Hypersensitivity Flashcards
what is hypersensitivity
immune mediated disease caused by inflammation & not by infection
what type of environment is the immune system essential
where many harmful microorganisms/pathogens are present
what has the immune system evolved to protect the body against
pathogens:
- viruses
- bacteria
- fungi
- parasites
what are immune responses mediated by
- a variety of cells
- soluble mediators that these cells produce
when can the immune system cause harm
- when it is absent of suppressed, so the body is open to opportunistic infections which lead to immunodeficiency i.e. an immune deficient disease such as AIDS
or - when the immune system responds in a very aggressive way in trying to alleviate the damage that he pathogen or other antigen causes, so the immune system does harm to our bodies
what are the components of the immune system as mixture of
chemicals and cells
name the two types of leukocytes which act as components of the immune system
lymphocytes & phagocytes
what are the lymphocyte components of the immune system
B cell
T cell
large granular lymphocyte LGL
what soluble mediator do B cells produce
antibodies
what soluble mediator do T cells produce
cytokines
what soluble mediator do large granular lymphocytes produce
cytokines
what are large granular lymphocytes also known as, and what are they involved in
natural killer cells
involved in defence against viruses
what are the phagocyte components of the immune system
mononuclear phagocyte
neutrophil
eosinophil
what soluble mediators do mononuclear phagocytes produce
- cytokines
- complement
how do mononuclear phagocytes work
engulf antigens & sometimes destroy them
or
sometimes act as antigen presenting cells
how many % of leukocytes do neutrophils account for
70%
what property do neutrophils have
they are principle white cells of the blood, and also have a phagocytic property
where can neutrophils exist
they can exists within the blood, but can also leave blood & enter the tissues & phagocytose within the tissues
what are all the possible soluble mediators
- antibodies
- cytokines
- inflammatory mediators
what are the two granulocytes
eosinophils
basophils
what are the auxiliary cells - components of the immune system
basophils
mast cells
platelets
what do the auxiliary cells - basophils, mast cells and platelets form
inflammatory mediators
what are T cells responsible for
cell mediator immunity
what type of mechanism are phagocytes a part of
innate defence mechanism
how do phagocytes destroy antigens and pathogens
by internalising them, and in order to destroy the engulfed particles, phagocytes have strong enzymes which if released to tissue can damage
give examples of phagocytes which internalise the antigens and pathogens and destroy them
monocytes (and macrophages) and polymorphonuclear neutrophils
what are the body’s first line of defence
barriers of our immune system within the body e.g. mucosal or skin barrier
what is the first defence of our body once a pathogen or antigen has passed the barriers of our immune system
phagocytes
what are B cells and T cells responsible for
recognition/detection of antigen
what are B cells/lymphocytes responsible for
antibody production
what do T helper cells produce
cytokines
what are cytokines
chemicals which regulate the immune system
what do type 1 T-helper cells (TH-1) cells do
activate/control macrophages
hat do TH-2 cells do
help B cells to divide and differentiate and make antibodies as well as produce cytokines
what do cytotoxic T cells (CTL or Tc) do
destroy virally infected cells and tumour cells
how do cytotoxic T cells (CTL or Tc) destroy virally infected cells and tumour cells
by recognising them via a mechanism and triggers a process of apoptosis and the cell dies
what do large granular lymphocytes (NK cells) have similar properties to and what are those properties
cytotoxic T cells
destroy virally infected cells and tumour cells
what do auxillary cells control
inflammation
what is the main purpose of inflammation
to attract leukocytes towards the site of infection
what is inflammation mediated by
a variety of other cells including mast cells and basophils
what do mast cells and basophils contain
granules
what do granules contain
soluble mediators of immunity
what are mast cells and basophils also capable of synthesising and secreting apart from soluble mediators of immunity
other mediators that control immune reactions
what do mast cells contain
histamine
what happens to blood vessels when histamine is released
dilate and become leaky
what is histamine
an inflammatory mediator which acts upon blood vessels
what are the variety of chemical mediators which are involved in the development of immune responses
- antibodies and cytokines - produced by lymphocytes
- other serum proteins e.g. complement
what is opsonisation
process which acts in conjunction with antibodies which facilitates phagocytosis
how do some complement destroy bacteria
through process of lysis
what is the complement system a group of
about 20 serum proteins that interact with each other and other elements of the immune system
list the functions of the complement system
- opsonisation of microorganisms e.g. bacteria
- attraction of phagocytes
- increased blood flow and increased vascular permeability
- damage to cell membranes
- release of mediators from mast cells
what does immune homeostasis require
a balance between:
- immunodeficiency (hypo-reactivity)
&
- immunopathology (hyperactivity)
what is immunodeficiency (hypo-reactivity) of the immune system, and give examples
suppressing of immune system which dampens down i.e. it is a poorly acting immune system e.g.
- neutrophil disorders
- antibody deficiency
- complement deficiency
- T-cell dysfunction
what is immunopathology (hyperactivity) of the immune system, and give examples
immune system responds in too much of an aggressive manner e.g.
- autoimmunity organ specific
- allergies and asthma
- pathogen induced pathology
what types of immunodeficiency can there be
- congenital - born with immunodeficient immune system
- mostly acquired, mainly through organ transplants where strong drugs suppress the immune system or by diseases such as AIDS caused by a virus
what are hypersensitivity reactions
exaggerated or inappropriate immune responses that lead to tissue damage, can be mild or life threatening
what are the four types of hypersensitivity reaction recognised by Coombs and Gel 1963
type 1
type 2
type 3
type 4
what type of hypersensitivity are the most common
type 1 mediated reactions
briefly list the type of reaction associated with each type of hypersensitivity
type 1 - immediate hypersensitivity reaction
type 2 - antibody mediated reactions
type 3 - immune complex mediated reactions
type 4 - cell mediated reactions
how long does it take for a type 1 hypersensitivity to occur
within minutes of exposure
what is another word for type 1 hypersensitivity
atopy
what causes type 1 hypersensitivity
exposure to a variety of environmental antigens e.g. - pollen - house dust mite - animal dander all termed allergens - mild hay fever (strong genetic link) - severe anaphylaxis - allergens also contribute to asthma
what is the meaning of an allergen
something that causes an allergy
what is another word for hay fever
seasonal allergic rhinitis
what are hay fever sufferers allergic to
airborne pollens ans spores
what are the symptoms of hay fever
- sneezing
- rhinorrhoea (runny nose), nasal congestion
- itching of the nose and eyes
- watering of the eyes
- wheezing and shortness of breathing
when do symptoms of hay fever usually occur
between march and September
when is tree pollen released and how many % does it affect
from march to may - spring affects 25% of sufferers
when is grass pollen released and how many % does if affect
from may to late July - affects 90% of sufferers
when is fungal spores released
until September
what is the most important allergen in ‘house dust’
dust mite
what causes the allergy from the dust mite
mite faecal pellets is what causes the allergy as they are similar size to pollen grains so give rise to similar symptoms to hay fever
which period do dust mites cause allergy symptoms
all year round
how severe is an anaphylaxis allergic reaction and what can it be caused by
very dangerous - life threatening
caused by particular foods especially nuts, insect bites or medicines
how many of the population does anaphylaxis affect
1-3 per 10,0000 per year (rare)
what are the early signs of an anaphylaxis allergic reaction
swelling and itching, the face may be flushed and wheals or hives (urticaria) bumps may erupt on the skin
what are the later signs of an anaphylaxis allergic reaction
- swelling of the face
- difficulty breathing and wheezing due to laryngeal oedema (mucous membrane swell & airways gets blocked) or asthma
- loss of colour, cold and clammy as blood pressure falls
- collapse/loss of consciousness
what is the emergency treatment for anaphylaxis
intramuscular pre loaded injection of adrenaline (epinephrine) followed by iv drip when they reach hospital of anti-histamine and corticosteroids
what happens when someone encounters the allergen for the first time
they have no signs and symptoms at all
what is type 1 hypersensitivity mediated by
mast cells
what do mast cells display a high affinity receptor for
IgE
what is IgE synthesised in response to
certain antigens (allergens)
when allergens are deposited on the mucous membranes, what are they taken up by
taken up and processed by antigen presenting cells (e.g. dendritic cells or B cells)
once the allergen is taken up by antigen presenting cells, what are they presented to
presented through an MHC receptor to TH2 cells which provide cytokine signals to (activate) B cells to produce IgE which binds to mast cells
what is IgE
an antibody which is unusual, so if your allergic to something, you produce IgE
what does cross linking of IgE by subsequent exposure to allergen (after the 2nd time) cause
calcium influx or cells and starts a mast cell degranulation
what receptors do mast cells have
Fc receptors
what is mast cell degranulation the major initiation of
the acute allergic reaction
name some mast cell mediators
- histamine
- heparin
and other factors
what do the mast cell mediators, histamine and heparin cause
- mucus secretion
- vasodilation
- oedema
describe the whole type 1 mechanism
- mast cells display a high affinity receptor for IgE
- IgE is synthesised in response to certain antigens (allergens)
- allergens are deposited on mucous membranes and taken up and processed by antigen presenting cells (e.g. dendritic cells or B cells)
- allergen presenting to TH2 cells which provide cytosine signals to B cells to produce IgE Ig E 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
- mast cell mediators include, histamine, heparin and other factors
- these causes, mucus secretion, vasodilation and oedema
what two types of mediators do mast cells include
pre formed & newly formed mediators
name some pre formed mast cell mediators
- histamine
- heparin
- neutral protease
name some newly formed mediators
- leukotrienes
- prostaglandin D2
- platelet activating factor
what does the degranulation of the mast cell cause
the allergy
what is hay fever and anaphylaxis due to
the mast cell mediators
what is type 2 hypersensitivity mediated by
antibody mediated response/hypersensitivity
in type 2 hypersensitivity, what is the antibody directed against
membrane and cell surface antigens (autoantibodies) which recognise our cells as foreign
in type 2 hypersensitivity, what do antigen-antibody reactions activate
complement, producing membrane damage
in type 2 hypersensitivity mechanism, what do the antibodies bind to
the cell surface
in type 2 hypersensitivity mechanism, what do phagocytes bind to the antibody via and what does it cause
their Fc receptor and causes phagocytosis of target cell
in type 2 hypersensitivity mechanism, what does antibody binding also activate and what does this set up
complement, which sets up the inflammatory process within the tissue & automatically leads to organ destruction/cell lysis
explain type 2 hypersensitivity antibody mediated mechanism on a blood vessel wall
- the antibodies are recognising the epithelium that are making up the wall of the blood vessel as foreign
- so they are binding onto those endothelial cells as they think it is foreign & initiate this inflammatory reaction
- the phagocytes then come along to try to destroy this antigen
- in doing so they release the toxic enzymes and chemicals into the vicinity of the blood vessel wall
- and that produces lots of localised cell damage
how do anti histamines work
antihistamines bind to the histamine receptor so that the histamine has got nothing to bind onto, so it works well by blocking histamine receptors
describe the whole of type 2 hypersensitivity mechanism
- antibodies bind to cell surface
- phagocytes bind to the antibody via their Fc receptor
- phagocytosis of target cell
- antibody binding also activates complement which sets up the inflammatory process within the tissue
- complement mediated cell lysis/destruction
what occurs during haemolytic disease of the newborn
- erythrocytes from a RhD+ foetus (first child) leak into the maternal circulation (who is RhD-), usually during birth which stimulates the production of anti-Rh antibody
- during subsequent pregnancies, IgG antibodies are transferred across the placenta into the foetal (2nd child) circulation
- if the foetus is again incompatible, the antibodies cause erythrocyte (red blood cell) destruction
at which pregnancy does a haemolytic disease of a newborn occur
2nd or after
instead of carrying out a blood transfusion on a baby who has haemolytic disease, what do hospitals do in order to avoid it from happening
after the first pregnancy, they treat the mother with a drug which takes out all the anti RhD+ antibodies, so when theres a 2nd baby, the antibodies are not able to cause haemolytic disease
what is type 3 hypersensitivity mediated by
immune complex response mediated
what does type 3 hypersensitivity cause excessive formation of
immune complexes eg persistent low grade infection, repeated inhalation of antigens
give some examples of type 3 hypersensitivity
- farmers lung
- immune complex glomerulonephritis
what is farmers lung
when farmers are exposed to hay spores & hay spores form immune complexes & often happens in the lung so they end up with breathing difficulties
what do immune complexes activate in type 3 hypersensitivity mechanism
complement
what do immune complexes deposit within in type 3 hypersensitivity mechanism
tissues
what and where a immune complexes degraded by in type 3 hypersensitivity mechanism
phagocytes, particularly in the liver and spleen
what does excessive immune complex formation result in, in type 3 hypersensitivity mechanism
deposition in the tissues, particularly arterioles, kidneys and joints
what do immune complexes induce in type 3 hypersensitivity mechanism
platelet aggregation and complement activation
what does attempted phagocytosis cause in type 3 hypersensitivity mechanism
enzyme release and results in tissue damage
in type 3 hypersensitivity mechanism, when theres an excess of immune complexes, what occurs
the immune system overloads and the phagocytes can’t cope with all those immune complexes & the immune complexes start to deposit in tissues such as lungs & kidneys which initiates this inflammatory reaction
what type of hypersensitivity is type 4 hypersensitivity
delayed type
how long does type 4 hypersensitivity take to develop after antigenic change
more than 12 hours (typically 12-48 hours)
give examples of type 4 hypersensitivity
- contact dermatitis = excema (coating of base metal)
- tuberculin reaction (mantoux test)
what type of molecules do antigens in type 4 hypersensitivity include
large or small (haptens) linked to carrier molecules
what other type of drug can cause a type 4 hypersensitivity
eye drops which treat an initial infection
in type 4 hypersensitivity mechanism, what do antigen presenting cells (APC) resident in the skin process and migrate
process antigen & migrate to regional lymph nodes
what do the antigen which has migrated to regional lymph nodes during type 4 hypersensitivity mechanism activate
T cells (CD4+ve)
during type 4 hypersensitivity mechanism, where do sensitised T cells migrate back to
the skin, where they produce cytokines
in type 4 hypersensitivity mechanism, what do cytokines attract
macrophages which cause tissue damage
describe the whole of type 4 hypersensitivity mechanism
- APC resident in the skin process antigen and migrate to regional lymph nodes where they activate T cells (CD4+ve)
- sensitised T cells migrate back to the skin where they produce cytokines which attract macrophages which cause tissue damage e.g. contact dermatitis mediated by mast cells
explain how type 4 hypersensitivity mechanism is used to test for TB immunity
- injection of TB antigens (not the bacteria)
- perform a skin test, to check if there was a reaction to the TB antigen, if there is, they do not need the vaccination as they have natural immunity and can react to the TB antigen
- if there was no skin reaction, they need the TB vaccination
what is hypersensitivity
exaggeration/inappropriate immune response mediated by 4 types
