ALS5: Hypersensitivity Flashcards
Hypersensitivity occurs when the immune system…?
over-or inappropriately reacts
Name the 5 classes of antibodies
IgG IgD IgE IgA IgM
What structure does IgA have?
It’s a dimer (2 antibodies joined by a J chain)
What structure does IgM have?
It’s a pentamer (5 antibodies in a cyclical structure with a J chain)
Very briefly outline T cell responses
Encounter specific antigen
Results in clonal expansion
Results in both effector cells and memory cells
What is Type I hypersensitivity?
Allergic reaction provoked by re-exposure to specific antigen called allergen
What does type I hypersensitivity include?
asthma, allergic rhinitis, atopic dermatitis
What is type I hypersensitivity mediated by?
antigen specific IgE antibodies
What do people with allergies produce?
Antibodies against common multivalent environmental pathogens
What are skin prick tests?
tests where skin is exposed to small amounts of allergen, often used to diagnose allergies
How can type I hypersensitivity occur?
Generation of type 2 helper CD4 T Cells and B cell helper follicular CD4 T cells.
These produce type 2 cytokines IL-4 and IL-13
When these act on B cells they can promote B cell to switch to producing antigen specific IgE
What happens to IgE once it’s produced in type I hypersensitivity?
IgE is rapidly bound to surface of innate immune cells, especially mast cells and basophils. These granulocytic cells express a high affinity IgE receptor, Fc epsilon receptor I.
What happens if an allergen is encountered by cell bound IgE?
Results in rapid cross-linking and degranulation of mast cell or basophil
What is the end product of these type I hypersensitivity reactions?
Release of histamine, a host of cytokines that recruit other cells and promote further Th2 (T helper cell type 2) differentiation, and highly active smooth muscle contracting molecules such as leukotrienes and prostaglandins.
What are the ‘phases’ of type I hypersensitivity response?
Early phase = result of bioactive small molecules produced directly by mast cells, occurs within mins of allergen exposure
Within few hours = recruitment of early inflammatory cells such as neutrophils
Late response = peaking at 3-4 days after exposure where high frequency of eosinophils are recruited and Th2 cells are present
What is Type II hypersensitivity?
antibody-mediated cytotoxic hypersensitivity - involves destruction of cells by IgG or IgM antibody bound to antigens present on cell surfaces.
What examples are there of type II hypersensitivity?
- Mismatched blood in blood transfusion –> antibodies recognise non-self antigens in transfused blood resulting in immune induced destruction of RBCs, inflammation and tissue damage.
- Haemolytic disease of newborn
- Immune thromobocytopenia
- Graves’ disease
What can type II sensitization involve?
Either exposure to a foreign antigen or aberrant response to self-antigen resulting in IgGs or IgMs that recognise cell surface structures.
How can IgGs and IgMs lead to disease?
- Anti-receptor activity - blocking or activating its function
- Antibody dependent cell-mediated cytotoxicity (ADCC)
- Classical activation of complement cascade
What is the complement cascade?
A complex process which antibody on the surface of cells is recognised by complement components, ultimately leading to formation of membrane attack complex in surface of cell and cell death due to loss of osmotic integrity.
What else can activation of the complement cascade result in?
Inflammation
Opsonisation
Recruitment and activation of immune cells
What happens in antibody dependent cell-mediated cytotoxicity?
Antibody-antigen complexes on surface of cells are bound by Fc receptors (which bind constant tail regions of IgM and IgG antibodies) expressed by cells such as granulocytes and NK cells lead to direct lysis of target cell, but also release of inflammatory mediators, chemokines and cytokines.
What multiple mechanisms of tissue injury can type II hypersensitivity result in?
Local or systemic inflammation
Cell depletion leading to loss of function or imbalance in organ function
What is type III hypersensitivity sometimes known as?
immune complex driven diseases
