SLIDE 1
Antigen presentation and peripheral tolerance T cells only recognize - - PowerPoint PPT Presentation
Antigen presentation and peripheral tolerance T cells only recognize - - PowerPoint PPT Presentation
Antigen presentation and peripheral tolerance T cells only recognize antigens presented in the MHC context characteristics Caractersticas Molcula que se liga ao antgeno Molecules bound to antigens Imunoglobulina (Ig) Receptor de clulas
SLIDE 2
SLIDE 3
Características Molécula que se liga ao antígeno Imunoglobulina (Ig) Receptor de células T(TCR) Moléculas de MHC* Sítio de ligação ao antígeno 3 regiões CDR nas porções variáveis das cadeias leve e pesada 3 regiões CDR nas porções variáveis α e β Fenda para ligação de peptídeo formada pelas cadeias α1 e β1 em classe II e α1 α2 em classe I Tipo de antígeno Macromolecules, organic Molecules, proteins, lipids, Sugars… MHC/peptide complex Peptídeos Antigen nature Linear or conformacional Linear; 2 to 3 aa residues Linear; 8 to 12 aa depending on the MHC molecule Binding affinity Kd 10-7 - 10-11 M; Affinity maturation Kd 10-5 - 10-7 M Kd 10-6 - 10-9 M; durable interaction
characteristics Molecules bound to antigens Immunoglobulin TCR MHC Binding site 3 CDRs in the light and heavy variable chains 3 CDRs in the alpha and beta variable chains Peptide grooves in the α1/β1 chains in II; In α1/α2 chain in I antigen peptides
SLIDE 4
T cell receptor complex
SLIDE 5
Characteristics II
SLIDE 6
SLIDE 7
Antigen presentation pathways
SLIDE 8
Class II pathway
SLIDE 9
HLA-DO ensures peptide presentation diversity
SLIDE 10
Class I pathway
SLIDE 11
Proteoasome and immunoproteasome
SLIDE 12
Immunoproteasome cleaves proteins preferentially after basic and hydrophobic residues generating peptides with higher affinity to MHC-I
SLIDE 13
SLIDE 14
CROSS-PRESENTATION how can a DC activate a CD8 T cell response if it is not infected by a virus?
SLIDE 15
SLIDE 16
PROFESSIONAL ANTIGEN PRESENTING CELLS
SLIDE 17
Function – antigen presentation
Antigen -
SLIDE 18
SLIDE 19
SLIDE 20
Location, location, location……
http://www.youtube.com/watch?v=Kh- XdNnTZUo&feature=player_embedded
SLIDE 21
SLIDE 22
- 1st and 2nd signals for lymphocyte activation, origin of 2nd signals
SLIDE 23
- Activation of T cells
Immunological synapse
SLIDE 24
SLIDE 25
Co-stimulatory molecules family
SLIDE 26
SLIDE 27
co-stimulation B7.1/B7.2 or CD80/CD86 Stabilization of NFAT Activation of
- ther txn factors
Co-stimulation
SLIDE 28
Diehn et al, PNAS, 18, 11796 (2002)
Stabilization of NFAT signaling
SLIDE 29
Activation of other transcription factors
SLIDE 30
IL-2 and its receptor
SLIDE 31
PERIPHERAL TOLERANCE
Tolerance to self or non harmful antigens triggered in the peripheral tissues. 1 - anergy 2- apoptosis (co-stimulus induce the anti-apoptotic protein Bcl-xL) 3 – Regulatory phenotype induction – dependent on the microenvironment
SLIDE 32
REGULATORY T CELLS
TGFb, IL-10 kinurenina naturais induzidas
SLIDE 33
FUNCTION – MECHANISMS OF ACTION
EXPRESSÃO DE CITOCINAS INIBIDORAS INDUÇÃO DE MORTE CELULAR ALTERAÇÕES METABÓLICAS INDUÇÃO DE TOLERÂNCIA EM DC INIBIÇÃO DE MATURAÇÃO E FUNÇÃO MORTE POR FALTA DE IL-2 mecanismo extrínsico de CTLA4
SLIDE 34
Tregs convert ATP in adenosine – a suppressor molecule
SLIDE 35
Tregs express high levels of CD25 and quench IL-2 from the environment
SLIDE 36
Tregs limit the proliferation rate of effector T cells
https://doi.org/10.3389/fimmu.2018.02461
SLIDE 37
Oral tolerance
Tolerance to antigens acquired through the oral and digestive tract/nasal TGFb expression TGFb e IL-10 rich mucosa – Treg inducion
SLIDE 38
Indução de T reguladoras na mucosa intestinal
SLIDE 39
Células dendríticas produtoras de ácido retinóico também participam do processo de tolerância
- RAR (receptor de ácido retinóico) liga-se a elementos resposivos no promotor de genes como CCR9 garantindo a
migração de células reguladoras e linfócitos B produtores de IgA para a mucosa;
- RA induz fenótipo regulador em linfócitos T, cooperando com TGFb;