Autoimmune Disease Flashcards
(24 cards)
What causes autoimmune disease?
- A harmful immune response is directed against self proteins (self-antigens).
- Occurs due to a failure of self-tolerance.
- Immune response mechanisms are the same as in normal immunity, but target the host.
- Target proteins may be expressed throughout an organ, causing severe immune responses.
What type of immune cells typically cause autoimmune diseases?
- T-lymphocytes, specifically CD4+ T-cells, mediate most organ-specific autoimmune diseases.
- These responses are often delayed-type hypersensitivity reactions.
What are examples of self-antigens targeted in autoimmune disease?
- Insulin-dependent diabetes mellitus – insulin.
- Rheumatoid arthritis – collagen.
- Multiple sclerosis – myelin basic protein.
- Peripheral neuritis – peripheral nerve myelin.
Why are these proteins considered self-antigens?
- They are endogenous (self) proteins.
- When presented by MHC molecules, they can activate T-cells, functioning as antigens in an autoimmune context.
What is the role of CD4+ T-cells in autoimmune disease?
- CD4+ T-cells recognize self-proteins presented by MHC class II molecules on antigen-presenting cells.
- They secrete cytokines like IFN-gamma to activate macrophages and phagocytes.
- This leads to inflammation and tissue injury through release of TNF-alpha, reactive oxygen species (ROS), and nitric oxide.
What is insulin and how is it involved in Type 1 diabetes?
- Insulin is a hormone composed of 2 peptides linked by disulphide bonds.
- It’s synthesized by β-cells in the Islets of Langerhans in the pancreas.
- Regulates blood glucose by promoting uptake and storage.
- In Type 1 diabetes, insulin production is impaired due to autoimmune β-cell destruction.
What are the clinical features of insulin-dependent diabetes mellitus (Type 1)?
- Multisystem metabolic disease.
- Results in impaired insulin production / function.
- Causes hyperglycaemia (high blood glucose concentration) and ketoacidosis (accelerated fat breakdown).
- Chronic complications include atherosclerosis, retinal damage, kidney damage, and nerve damage.
- Affects about 0.2% of the population, with peak onset at age 11–12.
How do T-cells cause Type 1 diabetes?
- IFN-gamma-secreting CD4+ T-cells surround the Islets of Langerhans.
- They activate macrophages and neutrophils, which release ROS, nitric oxide, TNF-alpha, and IL-1β.
- These mediators destroy β-cells and impair insulin production.
What genetic and environmental factors increase diabetes susceptibility?
- 95% of susceptible individuals express MHC class II alleles HLA-DR3 or HLA-DR4.
- These MHC molecules preferentially present self-antigens to CD4+ T-cells.
- Viral infection increases risk by upregulating co-stimulatory receptors on antigen-presenting cells, promoting T-cell activation.
What is multiple sclerosis and how does it manifest?
- An autoimmune disease of the central nervous system.
- Most common in young adults.
- Involves inflammation and demyelination of nerves.
- Symptoms include weakness, paralysis, and visual disturbances.
What is the immune mechanism behind multiple sclerosis?
- CD4+ T-cells secrete IFN-gamma and react against myelin antigens such as myelin basic protein.
- Activate macrophages in the brain and spinal cord, leading to demyelination and inflammation.
How does multiple sclerosis become a progressive disease?
- Myelin-activated T-cells migrate into the CNS.
- Activated macrophages and neutrophils produce ROS, nitric oxide, TNF-alpha, and IL-1β.
- Phagocyte-induced tissue injury releases more myelin, further activating T-cells and creating a damaging cycle.
What genetic and environmental factors increase MS susceptibility?
- Strongly associated with MHC class II allele HLA-DR2.
- Viral infections can enhance disease by increasing co-stimulatory molecule expression on APCs.
- This promotes effector T-cell responses against self antigens.
What is rheumatoid arthritis and what tissues does it affect?
- Autoimmune disease affecting joints such as fingers, knees, elbows, shoulders, and ankles.
- Inflammation of the synovium leads to joint cartilage and bone destruction.
- One-third of patients become severely disabled within 20 years.
What is the immune mechanism behind rheumatoid arthritis?
- CD4+ T-cells and macrophages infiltrate inflamed synovium.
- These cells release IFN-gamma and TNF-alpha.
- Cytokines stimulate resident synovial cells to produce proteolytic enzymes such as collagenase, leading to tissue destruction.
What is the suspected autoantigen in rheumatoid arthritis?
- Possibly collagen, but the exact self-protein is unknown.
What genetic and environmental factors increase RA susceptibility?
- Associated with MHC class II alleles HLA-DR1 and HLA-DR4.
- Viral infections increase risk by upregulating co-stimulatory molecules on APCs.
- Enhanced antigen presentation leads to effector T-cell activation.
What are the two major contributors to autoimmune disease development?
- Genetic susceptibility: certain MHC class II alleles (e.g. HLA-DR variants) preferentially present disease-related self antigens.
- Infections: enhance co-stimulatory molecule expression and promote effector T-cell responses.
What is T-cell mediated cytolysis?
- Immune process mediated by CD8+ T-cells (cytotoxic T-lymphocytes).
- CD8+ T-cells recognize intracellular antigens presented on MHC class I molecules of infected or altered cells.
- They kill these cells directly using cytotoxic molecules.
How do CD8+ T-cells induce tissue damage?
- Upon antigen recognition, CD8+ T-cells clonally expand and migrate to inflamed tissue.
- They release perforin to create pores in target cell membranes.
- They express FAS ligand, which activates the apoptotic cascade, causing cell death and tissue injury.
How do viral infections relate to CD8+ T-cell mediated autoimmune disease?
- CD8+ cytotoxic T-cells normally kill virally infected cells.
- Some viruses, known as latent viruses, do not cause direct cellular damage but still trigger immune destruction.
- CD8+ T-cells cannot distinguish between harmful and harmless infections, so they destroy all infected cells.
What are examples of CD8+ T-cell mediated autoimmune disease?
- Viral hepatitis.
- Viral myocarditis.
- These involve destruction of host tissues due to T-cell recognition of viral antigens presented on MHC class I molecules.
How does IFN-γ support immune responses?
IFN-γ enhances macrophage activation promotes antigen presentation via MHC upregulation and supports Th1-mediated immune responses against intracellular pathogens.
What are the specific functions of IL-1?
IL-1 has two forms IL-1α and IL-1β that induce IL-2 and IL-2R expression in T cells. It also mediates local inflammation. High levels can lead to septic shock.
