Immunology Flashcards
What will cause autoimmune diseases?
High titres of auto-antibodies and/ or auto-reactive T cells
This leads to significant tissue/ organ damage and chronic inflammation
What is the pathogenesis of autoimmune diseases?
Genetic susceptibility
Breakdown of self-tolerance and loss of immune regulation
Activation of auto-reactive T and B cells
Hypersensitivity reactions
Autoimmune phenomena and autoimmune disease
What is immunological tolerance?
Process by which the immune system recognizes and accepts self-tissue
How does self-tolerance restrain auto-reactive lymphocytes?
Immature self-reactive lymphocytes are killed as they develop in primary lymphoid tissues
Activity of any mature self-reactive lymphocytes that escape this killing process are suppressed by specialised Tregs in peripheral tissues
What does the FOXP3 gene code for?
Essential for the development of CD4+ regulatory T cells
What is IPEX syndrome?
Mutation in FOXP3 gene leads to severe infections, intractable diarrhoea, eczema, diabetes mellitus
What is the function of MHC molecules?
T cells require proteins to be procesed and peptides derived from these to be presented to their T cell antigen receptor by MHC molecules
What MHC molecule do all nucleated cells express?
Class 1 molecules
What cells express class 2 MHC molecules?
Sepcalised antigen-presenting cells
What chomosome expresses HLA/ MHC molecules?
Chromosome 6
How does sex influence autoimmune diseases?
Different hormonal influences on lympmhocyte function in males and females
Alteration of couse of some autoimmune diseases during pregnancy
What environmental factors influence autoimmune diseases?
Molecular mimicry
Intercurrent infections
Tissue damage
Superantigens
What is molecular mimicry?
T and B cells with cross-reactive antigen-receptors are activated by non-self peptides that resemble or are identical to endogenous peptides (rheumatic fever after streptococcal infection, halothane hepatitis)
What is antigen sequestration?
Some self-antigens are hidden from the immune system because the tissues in which they are present do not comminucate with blood or lymph
Developing T and B cells whose antigen-receptors recognise these self-antigens are not deleted
Any tissue damage that releases these hidden antigens results in activation of auto-reactive T and B cells
Where can hidden antigens be found?
Testis
Eye
Brain (BBB)
What is a bacterial superantigen?
Can activate T cells non-specifically without proper antigen presentation
What bactera can present superantigens?
Staphylococcal proteins
Clostridium endotoxin
TSS
What are the innate and adaptive immune mediators of type 1 hypersensitivity?
Th2, B cells, IgE, mast cells, basophils, eosinophils
What are the innate and adaptive immune mediators of type 2 hypersensitivity?
B cells, IgG/IgM, complement, NK cells, phagocytes
What are the innate and adaptive immune mediators of type 3 hypersensitivity?
B cells, IgG, complement, neutrophils
What are the innate and adaptive immune mediators of type 4 hypersensitivity?
Th1 cells, macrophages
What are autoimmune conditions associated with type 2 hypersensitivity?
Goodpastures syndrome
Rheumatic fever
Mysathenia Gravis
What are autoimmune conditions associated with type 3 hypersensitivity?
SLE
What is the pathophysiology of type 1 hypersensitivity?
IgE formed due to prior sensitization and coats mast cells and basophils
Encouter with antigen again results in IgE mediated reaction causing degranulation of mast cells
Histamine, prostaglanding, platele-activating factor, leukotrines, heparin and tryptase are released
What are the effects of mast cell degranulation?
Increased smooth muscle contraction, peripheral vasodilation and increased vascular permability
What is the pathophysiology of type 2 hypersensitivity?
IgM and IgG bind to antigens on cells in the body mistakenly detected as foreign
Complement activation
Cellular lysis or phagocytosis: opsonization, complement mediated lysis, antibody-dependent cell-mediated cytotoxicity (NK cells)
What is the pathophysiology of type 3 hypersensitivity?
Antigen binds to IgG to form an immune complex
Immune complex deposited in tissue (blood vessels) and initiated complement cascade. This causes the release of lysosomal enzymes from neutrophils, causing cell death which leads to inflammation and vasculitis
What is the pathophysiology of type 4 hypersensitivity?
Sensitization: antigen taken up by dendritic cells where it migrates to lymph nodes and activated CD4+ and CD8+ T cellls
Eruption: repeated contact with antigen causes the secretion of cytokines by Th1 cells causing macrophage super-activation and inflammatory reaction
Can cause granuloma formation
What is myasthenia gravis?
Autoimmune neuromuscular disorder due to auto-IgG binding to ACh nicotinic receptors
What are the clinical manifestations of MG?
Initially occular muscles
Muscles of eyes, face, mouth, throat and neck
Can cause resp failure
What medications can induce MG?
Some antibioitics
Propanolol
Lithium
Magnesium
What type of hypersensitivity is MG?
Type 2
What does complement activation result in?
Formation of membrane attack compleses
Lipophilic proteins that damage cell membranes
How is MG treated?
Anti-cholinesterase agents
Immunosuppressive drugs (methotrexate, aziothprine, prednisolone)
Eculizumab (mab means monoclonoal antibody)
What is the action of eculizumab?
Inhibits cleavage of C5, preveting MAC formation
What is RA?
Systemic disease with prominent involvement of joints
Inflammatory damage in synovial membrane
Fever, leukocytosis, malaise, anorexia, hyperfibrinogenemia
What type of hypersensitivty is RA?
Type 4 - infiltration of synovium by self-reactive CD4+ T cells; secondary involvement of activated B cells and auto-antibodies
What type of CD4+ T lymphocytes are involved in RA?
Th1 and Th17
What do synovial macrophages do in RA?
Activated by immune complexes and local danger molecules to produce pro-inflammatory cytokines (TFN-alpha)
These act on synonvial fiboblasts to promote swelling and amage to soft tissue and cartialge
How is RA managed?
Decrease inflammation - prednisolone
Decrease production of auto-antibodies - imuunosuppressive agents
Diseases modifying anti-rheumatic drugs - methotrexate, ciclosporin A
Anti-TNF drugs (infliximab)
