Hypersensitivity Reactions

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What is a hypersensitivity reaction?

Hypersensitivity is an immune response that results in bystander damage to the self. It is usually an exaggeration of the normal immune mechanism. It is also the pathophysiological basis for many chronic diseases including allergy, chronic inflammatory diseases and autoimmunity.

What are the four types of hypersensitivity reactions?

Type 1- Immediate hypersensitivity Type 2- Direct cell effects Type 3- Immune complex mediated Type 4- Delayed type hypersensitivity

What is the Type 1 hypersensitivity reaction?

The type 1 is an immediate hypersensitivity reaction that is triggered by allergens like dust mite, pollen, drugs etc. In the absence of parasitic infections, type 1 reactions to innocuous substances promotes allergic reactions.

What is the pathophysiology of allergic disease?

<ul> <li>Onset - seconds</li> <li>IgE-mediated antibody response to external antigen <ul> <li>Sensitisation stage: production of specific IgE by B cells (helped by T cells) in response to initial allergen exposure, residual IgE antibodies bind to circulating mast cells via Fc receptors</li> <li>Allergic stage: on re-exposure to allergen, the allergen will bind to IgE coated mast cells → cell degranulation (release of histamine and other inflammatory mediators)</li> </ul> </li> </ul> Signup and view all the answers

What are some clinical features of allergic reactions?

1)Occurs quickly after exposure to allergens (minutes to 1-2 hours) 2) Maybe associated with more than one organ system 3) Presentation is influenced by site of contact 4) Threshold for reactions may be influenced by co-factors such as exercise, alcohol and infection Signup and view all the answers

What are specific symptoms of allergic reactions?

Asthma, urticaria, angioedema, allergic rhinitis, conjunctivitis, diarrhoea, vomiting, anaphylaxis Signup and view all the answers

How can IgE mediated allergic disorders be managed?

<ol> <li>Avoidance of allergen</li> <li>Block mast cell activation</li> <li>Prevents effects of mast cell activation through anti-histamines, leukotriene receptor antagonists.</li> <li>Anti-inflammatory agents</li> <li>Adrenaline</li> <li>Immunotherapy</li> </ol> Signup and view all the answers

What is the Type 2 hypersensitivity reaction?

Type 2 hypersensitivity happens when the immune system targets tissue specific antigens. The reactions are characterised by tissue damage. The reaction involves a target cell, an antigen expressed by it and the antibody. The antibody antigen complex works to damage the target cell. Signup and view all the answers

What are the three mechanisms of type 2 hypersensitivity reaction?

<ol> <li>Antibody and complement mediated destruction</li> <li>Complement and Fc receptor mediated inflammation 3)Antibody mediated cellular dysfunction.</li> </ol> Signup and view all the answers

What is the mechanism of antibody and complement mediated destruction?

There are two subtypes within this category:- <ol> <li>When the target cell forms an antigen antibody complex, it activates the classical complement pathway. The protein C1 gets activated and induces the cleavage of C3 protein into C3a and C3b. This results in the formation of the membrane attack complex (MAC) which causes cell lysis and death.</li> <li>The other mechanism involves the opsonisation of the target cell with the attachment of antibodies and complement proteins. This attracts macrophages to phagocytose the target cell.</li> </ol> Signup and view all the answers

What are some examples of Type 2 hypersensitive reaction involving antibody and complement mediated destruction mechanism?

Autoimmune haemolytic anaemia Mismatched transfused blood cells Erythroblastosis fetalis Goodpasture's syndrome Signup and view all the answers

What is the complement and fc receptor mediated inflammation mechanism?

The antigen antibody complex on target cells activate complement proteins C3a and C5a which attract white blood cells to release granules and cause lysis in the cell. Signup and view all the answers

What are some examples of Antibody dependent cell mediated cytotoxicity or Complement and fc receptor mediated inflammation?

The diseases are often medication induced like:- <ol> <li>Medication induced haemolytic anaemia (decrease in RBCs)</li> <li>Medication induced thrombocytopenia (lower platelets)</li> <li>Medication induced neutropenia (lower neutrophils)</li> </ol> Signup and view all the answers

What are some examples of Antibody dependent cell mediated cytotoxicity or Complement and fc receptor mediated inflammation?

The diseases are often medication induced like:-1) Medication induced haemolytic anaemia (decrease in RBCs) 2) Medication induced thrombocytopenia (lower platelets) 3) Medication induced neutropenia (lower neutrophils) 4) Transplant rejections 5) Immune reactions against parasites and neoplasms Signup and view all the answers

What is the mechanism of Antibody mediated cellular dysfunction? Give an example.

In the follicular cells of the thyroid gland, there are thyroid stimulating hormone receptors that bind to the Thyroid stimulating hormone resulting in the formation of T3 and T4. In this situation, the the body produces auto antibodies TSI (thyroid stimulating immunoglobulins) that bind to TSH receptors. Since TSI is not inhibitory, it stimulates the thyroid gland to continuously produce thyroid hormone resulting in hyperthyroidism. Therefore, the idea is that autoimmune antibodies bind to receptors to stimulate a dysfunction in the cell. Signup and view all the answers

Give two examples of antibody mediated cellular dysfunction

Myasthenia graves (autoimmune antibodies bind with Acetylcholine receptors and limit the communication between muscles and neural tissue) and Graves disease (hyperthyroidism) Signup and view all the answers

What is the type 3 Hypersensitivity reaction?

Type 3 hypersensitivity is when antibodies bind to soluble antigens, deposit on body tissues and cause damage through complement activation. Signup and view all the answers

What is the mechanism of action of type 3 hypersensitivity reaction?

Soluble antigens (medication, insect venom, animal venom) bind to antibodies forming immune complex (antigen-antibody complex). This attaches to tissues like the endothelium of blood vessels, alveoli, glomeruli of kidney. This activates the complement system resulting in C1 activating C5a and C3b. Neutrophils are then attracted and bind to the antibodies using Fc receptors. Neutrophils release cytotoxic granules which damage body tissues. Signup and view all the answers

What are the two subtypes of type 3 Hypersensitivity reaction?

<ol> <li>Localised- antigens may be injected (tetanus), inhaled (farmer's lung) or ingested (celiac disease)</li> <li>Systemic- Serum sickness, lupus, rheumatoid arthritis.</li> </ol> Signup and view all the answers

What is the Type 4 Hypersensitivity reaction?

It is a cell mediated Hypersensitivity reaction that involves T helper cells and cytotoxic T cells. It does not involve antibodies therefore is not a humoral response. Signup and view all the answers

What is the mechanism of Type 4 hypersensitivity reaction?

1)An antigen presenting cell like a dendritic cell would present the recognised altered proteins (foreign) to the Naive T helper cell. 2)Then the binding of T helper cells and Antigen presenting cell via MHC II molecules allow it to proliferate and differentiate into effector TH1 cells. <ol start="3"> <li> It secretes IFN- gamma to lead to recruitment and activation of macrophages. </li> <li> Macrophages secrete TNF alpha and IL-1 to recruit more leukocytes. </li> <li> Macrophages perform phagocytosis and release reactive oxygen species and toxic lysosomal enzymes that cause tissue damage. </li> <li> APCs may also stimulate the recruitment of neutrophils for a similar effect in this reaction </li> </ol> Signup and view all the answers

Why is Type 4 Hypersensitivity also called delayed type hypersensitivity?

It is cell mediated so T cells must be activated and recruited to cause the response. It would take about 24-72 hours to have the symptoms of a reaction. Signup and view all the answers

Is there a role of Cytotoxic T cells in Type 4 Hypersensitivity reactions?

Generally, the type 4 hypersensitivity reaction is cell mediated via a T helper cell response. However, in certain situations, the Target cell may be recognised as foreign by the CD8 cells and it may release a vesicle containing a perforin & granzymes complex which is taken in by endocytosis by the cell. The granzymes cause apoptosis of the cell. Apoptosis may also take place via the Fas ligand binding to the target cell and CTL. Signup and view all the answers