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-complex-mediated 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

• 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

• 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