4/04 Flashcards
How can we fully activate a CD8 cell?
1- the APC contact the T helper and the CD8
2- helper and APC release IL2 for proliferation, IL12 and interferon for the granules enzymes, IL7 for survival and IL21 for generation of memory
What can a completely active CD8 cell do?
It can express T-bet and eomesodermin causing the production of interferon gamma, perforin and granzyme B to kill the pathogen or perform the kiss of death
What’s the kiss of death?
thanks to FAS ligand-FAS interaction or TNF α-TNF receptors interaction there’s a lose contact between the lymphocyte and the target and the latter will die because of the release of perforin and granzyme
Why a T lymphocyte do not undergo apoptosis in presence of apoptotic molecules?
Because lymphocytes membrane is protected by cathepsin
Against which kind of pathogen are CD8 lymphocytes particularly active?
virus and intracellular bacteria
Starting from a Th0 CD4+, how can we obtain a Th1 or a Th2 T cell?
INF-gamma -> block of GATA3 -> Th1
IL4, IL5, IL13 -> block of T-bet -> Th2
Which are the effects of the activation of a Th1 cell?
Th1 secrete INF gamma, INFalfa and IL2 causing the activation of pro-inflammatory macrophages, the expression of MHCclassII, the stimulation of NK and CD8 cells.
This happens expecially against bacteria
Which is the target of Th2 cells and why?
They target worms and parasites secreting IL4, IL5, IL9, IL13 causing a IgE and IgA response, anti-inflammatory macrophages activation and stimulation of eosinophils
Which is the main target of Th17 cells?
They mostly act against fungi or extracellular bacteria
How can we obtain a Tfh cell starting from a Th0?
APC secret IL6 and ICOS-Ligand, The T cells express the ICOS receptor and this binding cause the expression of CCR7 or CXCR6
What’s the role of follicular T cells?
Follicular T cell are necessary for the collaboration between B and T cells in the lymphatic organ: they may express CCR7 and be attracted in the T cell area, or they may express CXCR6 and move towards the B cell area. In both cases they follow cytokines’ gradients.
When a follicular T cell enter the B cell area, it can contact B cells (thanks to ICOS ligands) and activate them.
TFh also release IL21, necessary for the proliferation of B cells.
What are the microfold cells?
M cells are cells present in between enterocytes, intestinal cells and mucosa cells. They allow the antigen to enter without any damage to the anatomical barrier (transcytosis)
How happens the T dependent B cells activation?
Which B cell affect?
T helper express CD40ligans which binds CD40 (receptor) present on B cells. This bound cause the expression of the AID enzyme (activation-induced deaminase) that then:
- Induces the survival signals to the B cell
- Induces all the germinal centre reaction
- Allow the production of different kind of antibodies
- Induces the affinity maturation of the BCR: increases the variable portion of the BCR
- Induces the differentiation and the survival of memory B cells
T dependent B cells activation: type of cell affected, type of antigen used, antibodies produced and type of plasma cells obtained?
B2 follicular cells
protein antigen
IgE, A, G
long live plasma cells
T independent B cells activation: type of cell affected, type of antigen used, antibodies produced and type of plasma cells obtained?
B1 cells or marginal zone B2 cells
polysaccharide or lipidic antiged
IgM
Short live plasma cells
What’s a iccosome?
It’s a structure made of receptors that can bind the antibody bound to the antigen
Which are the differences between the centroblast and the centrocyte cells ?
- Centroblast are proliferating B cells, all the content is nucleus and at the histological staining they appear dark. Present in the dark area of the germinal center.
- Centrocytes are B cells which stopped the proliferation and started producing the BCR and cytokines. Present in the light area of the germinal center.
Which processes happen in the germinal center to B cells? (LIST)
Proliferation
hypermutation
affinity maturation
Isotype switch
What’s the key enzyme for the hypermutation in the germinal centre?
activation induced deaminase (AID), an enzyme which transforms the amidic group in the cytosine in oxidative group in uracil creating a uridine.
The presence of uridine is not usual for the DNA and it’s perceived as an error inducing the DNA repair mechanism.
The uridine can be excised as single nucleotide (mismatch repair) or it can be excited by the DNA strand with the adjacent nucleotide (base excision repair). The gaps will be filled with the DNA polymerase creating the differences in the variable portion of the BCR
What’s the isotype switch?
It’s a process that changes the class of the antibodies produced by the differentiated plasma cells.
How does a B cell decide which kind of antibody will be produced?
Thansk to cytokines released by helper cells, they can produce IgM, D, E, A, G
Where can we find B1 cells?
In the cavity tissues, in particular the peritoeum and the pleura.
In which order are the different kind of antibodies produced?
1- low affinity IgM from marginal and follicular B2 cells
2- higher affinity IgG from the germinal centre
3- fast IgG in the second encounter thanks to memory B cells
In a electophoresis of an healthy serum, where can we see the antibodies?
We have 4 peaks: albumin, alfa, beta and gamma globulin. The antibodies are in the gamma globulin peak
What’s the hinge region of a immunoglobulin?
It’s the region which allow the fragment antigen binding domain to rotate and adapt itself
Definition of the idiotypes of immunoglobulines
idiotypes are differences in the variable portion of heavy and light chains.
How can secreted immunoglobulin go into circulation?
They’re released in the tissue and then they bind the poly-Ig receptors which allows its transcytosis in the lumen
What are the epitopes? How an we classify them?
They’re antigenic determinants or immunogenic portion of an antigen and they’re recognized by the BCR and the TCR.
They can be linear or conformational
Which specific part of the antibody can contact the antigen?
The complementarity determining regions (hypervariable regions) determine the strenght of the binding
What’s the avidity of an immunoglobulin?
It’s the ability to have different binding sites
Which are the functions of immunoglobulins?
They can have direct function mediated by the antigen binding site or indirect function mediated by the constant portion
Which signals are essential for the developement of the centroblast and the centrocyte?
CD40 and then Blimp-1
Which are the direct activities of a immunoglobulin?
Toxin neutralization: The antibody binds the toxin and induce a conformation change in the toxin or interfere allosterically with the bound between the toxin and our cells.
Virus and microbe inhibition: opsonization
Immunocomplex formation: expecially IgM form a net with the antigen
Agglutination: formation of an immune complex against cells
Aggregation and internalization of membrane molecules and receptors
Which is the structure of Fc receptors?
alfa chain: bind the Fc region of the anibody
beta, gamma and zeta chain: transduce the signals
Which kind of FcR can we find?
High affinity: CD64
Low affinity CD32
pH dependent
Which are the indirect activities of antibodies?
Immune phagocytosis: opsonization
Antibody dependent cellular cytotoxicity
Mast cell and granulocyte degranulation: mediated by IgE
Antibody feedback: mediated by IgG
Which mediators are released in case of an allergic reaction?
After the binding of the IgE with the FcRε on basophils or mast cells we have 2 kind of mediators released:
- Immediate phase reaction (in the first 30 minutes): the degranulation causes the release of histamine, proteoglycans, proteases and TNF
- Late phase reaction (after 6-8 hours): there is the occurrence of the secretion of lipid mediators and the transcription of cytokines and chemokines, that mediate the inflammatory and immunoregulatory signals.
How can we switch off the production of antibodies when it’s no longer needed?
Thanks to the antibody feedback
There are two possibility:
1- IgG immunocomplexes are recognized by Fc gamma RIIB triggering a feedback
2- thanks to the C plasma receptor for IgM the B cells are switched off
