Flashcards in Immunology Deck (41):
What is autoimmunity defined as?
presence of immune responses against self-tissue/cells
What is the pathogenesis of autoimmune disease?
genetic susceptibilty and then there is an initating event and there is breakdown of self tolerance (loss of immune regulation)
Give an exmple of a monogenic autoimmune disease?
What does IPEX syndrome stand for?
immune dysregulation; polyendocrinopathy; enteropathy and X-linked inheritance
When does IPEX sybdrome present?
presents early in childhood
What are the symptoms of IPEX syndrome?
severe diarrhoea; eczema; very early onset IDDM; autoimmune manifestations
What is the cure for IPEX syndrome?
haematopoeitic stem cell transplantation
What causes IPEX sydnrome?
mutation in FOXP3 gene whic his essential for the delevopment of regulatory T-cells-failure of peripheral tolerance
What is the function of regulatory T cells?
suppress autoreactive T cells
What gives rise to thte hugely diverse popultation of T cells and B cells
random rearragnemnt of Ig heavy and light chain gene segments
What are the tolerance mechanisms required for autoreactive T cells and B cells
central tolerance- removal of self-reactive lymphocytes in primary lymphoid tissues: cells in tissue that present self-antigens, if cell recognises the antigen, the cell dies
peripheral tolerance- inactivation os self-reactive lymphocytes that escape central tolerance- regulatory T cells
What is the difference between MHC and HLA?
HLA is specific to humans whereas MHC is the name across all species
What type of HLA do all nucleated cell express?
class 1: HLA-A; HLA-B;HLA-C
What HLA do specialised APCs also present on their surface?
Class 2 MHC
How many variants of each HLA molecule does each individual possess?
What are the HLA types in class 2?
HLA-DP; DLA-DQ; HLA-DR
Why do individual HLA molecules exhibit significant diversity?
to maximise the net ability to bind peptides- on a population level, to maximise ability to respond to antigens and disease
Why do some HLA molecules protect aginast autoimmune diesase whilst some predispose?
some alleles are very able to present self antigen whilst others arent good at it
What suggests that there a hormonal infleucne of lymphocytes function?
there is an lateration in the course of autoimmune diseases during pregnancy
What is molecular mimicry?
an antigen from a particular pathogen shares features with self-antigen
What is an example of molecular mimicry?
acute rheumatic fever after streptococcal infection as strep M5 protein is similar to cardiac tissue proteins
What are the potential mechanisms for autoimmune disease?
molecular mimicry; unrealted bystander activation; super-antigens; antigen sequestration
What is bystander activation?
the stimulation of unrelated (heterologous) T cells by cytokines during an Ag-specific T-cell response
What is antigen sequestration?
when the immune systerm has never seen parts of the body so if during an infection the body sees self-antigens for the first time and it reacts to it
What is a superantigen?
antigens whic hnon-speciically activate a whole range of T cells and B cells outwith the MHC binding site and fully activate the cell
What is hypersensitivity reactions?
an immune response that results in bystander damage to the self and whic his usually an exaggeration of noral immune mechanismS
What is the hypersenstivity driving SLE?
type 3 HS disease
What is hypersensitivity driving RA?
What type of antibodies are implicated in immune complex mediated reactions?
IgG or IgM
What happens during type 3 hypersensitivity?
system fails to clear the immune complexes whic hthen get trapedf in blood vessels and induce inflammation
Who gets SLE
females; second and thrid decades
What induces the formation of apoptotic bodies>
UV radiation; infection (reactive oxygen species production)
What happens to the apoptotic bodies in SLE?
altered clearance/ increased apoptosis- mutations in complemetn or macrophages
What induces production of auto-antibodies in SLE?
apoptotic bodies and not removed and they degrade releasing otential auto-antigens whic hcauses the production of AA and immune complex formation
What is the SOAP-BRAIN MD mnemonic for the symptoms of SLE?
Serositis- pleurisy; pericarditis
Oral ulcers (oral or nasopharyngeal)
Blood disorders ( leukopenia; thrombocytopenia; haemolytic anaemia)
Renal involvment- urinalysis(proteinuria or red cell casts)
Immunologic phenomena ( dsDNA; Sm; antiphopholipid antibodies)
Neurologic disorder- depression; psychosis; seizures
Discoid rash- erythematous raised rimmed lesions with keratotic scaling, often scarring
What is RA characterised by?
destruction of joint cartilage and infalmmationg of the synovium
What are the initial manifestations of RA?
stiffness; pain; swelling; erythema
What cytokines have critial roles in the pathogenesis of RA?
TNF-alpha and IL-1 and IL6
What do TNF-alpha; IL1 and IL6 do in RA?
stimulate fibroblasts; osteoclasts and chondrocytes; stimulate release of matric metalloproteinases
What is RF?
an AA directed against the common Tc region of human IgG