Epitope Spreading in Autoimmunity Flashcards
describe a process known as epitope spreading in the context of autoimmune and virus-induced tissue immunopathology
Primary Epitope Presentation (a): The process begins with the presentation of the primary epitope, which could be a self-antigen (in autoimmune diseases) or a viral antigen. This presentation occurs in peripheral lymphoid tissue, where immune cells, particularly T cells, are activated.
Activation and Differentiation of Autoreactive TH1 Cells (b): The activated T helper 1 (TH1) cells are specific to the presented epitope. TH1 cells are a subtype of T cells that play a key role in cell-mediated immune responses.
Migration of TH1 Cells (c): The activated TH1 cells migrate from the lymphoid tissue to the target tissue where the antigen was presented.
Encounter with Antigen in Target Tissue (d): In the target tissue, the TH1 cells encounter antigen-presenting cells (APCs), which present the antigen to the T cells.
Antigen Restimulation and Release of Chemokines/Cytokines (e): Upon restimulation with the antigen, the TH1 cells release a cascade of chemokines and cytokines. These signaling molecules play a role in immune cell recruitment and activation.
Recruitment of Mononuclear Phagocytes (f): The released chemokines and cytokines attract additional mononuclear phagocytes from the peripheral blood. These cells, along with resident APCs, become activated.
Bystander Tissue Destruction (g): The activated mononuclear cells lead to tissue destruction through various mechanisms, including phagocytosis and the release of inflammatory molecules such as tumor necrosis factor (TNF-α), proteolytic enzymes, nitric oxide (NO), and oxygen radicals.
Tissue Debris Processing and Epitope Presentation (h, i): The tissue debris is processed and presented by resident and peripheral APCs. This leads to the activation and differentiation of a second wave of TH1 cells.
Activation of Second Wave of TH1 Cells (j): The second wave of TH1 cells is now activated and differentiated, and they can re-enter the tissue, perpetuating the cycle and causing additional tissue destruction.
This process describes a feedback loop where the initial immune response to a primary epitope leads to further waves of immune cell activation and tissue destruction, creating a cycle of chronic inflammation and autoimmune pathology.
