Hypersensitivity Flashcards
What is hypersensitivity?
condition where normally protective immune system has harmful effects on body
What is type 1 hypersensitivity?
Mediated by specific IgE antibodies e.g. asthma, allergic rhinitis
Most diseases thought of as an allergy is likely type 1 hypersensitivity
What is type 1 hypersensitivity also know as?
Anaphylactic hypersensitivity
Wheal and Flare
How does type 1 hypersensitivity relate to allergy?
Its an allergic reaction de to re-exposure to an antigen
1st allergen exposure= sensitisation
2nd exposure = allergic reaction
How does type 1 hypersensitivity work?
- Allergens presented by B cell
- Th2 cell binds to antigen presenting cell- releases IL-4, IL-12 (cytokines)
- Plasma cells and memory cells produced
- Plasma cells can produce specific IgE
- IgE bonds to sensitized mast cells
- Mast cells secrete histamine, heparin, proteases etc. after degranulation after re-exposure to allergen- further Th2 differentiation
What are the different phases of type 1 hypersensitivity?
Early Phase: mast cells only
Later Phase: recruitment of early inflammatory cells
Late Phase: recruitment of eosinophils and Th2 cells
What is type 2 hypersensitivity?
Destruction of cells by IgG or IgM bound to cell surface antigens- inflammation and tissue damage
What can cause type 2 hypersensitivity?
Mismatching of blood transfusion, haemolytic disease of newborn, immune thrombocytopenia, grave’s disease
What is type 2 hypersensitivity also called?
Antibody- mediated cytotoxic hypersensitivity
How does type 2 hypersensitivity work?
Mechanism 1: anti-receptor activity: receptor blockage or activation
Mechanism 2: classical activation of complement cascade
Mechanism 3: antibody dependent cell mediated cytotoxicity
What is type 3 hypersensitivity?
Immune complex deposited (in cell walls and tissues) promoting inflammation and tissue damage
Attracts neutrophils which degranulate if they can’t phagocytose
What is an immune complex?
non cell bound antigen-antibody complex which is normally cleared by immune system
What is type 3 hypersensitivity also known as?
Immune complex driven disease
What are symptoms of type 3 hypersensitivity?
Rash Fever Joint Pain Vasculitis Glomerulonephritis Arthritis
What immune diseases are involved in type 3 reactions?
Rheumatoid arthritis
Multiple sclerosis
Systemic Lupus Erythematosus (SLE)- IgG’s against DNA or proteins in nucleus which form persistent immune-complex deposits
What causes type 3 hypersensitivity?
Diseases develops from autoimmune origin encounters with foreign antigens e.g. persistent infections
What is type 4 hypersensitivity?
T cell mediated
Its a delayed type hypersensitivity
Sensitisation phase needs to occur where antigen is presented to naive T cell
What is type 4 hypersensitivity also known as?
delayed type or T cell mediated hypersensitivity
How does type 4 hypersensitivity work?
Th cell binds to dendritic cell
Dendritic cell secretes IL-12 which makes Th cell into Th1 cell
Th1 cell secretes IL-2, IFN gamma- results in Th cell proliferation and macrophages
What happens in type 4 hypersensitivity on exposure to antigen?
Memory cells promote inflammation at site of exposure however there’s a delay because memory T cells respond slower
What are examples of type 4 hypersensitivity?
Contact dermatitis (e.g. in poison ivy, hapten drives TH1 response), asthma (by Th2), graft tissue rejection
What is a hapten?
Small molecule which causes an immune response when attached to larger carrier such as protein
E.g. in poison ivy expose, uruhsiol is the hapten
Through what mechanisms does an antibody result in disease in type II hypersensitivity?
Anti-receptor activity: blocking or activating its function
Antibody dependent cell-mediated cytotoxicity
Classical activation of compliment cascade
What is the result of compliment pathway activation?
Antibody on cell surface is recognised by compliment components
This leads to formation of MAC on surface of cell and cell death due to loss of osmotic integrity
Activation of compliment pathways results in inflammation, opsonisation and recruitment and activation of immune cells
What occurs in antibody dependent cell-mediated cytotoxicity?
Antibody- antigen complex on surface of cells are bound by Fc receptors expressed by cells such as granulocytes and NK cells. This leads to direct lysis of the target cell but also the release of inflammatory mediators, chemokines and cytokines
How does serum sickness cause type III hypersensitivity?
Person is bitten by snake
They may be given anti-venom
These are foreign proteins and while neutralise venom, our body creates antibodies that recognise anti-venom
If person gets bitten again antibodies will quickly recognise anti-serum and drive rapid inflammation
