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Dr.T.V.Rao MD
Dr.T.V.Rao MD
Hypersentivity Reactions
Allergies Greek = altered reactivity
Hypersensitivity reactions over reaction of the immune system to harmless environmental antigens
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Definition
Definition : Hypersensitivity refers to the injurious consequences in the sensitized host ,Following contact with specific Antigen
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Hypersensitivity
Immunity protects against
Infections, Toxins. Many other functions. But Immunity can be Injurious, When exaggerated causes Tissue Damage, Disease and Death
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Initial contact sensitizes the Immune system. The antigen acts as priming dose
Causes the priming of B/T Lymphocytes,
Hypersensitivity reactions
Type I Mechanism Antigen Onset IgE-Ag triggers Allergen minutes Mast cell mediators IgG or IgM binds to Cell surface Few cell surface; ADCC molecule hours or complement Immune complexes, Soluble or Few inflammation particulate hours Cytokines (T cells, Chemicals, 1-3 Macrophages, CTL) intracellular days Dr.T.V.Rao MD
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Classification of Hypersensitivity
Immediate and Delayed. Immediate type Also called as Immediate Hypersensitivity Popularly called as B cell Mediated Hypersensitivity
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Anaphylaxis Atopy, Antibody mediated cell damage. Arthus Phenomenon Serum sickness
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Hypersensitivity-1
Inappropriate immune responses Type I are immediate type, in which antigen binds to IgE on mast cells, histamine released.
Histamine: smooth muscle contraction, vasodilatation. Results in asthma, diarrhea, shock depending on where antigen enters body. Ex. Bee sting
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Type II Hypersentivity
Type II are cytotoxic reactions like the Rh factor problem and bad blood transfusions.
Rh is one of many blood groups, like ABO An Rh+ fetus in an Rh- mother means she gets immunized by babys blood cells, makes Antibodies. Second pregnancy, fetal RBCs are attacked. Solution: give Rho-gam during 1st pregnancy.
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Type IV
Type IV are delayed type, T cell produces various cytokines which affect macrophages.
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The bar fight scenario: come, stay, get angry. Angry macrophages cause much tissue damage. Ex. Poison ivy; urushiol-coated cells killed.
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Type I Hypersensitivity
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Examples of Immediate Hypersensitivity Anaphylaxis Atopy, Antibody mediated cell damage. Arthus Phenomenon Serum sickness
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Type I hypersensitivity
Anaphylaxis = Ana means without Phylaxis protection ( Rich ) Sensitizing dose more effective when given parentally Antigen can hapten also may take 2-3 weeks to produce sufficient IgE Shocking dose is effective if given IV The nature of antigen should correspond to antibodies
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Type I
Anaphylactic Ig E ( Reagin ) Antibodies are fixed on Tissue cells Eg Mast cells and Basophils Antigen + Antibody combination causes release of Pharmacologically active substances Occurs in Acute and Chronic or recurrent form (Non Fatal and localized Atopy)
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Anaphylaxis
Classical Immediate Hypersensitivity Experiments in dogs with Sea anemones Guinea pigs By any route with Antigens and Haptens 2-3 weeks later with sensitizing or shocking dose I V
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Same is experienced in Humans With bee sting Penicillin administration Happens in sensitized individuals
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Nature of IgE
Present in low fractions compared with other Immunoglobulin's IgE is heat sensitive inactivated at 560c in 2 4 hours heat causes damage to Fc particle
IgA deficiency produces excessive IgE
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2. Leukotriene's:
Bronchial smooth muscles contract Asthmas
3. Prostaglandin:
High concentration of PGE low concentration of PGE
Inhibit the secretion of histamine
4. Common
2) Allergic rhinitis
4. Skin allergy:
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Atopy
When the antigen and antibody IgE react produce certain pharmacologically active substances Can cause Conjunctivitis, Rhinitis G E involvement Dermal involvement Urticaria
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Mechanism of Anaphylaxis
Ig E cell fixed on Mast cells and Basophiles. Antigen + Antibody Bridges the gap Leads to deregulation Releases Biologically active substances from granules of the cells.
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Serotonin
Produces on Decarboxylation of Tryptophan Found in Intestines, Mucosa, Brain tissue, Platelets Causes smooth muscle contraction Increases capillary permeability Vasoconstriction Human ?
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Other factors
Heparin Not in human Enzymatic mediators proteases and hydrolases
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Effects of Histamine
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Many of us suffer
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Other Mediators
By complement activation Bradykynin Anphylactoid reactions can be caused due to IV Peptone, Trypsin by IV routes
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Clinical effects
Causes smooth muscle contraction. Increased vascular permeability Many organs Target organ shock organ Causes Edema Fall of BP, Coagulation of Blood, Leucopenia, thrombocytopenia Guinea pigs most susceptible Humans Intermediate Bee stings, Penicillin, Causes the constriction of smooth muscles( Bronchioles )
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Skin tests
Skin test via intra dermal injection of allergens: if an individual is allergic to the substance injected, local mast cells de granulate producing a wheel and flare response within minutes
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Atopy
Agent Inhaled Pollens /Dust Ingested Egg , Milk Contact with skin Conjunctiva Ig E is over produced Bottle fed infants Estimation of Ig E by RAST
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Blocking antibody
3. Drug therapy
1) Stabilization of triggering cells sodium cromoglycate stabilize the membrane, inhibit mast cell degranulation
2) Mediator antagonism
Chlor-Trimeton Antihistamine
4. New immunotherapy
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Type II Hypersensitivity
Type II hypersensitivity or cytotoxic hypersensitivity is caused by antibody-mediated reactions. When the immune system reacts to antigens it produces various Immunoglobulin's or antibodies, usually long-lasting immunoglobulin G (IgG) antibodies.
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Type II (Cytotoxic) Reactions Involve activation of complement by IgG or IgM binding to an antigenic cell. Antigenic cell is lysed. Transfusion reactions:
ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.
Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.
Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.
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Type II Hypersensitivity
LATS Antibodies stimulate determinants on Thyroid Leads to excessive secretion of Thyroid hormones
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Type II Hypersensitivity
The binding of these antibodies to the surface of host cells then leads to: opsonization of the host cells whereby phagocytes stick to host cells by way of IgG, C3b, or C4b and discharge their lysosomes
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Type II Hypersensitivity
(Contd)
Anti erythrocyte antibodies Autoimmune Anemia's Hemolytic anemia's. Antigen + Antibody =Cell damage Even Hap tens act in the place of Antigen Disrupts the normal function Graves disease , Myasthenia gravis.
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The Fab of IgG reacts with epitopes on the host cell membrane. PhagocytesMD Dr.T.V.Rao bind to the Fc portion
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Step-2
Phagocytes binding to the Fc portion of the IgG Dr.T.V.Rao MD and discharge their lysosomes causing cell
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Type II Hypersensitivity
Salmonella , and Mycobacterium can produce Hemolytic crisis
Diagnostic tests include detection of circulating antibody against the tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence
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Introduction
Immune complexes(Ag and Ab) deposit in tissues such as blood vessels and glomeruli. activate complement, and cause tissue injury or dysfunctional responses.
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Arthus reaction
Injecting repeatedly sc Normal horse serum Later injections leads edema, indurations hemorrhagic necrosis manifest as localize from of generalized hypersensitivity Damage is caused due to Antigen and antibody complexes, leads to activation of complement Release of inflammatory molecules Vascular permeability, infiltration of neutrophils. Causes tissue necrosis Eg Inhalation of Actinomyctes from mouldy hay grain causes Farmers lung
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C5-C9
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2- Serum Sickness
* A systemic immune complex phenomenon * Injection of large doses of foreign serum * Antigen is slowly cleared from circulation * Immune complexes are deposited in various sites fever urticaria Arthralgia lymphadenopathy splenomegaly glomerulonephritis antidiphtheritic serum penicillin Dr.T.V.Rao MD sulphonamides
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Large complex
Endothelial cell
Small complex
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Serum Sickness
May last for 7-10 days. Bacterial Viral and Parasitic infection produce serum sickness. Important Diseases Post Streptococcal Glomerulonephritis Hepatitis B Infections Auto immune conditions. Disseminate malignancies.
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Type IV Hypersensitivity
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Type IV Hypersensitivity
Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response
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Delayed hypersensitivity.
The reaction elicited by antigen occurs relatively slowly (hence the name "delayed hypersensitivity"). The hypersensitivity is mediated via Tcells and macrophages. The hypersensitivity illustrates both antigen-specific (T-cell) and antigen nonspecific (macrophage) characteristics
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Type IV Reactions
Type IV reactions, which are also called delayed hypersensitivity reactions, as a rule occur 12 - 48 hours after exposure to the antigen. Type IV reactions lead to inflammatory tissue damage and infiltration of cells, which are principally mononuclear (lymphocytes and macrophages).
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Type IV reactions
The inflammatory reaction leads to irreversible damage with deterioration of the tissue. The classical examples of type IV hypersensitivity are the positive tuberculin reaction, contact dermatitis (e.g. caused by nickel or chrome) and rejection of tissues transplanted from other individual
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Tuberculin Type ( IV )
Tuberculin reaction. Tuberculin Injection Sensitized to Tuberculin protein. Indurations develop at the site < 48 hours. Unsensitized No response Bacteria, Fungi, Viruses, Parasites
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Tuberculin Test
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Measurement of Induration
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2) Contact dermatitis :
Paint, drug red rash, papula, water blister, dermatitis
3) Acute rejection of allogenic transplantation and immune response in local tumor mass
Same disease (SLE), multiple immune injury ,hypersensitivity involved
Same drug (penicillin), several types of hypersensitivity
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*a contact-sensitizing agent is usually a small molecule that penetrates the skin then binds to self-proteins, making the protein look foreign
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Contact dermatitis
Contact dermatitis or Irritant dermatitis is a term for a skin reaction resulting from exposure to allergens (allergic contact dermatitis) or irritants (irritant contact dermatitis).
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Contact Dermatitis ( IV )
Delayed hypersensitivity Skin contact. Cell Mediated response. Nickel, Chromium, Dyes , Penicillin's Antigens absorbed, Langerhams cells capture Migrate to draining lymph nodes, Present the processed Antigens with MHC molecules to Immune cells.
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Created by Dr.T.V.Rao MD for Undergraduate Medical and Paramedical students in the Developing world
Email
doctortvrao@gmail.com
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