Hypersensitivity Flashcards
Here’s a mnemonic for remembering the types of hypersensitivity:
ACID
1) Atopic
2) Cytotoxic
3) Immune Complex mediated
4) Delayed
What mediates type 1 hypersensitivity?
IgE
Why does Type 1 hypersensitivity occur?
Due to a genetic predisposition aka Atopy.
Some Th cells are genetically hypersensitive to certain non-harmful antigens e.g. pollen or nuts
What are the phases of a type 1 reaction?
Sensitization
Reaction
What happens to kick off the sensitisation phase of type 1 reactions?
1st encounter of allergen:
APC activates a predisposed Th cells which converts into a Th2 cell and release interleukins 4 & 5
During the sensitisation phase what happens to IL-4 & 5?
IL-4 makes B cells class switch to IgE which then attaches to Mast cells, priming them.
IL-5 activates granulocytes like eosininophils
The reaction phase of type 1 reactions is split into Early and Late, what happens in the early reaction phase?
Exposure to allergen triggers immediate degranulation of mast cells –> Histamine –> Inflammation
What happens in the late reaction phase of type 1 reactions?
~10hrs later ILs activate Th cells &other immune cells e.g. eosinophils and basophils are drawn in.
This creates further inflammation and priming of mast cells (hence the idea is that each exposure is worst than the last)
What’s the Atopic Triad?
Atopic Dermatitis (Eczema)
Asthma
Hayfever (Allergic Rhinitis)
How do we test for Atopy?
Skin prick testing
Patch Testing
Serum Tryptase (spikes right after a reaction)
How do we manage type 1 reactions?
Patient education Antihistamines CCS Sodium cromoglycate Steroids Leukotriene antagonists Desensitisation immunisation Specific treatment for anaphylaxis: Adrenaline Allergen Avoidance
Anaphylaxis is a severe life threatening type 1 reaction, what are the symptoms?
Hives Tightening of Face Swelling & oedema Constriction of airway Shock
What happens in a Type 2 Hypersensitivity reaction?
Defective B cells release tissue-specific Abs that attach to antigens on our host cells, triggering opsonisation.
This ends up in complement activation AND Ab mediated cytotoxicity against your own cells
Give some examples of Type 2 reactions?
Blood transfusion reactions (ABO mismatch)
Autoimmune Haemolytic Anaemia
Myasthenia gravis
What are the 2 types of type 2 reaction?
Intrinsic - Abs attach to antigens normally made in the body
Extrinsic - Abs attach to antigens from outside the body (e.g. penicillin bound to RBCs)
In both cases the antigen is still attached to host tissues
What happens in type 3 reaction?
Plasma cell presents an abnormal antigen on its MHC and bind to Th cells by CD4/CD40 ligand bonds.
Cytokines are released causing the plasma cell to change its immunoglobulin class.
Abs then bind to circulating antigens, forming complexes that are deposited throughout the body triggering an immune response
What happens in type 4 hypersensitivity?
Starts like type 1 (using Th cells and APC in lymph nodes) but it lacks the genetic predisposition and happens much slower (~48hrs)
End up with slow inflammation and tissue damage
Give some examples of Type 4 hypersensitivity?
Contact dermatitis
MS
RA
IBD
What genetic factors are thought to be involved in type I hypersensitivity
Polymorphisms to the filaggrin gene
- controls Ph
- moisturises surfaces
- Maintains epithelial barriers
which environmental factors are thought to be involved in type I?
- Effects of urbanisation
- Reduced exposure to microorganisms during childhood.
which are the main presentations of type I
SKIN:
- urticaria
- Atopic eczema
- Angio-oedema
AIRWAYS
- asthma
- Rhinitis
ANAPHYLAXIS
describe the pathogenesis of anaphylaxis?
- Mast cells produce prostaglandins and leukotrienes through the cyclooxygenase and lipoxygenase pathways.
- The result is vasodilation and increased vascular permeability.
- Shift of fluids from the vascular to the extra-vascular space resulting in a fall in vascular tone.
- Severe drop in blood pressure.
- IN the skin, mast cells release histamine further contributing to welling and fluid shift.
What do we use as controls in a skin prick test? after how long do they show a result?
- Saline
- Histamine- should trigger reaction within 10 mins
what is an allergen.
list some of the more severe ones.
- Antigens that trigger allergic reactions are called allergens.
- Peanut allergy is the most common cause of severe allergic reactions.
- Allergy to latex
- Penicillin allergy, the allergen is β-lactam
Management of type II hypersensitivity
-Prevention:
o Cross matching of blood
o Tissue typing
o Detection of rhesus incompatability
-Immune suppression
o Autoimmune disease
o Transplant rejection
