Tolerance and Auto-Immunity Flashcards
Self tolerance
Failure to react against own cells and their components/products
Antigen receptor rearrangement in adaptive immune cells (B and T cells) can result in what?
Some cells recognize self-epitopes, creating potential for auto-reactivity
These self-reactive cells need to be dealt with so they don’t cause autoimmune disease
Immune system balance
Key to functional immune system
Too much reactivity: autoimmune disease, chronic inflammation
Too much tolerance: immunodeficiency, persistent/overwhelming infection
Negative selection
Thymic destruction of self-reactive T cells: strong TCR signaling in response to self-antigen results in apoptosis
Immunologically privileged sites
Tissues that have barriers that normally prevent immune cells from entering
Brain, eye, testes, uterus
AIRE
Autoimmune regulator
Enables central tolerance to tissue-restricted antigens
Under control of AIRE protein, thymic medullary cells express tissue-specific proteins, deleting tissue-reactive T cells
Transcription factor expressed by T regulatory cells
FoxP3
CD4 T cells with strong reactivity to self can become what type of T cells?
T regulatory cells
Function of T regulatory cells
Suppression of peripheral immune responses
Mechanisms of T regulatory suppression
Production of immunosuppressive cytokines
Outcompete effector T cells for IL2, inhibiting their expansion
Interfere with ability of antigen presenting cells to provide activating signals
Peripheral (outside of bone marrow and thymus) mechanisms to control self-reactive T cells
Apoptosis, anergy, regulation
Anergy of T cells
Functional unresponsiveness: diminished ability to divide, produce cytokines, kill target cells
Induced by APCs presenting self-antigen to T cells in absence of inflammation through T cell receptor only, causing anergic tolerance of self-reactive T cells
Tolerance failure of B cells
Auto-antibodies, those directed against self, can result in autoimmune disease
Central tolerance mechanisms of B cells
Death of self-reactive cells
Induction of anergy
Receptor editing: B cell continues light chain rearrangement, producing new BCR
Peripheral tolerance mechanisms of B cells
Induced to die
Become anergic in spleen
B cells that have undergone somatic hypermutation can be tested for auto-reactivity again: those that remain self-reactive undergo apoptosis