Immunologia

1
Immunologia

• Citoquinas

2
Cytokines

• Cytokines are soluble molecules that transmit
  information between cells.
• They are released by their cells of origin in
  response to specific signals.
• They influence the response and function of their
  target cells.

3
Cytokines

• They bind to specific receptors on the target
  cell surface thereby firing a signal transduction
  pathway.
• The effect of a particular cytokine may depend on
  the state of differentiation of the target cell.

4
Nomenclature

• Cytokines
• interleukins (IL) 1 - 15
• interferons (IF) alpha, beta, gamma
• tumour necrosis factor (TNF) alpha and beta
• Colony stimulating factors (CSF)
• Transforming growth factor family (TGF)
• Other growth factors

5
Role Of Cytokines

• Immune function
• Haemopoiesis
• Inflammation

6
How immune cells communicate SOLUBLE MEDIATORS
Infection
CYTOKINES CHEMOKINES Diverse collection of
soluble proteins made by cells that affect the
behaviour of other cells. The balance level of
cytokines and chemokines secreted affects the
outcome of the response
INFLAMMATION Early events involve endothelial
cells and result in the accumulation of fluid,
plasma proteins leucocytes. Later events
involve the activation and maturation of
lymphocytes and other granulocytes.
7
How immune cells communicate CELL-CELL CONTACT
Peripheral lymphoid tissues trap
antigen-containing phagocytic cells and
concentrate cells together to promote cell-cell
contact. Cell-cell contact occurs at many stages
of immune responses.
8
Modo de Acção das citoquinas
9
Propriedades das citoquinas
10
The cytokine network.

• Cytokines have the ability to cause multiple
  effects overlapping and synergising with other
  cytokines.
• All of the presently characterised cytokines have
  a number of roles and it is now becoming clear
  that very few cytokines act optimally on their
  own.

11
The cytokine network.

• It is the synergistic action of several cytokines
  which is important.
• The biological response is the net effect of
  multiple factors.
• Redundancy more than one cytokine may exhibit
  the same biological activity.

12
Interaction with other systems

• Other mediators of inflammation e.g. prostanoids
  and leukotrienes.
• PGE2 depresses cytokine production while LTB4
  stimulates.
• Importance of link to endocrine system
  -neuroendocrine circuit
• Cortisol stimulates cytokine production and
  cytokines act to control cortisol production.

13
Detecção de citoquinas ELISA
14
Detecção de citoquinasBioensaios
Remove cytokine containing supernatant
Which cytokine?
15
Especificidade dos bioensaios
16
Actividade das citoquinas
17
Funções de algumas citoquinas (1)
18
Funções de algumas citoquinas (2)
19
Funções de algumas citoquinas (3)
20
Funções de algumas citoquinas (4)
21
As quimoquinas

• Superfamilia de pequenos polipéptidos (90-130 aa)
• Controlam
• Adesão
• Quimiotaxia
• Activação de leucócitos
• Reguladores do tráfico leucocitário
• Algumas quimoquinas envolvidas no desenvolvimento
  de tecidos não linfóides (ex coração)
• Possuem 4 residuos de cisteína posicionalmente
  conservados
• Subgrupo C-C
• Subgrupo C-X-C

22
Os receptores das quimoquinas

• 7 domínios transmembranares (serpentine
  receptors)
• Actuam através de proteínas G heterotriméricas
• Segundos mensageiros
• Ca2
• cAMP
• IP3
• Pequenas proteínas G

23
Exemplos de quimoquinas e seus receptores

• Neutrófilos
• CXCR1,CXCR2,CXCR4
• Eosinófilos
• CCR1,CCR3
• Naive T cells
• Poucos
• Activated T cells
• CCR1,CCR2,CCR3,CCR5,CXCR3,CXCR4,...

24
Familias de receptores para citoquinas
25
Subfamilias de receptores da classe I
26
Transdução de sinal através de subunidade comum
Explica Redundância Competição
27
Formas alternativas de Receptores de
interleuquinas
28
Transdução de sinal mediado por Receptores de
Citoquinas
29
(No Transcript)