4. Autoimmunity Flashcards
What is autoimmunity?
An immune response against the host due to the loss of immunological tolerance of self-antigen.
What is an autoimmune disease?
A disease caused by tissue damage or disturbed physiological responses due to an auto-immune response.
Where are the self antigens in an organ specific autoimmune disease?
One or multiple self antigens within one single organ or tissue.
Where are the antigens in a non-organ specific autoimmune disease?
Widely distributed self antigens throughout the body.
In Grave’s disease, what is the target autoantigen, and the clinical feature of the disease?
Thyroid-stimulating hormone receptor.
Hyperthyroidism.
What is the set of 6 criteria for the diagnosis of a disease as autoimmune?
Presence of autoantibodies/autoreactive T cells.
Levels of autoantibodies correlate with disease severity.
Autoantibodies/autoreactive T cells found at the site of tissue damage.
Transfer of auto-antibody or autoreactive T cells to a healthy host induces the autoimmune disease.
Clinical benefit provided by immunomodulatory therapy.
Family history.
Give a natural example where transfer of auto antibody or autoreactive T cells to a healthy host induces the autoimmune system.
IgG transfer during pregnancy and autoimmune diseases.
Explain the 2 mechanisms for tissue damage occurring in autoimmune diseases
Autoantibodies - complement activation, antibody-mediated cell cytotoxicity, neutrophil activation damage tissue.
Autoreactive T cells - cytotoxic T cells and macrophages damage tissue.
Describe how autoimmunity leads to an autoimmune disease
Breakdown of central tolerance leads to failure to delete autoreactive T cells.
Breakdown of peripheral tolerance leads to regulatory T cells (Tr e g ) defects, impaired immunomodulation and altered self-antigens .
Activation of autoreactive B cells leads to T cell-independent activation of B cells and carrier effect (complex foreign-self antigens).
Give 2 genetic factors that can trigger autoimmunity
Increased risk with an affected sibling (8X).
Increased risk with an affected identical twin (30X).
AIRE mutations (APECED syndrome) that affect central tolerance.
Autoimmune disease associated with MHC variants (HLADR3/DR4).
Give 2 environmental factors that can trigger autoimmunity
Hormones.
Infections.
Drugs.
What treatment targets the autoantibodies in an autoimmune disease?
Plasma exchange.
What treatment targets auto-reactive T cells in an autoimmune disease?
Immunosuppressive drugs.
What treatment targets tissue damage caused by an autoimmune disease?
Anti-inflammatory drugs.
What treatment targets both autoantibodies and autoreactive T cells in an autoimmune disease?
Monoclonal antibodies.
What does the drug name ending -mab indicate?
The drug is a monoclonal antibody
What 2 main disease categories are monoclonal antibodies used to treat?
Cancer.
Auto-immune conditions.
What are monoclonal antibodies?
Mono alert antibodies which bind to the same epitope and are produced from a single B-lymphocyte clone.
Give 2 ways in which monoclonal antibodies work
Binding with cell surface receptors to either activate or inhibit signalling within the cell.
Binding to induce apoptosis.
Binding with cell surface receptors to activate antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC).
Internalization (ie being taken in by the cell through the membrane) for antibodies delivering toxins into the cancer cell.
Blocking inhibitory effects on T cells thus activating T cells to help ‘kill’ the cancer cells.
What is follicular lymphoma?
Lymph node filled with small colonial B lymphocytes which retain the follicular pattern.
What is diffuse large B cell lymphoma?
Lymph node full of large colonial B lymphocytes which take over the node in a diffuse pattern (no follicles visible).
What 2 types of cells can be affect by lymphoma?
B and T cells.
What areas of the body other than lymph nodes can be affected in lymphoma?
Spleen, bone marrow, liver, skin, testes, bowel.
What are the 3 main symptoms patients may experience with lymphoma?
Drenching night sweats, fevers, weight loss.
