immunology Flashcards
What is a type 1 hypersensitivity reaction?
Classical allergy, mediated by the inappropriate production of specific IgE antibodies to harmless antigens
What atopic conditions are IgE mediated?
Food or drug allergy
Asthma
Allergic rhinitis
Hayfever
Eczema
In T1 hypersensitivity, what is sensitisation?
the initial event that lead to the specific IgE being developed for that allergen
What happens in sensitisation?
type 1 hypersensitivity
CD4 cells recognise the allergen
They proliferate and differentiate into T Helper 2 cells
These Th2 cells release IL-4, that stimulates the production of IgE by B Cells specific to that allergen
The IgE then circulates the blood and binds to mast cells
What happens during the allergic response in type 1 hypersensitivity?
- On re-exposure, IgE binds and causes mast cell degranulation, releasing cytokines including histamine and TNF-α.
- Histamine causes vasodilation, increased vascular permeability and broncho-constriction, causing symptoms of allergy. (happens within minutes of exposure to the allergen).
- TNF-α causes a localised inflammatory process at the site of exposure. (This takes a few hours and is called the late phase reaction)
- Allergic responses to allergens tend to get worse on repeat exposures due to increased sensitisation.
What can be measured after an anaphylactic reaction?
Mast cell tryptase can be measured to confirm the diagnosis of anaphylaxis
will be raised after an anaphylactic reaction
What is type 2 hypersensitivity?
an IgG or IgM antibody-mediated cytotoxic reaction occurring in hours to days
What happens in a type 2 hypersensitivity reaction?
Individual may possess or develop IgG and IgM antibodies
These antibodies can cause damage to cells or tissues (cytotoxicity) either directly by cell surface receptor binding, via activation of the complement pathway or by antibody-dependent cellular cytotoxicity.
What are some examples of type 2 hypersensitivity reactions?
Goodpasture’s
Haemolytic disease of the newborn
Blood transfusions reactions
What happens in a blood transfusion reaction?
t2hs
blood is transfused
ABO group of the donor does not match
Antibodies in the recipients blood attack the donors blood causing haemolysis of the donor RBCs
Rapid release of contents of cells and causing a toxic reaction.
What happens in haemolytic disease of the newborn?
t2hs
Rhesus negative mother has a rhesus positive baby
exposure to the babies blood during birth will cause the mother to produce IgG to rhesus
If she has another rhesus positive baby, that IgG will cross the placenta into the babies bloodstream and cause haemolysis of the babies RBCs
What happens in Goodpastures syndrome?
t2hs
antibodies specific to a type of collagen in the glomerular basement membrane in the kidneys and lungs lead to inflammation and destruction of the basement membrane
leading to pulmonary haemorrhage and kidney failure
What is type 3 hypersensitivity?
antigen-antibody immune complex-mediated reaction (IgG and IgM) which can occur over hours, days or weeks.
What happens in type 3 hypersensitivity?
- Soluble antigen in the circulation is bound to by antibodies forming immune complexes.
- complexes precipitate out of the circulation and deposit in tissues (blood vessels, synovial joints and the glomerular basement membrane).
- complexes trigger the classical complement pathway, leading to the recruitment of inflammatory cells including neutrophils that release enzymes and free radicals causing tissue damage
What happens in rheumatoid arthritis?
type 3
RFr is IgM antibody that recognises IgG antibodies as an antigen. (IgM against IgG).
This leads to formation of antibody-antigen complexes in the blood.
These become deposited in joints, skin, lungs and other organs where they activate the complement system and lead to chronic inflammation.
What happens in farmer’s lung?
type 3
Mould and hay spores are breathed into the lungs. Antibodies against the mould or hay antigens form antibody-antigen complexes.
deposited in the lung tissues and alveoli where they activate the complement system and lead to inflammation of the lung tissue
What happens in type 4 hypersensitivity?
- Antigens enter tissues and are picked up by dendritic cells
- Dendritic cells deliver the antigens to the relevant CD4 cell
- CD4 cells proliferate and differentiate into T helper cells
- T helper cells travel to the tissues where to original antigen presented and release cytokines that recruit macrophages
- both cells release proinflammatory cytokines that result in localised inflammation
- In skin this presents as a contact dermatitis
What is type 4 hypersensitivity and an example?
- delayed hypersensitivity, as the reaction typically occurs 24 to 72 hours after antigen exposure
- not antibody-mediated but T cell-mediated
e.g. mantoux test for TB contact
What are the physical and chemical barriers to invading pathogens?
Skin
Mucosa
- Resp tract (with cilia)
- GI tract
- GU
Chemical barriers
- Hydrochloric acid (stomach)
- Lysozyme (sweat and tears)
Which cells are involved in the innate immune response?
Neutrophil
Basophil
Mast cell
Eosinophil
Monocyte
Macrophage
Natural killer cell
Dendritic cell
What is a neutrophil and what does it do?
Primary phagocytic cell in acute inflammation
Granules contain myeloperoxidase and lysozyme
Most common type of white blood cell
Multi-lobed nucleus
Features and properties of basophils
Releases histamine during allergic response
Granules contain histamine and heparin
Expresses IgE receptors on the cell surface
Bi-lobed nucleus
What are the functions and properties of mast cells?
Present in tissues and are similar in function to basophils but derived from different cell lines
Releases histamine during allergic response
Granules contain histamine and heparin
Expresses IgE receptors on the cell surface
Functions and properties of eosinophils
Defends against protozoan and helminthic infections
Bi-lobed nucleus
Function and properties of monocytes
Differentiates into macrophages
Kidney shaped nucleus
Functions and properties of macrophages
Involved in phagocytosis of cellular debris and pathogens
Acts as an antigen presenting cell
Major source of IL-1
Function and properties of natural killer cells
Induce apoptosis in virally infected and tumour cells
Function of a dendritic cell
Acts as an antigen presenting cell
What happens in anaphylaxis?
severe type 1 hypersensitivity reaction.
Immunoglobulin E (IgE) stimulates mast cells to rapidly release histamine and other pro-inflammatory chemicals (mast cell degranulation)
This causes a rapid onset of symptoms, with airway, breathing and/or circulation compromise
What are the symptoms of anaphylaxis?
Urticaria
Itching
Angio-oedema, with swelling around lips and eyes
Abdominal pain
SOB
Wheeze
Swelling of the larynx, causing stridor
Tachycardia
Lightheadedness
Collapse
After A-E, how is anaphylaxis managed?
IM adrenalin, repeated after 5 minutes if required
Antihistamines, such as oral chlorphenamine or cetirizine
Steroids, usually IV hydrocortisone
What are common triggers for anaphylaxis?
Foods: peanuts, pulses, tree nuts (brazil nuts, almond, hazlenuts), fish and shellfish, eggs, milk, sesame
Venom: Bee stings, wasp stings
Drugs: antibiotics, opoids, NSAIDs, muscle relaxants (Baclofen, Diazepam)
Contrast agents
What monitoring is needed in anaphylaxis?
biphasic reactions: second anaphylactic reaction after successful treatment of first
What is measured to confirm a diagnosis of anaphylaxis?
serum mast cell tryptase within 6 hours of the event.
(Tryptase is released during mast cell degranulation)
What are plasma cell’s role?
differentiated B cells
- produce large quantities of antibodies against specific antigens
- respond to signals from T cells during infection and continue to produce antibodies until the infection is controlled
- chronic inflammation
What is the role of memory B cells?
- long-lived cells that remain within the body and allow a more rapid response to future infections as part of a secondary immune response
- rapidly proliferate on re-exposure
What are antigen-presenting cells?
dendritic cells, B cells, and macrophages.
APCs can digest proteins they encounter and display peptide fragments from them on their surfaces for other immune cells to recognise
What are the main features of the innate immune system?
Non-specific
1st line of defence
Provides barrier to antigen
Instinctive
Present from birth
Slow response
No memory
What are the 5 antibody classes?
IgG
IgA
IgM
IgE
IgD
What does rheumatoid factor target?
Fc portion of IgG
Features of IgG
- Most abundant
- Surface of mature B cells and in serum
- only antibody to cross the placenta so transfers passive immunity from mother to foetus.
- Newborn have high IgG concentrations in the first 3-6 months of life
Features of IgA
- most prevalent antibody in secretions, such as saliva and mucous
- Forms a dimer with 4 antigen binding sites
- resistant to enzymatic digestion and act principally as neutralising antibodies
- barrier layer at mucosal surfaces to prevent pathogenic invasion
Features of IgM
- surface of B-cells as monomers but secreted as pentameters (10 antigen binding sites)
- first immunoglobulin produced during foetal development
- first to be produced by B-cells against a new infection
- High avidity low affinity
Features of IgE
- mainly found on mast cells but is also present at low levels in the blood and ECF
- associated with allergy, particularly type I hypersensitivity reactions, including atopic disease (e.g. asthma and dermatitis) and anaphylaxis
- triggers histamine release from mast cells and basophils
part of the body’s response to parasitic infections.
Features of IgD
- present on the surface of B-cells.
- has a role in B-cell and antibody production.
- All naive B cells express IgD and IgM
