1: Intro / Hematopoesis 🏁 Flashcards
Name 3 major steps (history) for vaccination developement and a disease that was most severe without vaccination
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
Name 5 general differences between innate and adaptive immunity and 2 components for each
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
Here are 5 antigen subgroups:
Infection, harmless stimuli, transplant, self tissue and tumor
What happens with/without antigen response for each group?
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
Exam question
Content of blood based on 10.000 blood cells
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
Name 2 different classes of phagocytes (+ subclasses in %)
Granulocytes
Neutrophil: >90%,
Eosinophil: 2-5%,
Basophil: 0,1-1%,
Monocytes
differentiate into DCs and macrophages: AG-presentation and phagocytosis
Name lymphcyte classes of the innate and adaptive immune system (+% and function)
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
Sites (+when?) of hematopoiesis
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
Draw a chart for all hematopoetic lineages and their subclasses after differentiation
How do stem cells divide? Shortly explain how they differentiate into mature cells (steps)
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
How to identify blood cell types?
Surface markers (CD) measurable by flow cytometry or confocal microscopy
Regulation of hematopoesis
- 2 extracellular factor classes
- 5 specific examples and function of 2 of them
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
EPO
Regulation of EPO as a growth factor
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
In addition to EPO as a systemically regulated growth factor there are … that provide …
There are microenviromental niches
that provide distinct cytokine milieus supporting differentition into various hematopoetic lineages locally
Name 2 microenviromental niches in the bone marrow and explain their factors and function
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)
Lymphocyte developement
receptor domains / chains
how is varibaility achieved
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
Name 3 different mechanism on how to remove self reactive lymphcytes
deletion
pyhsical removal (e.g. apoptosis)
anergy
weaker signal that results in paralysis of function
Receptor editing
alteration of specificity via rearrangement
Name 2 microenviromental niches for B and T cell differentiation
- SDF-1 and reticular stromal cell for Pre-Pro B lymphcytes to differentiate
- IL-7 and stromal cell for Pro-B lymphcyte to differentiate
Master transcription factors
Activation
Function
3 specific examples
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
Primary immunodeficiency
Definition + 3 examples
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
Secondary immunodeficiencies
Definition + 3 examples
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
