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Hypersensitivities/ Infections
“The Immune System Gone Bad”
Hypersensitivities
1. Allergies – Exaggerated immune
response against environmental antigens
2. Autoimmunity – immune response
against host’s own cells
3. Alloimmunity – immune response
against beneficial foreign tissues, such
as transfusions or transplants
These immune processes initiate inflammation
and destroy healthy tissue. Four types:
Type I – IgE-mediated allergic reactions
Type II – tissue-specific reactions
Type III – immune-complex-mediated
reactions
Type IV - cell-mediated reactions
Type I - IgE-mediated allergic reactions or
immediate hypersensitivity
Characterized by production of IgE
Most common allergic reactions
Most Type I reactions are against
environmental antigens - allergens
Sometimes beneficial to host – IgE-mediated
destruction of parasites
Selected B cells produce IgE
Need repeated exposure to large quantities
of allergen to become sensitized
IgE binds by Fc end to mast cells after first
exposure
Second exposure (and subsequent
exposures) – antigen binds with Fab portion of
antibody on mast cells, and cross-links
adjacent antibodies, causing mast cell to
release granules.
Response is immediate ( 5- 30 minutes)
Histamine release:
• Increases vascular permeability, causing
edema
• Causes vasodilation
• Constricts bronchial smooth muscle
• Stimulates secretion from nasal, bronchial
and gastric glands
• Also hives (skin), conjunctivitis (eyes) and
rhinitis (mucous membranes of nose).
Late phase reaction
• 2 – 8 hours; lasts for 2 - 3 days
• Other mediators that take longer to be
released or act:
– Chemotactic factors for eosinophils and
neutrophils
– Leukotrienes
– Prostaglandins
– Protein-digesting enzymes
Treatment
• First wave – antihistamines or epinephrine
(blocks mast cell degranulation)
• Second wave – corticosteroids and
nonsteroidal anti-inflammatory agents that
block synthesis of leukotrienes and
prostaglandins
• Desensitization by repeated injections of
allergen – formation of IgG
Anaphylaxis – Type I allergic reaction
may be localized or general
immediate – within a few minutes of
exposure
Systemic anaphylaxis:
pruritus(intense itching)
urticaria (hives)
Wheezing; dyspnea; swelling of the
larynx
Give epinephrine
Anaphylactic shock
• Hypotension, edema (esp. of larynx), rash,
tacycardia, pale cool skin, convulsions and
cyanosis
• Treatment:
– Maintain airway
– Epinephrine, antihistamines, corticosteroids
– Fluids
– Oxygen
Can be life threatening, so
individuals should be aware
• Skin tests – injection – see wheal and flare
• Lab tests for circulating IgE
Type II – Tissue specific reactions
(antibody-dependent cytotoxicity)
• Most tissues have specific antigens in their
membranes expressed only by that tissue
• Antibodies bind to cells or surface of a
solid tissue (glomerular basement
membrane)
Destruction of tissue occurs:
– Destruction by Tc Cells which are not
antigen specific
– Complement-mediated lysis
– Phagocytosis by macrophages
(“frustrated phagocytosis”)
– Binding of antibody causes cell to
malfunction
Type III – Immune-complexmediated reactions
• Caused by antigen-antibody complexes
formed in circulation and deposited in
vessel walls or other tissues
• Not organ specific
• Effects caused by activation of
complement – chemotaxis of neutrophils
• Neutrophils release lysosomal enzymes
into tissues (“frustrated phagocytosis”)
Type IV- Cell- mediated reactions
• Sensitized T lymphocytes – either Tc Cells
or lymphokine producing Td cells
• Takes 24 – 72 hours to develop
• Damage by Tc Cell or inflammatory
response by Td Cells (lymphokines)
• Graft rejection, tumor rejection, TB reaction,
poison ivy and metal reactions
• Immune diseases
• Tissue rejection
Systemic lupus erythematosus SLE
Autoanitbodies against nucleic acids
and other self components
Infection - viral
• Viruses extremely small – can infect
bacteria
• Usually just composed of DNA (or RNA) +
protein “coat” or capsid
• Can’t reproduce on their own – need to
use a host cell
Infection
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Adsorbed to host cell receptor
Penetration
Coat removal
Uses host enzymes to replicate nucleic
acid and proteins
• New viruses are assembled
• Virus is released
– Lytic cycle
Cellular effects
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Decreased synthesis of host proteins
Disruption of lysosomal membranes
Changes in host cell membrane proteins
Transform into cancer cell
Tissue damage may promote bacterial
infection