Immune Recognition and Immune Tolerance Flashcards
Definition of immune tolerance
Prevents auto reactivity but permits appropriate anti pathogenic responses
Definition of thyme education
T cells learn how to work in the thymus and start to differentiate
Definition of anergy
T cell remains in circulation but is unresponsive to future stimulation
Why is the recognition of self and non self important
Prevents autoreactivity, allow appropriate responses
Random TCR diversity makes self reactivity
Where does thymic education
- occur
- how does thymic education start
- function?
Location
-thymus, precursors seeded by BM and trained by specialist cells
Function
- express functional TCRs, CD4/8
- learn how to use TCRs safely
Describe Stage 1
- function
- conditions to pass
- consequences of failing
Function
-TCR genes rearranged and paired => functional ab
Conditions
- Functional receptor
- Both CD4/8 expressed
Failure
-Apoptosis
Describe Stage 2
- function
- location
- conditions to pass
- consequences of failing
Function
-Positive weak selection for self MHC
Location
-Thymic cortex
Conditions
- Weak MHC I affinity => CD4 lost
- Weak MHC II affinity => CD8 lost
Failure
-No affinity => apoptosis
Describe Stage 3
- function
- location
- conditions to pass
- consequences of failing
Function
-Negative selection to eliminate high affinity self reactive TCRs
Location
-TMECs
Conditions
-Low/moderate affinity for self MHCs (TRA)
=> enter circulation
Failure
-High affinity => activation induced death
Describe the importance of TRAs
What are the consequences of non functional TRAs
Transcription factors => express exotic TRAs
Failure to express => autoimmune diseases (APS Type 1)
What TRAs represent these organs
- liver
- pancreas
- islets of langerhans
- eye
- thyroid
Liver
-serum amyloid p
Pancreas
-trypsin
Islets of Langerhans
-insulin
Eye
-crystallin
Thyroid
-thyroglobulin
What is anergy
Describe the process
Why is this important
APC loses costimulatory molecule when constantly exposed to same self antigen
TCR, MHC binds => S2 lost =>T cell loses con stimulatory molecule
Allows for tolerance against
- self antigens not represented in thymus
- food antigens/commensal bacteria
What is the function of Tregs
What happens when Tregs are non functional
What are the 2 types of Treg and their differences
Alter effector T cell/APC function
Lack of nTreg => autoimmunity (IPEX)
nTreg
- produced in thymus
- respond to self antigens
Adaptive Tregs
- develop in periphery
- respond to food antigens
In what 2 situations would you benefit from Treg suppression
Vaccination
Antitumour responses
Describe the role of APCs in an immune response
PAMPs, DAMPs recognized by tissue dwelling APCs via PRRs => lead to activation
What happens after APC activation
How do lymphocytes get involved?
APCs move from tissue => lymph node and secrete cytokines/chemokines
Results in up regulation of adhesion molecules on high endothelial venules that line arterioles entering lymph nodes
Leads to increased migration of naive T cells => node
Increased size, cellularity of nodes, signals causing T cell exit blocked
Describe the response of CD4/8 after interacting with APCs
S1 between TCR and MHC
S2 between APC CD86 and T cell CD28
S3 cytokines => maturation of naive cells
Th1
- triggered
- secretes
- pathogens
Triggered
-IL12
Secretes
-IFNy, IL2
Pathogens
-intracellular
Th2
- triggered
- secretes
- pathogens
Triggered
-IL4
Secretes
-IL4, 13
Pathogens
-extracellular parasites
Th17
- triggered
- secretes
- pathogens
Triggered
-IL6, TGFb
Secretes
-IL17, 21, 22
Pathogens
-extracellular bacteria
Treg
- triggered
- secretes
Triggered
-IL2, TGFb
Secretes
-TGFb, IL10
CD8
- triggered
- secretes
- action
Triggered
-IFNy, IL2
Secretes
-granzymes, perforin
Action
- cytokine release
- proliferation
How does the no of T cells in serum change during the course of an infection
- No of T cells low in nodes
- Cells sequestered into nodes => differentiate and proliferate
- Burst out of lymph node => migrate to infection site with increased no, effector function
How do T cells enter the bloodstream
Enter tissues when inflamed vessels encountered
If APCs with complementary MHC encountered => effector function
If APCs with complementary MHC not encountered => return to lymph nodes
What happens after the pathogen is cleared
Inflammation removed => innate system deactivated
Most effectors => death by neglect/cytokine starvation, removed by macrophages
Some remain as memory cells
What are the properties and the location of
- B memory
- T memory
- plasma cells
B memory
- Spleen
- develop into plasma cells
T memory
- Lymph node
- immediate effector function
Plasma cells
- Bone marrow
- secrete AB
