Disorders of Immune System
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Transcript of Disorders of Immune System
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Disorders of Immune System
- Hypersensitivity Reactions:
Immune response to exogenous antigens
- Autoimmune diseases:
Immune reactions against self antigens
- Immune deficiency syndromes
Congenital / acquired
- Amyloidosis
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Hypersensitivity reactions
- Group of immune reactions resulting from exposure to
exogenous antigens
- Designed as a protective response but usually results in
tissue injury
- Caused by mixture of humoral and cell mediated reactions
- Classified into 4 types based on immunologic basis
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Hypersensitivity reactions
- Type I (Immediate) hypersensitivity
- Type II (antibody mediated) hypersensitivity
- Type III (immune complex mediated) hypersensitivity
- Type IV (cell mediated) hypersensitivity
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Type I Hypersensitivity Reaction:
- Rapidly developing immunologic reaction
- Occurs within minutes of antigen-antibody reaction
- Antibody is bound to surface of sensitized mast cells
- Antigen is called allergen and reaction is called allergy
- Reaction may be localized or systemic
- Release of vasoactive and spasmogenic substances
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Local reaction:
Depends on the point of entry of allergen
- Localized cutaneous swellings (skin allergy, hives)
- Nasal / conjunctival discharge (allergic rhinitis / conjunctivitis)
- Hay fever, bronchial asthma (respiratory allergy)
- Allergic gastroenteritis (food allergy)
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Local reaction:
Depends on the point of entry of allergen
- Localized cutaneous swellings (skin allergy, hives)
- Nasal / conjunctival discharge (allergic rhinitis / conjunctivitis)
- Hay fever, bronchial asthma (respiratory allergy)
- Allergic gastroenteritis (food allergy)
Systemic
- Follows injection of allergen
- Produces state of shock within minutes
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Elements that participate in Type 1 hypersensitivity:
- B and T lymphocytes
- Antigen presenting cells
- Mast cells & Basophils
- IgE antibodies
- Chemical mediators
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Mast cells:
- Bone marrow derived, widely distributed in tissues
- Contain cytoplasmic membrane bound mediator granules
- Have high affinity IgE Fc receptors
- Also triggered by complement C5a and C3a (anaphylotoxin)
- Responsible for allergic reactions in tissue
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Mediators:
Primary: Secondary
- Histamine - Phospholipids
- Proteases (PGD2, Leukotrienes)
- Chemotactic factors - Platelet activating factor
- Cytokines
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Action Mediator
Vasodilation, Increased vascular permeability
HistaminePAFLeukotrienes C4, D4, E4Neutral proteases (activate complement)PGD2
Smooth muscle spasm
Leukotrienes C4, D4, E4HistamineProstaglandinsPAF
Cellular infiltration
Cytokines TNFLeukotriene B4Eosinophil and Neutrophil chemotactic factorsPAF
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Local hypersensitivity reactions
- Immediate phase (initial response):
Vasodilation and vascular leakage, smooth muscle contraction
Starts 5-30 minutes and subsides in 1 hour
Vasoactive amines are responsible
- Second phase (Late response):
Tissue infiltration by inflammatory cells including eosinophils
Starts 2-24 hrs and lasts for many days
Other mediators including cytokines
Major cause of symptoms in asthma etc. Inflammatory response
is sustained without further antigen exposure
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Type I Hypersensitivity may be genetically determined
(ATOPY)
Atopic individuals have higher levels of serum IgE
Family history of allergy is seen in 50% atopic individuals
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Antibody mediated (Type II) Hypersensitivity
- Antibody directed against antigens present on cells and tissues
- Antigen may be self or of external origin (drug metabolite)
- Basis for many auto immune diseases
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Mechanisms
1a) Opsonization and complement and Fc receptor mediated phagocytosis
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Mechanisms
1a) Opsonization and complement and Fc receptor mediated phagocytosis
1b) Complement mediated lysis of opsonized cells (C5-9) (MAC)
1c) Antibody dependent cellular toxicity (ADCC)
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Antibody mediated cell destruction and phagocytosis
- Blood transfusion reactions
- Erythroblastosis fetalis
- Autoimmune hemolytic anemia, agranulocytosis, thrombocytopenia
- Drug induced hemolytic anemia
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Mechanisms
2) Complement and Fc Mediated inflammation
- Antibody deposited in extracellular tissues
- Complement activation (C5a)
- Inflammatory cells recruited, activated
- Enzymes and reactive oxidative metabolites
- TISSUE INJURY
Causes- Glomerulonephritis- Vascular rejection- Acute rheumatic fever
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Mechanisms3) Antibody mediated cellular dysfunction
Antibody binds to cell surface
receptors and disrupts function
Myasthenia gravis,
Pemphigus vulgaris
Antibody binds to cell surface
receptors and stimulates function
Graves disease
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Type III Hypersensitivity (immune complex mediated)
- Antigens and antibodies form complexes either in circulation of locally
in tissues (Antigen may be exogenous (foreign protein, bacteria, virus)
or endogenous (ones own))
- The complexes get deposited in tissues
- Inflammatory reaction is initiated resulting in tissue damage
- May be generalized (serum sickness) or localized (arthus reaction)
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Serum sickness
- Injection of horse serum into humans (passive immunization)
- Antibodies (preformed / new) against horse proteins
- Antigen Antibody complexes deposit in tissues
- Fever, skin rash, arthritis, nephritis
- Resolution following clearing of complexes
- Chronic exposure / re-exposure --------------------------
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Arthus reaction: Local antigen stimulus in a sensitized individual
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Arthus reaction: Local antigen stimulus in a sensitized individual
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Arthus reaction: Local antigen stimulus in a sensitized individual
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Morphologic consequences:
- Fibrinoid necrosis of blood vessels
- Proliferative glomerulonephritis
- Arthritis
Vasodilation and edema
Neutrophil and monocyte infiltrate
Necrosis