Hypersensitivity Flashcards
Describe the potential benefits and possible harmful effects of the immune response. Define and distinguish between different types of hypersensitivity. Comment upon which diseases are associated with specific types of hypersensitivity reactions. Summarise the problems associated with graft‐rejection and transplantation of organs and tissues.
Another name for hypersensitivity?
Allergy/autoimmunity
Increased sensitivity in dental patients to…
Latex
Dental materials
Drugs used in the surgery
Immune system consists of
Two types?
Innate immune system
Adaptive/acquired immune system
Acquired immunity consists of
Two types of response?
Antibody response
Cell-mediated response
Hypersensitivity involves ………. and …….. responses
Antibody
Cell-mediated
Antibody response creation steps
- APC take up antigens
- APC processes and displaces antigen on surface
- B-cell attaches to displayed antigen
- Th2 cell (helper) releases cytokines to encourage proliferation
- B-cells proliferate and produce/release plasma cells and produce antibodies
Features of antibody response
Effect and speed
Rapid
Systemic/widespread
Why is antibody response widespread?
Adaptations of molecules
They are soluble proteins and can reach most parts of body quickly via blood, tissue fluids and body secretions
Cell mediated immunity: 1st exposure process
- Antigen presentation via MHC protein
- Complementary T cell attaches via receptor
- T cell becomes activated
- Activated T cell proliferates and forms antigen specific memory T cells which patrol body
Cell mediated immunity: 2nd exposure process
- Memory T-cell recognises antigen expressed on target cell
- T cells release cytokines, kill target cell via apoptosis
Cell Mediated Immune Targets (3x)
Cellular targets:
- immune cells
- virally transformed cells
- foreign cells
Characteristics of cellular immune response
- Localised
- Slow to develop
- Slow to resolve
Types of immune failure responses (2x) -
Failure to produce adequate immune response
Produce overactive, damaging response
Immunodeficiency definition
Failure to produce an adequate immune response
Hypersensitivity definition
Overactive, damaging immune response to an allergen
Usually results from second exposure to an antigen
Individuals have genetic susceptibility
4 types of hypersensitivity
1 - immediate i.e anaphylaxis
2 - cytotoxic
3 - immune complex
4 - delayed
Type 1, 2, 3 hypersensitivity are mediated by?
Antibody mediated
IgE, IgG, IgG
Type 4 hypersensitivity is mediated by?
Cell mediated - T cells
Type 1 HS characteristics Immune mediator Antigen type Effector mechanism Example
Acute Rapid onset IgE mediated Soluble Mast cell activation and mediator release Asthma
Type 1 HS mechanism - 1st exposure
When does it occur
What do these patients have more of
What does this lead to and what are the adaptations which allow this
Occurs on first exposure
HS people have more IL4 –> CD4 (humoral response)
More IL4 = More IgE production
Mast cells secrete IgE binding receptors and histamine granules
Receptors have high affinity for IgE
Allergen binds to IgE on
surface of mast cells
Cells become degranulated and release mediators
Second set released 4-8hrs later
Allergens are…
Mostly small proteins
Type 1 HS mechanism - 2nd exposure mechanism
What is triggered and how
What is secreted (by what) and what else is released
Antibodies have high affinity for antigen
Specific response is triggered
Receptors cluster together and trigger a signal in the mast cell to degranulate and secrete IgE
IL-5 also released –> histamine and eosinophils release
Mast cell degranulation involves
Histamine and enzyme release
Histamines are released from
Haemopoietic stem cells resident in tissues
Anti-histamines have to be taken
Before degranulation to limit reaction
Histamine release causes
Vascular dilation Increased vascular permeability i.e oedema Bronchospasm Urticarial rash Increased Nasal and lacrimal secretions
Histamine release present clinically as
Hay fever
Asthma
Acute allergic responses examples e.g anaphylaxis
Latex allergy
LA allergy
Bee venom
Peanut allergy
Diagnosis of allergy - testing and results
Apply small amount of allergen under skin - 5 min response
Wheel will form - extravasation of serum into skin - angio-oedema
Late phase of inflammation (6hrs later) due to leukocyte infiltration and further oedema
Management of type 1 hypersensitivity (4x)
Adrenaline
Antihistamines (before degranulation)
Corticosteroids
Avoidance of allergen
Type II hypersensitivity
What do the antibodies induce and how
Antibody mediated hypersensitivity
Antibodies target cell surface SELF antigens
Usually IgG/M
Cell damage and inflammation
Type II Hypersensitivity mechanism
What becomes activated
Antibodies target SELF antigen
Abs activate
1. Antibody Dependent Cell Cytotoxicity –> inflammation via neutrophils and macrophages
2. Complement cascade
Complement mechanism and what does it lead to
Complement binds to receptor and stimulates release of factors C5 and C5a –> inflammation and cell death
Type II hypersensitivity responses are important in which conditions
Acute transplant rejection/transfusion
haemolytic disease of the newborn
Auto immune disease e.g pemphigus
Type II Hypersensitivity - HDoFNb - difference between first and second pregnancies
Involvement of RhD
1st - RhD+ foetal blood enters RhD-ve mother’s circulation
Baby born but Abs against RhD+ve produced
2nd - if foetus is RhD+ve - mother produces IgG which crosses into foetal circulation and destroys foetal erythrocytes
Type II hypersensitivity - HDoFNb - treatment
Preformed anti-RhD ab is given to Rh- mothers of RhD+ve infants after delivery
Type II hypersensitivity - Pemphigus
What is it and what does it lead to
Autoimmune disease against desmoglein
Prevents formation of gap junctions
Epithelial shedding
Type III hypersensitivity - Pemphigoid
What is it and what does it lead to
Autoantibodies against hemidesmosomes
Prevent binding of epithelium at basement membrane/dermis layer
epithelium and connective tissue not bound –> blistering skin
Type III hypersensitivity mechanism
Where do they form?
What do complexes induce?
What do complexes act on during inflammation?
Immune complex-mediated HS Complexes form between antigen and antibodies Form in serum Deposit in lining of vessels, glomeruli, lung Complement activation Leukocyte binding Inflammation Act on platelets and basophils Activated and release peptides Increase vascular permeability
What does increased vascular permeability allow for and lead to?
More immune complexes can be deposited
Platelet aggregation
Complement cascade activation
Neutrophils attracted and secrete lysosomal enzymes
Lysosomal enzymes cause further tissue damage
Type III HS is important in
2 examples
Erythema multiforme
Lupus
Treatment of Type III hypersensitivity
Immunosuppression with steroids
Erythema multiforme
Type?
Appearance?
Type III
Target lesion appearance
Deposition of immune complex in superficial microvasculature of skin and oral mucous membrane following infection or drug exposure
Type IV Hypersensitivity
What kind of response?
What does this mean?
Characteristics
Cell-mediated/delayed type Mediated by T cells Cell mediated Slow to develop 12-48hrs Slow to resolve Localised
Type IV mechanism
How do T-cells respond
Cell mediated
T cell recognises antigen expressed via MHC protein on another cell
T cell responds by releasing cytokines or killing target cell
Cell mediated immune responses are important in
Delayed type reactions
Contact hypersensitivity e.g contact dermatitis
Lichenoid reactions to amalgam filling and other materials
Contact dermatitis stages (2x)
Sensitisation
Elicitation
Sensitisation stage of Contact Dermatitis
What are langerhans cells
- Antigen gets into skin and is internalised by langerhans cells - special antigen presenting cells in epidermis
- Travel to lympnodes and present antigens to CD4 and T cells
- MEMORY CD4 and T cells are produced
Elicitation stage
What happens? - which cells involved
What does this lead to?
Langerhans cells move to dermis
Expose memory CD4 and T cells to antigen
Cells activated and express IFN𝛾
Increased expression of ICAM-1 and MHCII proteins on keratinocytes and secretion of pro inflammatory cytokines
More leukocytes attracted to sites
Neutrophils arrive post4hrs, Monocytes + Tcells 12hrs
Both secrete tissue damaging cytokines
Tissue damage seen 12hrs+
If Ag removed then damage is resolved
Skin patch testing
what does it test for
where is it tested
Tests for type IV delayed response reactions
Samples applied to back of arm for 72-96hrs
Denture acrylic allergy
What does it look like
Red areas due to uncontrolled inflammation
Epidermal thickening due to leukocytes and proliferating keratinocytes
Lichenoid reaction to amalgam
What kind of reaction
Associated with ? and how is this tested and resolved?
Type IV contact hypersensitivity
Amalgam fillings
Positive skin patch test to mercury/amalgam
Removal of filling
