Hypersensitivity Flashcards
What is an antigen?
An antigen is a molecule which can be recognised by an antibody or the adaptive immune system
What is meant by hypersensitivity?
Refers to the undesirable reactions produced by the immune system, including autoimmunity and allergies
What is the name of Type 1 hypersensitivity?
Immediate hypersensitivity / anaphylactic hypersensitivity
What is type 1 hypersensitivity triggered by?
The re-exposure to a specific antigen which is referred to as an allergen
What type of antibodies are type 1 hypersensitivity reactions mediated by?
IgE antibodies
Which cytokines promote the B cell to class switch into an IgE producing cell?
IL-4 and IL-13
Which cells does IgE bind to?
Mast cells and basophils
What receptor do IgE use to bind to the mast cells?
Fc epsilon receptor 1
what happens if an allergen encounters cell bound IgE?
Rapid cross linking and degranulation of the mast cell
What is released when the mast cell degranulates?
Histamine
What affect does histamine have?
Promotes further Th2 differentiation and highly active smooth muscle contracting molecules like leukotrienes
What is the name of Type 2 hypersensitivity?
antibody mediated cytotoxic hypersensitivity
What does type 2 hypersensitivity involve?
The destruction of cells by IgG or IgM antibodies that are bound to antigens present on the surface of cells - normally healthy cells
What are examples of type 2 hypersensitivity reactions?
- Graves disease - antibodies bind to thyrotrophin receptor resulting in the over production of thyroid hormones
- Haemolytic disease of newborns - maternal antibodies can cross the placenta and destroy fetal red blood cells
- Immune thrombocytopenia - antibodies develop gainst platelets
What are the three mechanisms by which Type 2 hypersensitivity reactions can occur?
- Anti-receptor activity
- Antibody dependant cell mediated cytotoxicity
- Classical activation of the complement cascade - formation of membrane attack complexes which results in a destruction of the cells osmotic integrity and
What happens in type 3 hypersensitivity?
When immune complexes are not cleared - leads to an inflammatory response and the attraction of leukocytes
What is an immune complex?
A soluble antigen bound to antibody
What is the difference between complement activation in type 2 and type 3 hypersensitivty?
Type 2 results in small amounts of proteins generated, large amounts in type 3
What affect do C3 and C4 have in type 3 hypersensitivity?
They act as chemokines by attracting neutrophils to the side
What do neutrophils do when they arrive at the immune complex in type 3 hypersensitivity?
They degranulate and result in tissue necrosis and vasculitis
Describe serum sickness?
When a patient is biten by a snake, the venom of the snake enters into the blood stream
Patient is given anti-venom, which the patient produces antibodies against
Therefore during the second bite, immune complexes may be formed
Why is the degranulation of neutrophils so toxic to cells?
They degranulate and release oxygen radicals
What is a membrane attack complex?
When fragments of the complement system come together, they form a MAC which attaches to the cell surface membrane and this creates a channel that allows fluid to pass in and out the cell
What is a membrane attack complex?
When fragments of the complement system come together, they form a MAC which attaches to the cell surface membrane and this creates a channel that allows fluid to pass in and out the cell which disturbs the osmotic integrity of the cell = lysis
How does antibody independent cell-mediated Cytotoxicity work?
When a NK cell binds to the immune complex by recognising the Fc tail
Releases perforin which allows for the entry of granzymes and granulysin - results in cell death in an apoptotic way
What are the primary cells involved in Type 4 Hypersensitivity reactions?
T cells
Using poison ivy as an exmaple describe how type 4 hypersensitivity reactions occur?
- Skin touches poison ivy
- Antigens through epidermis and picked up by dendritic cells - they become antigen presenting
- Taken to lymph nodes, antigen presented to T cells, using MHC II
- T cell binds to MHC on DC using TCR and CD4 as well as CD28 which binds to B on DC
- DC releases cytokines which trigger the T helper cell to differentiate into Th1 effector
- Releases IFN-gamma which activates macrophages that release pro-inflammatory cytokines
What do active macrophages release?
Pro-inflammatory cytokines like TNF, IL-1 and IL-6
What cytokine does the DC release which allow the naive T cell to differentiate?
CD12
Which Interleukin has an autocrine effect?
IL-2
What does IL-2 do?
Has an autocrine effect, allows for t cell proliferation
The test for what infection is conducted via the means of a type 4 hypersensitivity reaction?
tuberculosis - positive test = raised bump due to oedema / tissue swelling initiated by pro-inflammatory cytokines
In which auto-immune disease do patients develop IgGs against DNA or proteins present in the nucleus (nucleoproteins) forming persistent immune complex deposits and a variety of pathologies?
Systemic lupus erythematosus
What symptoms can immune complexes not being efficiently cleared lead to?
Symptoms such as fever, rashes, joint pain or protein in the urine
Why do immune complexes not initiate complement cascade?
The classical pathway activation results in formation of membrane attack complex which occurs in cell wall
Whereas immune complexes are free-floating
What needs to occur before T cells can initiate type IV?
Sensitisation phase where antigen is presented to naive T cells by antigen presenting dendritic cells → results in the generation of antigen specific memory T cells
