Transcript Immune System Disorders (Hypersensitivities ≈ Allergies)

Immune System Disorders
Hypersensitivities (≈ Allergies)
I) Anaphalactic
II) Cytotoxic
III) Immune Complex
IV) Cell-mediated (Delayed)
Autoimmune Diseases
Transplant Rejection
Hypersensitivity results from a second exposure to what could be
normally harmless antigen (≈ allergen). The second response is not
an appropriate normal one. The immune system goes too far.
I) Anaphalaxis
Allergies to pollen, pet dander,
insect venoms, fungal spores,
dust mites, peanuts, & penicillin.
Localized: (asthma, allergic
rhinitis; true food allergies)
Systemic (anaphalactic shock):
vasodilation throughout body,
BP drops; capillaries become
porous; edema; constricts
brachioles; fatality.
IgE from first exposure to
antigen (≈ allergen) bind to mast
cells and basophils; the person
is “sensitized”.
Treatment of
Anaphalaxis
• Short-Term:
- anti-histamines; epinephrine
- leukotriene receptor blockers
• Long-Term:
- Controlled repeat exposures; boost IgG
II) Cytotoxic
• IgG and IgM antibodies bind to foreign antigens on the
surface of otherwise healthy human blood cell types.
• This results in activation of the complement cascade via
the classic pathway, which leads to cytolysis of blood cells
with the foreign antigen.
• Further antibody and complement C3b binding results in
opsonization (i.e. enhanced phagocytosis by phagocytes)
of the blood cells with the foreign antigen.
• Which foreign antigens will cause a cytotoxic reaction?
– AB red blood cell (RBC) antigens & Rh RBC antigen
– Drugs (haptens) that bind to blood platelets to become antigenic.
Transfusion Rh Incompatibility &
Hemolytic Disease of the Newbornes
= thrombocyte
Thrombocytopenic
purpura
Intracerebral
hemorrhaging
Stroke
Bruising due to low
platelet count; poor
clotting favors
hemorrhages.
III) Immune Complex
The right proportions of antigen to IgG antibody results in small immune
complexes avoid phagocytosis and instead get stuck beneath endothelial
cells of capillaries. Damaging to kidney glomeruli (glomerulonephritis).
IV) Cell-Mediated (Delayed)
Takes days not hours or minutes; requires T cell and
macrophage migration to foreign antigen exposure sight.
Allergic Contact Dermatitis:
Latex gloves
Poison ivy
TB skin test is cell-mediated.
Autoimmune Diseases
• Lymphocytes become involved in attacking the bodies own cells (antigens).
• Self-tolerance of lymphocytes is lost: B cells produce antibodies and Tc cells
activate their cytotoxicity.
Causes:
• Similarities between viral and self antigens (Hepitius C autoimmunity).
• Cell malfunction due to antibody binding (Grave’s Disease; thyroid gland).
• Immune complex forms (rheumatoid arthritis; joints).
• Cell-mediated destruction of specific cell types (insulin-dependent diabetes
mellitus; insulin-secreting cells of pancreas).
• Some individuals are genetically predisposed (higher risk) due to specific
human leukocyte antigen (HLA) gene alleles that they possess.
Transplant Rejection
• Non-self hypothesis: for most tissues if the HLA classes do not match
there will be rejections by T cell, antibody, and complement attack on
transplant blood vessels; see graft-versus-host (GVH) disease.
• This does not apply for privileged sites; those that are non-vascular
(cornea, heart valves); rare exceptions.
• Grafts are the new tissues transplanted to a target site.
– Autographs;
– isographs;
– allographs; and
– xenographs.
• Immunosuppression by cyclosporine to minimize transplant rejection; its
action is suppression of IL-2 release. Other IL-2 receptor blockers are
also available (rapamycin).