Lec7 Cell Mediated Immune Response and Ag Processing Flashcards
T cell activation
- by professional antigen presenting cells [pAPC] in lymph node
- requires signal 1 and signal 2
CD4+ Cells
- secrete cytokines, provide help to other immune cells
- – secrete IFN-gamma: helps macrophages destroy pathogens
- – secrete IL4 and IL5: help B cells make antibodies
suppress responses that could lead to autoimmunity or ongoing inflammation
CD8+ Cells
- called CTLs
- kill infected cells to clear infection
- kill tumor cells
- may also kill healthy cells in autoimmune response or during transplant rejection
What types of cells can be pAPC? What do they do?
pAPC are: macrophages, activated B cells, or dendritic cells [DCs]
- process protein antigens into peptides and present them on surface with MHC
- only cells that express class I and class II
- only cells that produce both signals 1 and 2 required for naive T cell activation
What kind of cells can express class I and II MHC?
ONLY pAPC
What is unique about pAPC?
- only cells that express both class I and class II MHC
- only cells that deliver both signals 1 and 2 that are required to activate naive T cells
What are the most effective pAPCs?
Dendritic Cells – activate T cells most efficiently because have lots of co-stimulatory molec
Three antigen processing pathways
Exogenous: antigen taken from outside cell, presented by class II to effector CD4 cell
Endogenous: antigen from inside cytosol [ie replicating virus], presented by class I to effector CD8 cell
Cross-presentation: infected cell/viral antigen picked up by pAPC exogenously and goes through exogenous path, but some viral protein leaks out of endosome into cytosol and processed by endogenous path, presented by class 1 to naive CD8
Which cells express class II MHC?
Only pAPCs
How are cytosolic pathogens processed?
- Endogenous pathway
- can occur in any cell
- degraded protein in cytosol
- displays MHC class I to effecor CD8
- causes cell death
Describe the cross-presentation pathway of exogenous antigens?
- occurs in pAPC, mostly in dendritic cell
- pathogens start on exogenous path but then end up in cytosol where degraded
- displays MHC class I to Naive CD8
- can cause activation of CD8
Describe the exogenous pathway?
- occurs in pAPCs [macrophages, B cells, etc]
- pathogen degraded in endocytotic vesicle
- displays MHC class II to effector CD4
- activates macrophage killing of the bacteria or activates B cell to secrete Ig
What is the role of the adhesion molecule in Antigen recognition?
Adhesion molecule is non-specific, glues CD4 and pAPC together to allow for recognition
What are signal I and II?
Signal I: TCR binding MHC Class II
Signal II: costimulation signal
What are 2 main examples of signal II?
Signal 2 = Costimulation
- CD28 on T cell binds B7 on pAPC
- CD40 on pAPC binds CD40 Ligand [CDroL] on T cell
What is role of CD40?
It is a receptor on pAPC, binds CD40L on T cell and causes costimulation [signal 2]
What is role of B7?
It is on the surface of pAPC
- can bind CD28 for costimulation
- can bind CTLA-4 for suppresion
What is role of CD28?
It is a receptor on T cell, binds B7 on pAPC and causes costimulation [signal 2]
What is role of CTLA-4?
It is a receptor on T cell, binds B7 and suppresses costimulation
Describe signal I
T cell receptor binds MHC
MHC restriction: TCR sees self MHC and specific peptide
Describe signal II pathway
- happens in lymph node
- signal 1 causes upregulation of CD40 ligand on T cell
- CD40L binds CD40 increases expression of B7 and secretion cytokines
- B7 binds CD28
What is signal 3?
- Cytokines are secreted following signal I and 2
- type of cytokines determines type of effector cells and response that takes place
properties of cytokines
- pleotropic: multiple actions
- redundant: more than one cytokine has same function
- produced transiently in small amounts
- act locally [autocrine or paracrine]
- can be toxic [cytokine storm] at high systemic level
What determines specificity of TCR?
Alpha and beta chains
What roles does CD3 complex play in T cell activation
- CD3 complex responsible for activation signal after signal 1 and 2 received
- also acts as cell surface marker of mature T cells
What does Th1 cell secrete?
- type of CD4
- secrete IL-2 and IFN-gamma
Function of IL-2
induces T cell proliferation
Function of IFN gamma
- activates pAPC
- promotes development effector response
- helps B cells make complement fixing antibodies
What does Th2 cell secrete?
- type of CD4
- secrete IL-4 and IL-5
- involved in anti-parasitic response [helminths]
Function of IL-4
- Induces production IgE that mediate allergic response
Function of IL-5
- Activates eosinophils involved in allergic response
What do Th17 cells secrete
IL-17
Function of IL-17
- Induce inflammatory responses by activating neutrophils
- Involved in mediating autoimmune disease
What do T regulatory cells do? What do they secrete?
- secrete TGFB and IL-10, suppressive cytokines
- Prevent autoimmune response and transplant rejection
Natural T regulatory cells
- CD4/CD25/FoxP3
- secrete Il-10 and TGF-B
Tr1 cells - what do they secrete?
- abundant in gut
- secrete IL-10
Th3 cells - what do they secrete?
- abundant in gut
- secrete TGF-B
Central tolerance
- immature self-reactive T cells undergo negative selection in thymus
Peripheral tolerance
- mature self-reactive T cells that escape central tolerance undergo anergy, deletion, regulation/suppression
