Topic: 'Hyper sensitivity' Presented by: Sadya Laraib 6 th semester (A) Roll no. 30.
May 24, 2015
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?