Lecture 12 9/22/23 Flashcards
What is immune tolerance?
body’s ability to recognize and tolerate its own cells/molecules while mounting immune responses against foreign/harmful substances
What does a breakdown in self tolerance result in?
autoimmune disease
What are the characteristics of central tolerance?
-established during immune cell development in primary lymphoid organs
-immature immune cells undergo selection process to eliminate cells that recognize self-antigens
What are the characteristics of peripheral tolerance?
-occurs in secondary lymphoid organs and peripheral tissues
-achieved through regulatory T cells
What is the overarching goal of Tregs?
regulate and suppress immune responses to self-antigens that escape central tolerance
What are the general properties of Tregs?
-generated by exposure to TGF-beta
-produce IL-10 and TGF-beta
-involved in immune suppression and maintenance of mucosal homeostasis
What receptors/proteins are present on the surface of Tregs?
-CD3
-CD4
-CD25
-CD39
-CD73
-PRRs
-CTLA-4
-LAG-3
-TCR
What cells are inhibited by Tregs?
-CD4 T cells
-CD8 T cells
-NK cells
-APCs
What are the mechanisms of Treg-mediated suppression?
-cell surface molecules
-immunosuppressive cytokines
-IL-2 consumption
-cytolysis
What is the function of CTLA-4 and LAG-3?
to suppress APC function and inflammatory cytokines
What is triggered by the binding of CTLA-4 to CD80 or CD86?
production of IDO by DCs, which suppressed Teff cell activity
What is the result of high expression of CD25 and high affinity of cytokine receptors?
-inhibition of Teff cell proliferation
-inhibition of IL-2 synthesis
What immunosuppressive cytokines are produced by Tregs?
-TGF-beta
-IL-10
How do TGF-beta and IL-10 function?
-prevent 1st order cytokines from activating their associated T helper cells
-promote naïve T cells to produce more Tregs
What is the result of high expression levels of CD39 and CD73 on Tregs?
production of adenosine
How does adenosine impact the immune system?
-inhibits NK cells, APCs, and active T cells
-increased number of Tregs
-increases immunosuppressive activity of Tregs
How do the immunosuppressive cytokines function in tissue repair?
they promote tissue repair and stimulate M2 macrophages
Which granules allow Tregs to kill unwanted immune cells?
-perforin
-granzymes
Which bacteria are able to activate DCs?
-Bacillus fragilis
-Clostridia
How do B. fragilis and Clostridia activate DCs?
by stimulating TGF-beta and retinoic acid production
What do TGF-beta and retinoic acid do?
promote Treg activation
Why is it important that Lactobacillus dominate the vaginal microbiome during reproductive age?
-Lactobacillus break down glycogen and produce lactic acid
-lactic acid causes acidic pH
-acidic pH inhibits growth of other bacteria and fungi and suppresses inflammatory reactions
