Subject - Immunology

Type 1 - immediate (or atopic, or anaphylactic)Main article: Allergy

Type 1hypersensitivity is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen.[2] Exposure may be by ingestion, inhalation, injection, or direct contact. The difference between a normal immune response and a type I hypersensitive response is that plasma cells secrete IgE. This class of antibodies binds to Fc receptors on the surface of tissue mast cells and blood basophiles. Mast cells and basophiles coated by IgE are "sensitized." Later exposure to the same allergen, cross-links the bound IgE on sensitized cells resulting in de-granulation and the secretion of pharmacologically active mediators such as histamine, leukotriene, and prostaglandin that act on the surrounding tissues. The principal effects of these products are vasodilation and smooth-muscle contraction. The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock. Treatment usually involves epinephrine, antihistamines, and corticosteroids. If the entire body gets involved, then anaphylaxis can take place; an acute, systemic reaction that can prove fatal. Some examples:

Allergic asthma Allergic conjunctivitis Allergic rhinitis  ("hay fever") Anaphylaxis Angioedema Urticaria  (hives) Eosinophilia Penicillin Cephalosporin

Usually, there are 10-12 allergens for which hypo sensitization is done through the same lab.

Hypo sensitization is contraindicated in Hymenoptera venom-allergic children treated with cyclosporine.

DeSpecific hypo sensitization is the practice of administering gradually increasing quantities of a specifically relevant allergen to allergic patients until reaching a maintenance dose or loss of symptoms.

Hypo sensitization: Hypo sensitization is used when a patient’s allergies  span the seasons or are year round; when symptoms are not controlled by reasonable amounts of medication; or when corticosteroids  cannot be used for other health reasons.

Ring Summary: Specific hypo sensitization is the practice of administering gradually increasing quantities of a specifically relevant allergen to allergic patients until reaching a maintenance dose or loss of symptoms.

Prick Test

IgE, a special type of antibody, mediates Allergic (type 1 hypersensitivity) reactions. When it

encounters a specific allergen IgE activates specialized cells called mast cells to produce

chemicals such as histamine and leukotrienes that cause the visible symptoms typical of an

allergic response. The skin prick assay is an ‘exposure’ test that uses this hypersensitivity

reaction, under controlled conditions, to identify what a person may be allergic to by measuring

the overactive immune response to the potential allergen.

In the allergy clinic, the patient is asked to sit and role their sleeves up. A marker pen is used to

identify on the arm where the allergens are to be applied. For every different allergen a solution

is prepared that contains the proteins that may cause an adverse reaction. Some of these

solutions are commercially produced specifically for skin prick testing but they can also be

prepared in the clinic using fresh extract from the substance suspected of causing the allergy. A

fine needle is used to gently prick the skin under the allergen solution. If IgE is present that

specifically recognizes the allergen it will activate mast cells to produce histamine, the outcome

of this will be a raised circle of reddened skin called a wheal and flare around the point of

allergen application. The presence of this wheal indicates that the patient has become

sensitized to the particular substance via a previous exposure. To check if the test is working

correctly a positive control is applied that contains histamine and should produce a reaction in

all individuals. Also a negative control is used; this is simply a saline (salty) solution.

Type 2 - antibody-dependent

In type 2 hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (absorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells which act as antigen presenting cells, this causes a B cell response where antibodies are produced against the foreign antigen. An example here is the reaction to penicillin where the drug can bind to red blood cells causing them to be recognised as different, B cell proliferation will take place and antibodies to the drug are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation for eliminating cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lyses and death. The reaction takes hours to a day. Another form of type 2 hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognized by natural killer (NK) cells and macrophages (recognized via IgG bound (via the Fc region) to the effectors cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells. Some examples:

Autoimmune hemolytic anemia Goodpasture's syndrome Pemphigus Pernicious anemia  (if autoimmune) Immune thrombocytopenia Transfusion  reactions Hashimoto's thyroiditis Graves disease  (see type V below) Myasthenia gravis  (see type V below) Rheumatic fever Hemolytic disease of the newborn  (erythroblastosis fetalis) Acute transplant rejection

TYPE-3

Type 3 - immune complex

Type 3 hypersensitivity occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking. Large immune complexes that cannot be cleared are deposited in vessel walls and induce an inflammatory response. The reaction can take hours, days, or even weeks to develop. Some clinical examples:

Rheumatoid arthritis Immune complex glomerulonephritis Serum sickness Subacute bacterial endocarditis Symptoms of malaria Systemic lupus erythematosus Arthus reaction Farmer's lung  (Arthus-type reaction)

Type 4 - cell-mediated (delayed-type hypersensitivity, DTH)See also: Cell mediated immunity

Type 4 hypersensitivity is often called delayed type as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response. CD8+ cytotoxic T cells and CD4+ helper T cells recognise antigen in a complex with either type 1 or

2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages which secrete IL-12, which stimulates the proliferation of further CD4+ T cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Type 1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact while activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells. Some clinical examples:

Contact dermatitis  (poison ivy rash, for example) Atopic dermatitis  (eczema) Temporal arteritis Symptoms of leprosy Symptoms of tuberculosis Mantoux test Coeliac disease Chronic transplant rejection

Tuberculin is an antigen used to aid in the diagnosis of tuberculosis infection. An infection with the bacterium that causes tuberculosis frequently leads to a sensitivity to these antigens. Tuberculin was discovered by German scientist and physician Robert Koch in 1890.

The original tuberculin discovered by Koch was a glycerin extract of the tubercle bacilli and was developed as a remedy for tuberculosis, but it was ineffective in this role. Clemens von Pirquet discovered that patients who had previously received injections of horse serum or smallpox vaccine had quicker, more severe reactions to a second injection, and he coined the word allergy to describe this hypersensitivity reaction. Soon thereafter von Pirquet discovered the same type of reaction took place in those infected with tuberculosis, and he thus found the utility of what would become the tuberculin skin test. The test used in the United States at present is referred to as the Mantoux test, in the United Kingdom it is referred to as the Heaf test. Both of these tests use "Purified Protein Derivative", or "PPD", which is a tuberculin derivative.

Measure of area of skin reacting to the injected antigen is tally with standard medical graphs to confirm infection.

Lecturer in-charge- Mrs., Beena Vinod

Salman Khan

II Sem, M.Sc Biotechnology

CMRIMS