Autoimmune Disease Flashcards
(19 cards)
Autoimmune disease
Immunological mechanisms same as normal immune response
Difference is the source of antigen - self-protein
Protein is expressed in every cell so the immune response is exaggerated
Delayed-type hypersensitivity
Cause of many organ-specific autoimmune diseases
Cell-mediated autoimmune disease
CD4+ T cells activated by self-antigens that are extracellular proteins
Peptides associate with MHCII and presented on APC surface
T cell secretes IFN-gamma
IFN-gamma activates phagocytes
Phagocytes secrete TNF-alpha, produce ROS and NO in high levels
Produces inflammation in tissue
Insulin-dependent diabetes mellitus
Multi-system metabolic disease
Results in impaired insulin production / function
Hyperglycemia (high blood glucose concentration) and ketoacidosis
(accelerated fat breakdown)
IFN-gamma secreting T-cells found around Islets of Langerhans in the pancreas
Kill insulin producing ß cells decreasing insulin production
Chronic symptoms of insulin-dependent diabetes
atherosclerosis of arteries → necrosis of organs
Damage to retina, renal glomeruli and peripheral nerves
Susceptibility factors of diabetes mellitus
95% of susceptible individuals express HLA-DR3 or DR4 - these HLA molecules preferentially present antigens to CD4+ T cells making the individual more likely to develop diabetes
Viral infections - lead to upregulation of co-stimulatory receptors expressed on APCs → antigen presentation leads to effector T cell response
Multiple sclerosis
Disease of the central nervous system
Most common in young adults
Inflammation and demyelination of nerves
Disease is characterised clinically by weakness, paralysis and ocular
symptoms
Multiple sclerosis - autoimmune mechanism
CD4+ T-cells which secrete IFN-gamma react against myelin antigens (e.g.,
myelin basic protein)
Activation of macrophages around nerves in brain and spinal cord.
Myelin activated T-cells migrate into the CNS
Encounter further myelin proteins and secrete cytokines
Recruitment of macrophages which leads to myelin destruction
MS progression
MS is a progressive disorder - when phagocytes cause tissue injury, further myelin-related proteins are released into the extracellular environment → positive feedback cycle
MS susceptibility factors
HLA-DR2
viral infection
Rheumatoid Arthritis
Disease of the joints (eg fingers, knees elbows, shoulders and ankles)
Inflammation of synovium associated with destruction of joint cartilage and
bone surrounding joints
CD4+ T-cells and macrophages have been found in inflamed synovium
Rheumatoid Arthritis - autoimmune mechanism
When CD4+ T cells and macrophages are activated, they secrete cytokines
Cytokines (eg IFN-gamma and TNF-alpha) secreted in the synovium act on
resident synovial cells that produce proteolytic enzymes (eg collagenase)
that mediate destruction of the joints
Nature of the antigen is not known - thought to be collagen but may be other self-proteins
RA susceptibility factors
HLA-DR1 and 4
viral infection
Genetic susceptibility
MHC class II gene HLA DR - different for each disease, preferentially present peptides derived from self-protein
Corresponds with the observation that CD4+ T-cells are involved in disease progression
Infections
By up regulating expression of co-stimulatory molecules on antigen presenting cells thus enhancing antigen presentation
Cell-mediated autoimmune disease
Diseases caused by T-lymphocytes
T-cell mediated cytolysis
Mechanism of T-cell mediated cytolysis
-brought about by CD8+ T cells so antigen must be intracellular
-broken down in cytosol
-associated with MHCI
-migrate to surface and present to CD8+ T cells
-when CD8+ TCR is stimulated, they undergo clonal expansion
-clones migrate to site of inflammation (i.e. site of autoimmune disease)
-CD8+ T cells come into contact with peptides expressed on tissue cells
-release perforin, forms holes in cell membrane
-release FAS ligand, inducing apoptosis
-cause tissue damage and destruction
Why T-cell mediated cytolysis happens
CD8+ cytotoxic T-cells kill virally infected cells
Virus may injure infected cells; THUS destruction of the host cell and virus is usually advantageous to the host
HOWEVER, certain viruses have no adverse effects - latent viruses cause no obvious damage → allows virus to infect every cell in a given organ
T-cells cannot discriminate between latent and destructive viruses and therefore destroy ALL infected cells
Examples of autoimmune cytolysis
Viral hepatitis
Viral myocarditis
