Exam questions Flashcards
1: Hematopoesis
10.000 blood cells, how many leucocytes (number), how many of them are lympocytes and granulocytes in %
0,15% Leucocytes -> 15 cells
66% granulocytes
30% lymphocytes
1: Hematopoesis
What is non symmetric cell division? In which context of hematopoesis is it important?
Stem cells can divide non symmetric to form another stem cell and 1 differentiated cell (progenitor)
That makes self renewal of the stem cell population + differentiation possible at the same time
4: Complement and inflammation
Classical pathway of the complement system?
Trigger?
Name an example and it’s role.
Trigger: Antigen bound IgM or IgG that makes Fc part of antibody accessible and for binding of C1q, cascade is activated
Example and role
Invasion of bacteria leads to antibody secretion (IgM and IgG isotype) that result in activation of classic pathway, role is clearance of pathogen via formation of Membrane attack complex, opsonitation, analphylatic reaction and help for B cells (C3b/C3d)
1: Hematopoesis
What are commited myeloid progenitors?
Give 3 examples. what cells can these progenitors differentiate to?
Common myeloid progenitor cell differentiate into commited myeloid progenitors. These are cells that already commited on a special lineage
Examples
meg-CFC: megakaryocytes or platelets
eo-CFC: eosinophilic granulocytes
Mast-CFC: mast cells / basophilic granulocytes
G-CFC: neutrophilic granulocytes
M-CFC: Monocytes/Macrophages/DCs/..
7: Immunological memory
Please explain the term hypermutation. Which molecule in which cell is mutated? Which property of the molecule is altered?
T helper signal promotes somatic hypermutation of B cells in the CDR encoding parts that are responsible for antibody specificity
Multiple B cell clones arises with different affinities for antibodies that results in affinity maturation
2: Innate immune cells
Please explain the term extracellular traps (NETs) Which cells? Which property does it consist of? Which function does it have? Provide details about their composition and function.
NETs (neutrophillic extracellular traps) consists of fibres (chromatin and antimicrobial peptides) that are released from neutrophils that undergo cell death (NETosis).
Works as physical barrier to prevent further infection + helps recruiting other immune cells
7: Immunological memory
What is cytokine memory?
Cytokine memory refers to the ability of memory T and B cells to express the same cytokine profile like after the 1st exposure, this is possible to due the histone modification and DNA methylation of cytokine genes that leads to a specific profile once being reactivated
11: Mucosal immunity
IgA can be in 2 formations. Which ones and how do they differentiate in their function? One has a special function. which?
monomeric form:
forms immune complexes and binds to CD89, activates APCs, induced cellular immune response
dimeric form with j chain and secretory component: neutralization of antigen on mucosal surfaces, prevents attachement and movement of microbes and transport antigens from lamina propria into lumen
Special function of dimeric IgA: mucosal immunity functions
7: Immunological memory
FDCs
What are FDcs, in which organ do they occur? Which substructure? What would be the outcome if FDCs would be impaired? Function of FDCs
Folicular DCs cells occur in the geminal centre of lymphoid tissue, these cells lead to an increased antigen exposure via immune complexes to B cells that supports the germinal centre reaction.
The also support interaction between T helper cells and B cells that support activation, somatic hypermutation, affinity maturation and clonal expansion
Impairing would result in an inefficient germinal centre reaction with less functional B memory and long-lived plasma cells and less high affinity antibodies
5: adaptive immunity B cells
What ar natural antibodies? Which molecule do they bind, by which B cell subset are they produced? What induced it’s production?
Natural antibodies are antibodies with no prior exposure to an antigen, against conserved PAMPs of different pathogens (carbohdrates, lipids, …) that are germline encoded, activated by B-1a subset. Induced by commensal bacteria, enviromental antigens such as pollen, dust or genetics
? 2 or 4 maybe
What are defensins? Name 2 cellular sources
Defensive are small peptides that support antimicrobial functions e.g. disrupting cell membrane of pathogens
Neutrophils produce alpha and beta defensins
Epithelial cells produce mainly beta defensins
11: Mucosal immunity
What would happen if oral tolerance fails completely?
If oral tolerance fails completely, chronic inflammation will occur:
Normally harmless stimuli like commensals or food proteins will inhibit DC maturation, these immature DCs will lead to differentiatiin of regulatory T cells to induces supression of other immune function.
If oral tolerance fails, even harmless stimuli lead to differentiation of effector TH1/2 cells and a high inflammation resulting in tissue damage.
?
What function does the extracellular matrix have for migratory immune cells?
Extra cellular matrix components are important for lymphoid tissue architecture
provides barrier and routes for migration
3: Innate immune system: pathogen recognition
What is the evolutionary ancestry of ILR/NF-kappyB?
The Spätzle/Toll/Cactus gene casette in drosophila
3: PRR
Name a receptor that is germ-line encoded and one that’s not + function of these receptors
Germ line encoded:
TLR4: recognition of gram- bacteria (LPS) or fungi surface molecules
non germ line encoded:
TCR: binding of specific antigen bound to MHC molecule for activation resulting in cell killing (CD8+) or B cell help (CD4+)
?
Different homing capacities of naive T cells an memory T cells. Name a receptor that is differently expressed in these cells.
CCR7 more in naive T cells: lymph node associated
5: Adaptive immunity B cells
What is the difference between constitution of pre-BCR and BCR? What is the pre-B cell doing if the pre-B cell receptor is triggered? Provide at least two direct consequences resulting from activation of the pre-B cell receptor.
The difference is that pre-BCR has a surrogate light chain that is expressed as a precursor of the rearranged light chain
so BCR consist of a somatically rearranged light chain
If the pre-B cell receptor is triggered , differentiation and proliferation is induced.
+ it induces the rearrangement of the light chain gene segments (VDJ) for a unique heavy AND light chain
5 Adaptive immunity B cells + ?
What is anergy? Name 2 cell types that can become anergetic. How and when is anergy induced? What would happen if this mechanism istnt available?
Anergy is the functional unresponsiveness of T and B cells to antigens. This mechanism is useful to prevent autoreactivity towards self antigens (autoimmunity). Induced when B or T cell react against self antigen for central tolerance (bone marrow B cells, thymus T cells) + peripheral tolerance
If this mechanism is not available this would result in loss of T and B cell tolerance to a certain degree
(there are other tolerance mechanisms like deletion, B receptor editing or T regulatory dells),
probability result in autoimmune disease
6 Adaptibe immunity T cells
Which coreceptor does the TCR have for MHC recognition?
CD4 (MHC II) or CD8 (MHC I)
Adaptive immunity B cells
Somatic recombination is not existant: What happens to an individual who gets infected? How would an immune response differ from that to a normal person? If the person survives, would the immune response of reinfection differ from that of a normal person?
This can lead to death because:
The adative immune response would be impaired, APCs would find to fitting T and B cells because there is no variability due to impaired somatic recombination. No functional B and T cells can develope and the infection can´t be cleared.
It is necessary to treat the person with antibiotics/antivirals, probably also cytokine and antibody therapy to induce a immune response
Immune response of reinfection would differ. The healthy person would have memory T and B cell that lead to fast adaptive immune response (high IgG levels) and probably fast clearance. For the unhealthy person it can even be more dangerous than before, cause there is no memory + the immune system is even more susceptible due to prior illness.
?
What does immune priviliged mean? Name 2 tissues / organs.
Examples: Brain, eye
Sites with limited immune response (limited access leucocytes) so inflammation is limited and does not lead to damage of tissue
?
Memory: Name 4 examples in which immunization is helpful. What is it good for?
Immunization helps to eradicate diseases that would kill many people (e.g. Polio, Measles, BCG,…)
It helps to prevent susceptible groups through herd immunity
It helps to protect newborn that get antibodies through maternal placenta or breast milk
It helps to protect against reinfection after 2nd exposure
Adaptive immunity B cells
TI-1 antigen
Which molecule resemble typical T cell independent TI-1 antigens? Which receptors are involved in TI-1 B cell activation at low or high antigen concentration? How does antigen concentration influence the B cell response?
can activate B cell without help of T cells, usually antigens with repeated structures like LPS or peptidoglycan, …
Activation of B cells is mediated by BCR and TLR
low concentration supports activation by TLRs to promote proliferation and antibody secretion
high concentrations lead to stronger B cell response including memory cell generation and class switching
3: Innate immune system: pathogen recognition
Different recognition of gram+ and gram- via which receptor?
TLR 4 (LPS of gram-) and TLR2 (Lipid of gram+)
1: Intro
Name 2 immunodeficiencies and examples for each of them
Primary
- genetic diseases
- Severe Combined Immunodeficiency like ADA that leads to high amount of infection in 1st year due to absense of functional T or B cells
- 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
Secondary
- aquired through disease or therapy
- AIDS induced by HIV
- Glucocorticoid induced Immunodeficiency that suppresses cytokine and t cell proliferation genes
1: Hematopoiesis
Explain hematpoietic hierachy. How do cells clones at beginnign and end of hierachy differ?
hematopoietic hierarchy refers to the different stages of blood cell development, starting with HSCs and progressing through various progenitor cells to mature blood cells.
Cells at the start (stem cells) can self-renew + differentiate into 2 main types of progenitor cells, common lymphoid progenitor and common myeloid progenitor cell, these cells can still differentiate into several types of cells.
Master transcription factors will lead to commitment to a specific cell colony / lineage (committed progenitors)
After differentiation to mature hematopoietic cells these cells lost the ability to differentiate into other cell lineage, also proliferation is limited + mature cells have specific effector functions
1: Hematopoiesis
Colony stimulating factor: general function, where are these molecules expressed and what is their function there?
Colony stimulating factors are differentiation factors that lead to differentiation into specific progenitor cell or also mature cells
Expressed by various different cell types, one example stromal cells in the bone marrow that offers a microenvironmental niche for differentiation on a local level
Name 2 distinct cell types of adaptive and innate immunity and their functions
Innate
- Macrophages for antigen presentation and phagocytosis, inflammation, …
- NK cells for cell killing
Adaptive
- B cells to secrete antibodies (plasma cells), generate memory (memory B cells, long-lived plasma cells)
- T cells to kill infected cells (CD8+) or T helper cells (CD4+) that help B cells to survive, proliferate, …
1: Hematopoiesis
Which cytokine is produced in kidney dependent on oxygen level?
EPO
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
Mucosal immunity (last slides)
Which CD4+ T cell subpopulation produces IFN-Gamma and what is the function?
IFN-Gamma is produced by TH1 effector cells that activate B cells to produce IgG for complement activation and other immune functions
What are pattern recognition receptors? Name 2 examples and their respective ligand
PRR are receptor that bind conserved antigens shared by a broad range of microorganisms to induce a proinflammatory immune response
TLR 4: LPS
TLR 5: Flaggelin
FC receptor: Fc part of antigen bound antibody
…
Name 4 hallmarks of inflammation and 4 clinical paramters of inflammation.
Hallmarks
Redness
Swelling
Heat
vascular permeability
Clinical parameters
increased white blood cell count
fever
pain
CRP protein
Name 3 types of complement activation and their initial trigger (upstream complement)
Lectin: Mannose recognized by MBL
Classical: Fc part of antigen binding antibody IgM and IgG
alternative: spontaneous hydrolysis of C3 and binding of factor B
