Hypersensitivity Ppt

4th SEMESTER PHARM.D SESSION (2007-2012)

Defense against microbes is mediated by: Innate immunity

Early reactions Also called natural or native immunity

Adaptive immunity Late responses High specificity Memory

Adaptive immunity Is important for host defense against microbial

infections Can cause tissue injury and disease

Hypersensitivity diseases Disorders caused by immune responses

A common cause of hypersensitivity disease is failure of self-tolerance Property of the immune system that

ensures that individuals do not respond to their own antigens

Disorders caused by failure of self-tolerance are called autoimmune

diseases

Hypersensitivity diseases may also result from uncontrolled or excessive responses against foreign antigens

Microbes Noninfectious environmental antigens

TYPES, MECHANISMS AND DIAGNOSTIC TESTS

The term hypersensitivity is used to describe immune responses which are damaging rather than helpful

to the host.

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

hypersensitivity reactions.

The four types of hypersensitivity are:1.Type I Hypersensitivity- IgE mediated2.Type II Hypersensitivity- Antibody

mediated3.Type III Hypersensitivity- immune complex4.Type IV Hypersensitivity- cell mediated

The first three are mediated by antibody, the fourth by T cells.

THE “IMMEDIATE” ALLERGIC REACTION

A hypersensitivity due to excessive production of the class of antibody known as IgE. Reactions between

allergens and IgE bound to mast cells and basophils cause a greatly

heightened inflammatory response.

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)

BASIC ELEMENTS ARE:

1. MEDIATOR = IgE2. PRIMARY CELLULAR COMPONENT =

MAST CELL AND BASOPHILS3. AMPLIFIER = PLATELETS,

NEUTROPHILS AND EIOSINOPHILS

STEP 1:EXPOSURE OF ANTIGEN TO ANTIGEN

PRESENTING CELL

STEP 2:RECOGNITION BY T- HELPER CELLS

ACTIVATION OF B-CELLS INTO PLASMA AND MEMORY CELLS

SECRETION OF ANTIBODIES (IgE)

STEP 3:IgE BINDS TO HIGH AFFINITY RECEPTORS

(FC EPSILONRI)ON THE SURFACE OF MAST CELLS

STEP 4:SUBSEQUENT EXPOSURE OF ANTIGEN

ANTIGEN BINDS WITH IgE ON THE SURFACE OF MAST CELLS

STEP 5:RELEASE OF PRIMARY INFLAMMATORY

METABOLTES

ACTIVATION OF SECONDARY METABOLITES

MOLECULE 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

The reactions, mediated by agents without IgE-allergen interaction, are not hypersensitivity reactions although they produce the same

symptoms. 

1. Anaphylaxis2. Asthma3. Allergic Rhinitis 4. Food Allergy

1. PRICK TEST2. TRANSDERMAL TEST3. ELISA

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

THE CYTOTOXIC HYPERSENSITIVITY

DefinitionA 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.

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

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

THESE FACTORS LEAD TO:

1. OPSONIZATION2. MAC LYSIS3. ADCC

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.

MECHANISMTHE OPSONIZATION IS OF THE HOST CELL

PHAGOCYTES STICK TO MEMBRANES OF HOST CELL

VIA IgG, C3B, C4B

PHAGOCYTES DISCHARGE THEIR LYSOSOMES

RESULT:LYSIS OF HOST CELL

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.

MECHANISMIgG / IgM

BINDS WITH EPITOPS ON CELL SURFACES

ACTIVATE CLASSICAL PATHWAY OF COMPLEMENT SYSTEM

MAC CAUSES LYSIS OF CELL

MECHANISM

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.

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

MECHANISM

MECHANISM

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;

SOME DRUG REACTIONS. TYPE II HYPERSENSITIVITY ALSO

PARTICIPATES IN EARLY TRANSPLANT REJECTIONS.

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).

ANTI-INFLAMMATORY DRUGS

IMMUNOSUPPRESSANT DRUGS

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.

1. SELF OR NON-SELF ANTIGEN

2. ANTIBODIESMOSTLY IgG RARELY IgM

PATHOLGY OCCURS AT THE SITE OF DEPOSITION

NORMALLYSOLUBLE ANTIGEN-ANTIBODY COMPLEX

FORMATION

REMOVED BY MACROPHAGES IN SPLEEN AND LIVER

ABNORMALLYINCREASED SOLUBLE ANTIGEN-ANTIBODY

COMPLEX FORMATION

NOT ALL REMOVED BY MACROPHAGES IN SPLEEN AND LIVER

DEPOSITION OF COMPLEXES VIA BLOOD VESSELS

STEP 1 Large quantities of soluble antigen-antibody

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

STEP 2 These antigen-antibody complexes lodge in the blood

vessels between the endothelial cells and the basement membrane.

STEP 3 These antigen-antibody complexes activate the classical complement pathway leading to vasodilation

STEP 4 The complement proteins and antigen-antibody complexes attract leukocytes

to the area.

STEP 5 The leukocytes discharge their killing

agents and promote massive inflammation. This can lead to tissue

death and hemorrhage.

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

2. AUTOIMMUNE ACUTE GLOMERULONEPHRITIS

3. RHEUMATOID ARTHRITIS4. SOME CASES OF CHRONIC VIRAL

HEPATITIS

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

ANTI-INFLAMMATORY DRUGS

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.

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

CYTOKINES2.MAINLY BY CYTOTOXIC T-CELLS BY

DIRECT DAMAGE

STEP 1ANTIGEN ENTERS THE BODY

ENGULFED BY MACROPHAGES

PRESENTED TO T-H CELLS

T-H CELLS BECOMES ACTIVATED AND INCREASED IN NUMBER

STEP 2SECOND EXPOSURE

ENGULFED BY MACROPHAGES

PRESENTED TO T-H CELLS

T-H CELLS RELEASE CYTOKINES

STEP 1ANTIGEN BINDS TO NORMAL CELL

EPITOPE PRESENTED WITH MHC-1

CTL ATTACHED BY TCR/CD8+

ACTIVATION OF T-CELL

STEP 2

ACTIVATION OF CYTOTOXIC T-CELL

RELEASE OF 1. PORE-FORMING PROTEINS CALLED

PERFORINS2. PROTEOLYTIC ENZYMES CALLED GRANZYMES

3. CHEMOKINES

STEP 3

PERFORINS FORM PORES

GRANZYMES PASS THROUGH PORES

ACTIVATE ENZYMES OF CELLS

APOPTOSIS

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

1. IN VIVO1. Mantoux test2. Patch test

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

Corticosteroids and other immunosuppressive agents

CHARACTERISTICS

type-I(anaphylacti

c)

type-II(cytotoxic)

type-III(immune complex)

type-IV(delayed

type)

ANTIBODY IgE IgG, IgM IgG, IgM None

ANTIGEN exogenous cell surface soluble tissues & organs

RESPONSE TIME

15-30 minutes

minutes-hours

3-8 hours 48-72 hours

APPEARANCE weal & flare lysis and necrosis

erythema and edema, necrosis

erythema and

induration

HISTOLOGY basophils and eosinophil

antibody and

complement

complement and

neutrophils

monocytes and

lymphocytes

TRANSFERRED WITH

antibody antibody antibody T-cells

EXAMPLES allergic asthma, hay

fever

Erythro-blastosisfetalis,

Farmer's lung disease

tuberculin test, poison

ivy, granuloma