8/04 Flashcards
Definition of anergy
inability to respond to an antigen
Which are the characteristics of B cells anergy?
It’s T indepentent
Fast
Short-lasting
reversible
What and which are the immune checkpoint molecules?
These are molecules that determine the inhibition or deletion of T cells and they’re:
- CTLA4: switch off all the signals causing apoptosis
- PD1: bind PDL1 and PDL2
Which type of regulatory T cells can we find? How can we differentiate them?
Native: CD4, CD25 expressed costitutively, express Foxp3 causing the release of TGF beta and IL10
Induced: became CD25+ after encountering the APC and then start expressing Foxp3
Regulatory T cells: what and how do they regulate?
Native regulate T, B and NK cells activation through CDLA4 of other inhibitory cytokines.
Innate suppress T, B, Nk and dendritic cells thanks to indolamine dioxygenase (IDO).
Both suppress the immune response also thanks to IL2 deprivation, grnazyme release and ATP deprivation
What’s the effect of TGF beta on T cell differentiation?
It inhibits Th1 and Th2 differentiation and cause the Treg differentiation.
In presence of IL1 and IL6 cause Th17
What characterize an immuno privileged site?
very low or no expression of HLA class I
Expression of death ligand (FAS) against T cells
Switching the response towards a Th2 response: antibody production could be less dangerous
Give some examples of immuno-privileged sites
The eye, the testis and the CNS, expecially the brain
What does immune ignorance mean?
It means that the antigens are so little represented that they’re not able to activate efficiently the T cells
How can we cause tolerance in vivo?
Modulating the dose of the antigen
Modificating physical or chemical feature of the antigen (ex: size)
changing the solubility
changing the administration route: oral is the more tolerogenic
Definition of hypersensitivity reaction
Exaggerated response of the immune system to an antigen that is usually harmless (allergen)
Type I hypersensitivity: type of antibody, antigen , cells involved and type of diseases
IgE
soluble antigens
mast cells or basophils
allergy, atopy, astham and anaphylaxis
What’s the difference between allergy and atopy
the symptoms can be the same, while for allergy we know the allergen and so we know the antigen, whereas for atopy the cause is not known.
Type I hypersensitivity: which phases can we recognize in the effector phase?
Immediate phase: degranulation of mast cells
Late phase: recruitment of other innate cells
Which tests can you do to diagnose the allergies?
- Prik test: you will inject in each quadrant with a different antigen and in few minutes, if you’re allergic to the antigen, a reaction will appear
- RIST: you put the patient’s blood in contact with small beads coated with the anti-IgE and radio labelled. If there are the IgE there’s an allergy occurring, and you will have a signal directly proportional to the amount of IgE.
- RAST: on the beads there’s the antigen, in contact with the blood IgE will bind and you can evaluate the results quantitatively
Which new terapies are studied for the type I hypersensitivity ?
- Monoclonal antibodies: such as Omalizumab.
It’s a humanized anti-IgE which bind IgE and inhibit their natural binding with Fcε. - Hypo-sensitization: the antigen is given at a high dose, it should induce tolerogenic response which cause the activation of Th1, inhibiting Th2
- Fusion proteins: they’re antibodies made with the antigen binding site of the IgE against the specific allergen and the Fc portion by an IgG. The fused protein is able to bind the IgE but the Fc is not binding the Fcε again. So, again, they can block the degranulation of the mast cells.
Type II hypersensitivity: type of antibody, antigen , cells involved and type of diseases
IgG
cell-associated antigen
macrophages and NK cells
Anemia, hemolytic diseases, goodpasture syndrome
Type III hypersensitivity: type of antibody, antigen , cells involved
IgG
soluble antigen
complement activation + innate cells
Type IV hypersensitivity: antigen , cells involved and type of diseases
soluble or surface antigens
Th1, Th2 cause the activation of eosinophils, macrophages and CD8 T cells
persistent pathogens, persisting non-infectious chemical agents
Definition of molecular mimicry
It’s a similarity of the peptide from a pathogen and the self-antigen
Give an example of type 3 hypersensitivity
Paroxysmal nocturnal hemoglobinuria: the complement target red blood cells
Lupus: autoantibodies make immunocomplexes with self antigens
Why some people are more affected by immune diseases than others?
Genetic predisposition
External triggers
Hormonal influences
Which type of therapy can we use for autoimmune diseases?
Targeting the inflammation
Control of the autoantibodies
immunotheraphy: mAb or recombinant cytokines
Switch off of self reactive B and T cells
Which molecules are essencial for avoiding the formation of tumors
INF gamma and perforin
Which phase of immune response we can find when fighting against a tumor?
Elimination phase: CD4 and CD8 kills the more immunogenic clones in the primary tumor
Escape phase: the immune system is not able to counteract and the tumor can be diagnosed
Why inflammation is important for tumor development?
Because it lead to genetic instability
The cytokines, chemokines, alarmines help tumor progression and metastatization
Which are the most common mechanisms that tumor cells use to avoid immune recognition?
- TAA negative clones: some tumor cells stop the expression of TAA (tumor associated antigen) usually recognized during the elimination phase
- MHC low clones: tumor cells decrease the expression of MHC class I and II
- Clones resistant to immune attack: some clones become resistant to perforin, granzymes and INF γ signal.
Which cytokines have an important role in the suppression of immune reactivity against a tumor?
G-CSF and CM-GSF can recruit and cause the differentiation of myeloid cells in a suppressive phenotype. These cells can become:
- MDSC: myeloid derived suppressor cells
- Suppressive DC: suppressive dendritic cells
- TAM: tumor associated macrophages
MANCA TUMOR IMMUNOTHERAPY
