Hypersensitivity Ppt
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Transcript of 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