Hypersensitivity Type 3 Flashcards
What is the basis of type 3 hypersensitivity?
Antigen-antibody complexes deposit in blood vessel walls > inflammation and tissue damage
What is type 3 hypersensitivity mediated by?
Immune complexes (aka antigen-antibody complexes)
Antibodies (immunoglobulins) are made by matured and differentiated B cells (plasma cells)
How do B cells mature?
B cells initially make IgM (secreted or attached to cell surface)
B cells encounter an antigen
Antigen binds to two B cell receptors that get cross-linked
B cell takes up antigen and digests it
Present partial antigen to T helper cell via MHC class 2 molecule
T cell receptor binds to partial antigen as well as costimulatory molecule (CD4)
B cell’s CD40 binds to T cell’s CD40 Ligand (CD40L)
T cell releases cytokines > B cell undergoes class (isotype) switching
In type 3 hypersensitivity: IgM -> IgG
What are immune complexes?
Antigen-antibody complexes where antibodies bind to free (soluble, not cell-bound) antigens
What is the main difference between type 2 and type 3 hypersensitivity?
Type 2: antibodies bind to antigens on cell surfaces
Type 3: antibodies bind to free (soluble) antigens
Type 2: complement proteins used in small amounts
Type 3: complement proteins used in large amounts (esp. C3 + C4)
Type 2: symptoms correspond to site of antibody binding and destruction of cells
Type 3: symptoms corresponds to where immune complexes are deposited, not made
What is an example of a type 3 hypersensitivity?
Systemic Lupus Erythematosus:
- IgG antibodies are specific for DNA and nucleoproteins, making them self-reactive
- Antigens of ‘self’ molecules are also referred to as autoantigens or self-antigens
- Autoantigens might be released from a damaged cell
- DNA is in a lot of cells, so this would result in many IgG-DNA autoantigen complexes
Serum sickness:
- Patient receives foreign serum -> elicits antibody response against foreign antigens
- Eg. get bitten by snake and receive serum with anti-venom antibodies
- Body generates antibodies against the anti-venom antibodies
- If person gets bitten again and receives same serum, the antibodies make immune complexes with the anti-venom antibodies (that are beig treated as the antigen)
Is there a size relevance of immune complexes?
Small complexes (fewer antigens + antibodies) are less immunogenic (less attractive to machrophages) > aren’t removed as quickly
What is the process of type 3 hypersensitivity?
Imune complexes make their way to basement membranes of various blood vessels > deposited > activate complement system > C1 binds to the immune complex > activates C2-C9 (some are cleaved upon activation) > fragments C3a, C4a, C5a > act as anaphylotoxins (cause oedema) and chemokines (recruit neutrophils) > neutrophils attempt to phagocytose the immune complex unsuccessfully, and degranulate > releases lysosomal enzymes + reactive oxygen species > inflammation + tissue necrosis > vasculitis (inflammation of blood vessels) > more cellular damage + antigen release
What are anaphylatoxins?
Molecules that increase vascular permeability
How can disease progression of type 3 hyersensitivity be tracked and why?
By measuring the amount of complement proteins in the blood over time
This is because complement proteins in type 3 hypersensitivity are used in large amounts
Where does type 3 hypersensitivity commonly take place?
Kidneys (blood is flitered) -> causes glomerulonephritis
Joints (plasma filtered to create synovial fluid) -> arthritis
