Hypersensitivity Flashcards
What is type 3 hypersensitivity?
Immune complex driven
If there is consistent antigen present the complexes will not be cleared away, they can become deposited in blood vessel walls ands tissues causing inflammation
What is type 4 hypersensitvity?
T cell or known as delayed type as the inflammation occurs 2-3 days after.
sensitization phase with naive t cell and dendrite cells. creating antigen specific t memory cells
Which hypersensitivity are the following?
- Skin grafts
- Glomerulonephritis
- Autoimmune hemolytic anemia
- Hives
Type 4
type 3
type 2
type 1
What are the inflammatory mediators?
Auxiliary cells: basophils, mast cells, platelets
What is an antigen?
Any molecule or molecular structure that can be recognised by an antibody or the adaptive immune system
Hence why all hypersensitivity reactions happen when the immune system is pre-sensitized and thus have existing adaptive immunological memory
What antigen do T cells recognise?
Linear epitopes in the context of MHC, epitope - region of antibody which the receptor binds to - is primary structure of protein
What dimer immunoglobulins are there?
IgA
What immunoglobulin is a pentamer?
IgM
Which immunoglobulins are isomers of eachother?
IgD
IgE
What does IgG3 activate?
Complement and Fc receptor phagocytosis
What can IgA do?
Cross mucosal epithelial
what does IgE do?
mast cell degranulation
What can a naive CD4+ T cell differentiate into after clonal expansion?
Effector CD4+ : activation of other macrophages / B cells
Memory CD4+
What can a naive CD8+ t cell differentiate into?
Effector CD8+ = CTL : Killing infected target cells / macrophage activation
Memory CD8+
What is Type I hypersensitivity known as?
Immediate
Anapylaxtic hypersensitivity
Due to provocation from re-exposure to previous antigen allergen
peanuts, timothy grass, birch trees, cats, dogs, penicillin, sulphonamides, venom, house dust mites
Examples of Type I hypersensitivity?
Asthma
Allergic rhinitis
Atopic dermatitis
What antibodies cause hypersensitivity I, why ?
IgE antibodies
Should be made in response to parasitic infection or venoms
Allergic people will produce it against environmental allergens
What is the skin prick test?
Exposing skin to small amounts of allergen can be used to diagnose allergy
Wheal and flare seen
How is IgE produced?
Type 2 helper CD4 T cells + B cell helper follicular CD4 T cells
– > act on B cells
–> B cells promote antigen specific IgE
Where do are IgEs found?
Not found circulating until stimulated
Once produced bound to surface of mast cells and basophils
Bind to their high affinity IgE Fc epsilon receptor ( Fc RI )
What happens when the IgE antibody comes into contact with an allergen?
Rapid cross-linking and degranulation of mast cells or basophils
Releases histamine
heparin
proteases
Leukotrienes and prostaglandisn to contract smooth muscles
What are the phases involved in type 1 hypersensitivity ?
Early phase : molecules produced by mast cells
Later response : recruitment of inflammatory cells
Third phase / late response : Eosinophils recruited 3-4 days later and Th2 cells present
What is Type II hypersensitivity known as?
Antibody mediated cytotoxic hypersensitivity
–> destruction of cells bound to antigens
What antibodies are involved in Type II hypersensitivity?
IgG or IgM
What are examples of type II hypersensitivity?
- Mismatched blood transfusion:
antibodies recognise different non-self, carb groups of red blood cells causing destruction and tissue damage - Haemolytic disease of newborns, maternal antibodies cross over placenta with Rh D alleles
- Immune thrombocytopenia:
Where antibodies develop against platelet surface proteins - Graves disease :
Px develop thyroid stimulating antibodies that bind the thyrotropin
In what three ways do hypersensitivity II antibodies cause disease?
Anti-receptor activity : blocking or activating its function
Antibody dependent cell - mediated cytotoxicity ADCC
Classical activation of the complement cascade
What is the complement cascade?
antibody on the surface of cells is recognised by the complement components leading to the formation of the membrane attack complex - MAC on the cell surface
Cell death occurs due to loss of osmotic integrity
What are the three types of complement?
Classical pathway : antibody antigen complexes
Lectin pathway : lectinins find PAMPS
Alternate pathway : hydrolyse pathogen surface directly
What occurs in the ADCC mechanisms for hypersensitivity 2?
Antibody-antigen complexes bound to surface of granulocytes via FC receptor
Allows lysis of target cell connected to variable region of antibody
What is the ultimate result of hypersensitivity?
Mechanisms of tissue injury allow for local or systemic inflammation, cell depletion leading to loss of function or organ function imbalance
What are immune complexes?
Non cell bound antigen-antibody complexes.
Should normally be cleared away
In what cases are immune complexes not cleared away?
What happens then?
the result of antibodies reacting against self-antigens such as nuclear DNA
the immune complexes end up being deposited in the blood vessel walls and tissues, promoting inflammation and tissue damage. This can lead to symptoms such as fever, rashes, joint pain or protein in the urine: vasculitis if deposited in blood vessels, glomerulonephritis if in the kidneys or arthritis if in the joints.
What auto-immune diseases are due to type III hypersensitivity?
Rheumatoid Arthritis
Multiple sclerosis
Systemic Lupus Erythematosus
How is serum sickness an example of type III hypersensitivity?
Not self antigens but foreign antigen:
Anti-venom given for a snake bite for example. The body may produce antibodies against the anti-venom given.
Process takes several weeks even when snake venom is gone
Why is type IV hypersensitivity also known as?
Delayed Type or T cell mediated
Because it is mediated and initiated by T cells
What sensitisation phase occurs in Type 4 hypersensitivity?
Naive T cells are presented to with antigens.
Memory T cells then respond by initiating inflammation in the future.
Why is Type 4 hypersensitivity delayed?
However because the memory T cell response (which requires recruitment and expansion) is slightly slower than antibody mediated memory there is often a delay between exposure and response, with peak responses often seen 2-3 days after inflammation.
Why is exposure to poison IVY a good example of type 4 hypersensitivity?
Exposure to a hapten - urushiol drives a T helper 1 response
Doesn’t lead to antibody production initially due to small exposure
–> re-exposure : memory cells produce IFN-gamma which is pro-inflammatory:
Activated macrophages resulting in Swelling, Oedema, blister lesions
- another example of graft rejection
Extra info?
Defination : inflammation causing pain and discomfort, ad due to a wide range of toxic molecules and proteins produced by the immune system - tissue damage which can be fatal
Half lives : IgG 1/2/4 = 23 days
IgG 3 = 8 days
mucosal transport? IgA1, IgA2, IgM
present on B cell membrane IgM
Induces mast cell degranulation IgE
IgG can cross placenta
Type II - SLE, RA, MS. SLE: px develop IgG against DNA or nucleoproteins and form persistent immune-complex deposits, Hepatitis
