Cellular Immune ResponseAndHypersensitivity

8/12/2019 Cellular Immune ResponseAndHypersensitivity

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Cellular Immune Response

& HypersensitivityTerry Kotrla, MS, MT(ASCP)BB

Fall 2007


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The Cellular Immune Response

Important defense mechanism against: viral infections,some fungal infections,parasitic disease andagainst some bacteria, particularly those insidecells.


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Responsible for :delayed hypersensitivity,transplant rejection andpossibly tumor surveillance.


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Scanning Electron Micrograph (SEM) of T cellLymphocytes attacking a cancer cell.


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This branch of the immune system dependson the presence of thymus-derivedlymphocytes (T lymphocytes).

Initiated by the binding of the antigen withan antigen receptor on the surface of thesensitized T lymphocyte.

Causes stimulation of the T lymphocyte intodifferentiation into two main groups of cells.


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T Lymphocytes

Helper and suppressor T cells that regulate theintensity of the body's immune response.

T cells capable of direct interaction with theantigen. This group can be divided further.

T cells which, on contact with the specific antigen,liberate substances called lymphokines.

Cytotoxic T cells which directly attack antigenon the surface of foreign cells.


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Lymphokines

A mixed group of proteins. Macrophages are probably the primary

target cells.Some lymphokines will aggregate macrophagesat the site of the infection,others activate macrophages, inducing them tophagocytose and destroy foreign antigens morevigorously.


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Lymphokines

Attract neutrophils and monocytes to thesite of infection.

The end result of their combined action isan amplification of the local inflammatoryreaction with recruitment of circulating cellsof the immune system


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Lymphokines

Contact between antigen and specificsensitized T lymphocytes is necessary tocause release of lymphokines.

Once released the lymphokine action is notantigen specific ; for example, an immunereaction to the tubercle bacillus may protectan animal against simultaneous challengeby brucella organisms.


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Cytotoxic T cells

Attach directly to the target cell via specificreceptors.

The target cell is lysed; The cytotoxic cell is not destroyed and may

move on and kill additional targets.


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Natural Killer Cell At least two types of

lymphocytes are killer cells --cytotoxic T cells and naturalkiller cells.

To attack, cytotoxic T cells needto recognize a specific antigen,whereas natural killer or NKcells do not.

Both types contain granulesfilled with potent chemicals, andboth types kill on contact.

The killer binds to its target,aims its weapons, and delivers aburst of lethal chemicals.


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Control of the Immune Response

Genetic controlRabbits usually produce high levels ofantibodies to soluble proteins, while micerespond poorly to such antigens.Within a species it has been found that somegenetic types are good antibody producers,

while others are poorTermed responders and non-responders.


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Cellular control Specific immune response is classically divided into two branches,

antibody medicated immunity of B lymphocytes and cell mediatedimmunity of T lymphocytes.

T cells play an important role in regulating the production of antibodiesby B cells.

Helper T cell - upon interaction with an antigenic molecule theyrelease substances which help B lymphocytes to produce antibodiesagainst this antigen.

Suppressor T cell are thought to "turn off" B cells so that they canno longer cooperate with normal T cells to induce an immuneresponse.

Normal immune response probably represents a very fine balancebetween the action of helper and suppressor T cells.


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Hypersensitivity Reactions When the immune system "goes wrong" Hypersensitivity denotes a state of increased reactivity of

the host to an antigen and implies that the reaction isdamaging to the host.

The individual must first have become sensitized by previousexposure to the antigen.On second and subsequent exposures, symptoms and signs of ahypersensitivity state can occur immediately or be delayed untilseveral days later.

Immediate hypersensitivity refers to antibodymediated reactions, while delayed hypersensitivity refers to cell mediated immunity.


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Four Classifications

Type I ( Immediate ) Hypersensitivity Type II ( cytotoxic ) hypersensitivity

Type III ( immune complex mediated )hypersensitivity Type IV ( delayed ) hypersensitivity


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Type I ( Immediate ) Hypersensitivity

Reactions range from mild manifestations associated withfood allergies to life-threatening anaphylactic shock.

Atopic allergies include hay fever, asthma, food allergies andeczema.

Exposure to allergens can be through inhalation, absorption fromthe digestive tract or direct skin contact.Extent of allergic response related to port of entry, IE, bee stingintroduces allergen directly into the circulation.Caused by inappropriate IgE production

This antibody has an affinity for mast cells or basophils.


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When IgE meets its specific allergen it causes themast cell to discharge its contents of vasoactivesubstances into the circulation.

This release leads to symptoms of: sneezing,runny noses,red watery eyes andwheezing.

Symptoms subside when allergen is gone. The most common immunological

abnormality seen in medical practice.


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Doctors sometimes use skin tests to diagnose allergies. The

reactions shown here demonstrate allergic response.


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Anaphylactic shock is the most serious and fortunatelythe rarest form of this Type I hypersensitivity.

Symptoms are directly related to the massive release ofvasoactive substances leading to fall in blood pressure,

shock, difficulty in breathing and even death. It can be due to the following:

Horse gamma globulin given to patients who are sensitized tohorse protein.Injection of a drug that is capable of acting as a hapten into apatient who is sensitive, ie, penicillin.Following a wasp or bee sting in highly sensitive individuals.Foods peanuts, shellfish, etc.


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Anaphylaxis


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Anaphylaxis


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Anaphylaxis


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Epipen


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Type II ( cytotoxic ) Hypersensitivity

Manifested by the production of IgG or IgMantibodies which are capable of destroying cellssurface molecules or tissue components.

Binding of antigen and antibody result in theactivation of complement and destruction of cell towhich the antigen is bound.

Well known common example of this type ofhypersensitivity is the transfusion reaction due to

ABO incompatibility.


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In addition to hemolytic reaction to bloodthe following types of reactions are includedin this category:

Non-hemolytic reaction to platelets and plasmaconstituents.Immune hemolytic anemias

Hemolytic disease of the newborn Anaphylactic reactions


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Peripheral Smear


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Some individuals make antibody which crossreacts with self antigens found in both the lungand kidney.

Goodpasture syndrome associated with symptoms ofboth hemoptysis and hematuria. Some drugs may act as haptens, attach to the

RBC membrane causing antibodies to be formedthat react with the penicillin and lead to red celldamage and even hemolysis of the coated cells.


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Type III ( immune complex mediated )Hypersensitivity

Antibody produced in response to exposure to antigen, forms immunecomplexes of antigen and antibody which may circulate.

Complexes cause no symptoms, quickly disappear from the circulation. In some individuals the immune complexes persist in circulation

causing clinical symptoms, some of them serious.

Size of complexes produced seems important in determining whetherthey will be eliminated quickly from the body or retained long enoughto cause damage.

Classical clinical symptoms of immune complex disease are due toblood vessel involvement, i.e., vasculitis.

Blood vessels of joints and the kidney are most frequently affected,

giving rise to symptoms of arthritis and glomerulonephritis.


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Mechanisms are as follows:Soluble immune complexes which contain a greater proportion ofantigen than antibody penetrate blood vessels and lodge on the basementmembrane

At the basement membrane site, these complexes activate thecomplement cascade.

During complement activation, certain products of the cascade areproduced,`attract neutrophils to the area. Such substances are known aschemotactic substances.

Once the polymorphs reach the basement membrane they release theirgranules, which contain lysosomal enzymes which are damaging to theblood vessel.This total process leads to the condition recognized histologically asvasculitis.When it occurs locally (in the skin) it is known as an Arthus Reaction ,when it occurs systemically as a result of circulating immune complexes itis know as serum sickness .


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Chronic immune complex diseases arenaturally occurring diseases caused bydeposits of immune complex andcomplement in the tissues.

Systemic Lupus Erythematosus (SLE) Acute glomerulonephritis

Rheumatic feverRheumatoid arthritis


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Type IV ( delayed ) Hypersensitivity

Used to describe the signs and symptomsassociated with a cell mediated immune response.

Results from reactions involving T lymphocytes. Koch Phenomenon caused by injection of

tuberculoprotein (PPD test) intradermally resultingin an area of induration of 5 mm or more indiameter and surrounded by erythema within 48hours is a positive.


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Positive TB Test


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Summary


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Immunoglobulin Deficiency Diseases

Primary immunodeficiency syndrome Secondary immunodeficiency syndrome Acquired Immunodeficiency Syndrome (AIDS)


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Wiskott-Aldrich syndrome Condition with variable expression, but commonly includes

immunoglobulin M (IgM) deficiency. Always causes persistent thrombocytopenia and, in its complete form,

also causes small platelets, atopy, cellular and humoralimmunodeficiency, and an increased risk of autoimmune disease andhematologic malignancy.

In one study of 154 patients with WAS, only 30% had a classicpresentation with thrombocytopenia, small platelets, eczema, andimmunodeficiency; although 84% had clinical signs and symptoms ofthrombocytopenia, 20% had only hematologic abnormalities, 5% hadonly infectious manifestations, and none had eczema exclusively.

WAS is an X-linked recessive genetic condition; therefore, this disorderis found almost exclusively in boys.

WAS has been the focus of intense molecular biology research, whichrecently led to the isolation of the affected gene product.


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Acquired Immunodeficiency Syndrome (AIDS)

A condition in which T cell dysfunctionresults from a viral agent.

Loss of T cell activity renders the patientsusceptible to a wide variety of rare orunusual infections.

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The Immune Response, Functional Aspects

Recognition Processing

Production


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Recognition

An individual does not generally produceantibodies to antigens regarded as "self".

The system must have a memory so thatthe same antigen can be recognized afterre-exposure.

Lymphocytes are the recognition cells whichinitiate the immune response.

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Processing

Subsequent to recognition as foreign, anantigen's determinants must be processedin such a way that a specific antibody canbe produced.

Macrophages are believed to perform thisfunction because they ingest the antigen.


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Production

The final phase of the immune response isthe production of antibody.

This manufacturing system must beregulated in some way so that the immuneresponse can be discontinued when theantigen stimulation is withdrawn


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Terms Used to Describe Immunity

Active immunity - two typesNaturally from disease

Artificially such as from injection or purposeful exposureto antigen, i.e., measles.

Passive immunity involves receiving antibody orantibody protection produced by another.

Naturally such as the transfer of maternal antibodyacross the placenta to the fetus or by colostrum.

Artificially such as Hepatitis B Immune Globulin (alsoknown as gamma globulin) given after exposure toHepatitis B.


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References http://www.thebody.com/nih/immune_system.html http://pathmicro.med.sc.edu/ghaffar/hyper00.htm http://home.kku.ac.th/acamed/kanchana/bsi.html
http://www.thebody.com/nih/immune_system.htmlhttp://pathmicro.med.sc.edu/ghaffar/hyper00.htmhttp://home.kku.ac.th/acamed/kanchana/bsi.htmlhttp://home.kku.ac.th/acamed/kanchana/bsi.htmlhttp://pathmicro.med.sc.edu/ghaffar/hyper00.htmhttp://www.thebody.com/nih/immune_system.html

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