How does epitope spread cause autoimmune?
Recent data in animal models of autoimmune diseases suggest that the targets of immune responses in autoimmunity do not remain fixed, but can be extended to include other epitopes on the same protein or other proteins in the same tissue, a phenomenon termed “epitope spreading.” The “epitope spreading” phenomenon also …
How does epitope spreading happen?
Abstract. Epitope spreading is a process whereby epitopes distinct from and non-cross-reactive with an inducing epitope become major targets of an ongoing immune response.
What is epitope spreading in multiple sclerosis?
By studying multiple sclerosis (MS) and its related animal model, experimental autoimmune encephalomyelitis (EAE), we have found that chronic progression of autoimmune disease is invariably linked to the development of an epitope-spreading process that manifests as a cascade of inflammatory T cell neoautoreactivities …
What initiates autoimmune disease?
On a basic level, autoimmune disease occurs because the body’s natural defenses — the immune system — attack the body’s own healthy tissue. Researchers have several ideas about why this happens. When the body senses danger from a virus or infection, the immune system kicks into gear and attacks it.
What is cryptic antigen?
D | Cryptic antigen model describing the initiation of autoimmunity by differential processing of self peptides. Following microbial infection (a) IFN-γ is secreted by both activated microbe-specific TH1 cells (b,c) and microbe-infected tissue cells (d).
What are cryptic antigens how do they contribute in the development of autoimmune diseases?
Hidden/ Cryptic Antigens Tissue damage that results in the release of hidden antigens can activate preexisting autoreactive immune cell clones resulting in autoimmune disease.
What is auto immune response?
An autoimmune disease is a condition in which your immune system mistakenly attacks your body. The immune system normally guards against germs like bacteria and viruses. When it senses these foreign invaders, it sends out an army of fighter cells to attack them.
Do antibodies have epitopes?
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The part of an antibody that binds to the epitope is called a paratope.
What is bystander activation?
Bystander activation, occurs when CD8+ T, CD4+ T, or B cells are activated in an antigen-independent manner. • In some infections, bystander activation of immune cells is beneficial for pathogen clearance. • Pathogens may trigger auto-reactive T and B cells bystander activation in autoimmune susceptible individuals.
What are hidden epitopes?
A cryptotope is an antigenic site or epitope hidden in a protein or virion by surface subunits.
What can we do about epitope spreading in autoimmune disease?
Knowledge of the pattern of epitope spreading in human autoimmune disease or transplant rejection could be used to design antigen-specific therapies that block ongoing tissue destruction or organ rejection, respectively. Alternatively, therapies could be designed to enhance the natural downregulatory mechanisms.
What are the implications of epitope spreading for immunotherapy?
Implications for immunotherapy. Substantial evidence from studies of numerous animal models and of various human diseases supports the hypothesis that tissue damage, regardless of the initiating event, can lead to epitope spreading, which can then contribute to ongoing disease.
Can a persistent virus infection lead to autoimmunity via epitope spreading?
The first description that a persistent virus infection can lead to autoimmunity via epitope spreading. Katz-Levy, Y. et al. Temporal development of autoreactive TH1 responses and endogenous antigen presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus-infected mice. J. Immunol. 165, 5304–5314 (2000).
Is epitope spreading “protective”?
In certain situations, however, epitope spreading has been found to be “protective” or “disease-regulating”. Studies of experimental models have revealed a “window” of therapeutic opportunity in the face of disease-propagating epitope spreading.