Hypersensitivity

Question 1

Here’s a mnemonic for remembering the types of hypersensitivity:
ACID

Answer 1

1) Atopic
2) Cytotoxic
3) Immune Complex mediated
4) Delayed

Question 2

What mediates type 1 hypersensitivity?

Answer 2

IgE

Question 3

Why does Type 1 hypersensitivity occur?

Answer 3

Due to a genetic predisposition aka Atopy.

Some Th cells are genetically hypersensitive to certain non-harmful antigens e.g. pollen or nuts

Question 4

What are the phases of a type 1 reaction?

Answer 4

Sensitization

Reaction

Question 5

What happens to kick off the sensitisation phase of type 1 reactions?

Answer 5

1st encounter of allergen:

APC activates a predisposed Th cells which converts into a Th2 cell and release interleukins 4 & 5

Question 6

During the sensitisation phase what happens to IL-4 & 5?

Answer 6

IL-4 makes B cells class switch to IgE which then attaches to Mast cells, priming them.

IL-5 activates granulocytes like eosininophils

Question 7

The reaction phase of type 1 reactions is split into Early and Late, what happens in the early reaction phase?

Answer 7

Exposure to allergen triggers immediate degranulation of mast cells –> Histamine –> Inflammation

Question 8

What happens in the late reaction phase of type 1 reactions?

Answer 8

~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)

Question 9

What’s the Atopic Triad?

Answer 9

Atopic Dermatitis (Eczema)
Asthma
Hayfever (Allergic Rhinitis)

Question 10

How do we test for Atopy?

Answer 10

Skin prick testing
Patch Testing
Serum Tryptase (spikes right after a reaction)

Question 11

How do we manage type 1 reactions?

Answer 11

Patient education 
Antihistamines
CCS
Sodium cromoglycate 
Steroids 
Leukotriene antagonists 
Desensitisation immunisation 
Specific treatment for anaphylaxis: Adrenaline
Allergen Avoidance

Question 12

Anaphylaxis is a severe life threatening type 1 reaction, what are the symptoms?

Answer 12

Hives
Tightening of Face
Swelling & oedema
Constriction of airway
Shock

Question 13

What happens in a Type 2 Hypersensitivity reaction?

Answer 13

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

Question 14

Give some examples of Type 2 reactions?

Answer 14

Blood transfusion reactions (ABO mismatch)

Autoimmune Haemolytic Anaemia

Myasthenia gravis

Question 15

What are the 2 types of type 2 reaction?

Answer 15

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

Question 16

What happens in type 3 reaction?

Answer 16

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

Question 17

What happens in type 4 hypersensitivity?

Answer 17

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

Question 18

Give some examples of Type 4 hypersensitivity?

Answer 18

Contact dermatitis
MS
RA
IBD

Question 19

What genetic factors are thought to be involved in type I hypersensitivity

Answer 19

Polymorphisms to the filaggrin gene

• controls Ph
• moisturises surfaces
• Maintains epithelial barriers

Question 20

which environmental factors are thought to be involved in type I?

Answer 20

• Effects of urbanisation

- Reduced exposure to microorganisms during childhood.

Question 21

which are the main presentations of type I

Answer 21

SKIN:

• urticaria
• Atopic eczema
• Angio-oedema

AIRWAYS

• asthma
• Rhinitis

ANAPHYLAXIS

Question 22

describe the pathogenesis of anaphylaxis?

Answer 22

• 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.

Question 23

What do we use as controls in a skin prick test? after how long do they show a result?

Answer 23

• Saline

- Histamine- should trigger reaction within 10 mins

Question 24

what is an allergen.

list some of the more severe ones.

Answer 24

• 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

Question 25

Management of type II hypersensitivity

Answer 25

-Prevention:
o Cross matching of blood
o Tissue typing
o Detection of rhesus incompatability

-Immune suppression
o Autoimmune disease
o Transplant rejection