B11. Type I and II hypersensitivity

Question 1

Type I - allergy, immediate anaphylaxis

Answer 1

• Allergic reaction. Allergens can be pollen, mites, spores, medicines, toxins, food.
• Immediate onset and fast disappearance of symptoms, 1-2 min.
• Can also be a late phase reaction, 2-8 hours later.
• The immediate reaction is degranulation of granulocytes - histamine, serotonin, serene proteases and carboxy peptidases are released. Smooth muscle contraction will occur, itching tears, sneezing etc.
• In the late phase reaction other cells like neutrophils, macrophages and eosinophils will synthesise mediators;
o IL-3-6, GMCSF, leukotrienes, prostaglandins.
o These will cause smooth muscle contraction, inflammation, proliferation and oedema.
• Mainly IgE (IgG) production, the allergy is dominated by Th2 - improved hygienic conditions are in part responsible for the dominance.
• Systemic form is known as serum sickness.

Question 2

Type I Mechanism:

Answer 2

o FceRI (mast, basophils) and FceII (macrophages, lymphocytes, eosinophils and platelets).  
o Cross linking an degranulation. 

• There are two types of mast cells:
o One in connective tissue which are present in a constant number and live for approximately 6 months. o The other type is present in the mucosa.
• Its numbers are increased after IL-3 and IL-4.
• Short lived, dies after only 40 days.
• Hangs around and waits for nematodes.
• Can be in localised form, showing symptoms like hay fever, asthma or food allergy.

Question 3

Type 1 Diagnostics

Answer 3

o i.d. allergen test o passive cutaneous anaphylaxis
o local atb, iv atg and Evans blues (binds to albumin or stains atg) leaves the blood vessels at the site of inflammation
o IgE ELISA (specific and non specific)

Question 4

Type 1 Treatment

Answer 4

o IgG induction
o Corticosteroid and anti-inflammatory drugs o Epinephrine
o Antihistamines.
• The development of allergy depends on many factors like tolerance at young age, allergen, Th2 regulation, IgE production and FceRI gene expression.

Question 5

Type II - atb mediated cytotoxic reactions

Answer 5

• Single cell cytotoxic reaction that is atb mediated.
• On the cell surface (usually this happens to RBC) there is an atg that can be recognised by an atb. If the atg appears on to many cells, the cells will be lysed by the complement system or by Tc activation.
• Occurs within 4-8 hours and involves mainly IgM and IgG.
• The result is hemolytic anemia, e.g. Eq infectious anemia (virus attach to RBC).
• Can be acquired via transfusion (different blood groups with repeated transfusion), neonatal (through placenta or colostrum), autoimmune or drug induced

Question 6

Type III - immune complex mediated

Answer 6

• Atb, usually IgG or IgM react with soluble atg forming immune complexes.
• Usually these complexes are removed, but during type 3 (e.g. FIP) a huge number of these complexes are formed and they cannot be neutralised (the atb cannot block the binding of the virus to the receptor and the replication cannot be stopped).
• Complexes will be deposited on cell surfaces in the different tissues in the body, and the cells are attacked by the complement system or by cytotoxic reactions. Remember, the cells are not infected but the complexes are on the surface! The activation of the complement system and the Tc are known as “serum sickness”.
• Arthus reaction: locally administered atg + circulating atbs.
• Causative agents can be chronic diseases, autoimmunity or extrinsic factors (environment, milk replacement protein, durgs)
• Chronic diseases
o Viral infection: EIA, ASF, BVD
o Bacterial infecton: Streptococcus (pneumonia, pyometra, polyarthritis)
o Parasites
o Tumours

Question 7

Type III severity

Answer 7

Severity depends on size and number of immune complexes and the site of deposition of them.
o Locally they can be deposited in any tissue.
o Vessels —> vasculitis
o Kidneys —> glumerulo-neprhitis
o RBC —> anemia

Question 8

Type IV - delayed hypersensitivity

Answer 8

• Results from activation of Th1 and Tc.
• A substance act as hapten and binds the host proteins (contact dermatitis).
o The first exposure does not produce a response - subsequent dermal exposure can activate Langerhans cells, which migrate and activate Tc in the local lymph nodes. The T cells return to the skin and innate an immune response.
• Repeated exposure can trigger a massive immune response, a “cytokin storm” that can lead to fever, hypotension and even organ failure.
• FIP also have another trick. caused by corona virus, enveloped and the proteins not he envelop are very similar to the Fcr - they may cross react with the cells! The virus can also use the atb as a bridge to enter the cells.