Regulation of Immune Response Flashcards
What is immune tolerance + 3 things its important for
A state of immune non responsiveness towards an antigen
- Avoiding rxns to self antigens
- minimizing tissue damage
- minimizing immune rxns
Where does t cell negative selection take place
occurs in the thymus to self antigens loaded on MHC
what are the 3 outcomes of t cell negative selection
weak binding- thymocyte survives
moderate binding- t cell may undergo apoptosis/ transform into nTreg cells
Strong binding- apoptosis
Where does b cell negative selection take place
Takes place in bone marrow, does not require MHC
rxn with self antigens
What are the 3 outcomes of b cell negative selection
no self rxn- migrate to periphery
multivalent self- cross linked to 2 b cell receptors- clonal deletion or receptor editing
Non cross linking (low affinity)- migrates to periphery as anergic or clonally ignorant (can respond to other antigens but not self)
What is the main method of central immune tolerance
Negative selection of t or b cells
What is costim blockage
when a tell attempts to interact with a non activated APC the t cell doesn’t receive all necessary signals and may undergo apoptotic death/anergic etc)
When an APC is not activated what inhibitor costim can it express
CTLA-4
-inhibitory to t cells
How are Treg cells created
during neg selection T cells may bind with moderate activity to self antigens and may survive to become ntregs
What is the function of naturel T reg cells
Patrol body to find self epitope and if they do they exert regulatory functions to minimize response to self antigens in the periphery
What do induced T reg cells do + are specific for
made in peripheral lymphoid organs
- typically specific for non self antigens and are important for control of inflammatory responses
What do t reg cells release and what do they do (2)
- Immunosuppressive cytokines (IL10, TGFB)
2. Cytotoxic molecules (perforin, granzyme)- to attack t cells that are attacking self
How does IL10 work and what does it attach to
Binds to IL 10 receptors on immune cells/tissues
- impairs expression of pro inflammatory cytokine genes
- down regulates MHC class II expression + co stim molecules
What can TGFb do
can impair th1, th2 and b cell activation
how are tolerogenic Dendritic cells made
Tregs induce dendritic cells to become tolerogenic
What are the differences with tolerogenic DCs (4)
- Display lower expression of costims
- Maturation resistance
- Inhibit activity of effector t cells in periphery
- secrete immunomodulatory molecules (IL10, IDO)
What can Tregs do to ATP
has cell surface enzymes that hydrolyze extracellular ATP to free adenosine
-adenosine inhibits the effector functions of various immune cell pops
what is an example of a myeloid derived suppressor cell
M2 macrophages
What are the main targets of myeloid derived suppressor cells and what do they release (3)
t cells are main target
-immune suppression by releasing TGFb, IL10, IDO
How are t cells killed off after completing immune response
Fas on activated t cells bind to FasL on activated CTLs (leads to death by apoptosis via caspases)
What are immune privillaged sites and why are they
less subject to immune responses and attack (brain, eyes, testes, overy, placenta)
-rich in anti-inflammatory cytokines and high amounts of FasL
What is immune deviation and an example of where it can happen and why
Shift in immune responses usually involving Th1/Th2 cells
-during pregnancy
Why is placenta immune privaleged (5)
- lack MHC1/2
- expresses HLA-G (prevents NK cells)
- expresses IDO
- immune deviation
- TGFb and IL10
What is oral tolerance and what does it activate
peripheral tolerate induced by antigens given by mouth and exposed to gut mucosa
-may activate iTreg
What is an underdeveloped oral tolerate associated w/
food allergy
