4.13 - Hypersensitivity Flashcards
T cell responses
- process of activation of naive T cells requires them to encounter a specific antigen, results in rapid proliferation (clonal expansion) –> effector cells and memory cells
- CD4 T cells can acquire distinct functional capacities (or helper functions) that promote distinct parts of the immune system
- e.g. cells that become Th1 cells produce molecules that promote control of intracellular pathogens
What is type I hypersensitivity?
- AKA immediate / anaphylactic hypersensitivity
- an allergic reaction provoked by re-exposure to a specific type of multivalent antigen referred to as an allergen
- multivalent antigen has multiple sites at which an antibody can attach/antigen can be produced
- type I hypersensitivity causes asthma, allergic rhinitis and atopic dermatitis
What different substances can be allergens?
- food
- plants
- animal dander
- drugs
- insect products
- all allergens have proteins/protein conjugates as part of them
What type of antibodies are type I hypersensitivity reactions mediated by?
- IgE antibodies
- non-allergic individuals predominantly only make IgE in response to parasitic reactions or very potent venoms
How can you test for allergies?
- skin prick tests - expose skin to small amounts of allergen and look for inflamed, raised tissue (AKA wheal and flare)
What factors influence the initial sensitisation of the immune response to allergens?
- genetics, age, environment
How do allergies happen immunologically?
- generation of Th2 cells and B helper follicular T cells that produce type 2 cytokines IL-4 and IL-13
- when these act on B cells, the cells switch to producing antigen specific IgE
- once IgE made, it is rapidly bound to the surface of innate immune cells like mast cells + basophils - express high affinity IgE receptor (Fc epsilon receptor I)
- if allergen encounters cell-bound IgE it results in rapid crosslinking and degranulation of mast cell/basophil
What is the end product of allergic reactions?
Release of:
- histamine
- cytokines that can recruit other cells and promote further Th2 differentiation
- prostaglandins
- highly active smooth muscle contracting molecules like leukotrienes
What are the three phases of a type I response?
- early phase - result of bioactive small molecules produced directly by mast cells, occurs within minutes of allergen exposure
- later response - often seen within few hours and is a result of recruitment of early inflammatory cells like neutrophils
- late response - often peaks 3-4 days after exposure where high frequencies of eosinophils are recruited and Th2 cells are present
What is type II hypersensitivity?
- AKA antibody mediated cytotoxic hypersensitivity
- destruction of cells by IgG/IgM antibodies bound to antigens present on the surface of the cells
What are some examples of type II hypersensitivity?
- mismatched blood transfusion - antibodies recognise different, non-self, carbohydrate groups of transfused RBCs –> destruction of those RBCs, inflammation and tissue damage
- haemolytic disease of newborns - maternal antibodies can cross placenta and destroy foetal RBCs if foetus and mother have mismatched RhD alleles
- immune thrombocytopenia - antibodies develop against platelet surface proteins
- Graves disease - patients develop thyroid stimulating antibodies that bind the thyrotropin receptor = secretion of thyroid hormones
What are two causes of type II hypersensitivity?
- exposure to a foreign antigen (e.g. some drugs can bind to surface of blood cells, or non-self antigens blood transfusion or organ transplants)
- aberrant response to a self-antigen resulting in IgGs / IgMs that recognise cell surface structures
What are three mechanisms through which IgG and IgM antibodies can cause disease?
- anti-receptor activity - blocking or activating its function
- antibody dependent cell-mediated toxicity (ADCC)
- classical activation of the complement cascade
What happens in antibody dependent cell-mediated toxicity? (ADCC)
- antibody-antigen complexes on the surface of cells are bound by Fc receptors (which bind the constant regions of IgM/IgG) expressed by cells like granulocytes and NK cells
- leads to direct lysis of target cell and release of inflammatory mediators - chemokines and cytokines
What is the classical complement cascade?
- process by which antibody on the surface of cells is recognised by complement components, leading to the formation of membrane attack complex (MAC) in cell surface, and cell death due to loss of osmotic integrity
- activation of complement cascade results in inflammation, opsonisation, recruitment and activation of immune cells