allergy

Topic: 'Hyper sensitivity'

Presented by: Sadya Laraib6th semester (A)

Roll no. 30.

1. Definition:

It is excessive immune response which leads to undesirable consequences, i.e. tissue or organ damage/ dysfunction.

immune responses which are damaging rather than helpful to the host.

Excessive immune response in a sensitized individual (atopic) leading to tissue damage.

Why hypersensitivity occurs in some people? (not all) Allergins Low immunity from childhood Host factors include heredity, gender, race, and

age, with heredity being by far the most significant.

 However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone.

Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.

Types of Hypersensitivity:

Nearly 45 years ago Gell and Coombs proposed a classification scheme which defined 4 types of hypersensitivity reactions.

Ab mediated: type:Ⅰ, Ⅱ, Ⅲ (Immediate)T-cell mediated: type Ⅳ (Delayed)

Hypersensitivity type I

Hypersensitivity type II

Hypersensitivity type III

Hypersensitivity type IV

Hyper sensitivity type I:

IgE mediated, immediate hypersensitivity/ allergyMajor features: React and disappear quickly on re-exposure to AgDysfunction rather than severe tissue and cell damage occursObvious individual difference and genetic correlationBy mast cells and basophils

MECHANISM OF ACTION

BASIC ELEMENTS ARE:

1. MEDIATOR = IgE2. PRIMARY CELLULAR COMPONENT =

MAST CELL AND BASOPHILS3. AMPLIFIER = PLATELETS,

NEUTROPHILS AND EIOSINOPHILS

MECHANISM OF ACTION

MECHANISM OF ACTION

STEP 1:EXPOSURE OF ANTIGEN TO ANTIGEN

PRESENTING CELL

MECHANISM OF ACTION

STEP 2:RECOGNITION BY T- HELPER CELLS

ACTIVATION OF B-CELLS INTO PLASMA AND MEMORY CELLS

SECRETION OF ANTIBODIES (IgE)

MECHANISM OF ACTION

STEP 3:IgE BINDS TO HIGH AFFINITY

RECEPTORS (FC EPSILONRI)

ON THE SURFACE OF MAST CELLS

MECHANISM OF ACTION

STEP 4:SUBSEQUENT EXPOSURE OF ANTIGEN

ANTIGEN BINDS WITH IgE ON THE SURFACE OF MAST CELLS

Mechanism of action

MECHANISM OF ACTION

STEP 5:RELEASE OF PRIMARY INFLAMMATORY

METABOLTES

ACTIVATION OF SECONDARY METABOLITES

SYMPTOMS

1.May vary from minor inconvenience to death

2.Usually take 10 to 30 mins to appear after exposure to antigen

3.Sometimes delayed onset of reaction (10-12h)

MECHANISM OF ACTIONMOLECULE EFFECTS

PRIMARY MEDIATORS

HISTAMINE VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

SEROTONIN VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

ECF-A EOSINOPHIL CHEMOTAXIS

NCF-A NEUTROPHIL CHEMOTAXIS

PROTEASES MUCUS SECRETION, CONNECTIVE TISSUE DEGRADATION

SECONDARY MEDIATORS

LEUKOTRIENES VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

PROSTAGLANDINS VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTIONAND PLATELET ACTIVATION

BRADYKININ VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION

CYTOKINES NUMEROUS EFFECTS INC. ACTIVATION OF VASCULAR ENDOTHELIUM, EOSINOPHIL RECRUITMENT AND ACTIVATION

CLINICAL DISEASESAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites, foods, and medications.

Asthma (from the Greek, "panting") is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, etc

Allergic rhinitis is an allergic inflammation of the nasal airways. It occurs when an allergen, such as pollen, dust or animal dander (particles of shed skin and hair) is inhaled by an individual with a sensitized immune system.

The protein in the food is the most common allergic component. These kinds of allergies occur when the body's immune system mistakenly identifies a protein as harmful. Some proteins or fragments of proteins are resistant to digestion and those that are tagged by the IgE. The immune system, thinking the organism (the individual) is under attack, triggers an allergic reaction. These reactions can range from mild to severe. Allergic responses include dermatitis, gastrointestinal and respiratory distress, including such life-threatening anaphylactic responses  and vasodilation; these require immediate emergency intervention. Individuals with protein allergies commonly avoid contact with the problematic protein. Some medications may prevent, minimize or treat protein allergy reactions. injectable form of epinephrine such as an EpiPen

Anaphylaxis

Allergic Rhinitis

Asthma

Food Allergy

DIAGNOSTIC TESTS

1. PRICK TEST2. TRANSDERMAL TEST3. ELISA

TREATMENT

1. ANTIHISTAMINES2. Chromolyn sodium3. leukotriene receptor blockers 4. use of IgG antibodies

Hyper sensitivity type II:

Definition:

A hypersensitivity resulting from antibodies mistakenly reacting with normal self antigens on body cells. Binding of the antibodies to these normal cells results in immune destruction.

MEDIATORS

IgG OR IgMIN THIS CASE

1. MADE AGAINST SELF ANTIGENS

2. ATTACH TO THE SURFACES OF CELLS HAVING SELF EPITOPS

SELF ANTIGEN=Any constituent of the body's own tissues capable of stimulating autoimmunity

FACTORS FOR RELEASE OF MEDIATORS

1. FAILURE IN IMMUNE TOLERANCE

2. ENTERANCE OF FOREIGN ANTIGEN RESEMBLING SOME MOLECULE ON THE SURFACE OF HOST CELLS

'IMMUNE TOLERANCE' is the process by which the immune system does not attack an antigen

MECHANISM OF ACTION

THESE FACTORS LEAD TO:

1. OPSONIZATION2. MAC LYSIS3. ADCC

1- OPSONIZATION

DEFINITION:The attachment of microbes and other

foreign cells to phagocytes by antibody molecules such as IgG and complement proteins such as C3b. Also called enhanced attachment or immune adherence.

OPSONIZATION

MECHANISMTHE OPSONIZATION IS OF THE HOST CELL

PHAGOCYTES STICK TO MEMBRANES OF HOST CELL

VIA IgG, C3B, C4B

PHAGOCYTES DISCHARGE THEIR LYSOSOMES

OPSONIZATION

RESULT:LYSIS OF HOST CELL

2- MAC LYSIS

DEFINITION

A protein complex produced during the complement pathways. C5b6789 (MAC or membrane attack complex) puts pores into lipid bilayer membranes of human cells to which antibodies have bound. This results in cell lysis.

MAC LYSIS

MECHANISMIgG / IgM

BINDS WITH EPITOPS ON CELL SURFACES

ACTIVATE CLASSICAL PATHWAY OF COMPLEMENT SYSTEM

MAC CAUSES LYSIS OF CELL

MAC LYSIS

MECHANISM

3-ANTI-BODY DEPENDENT CYTOTOXICITY (ADCC)

DEFINITION

The process of NK cells binding to the Fc portion of antibodies that have bound to epitopes of cells recognized as nonself such as infected cells and tumor cells. Once bound to the Fc portion of the antibody, the NK cell will then lyse that cell with perforins.

ADCC

MECHANISMIgG / IgM

BINDS WITH EPITOPS ON CELL SURFACES

NK CELLS ATTACH TO THE Fc PORTION OF IgG/IgM

RELEASE OF PERFORINS AND GRANZYMES BY NK

APOPTOSIS

ADCC

MECHANISM

ADCC

MECHANISM

EXAMPLES OF TYPE 2 HYPERSENSITIVITY AB AND RH BLOOD GROUP REACTIONS;

AUTOIMMUNE DISEASES SUCH AS: RHEUMATIC FEVER where antibodies result in

joint and heart valve damage; IDIOPATHIC THROMBOCYTOPENIA PURPURA

where antibodies result in the destruction of platelets;

MYASTHENIA GRAVIS where antibodies bind to the acetylcholine receptors on muscle cells causing faulty enervation of muscles;

GOODPASTURE'S SYNDROME where antibodies lead to destruction of cells in the kidney;

EXAMPLES OF TYPE 2 HYPERSENSITIVITY

SOME DRUG REACTIONS. TYPE II HYPERSENSITIVITY ALSO

PARTICIPATES IN EARLY TRANSPLANT REJECTIONS.

DIAGNOSTIC TESTS

1. DETECTION OF CIRCULATING ANTIBODY AGAINST THE TISSUES INVOLVED

2. THE PRESENCE OF ANTIBODY AND COMPLEMENT IN THE LESION (BIOPSY) BY IMMUNOFLUORESCENT STAINING (PATTERN = LINEAR).

TREATMENT

ANTI-INFLAMMATORY DRUGS

IMMUNOSUPPRESSANT DRUGS

Hyper sensitivity type III: (THE IMMUNE COMPLEX HYPERSENSITIVITY)Definition:

A hypersensitivity resulting from large quantities of soluble antigen-antibody complexes passing between endothelial cells of the blood vessels and becoming trapped on the surrounding basement membrane.

COMPOSITION OF IMMUNE COMPLEX

1. SELF OR NON-SELF ANTIGEN

2. ANTIBODIESMOSTLY IgG RARELY IgM

PATHOLGY OCCURS AT THE SITE OF DEPOSITION

CAUSE OF TYPE 3 HYPERSENSITIVITY

NORMALLYSOLUBLE ANTIGEN-ANTIBODY

COMPLEX FORMATION

REMOVED BY MACROPHAGES IN SPLEEN AND LIVER

CAUSE OF TYPE 3 HYPERSENSITIVITYABNORMALLY

INCREASED SOLUBLE ANTIGEN-ANTIBODY COMPLEX FORMATION

NOT ALL REMOVED BY MACROPHAGES IN SPLEEN AND LIVER

DEPOSITION OF COMPLEXES VIA BLOOD VESSELS

MECHANISM OF ACTION

STEP 1 Large quantities of soluble antigen-antibody

complexes form in the blood and are not completely removed by macrophages.

MECHANISM OF ACTION

STEP 2 These antigen-antibody complexes lodge in the

blood vessels between the endothelial cells and the basement membrane.

MECHANISM OF ACTION

STEP 3 These antigen-antibody complexes

activate the classical complement pathway leading to vasodilation

MECHANISM OF ACTION

STEP 4 The complement proteins and antigen-

antibody complexes attract leukocytes to the area.

MECHANISM OF ACTION

STEP 5 The leukocytes discharge their killing

agents and promote massive inflammation. This can lead to tissue

death and hemorrhage.

EXAMPLES OF TYPE 3 HYPERSENSITIVITY

1. SERUM SICKNESS, A COMBINATION TYPE I AND TYPE III HYPERSENSITIVITY

2. AUTOIMMUNE ACUTE GLOMERULONEPHRITIS

3. RHEUMATOID ARTHRITIS4. SOME CASES OF CHRONIC VIRAL

HEPATITIS

DIAGNOSTIC TESTS

1. Examination of tissue biopsies for deposits of immunoglobulins and complement by immunofluorescence (pattern = granular)

2. The presence of immune complexes in serum

3. Depletion in the level of complement

TRAETMENT

ANTI-INFLAMMATORY DRUGS

Hyper sensitivity type IV: (THE CELL MEDIATED OR DELAYED TYPE HYPERSENSITIVITY)Definition:

A hypersensitivity resulting from cell-mediated immunity (cytotoxic T-lymphocytes and cytokines) causing harm to the body.

CAUSE OF TYPE 4 HYPER-SENSITIVITY

CAUSED BY T-CELLS1. T-HELPER CELLS BY SECRETION OF

CYTOKINES2. MAINLY BY CYTOTOXIC T-CELLS BY

DIRECT DAMAGE

MECHANISM OF ACTION T-H CELLS INDUCED

STEP 1ANTIGEN ENTERS THE BODY

ENGULFED BY MACROPHAGES

PRESENTED TO T-H CELLS

T-H CELLS BECOMES ACTIVATED AND INCREASED IN NUMBER

MECHANISM OF ACTION T-H CELLS INDUCED

STEP 2SECOND EXPOSURE

ENGULFED BY MACROPHAGES

PRESENTED TO T-H CELLS

T-H CELLS RELEASE CYTOKINES

MECHANISM OF ACTION T-H CELLS INDUCED

STEP 3 T-H 1 or TD CELLS

RELEASE CYTOKINES

ATTRACTION FOR MORE MACROPHAGES AT THE

SITE OF ATTACK

MORE INFLAMMATION

SKIN LESIONS

T-H 2 CELLS RELEASE

IL-4 AND IL-5

PROMOTE EXTRACELLULAR

KILLING BY EOSINOPHILS

TISSUE DAMAGE

MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED

STEP 1ANTIGEN BINDS TO NORMAL CELL

EPITOPE PRESENTED WITH MHC-1

CTL ATTACHED BY TCR/CD8+

ACTIVATION OF T-CELL

MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED

STEP 2

ACTIVATION OF CYTOTOXIC T-CELL

RELEASE OF 1. PORE-FORMING PROTEINS CALLED

PERFORINS2. PROTEOLYTIC ENZYMES CALLED GRANZYMES

3. CHEMOKINES

MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED

STEP 3

PERFORINS FORM PORES

GRANZYMES PASS THROUGH PORES

ACTIVATE ENZYMES OF CELLS

APOPTOSIS

MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED

EXAMPLES OF TYPE 4 HYPERSENSITIVITY

THE CELL OR TISSUE DAMAGE done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections.

THE SKIN TEST REACTIONS seen for tuberculosis and other infections

CONTACT DERMATITIS like poison ivy TYPE -1 INSULIN-DEPENDENT

DIABETES where CTLs destroy insulin-producing cells

DIAGNOSTIC TESTS

1. IN VIVO1. Mantoux test2. Patch test

2. INVITRO1. Lympho-cytotoxicity2. IL-2 production

ANY QUESTIONS?