Regulation of immunity 2 Flashcards
What is immune tolerance?
A state of unresponsiveness of the immune system to specific antigens, immune tolerance usually occurs to prevent immune attacks against self-tissues
What are the two main types of immune tolerance?
Central tolerance and peripheral tolerance
Where does central tolerance occur for T cells?
In the thymus during T cell development
Where does central tolerance occur for B cells?
In the bone marrow during B cell development
What is the role of AIRE in central tolerance for T cells?
AIRE facilitates the expression of peripheral tissue antigens in the thymus for negative selection of self-reactive T cells
What is clonal deletion in central tolerance?
The process where self-reactive T or B cells are eliminated through apoptosis during development
What is receptor editing in central tolerance for B cells?
A mechanism where B cells rearrange their immunoglobulin genes to generate a new non-self-reactive B cell receptor
What is clonal anergy?
A state of functional unresponsiveness in T or B cells that recognize self-antigens without co-stimulatory signals
What is clonal ignorance?
When self-reactive T or B cells ignore antigens in immune-privileged sites such as the brain or the eye
What is peripheral tolerance?
Mechanisms that regulate immune responses to self-antigens in peripheral tissues
What are T regulatory cells (Tregs)?
CD4+ T cells that suppress immune responses and maintain self-tolerance
What are the two main types of Tregs?
Thymus-derived Tregs (nTregs) and peripheral-induced Tregs (pTregs or iTregs)
What cytokines are critical for Treg function?
TGF-beta and IL-10
How do Tregs suppress immune responses?
Through secretion of suppressive cytokines like IL-10 and TGF-beta and by directly interacting with antigen-presenting cells and effector T cells
What is activation-induced cell death (AICD)?
A process where persistent antigen exposure induces apoptosis in activated T cells through Fas-FasL interactions
What is immune deviation?
A mechanism where the immune system shifts responses to reduce tissue damage, such as shifting from Th1 to Th2 responses
How does the CTLA-4 receptor regulate T cell activation?
CTLA-4 competes with CD28 for B7 ligands on APCs to deliver inhibitory signals to T cells
What is the role of PD-1 in immune regulation?
PD-1 inhibits signals from TCR and CD28 in already activated T cells to limit immune responses
What is the function of inhibitory receptors like CD22 and FcγRIIb on B cells?
They dampen activation signals to prevent inappropriate responses to self-antigens
What is the role of IL-2 in Tregs?
IL-2 is required for the differentiation, survival, and functional competence of Tregs
What happens when self-reactive T or B cells encounter antigens in immune-privileged sites?
They are either ignored, suppressed by inhibitory molecules, or undergo apoptosis
What are some diseases caused by failed central tolerance?
APECED (T cell failure due to AIRE mutation) and SLE (B cell failure in receptor editing)
What are some diseases caused by failed peripheral tolerance?
IPEX syndrome (defective Tregs due to FOXP3 mutation) and rheumatoid arthritis (failure of B cell anergy)
What are the therapeutic applications of immune tolerance mechanisms?
Autoimmune disease treatments, cancer immunotherapy, and transplantation tolerance
What are the key cytokines for maintaining immune homeostasis?
IL-10 and TGF-beta
How does chronic weak signaling lead to B cell anergy?
Chronic signaling without co-stimulatory signals reduces IgM expression and impairs BCR signaling, leading to apoptosis
How do inhibitory receptors like PD-1 and CTLA-4 contribute to tolerance?
They block T cell activation and maintain immune regulation by preventing overactivation
What is the role of TGF-beta in inflammation and tolerance?
It induces Tregs and regulates inflammation by suppressing Th1 and Th2 responses while promoting Th17 differentiation during infection
