hypersensitivity lecture Flashcards
why do we have an immune system ?
- an immune system is essential in an environment where many harmful microorganisms ( pathogens ) are present
- the immune system have evolved to protect the body against these pathogens ( bacteria , fungi , virus )
what are immune system responses mediated by ?
- a variety of cells
- soluble mediators that these cells produces
what are cells of the immune system ?
phagocytes are cells that will internalise and destroy threats
- e.g. neutrophil which is the predominant white blood cell ( 70% of our white blood cell)
- lymphocytes
- auxillary cells that are involved in the inflammatory response such as mast cells , basophils - they have granules , when granules are released there are changes in blood vessels
what are phagocytes ?
phagocytes internalise antigens and pathogens and destroy them
- there are two types
1. neutrophils
2. macrophages - when that cell is in the blood it’s known as a monocyte and when it leaves the blood it’s a macrophage
e.g. monocytes and macrophages and polymorphonuclear neutrophils
what are lymphocytes ?
- we have two types of lymphocytes
- B and T lymphocytes and they have one thing in common - they both have an antigen receptor on their surface that very specifically recognise is the pathogen
- we have two types of lymphocytes because they have different functions
- B cells and T cells are responsible for specific recognition of antigen
- B cells are responsible for antibody production
what are the types of T-lymphocytes ?
. type 1 - T-helper cells ( TH-1)
cells activate macrophages
. type 2 T-helper cells ( TH-2) cells help B cells to divide differentiate and make antibody
T-helper cells produce chemical mediators and those chemical mediators acts as signals to activate or stimulate cells
. cytotoxic T cells ( CTL or Tc) destroy virally infected cells and tumour cells
. large granules lymphocytes ( NK cells ) have similar properties to cytotoxic T cells
what are mast cells ?
- type of auxillary cells of the inflammatory response
- mostly prevalent in the surface of the eye within the conjunctiva , tissues of eyelids
- responsible for generating the inflammatory response
- contain granules which contain soluble mediators of immunity
- they are also capable of synthesizing and secreting other mediators that control immune reaction
what is the main purpose if inflammation ?
the main purpose of inflammation is to attract leukocytes towards the site of infection
what is inflammation mediated by ?
- inflammation is mediated by a variety of other cells including mast cells and basophils
what are examples of chemical mediators of inflammation ?
proteins involved in complement system
what are example of chemical mediators that are involved in the development of immune response ?
- antibodies and cytokines produced by lymphocytes
what is the complement system?
- the complement system is a group of about 20 serum proteins that interact with each other and other elements of the immune system
what is the function complement system in immune response ?
- can trigger the destruction of other cells
- can break bacterial cell wall
- stimulate and enhance process of phagocytosis
- can attract those phagocytes to the site of injury or site of infection
- increased blood flow and increased vascular permeability
- release of mediators from mast cells
what is hypersensitivity ?
- if immune system becomes overreactive
what is immunodeficiency ?
- when immune system becomes deficient - vulnerable to infection
- this can happen in two ways , it can be congenital or it can be acquired
- acquired can be through a disease such as aids or steroids which can cause immunosuppression
what is autoimmunity ?
when immune system recognises our body components as foreign and triggers destruction of our normal healthy cells
what are examples of immunopathology ?
- hypersensitivity
- autoimmunity
- immunodeficiency
what is the definition of hypersensitivity ?
- hypersensitivity reactions are exaggerated or inappropriate immune responses that lead to tissue damage
- e.g. hay fever
what are the four types of hypersensitivity reaction ?
- type I, II, III and IV
- type V is an additional type that is sometimes used as a distinction from type 2 to include autoimmune mechanisms where autoantibodies bind to receptors
what are the other names of the types of hypersensitivity ?
. type I - immediate hypersensitivity reactions
. type II - antibody mediated reactions
. type III - immune complex mediated reactions
. immune complex is combination of antibody and antigen
. type IV - cell mediated reactions
what is an example of type I hypersensitivity ?
- also referred to as atopy
- triggered within minutes of exposure to a variety of environmental antigens
e. g. pollen, house dust mites, animal dander - mild ( hay fever )
- severe ( anaphylaxis )
- allergens also contribute to asthma
- strong genetic link
what is hay fever ?
- hay fever also known as ( seasonal allergic rhinitis )
- sufferers are allergic to airborne pollens and spores
- systemic disease that tends to affect mucous membrane either within the nose or the eye
- symptoms include
. sneezing
. itching of the nose and eyes
. watering of the eyes ( epiphora )
. wheezing and shortness of breath
. rhinorrhoea ( runny nose ), nasal congestion
when does hay fever mostly occur ?
- symptoms usually occur between march and September
- fungal spores are released until September
what is the main mite in house dust ?
. the dust mite is the most important allergens in house dust and mite faecal pellets are a similar size to pollen grains
. most people allergic to house dust mite faeces
. inhalation of these particles give rise to similar symptoms to hay fever but tends to be perennial which means is all year round
what is anaphylaxis ?
- is a dangerous type of allergic reaction which is most likely to be caused by particular foods (especially nuts ) , insect bites or medicines
- affects 1-3 per 10,0000 per year
- early signs : swelling and itching : the face may be flushed and wheals or hives may erupt on the skin
later signs :
- difficulty in breathing this is because the mucosa associated with the larynx is starting to swell and close airways
- swelling of the face
- loss of colour : cold and clammy as the blood pressure falls
- collapse / loss of consciousness
- emergency treatment : intramuscular injection of adrenaline ( epinephrine ) followed by iv anti-histamine and corticosteroid
what is the mechanism of type 1 hypersensitivity ?
- mast cell mediated disease
- mast cells display a high affinity receptor for IgE
- IgE is synthesised in response to certain antigens ( allergen )
- the allergen is deposited on the surface of the mucous membrane and it’s taken up and traverses through the membrane where its taken up by one of the antigen presenting cells and this is a type of phagocytic cell which is able to internalise the antigen but rather than destroy it , its role it to present antigen on surface of cell
- allergen presented to TH2 cells which provide cytokine signals to B cells to produce IgE ( antibody )
- IgE binds to mast cells
- cross linking of IgE by subsequent exposure to allergen causes mast cell degranulation
- mast cell degranulation is the major initiation of the acute allergic reaction
what are example of mast cell mediators ?
- histamine
- heparin
- these cause mucus secretion, vasodilation and oedema
what are the types of mast cell mediators ?
- mast cell mediators include pre-formed and newly formed mediators
- pre-formed mediators include : histamine , heparin and neutral protease
- newly formed mediators include leukotrienes, prostaglandin D2 and platelet activating factor
what is type II hypersensitivity ?
- antibody mediated hypersensitivity
- antibody directed against membrane and cell surface antigens ( autoantibodies)
- antigen-antibody reactions activate complement producing membrane damage
- examples include : transfusion reactions and haemolytic disease of the newborn
how do antibodies produce damage ?
- antibodies bind to cell surface
- phagocytes bind to the antibody via their Fc receptor
- phagocytosis of target cell
- antibody binding also activates complement
- trigger complement pathway where complement mediated cell lysis ( destruction of cell)
example of haemolytic disease of the newborn ?
- haemolytic means breaking down blood
- this would happen when a mother who is Rh- but the developing baby is Rh+( have antigen on there surface )
- the mother’s antibodies wont cross the placenta to start to destroy baby’s red cell
- but usually during the birth process the red cells of the baby are released into mother’s circulation
- mother’s immune system destroys Rh+
- but with the second baby who is Rh+ the mother’s antibody then are able to cross the placenta and destroys red cells of baby
- thus a child with haemolytic disease is born
what is type III hypersensitivity ?
- immune complex mediated
- immune complex is the interaction between an antigen and antibody forming immune complex
- immune complex are phagocytosed and destroyed
- excessive formation of
immune complexes so they can be pahgocytosed fast enough and are deposited in tissue
e.g. persistent low-grade infection, repeated inhalation of antigens - examples of type III hypersensitivity include :
farmers lung- where farmers are constantly inhaling hay spores and these form immune complexes with antibodies , this overloads the capacity of the phagocytic system , the immune complexes get deposited in lungs and cause breathing difficulty
- immune complex glomerulonephritis ( where immune complexes are deposited in kidney )
how can immune complexes cause damage to tissues ?
- once the immune complexes are deposited in the tissues , they can activate the complement pathway and complement leads to cell damage
- they also attract phagocytes which when they internalise the deposited immune complexes tend to release strong chemicals into tissues and causes localised tissue damage
- therefore attempted phagocytosis causes enzyme release and results in tissue damage
what are immune complexes degraded by ?
- normally degraded by phagocytosis , particularly in the liver and spleen
what does excessive immune complex formation cause ?
- results in deposition in the tissues particularly arterioles , kidney and joint
- complexes induce platelet aggregation and complement activation
what is type IV hypersensitivity ?
- delayed type hypersensitivity
- takes more than 12hrs ( typically 24-48 hours ) to develop after antigenic challenge
- examples include : contact dermatitis and tuberculin reaction
- antigens include large molecules or small molecules ( haptens ) linked to carrier molecules
what are ocular example of type IV hypersensitivity?
1- giant papillary conjunctivitis - due to deposits built up on the surface of the lens as a result of contact lenses
2- ophthalmic drug adverse reaction - px is allergic to the drug used
explain type IV mechanism?
- APC resident in the skin process antigen and migrate to regional lymph nodes where they activate TH cells ( CD4 +ve)
- sensitised T cells migrate back to the skin where they produce cytokines which attract macrophages which cause tissue damage
