hypersensitivity lecture

Question 1

why do we have an immune system ?

Answer 1

• 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 )

Question 2

what are immune system responses mediated by ?

Answer 2

• a variety of cells

- soluble mediators that these cells produces

Question 3

what are cells of the immune system ?

Answer 3

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

Question 4

what are phagocytes ?

Answer 4

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

Question 5

what are lymphocytes ?

Answer 5

• 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

Question 6

what are the types of T-lymphocytes ?

Answer 6

. 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

Question 7

what are mast cells ?

Answer 7

• 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

Question 8

what is the main purpose if inflammation ?

Answer 8

the main purpose of inflammation is to attract leukocytes towards the site of infection

Question 9

what is inflammation mediated by ?

Answer 9

• inflammation is mediated by a variety of other cells including mast cells and basophils

Question 10

what are examples of chemical mediators of inflammation ?

Answer 10

proteins involved in complement system

Question 11

what are example of chemical mediators that are involved in the development of immune response ?

Answer 11

• antibodies and cytokines produced by lymphocytes

Question 12

what is the complement system?

Answer 12

• the complement system is a group of about 20 serum proteins that interact with each other and other elements of the immune system

Question 13

what is the function complement system in immune response ?

Answer 13

• 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

Question 14

what is hypersensitivity ?

Answer 14

• if immune system becomes overreactive

Question 15

what is immunodeficiency ?

Answer 15

• 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

Question 16

what is autoimmunity ?

Answer 16

when immune system recognises our body components as foreign and triggers destruction of our normal healthy cells

Question 17

what are examples of immunopathology ?

Answer 17

• hypersensitivity
• autoimmunity
• immunodeficiency

Question 18

what is the definition of hypersensitivity ?

Answer 18

• hypersensitivity reactions are exaggerated or inappropriate immune responses that lead to tissue damage
• e.g. hay fever

Question 19

what are the four types of hypersensitivity reaction ?

Answer 19

• 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

Question 20

what are the other names of the types of hypersensitivity ?

Answer 20

. 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

Question 21

what is an example of type I hypersensitivity ?

Answer 21

• 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

Question 22

what is hay fever ?

Answer 22

• 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

Question 23

when does hay fever mostly occur ?

Answer 23

• symptoms usually occur between march and September

- fungal spores are released until September

Question 24

what is the main mite in house dust ?

Answer 24

. 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

Question 25

what is anaphylaxis ?

Answer 25

- 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

Question 26

what is the mechanism of type 1 hypersensitivity ?

Answer 26

- 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

Question 27

what are example of mast cell mediators ?

Answer 27

- histamine - heparin - these cause mucus secretion, vasodilation and oedema

Question 28

what are the types of mast cell mediators ?

Answer 28

- 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

Question 29

what is type II hypersensitivity ?

Answer 29

- 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

Question 30

how do antibodies produce damage ?

Answer 30

- 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)

Question 31

example of haemolytic disease of the newborn ?

Answer 31

- 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

Question 32

what is type III hypersensitivity ?

Answer 32

- 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 )

Question 33

how can immune complexes cause damage to tissues ?

Answer 33

- 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

Question 34

what are immune complexes degraded by ?

Answer 34

- normally degraded by phagocytosis , particularly in the liver and spleen

Question 35

what does excessive immune complex formation cause ?

Answer 35

- results in deposition in the tissues particularly arterioles , kidney and joint - complexes induce platelet aggregation and complement activation

Question 36

what is type IV hypersensitivity ?

Answer 36

- 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

Question 37

what are ocular example of type IV hypersensitivity?

Answer 37

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

Question 38

explain type IV mechanism?

Answer 38

- 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