cells
GATA-3: T cells

Question 19

Primary immunodeficiency
Definition + 3 examples

Answer 19

genetic diseases

Bruton’s Agammaglobulinemia
X recessive mutation in Bruton’s Tyrosine kinase where bacterial infection in the first year occur due to absence of antibodies / functional B cells, can be cured with Ig therapy

Severe Combined Immunodeficiency
different genetic defects like ADA (adenosine deaminase) that lead to high amount of infection in the first year due to adsense of functional B and/or T cells

Question 20

Secondary immunodeficiencies
Definition + 3 examples

Answer 20

aquired through disease or therapy

examples:
- AIDS induced by HIV
- Glucocorticoid induced Immunodeficiency that suppresses cytokine and t cell proliferation genes
- Multiple Myeloma (plasma cell tumor of bone marrow) that desturbed hematopoiesis and produce immumusupressive factors like IL-10