when the immune system goes wrong Flashcards
what is atopy
inherited tendency to make immediate hypersensitivity responses (30-50% of the population has this)
what happens in allergies
APC presents allergen to cd4-> cd4 differentiates into Th2 (triggered by IL4)-> il2,4,5,13 released-> b cells proliferate-> class switch to IgE and differentiate into plasma cell IgE binds to allergen-> mast cell degranulates-> histamine release
Allergy-related diseases and treatments
Asthma Perennial rhinitis Eczema Anaphylaxis Treatments: antihistamines/beta-2 adrenoreceptor agonist/corticosteroids/desensitisation/monoclonal antibody
What class are serum autoantibodies ? What are they used for ?
IgG
Monitor disease activity
Diagnostic tools
Predict future disease
Proof of autoimmunity
Transfer of disease by immune effectors into reciepient without disease eg placental transfer of antibodies
Clinical responsiveness to immune suppression
Graves’ disease
Usually, pituitary gland produces TSH-> thyroid produces thyroxine-> negative feedback by thyroxine prevents further TSH production
In Graves’ disease, igG autoantibodies bind to TSH receptor-> thyroid gland keeps making thyroxine in an unregulated manner -> hyperthyroidism
Myasthenia Gravis
Pt develops antibodies against ach receptor-> ach receptors at effector is damaged-> less ach receptors-> insufficient engagement between ach and ach receptors-> no/poor muscle contraction-> muscle weakness and fatigue
Why is type 1 diabetes T cell mediated
Treg fails to suppress
CD8 T cells kill beta-cells
APC presents beta-cell antigens to CD4 T cells -> differentiation into
Th1-> macrophage activation/CD8 proliferation
Th17-> epithelium and fibroblasts secrete antimicrobials/neutrophil attraction
Th2-> B cell div/class switching/plasma cell differentiation/affinity maturation/eosinophil activation
Primary vs secondary immunodeficiencies
Primary: inherited
Secondary: acquired
Examples of primary Immune deficiencies
Chronic granulomatous disease: neutrophils surround area of infection but no antimicrobial properties-> granuloma formation
SCID(secrete combined immune deficiency): no B and T cells
Di George syndrome: no thymus-> no T cells
Hypergammaglobulinemia: defect in gene encoding CD40 ligand-> Tcells and B cells cant interact-> plasma cells don’t develop, no class switch-> only igM made
What happens in AIDSD
Virus infects CD4 cells-> CD4 count falls-> CD8 increases to bring infection under control (to an extent)-> infected CD4 cells fall further
What are iatrogenic immune deficiencies? 2 examples
Immune based therapies-> secondary immune abnormalities
Eg monoclonal anti-TNFalpha therapy for rheumatoid arthritis-> opportunistic infections including mycobacterial infections
Eg monoclonal anti-IL17 therapy for psoriasis-> fungal infections
Why is there failure of immune surveillance in cancer? Treatment
PDL1 on cancer cell (Programmed death ligand-1) engages PD1-> T cell inactivated-> immune response evaded
Antibody to PD1 OR PDL1