This document discusses hypersensitivity reactions and autoimmune diseases. It describes the different types of hypersensitivity reactions (Type I-IV) and their mechanisms and examples. It also discusses autoimmune diseases, noting they arise due to genetic susceptibility and environmental triggers damaging self tolerance. Autoimmune diseases can affect many organ systems. The document also briefly touches on tissue transplant rejection, immunodeficiencies, HIV/AIDS, and amyloidosis.

1. Hypersensitivity and
autoimmune diseases

2. • Medical news reports a rise of
hypersensitivity reactions to various
foodstuffs, particles and even personal
stuff. In what 3 ways do you think would
help you as well as the patient in
preventing catastrophic events arising
from hypersensitivity reactions in the
dental clinic?

3. Hypersensitivity
• The phenomenon of damage caused by
the immune system while trying to combat
an insult.
• Precipitating factor (external), instead of
the immune system coping and restoring
the body’s homeostasis, the immune
response is altered and becomes the
“internal” cause of disease.

4. Type I hypersensitivity
• Anaphylactic
• Release of allergic mediators
• Asthma, eczema, hay fever and reactions
to certain food
• Grass pollen, house dust mite feces or
seafoods

6. • Immediate injections of epinephrine
• Antihistamine or steroids as back up
medications
• Avoidance of allergens

7. Type II hypersensitivity
• Antibody dependent cytotoxic
hypersensitivity
• Antibodies react with antigens fixed to the
surface of various types of cells and cause
damage
• Complement fixing (the antibodies cause
the destruction of the target cell or
damage the surrounding cells)

8. • Functional fixing (antibodies interfere
with cell function)
• Drug reactions where a binding of a drug
may alter a normal self antigen and thus
produce something that can no longer be
tolerated

9. Type II hypersensitivity - Rhesus incompatibility

11. Type III hypersensitivity
• Immune complex mediated
hypersensitivity
• Antibody driven process
• The antibodies react with free antigen and
under the right circumstances they form
soluble immune complexes that circulate
in the blood giving rise to “serum sickness”

12. Type III hypersensitivity – Farmer’s Lung Alveolitis

14. Type IV hypersensitivity
• Cell mediated (delayed type)
hypersensitivity
• T lymphocytes which over several hours
and days recruit and activate other T cells
and macrophages and produce local
tissue damage and granuloma formation

15. Type IV hypersensitivity – Mantoux Test

16. Autoimmune Diseases
General Principles
• Autoimmunity arises through some
combination of susceptibility genes
(causing loss of self tolerance) and
environmental triggers (specially infection)

17. • Self antigens or abnormal immune cells
develop that incite the immune response
into abnormal or excessive activity of T or
B lymphocytes
• Once induced tend to be progressive,
albeit with occasional relapses and
remissions

18. • Most autoimmune disorders are complex
multigenic disorders
- associated with specific
histocompatibility molecule HLA alleles
- defects in pathways that normally
regulate either peripheral or central
tolerance
- polymorphisms in other genes
(PTPN- 22, NOD-2, IL-2 and IL-7)
• Role of infection

19. • GI: primary biliary cirrhosis, ulcerative colitis and
atrophic gastritis
• Cardiovascular: pernicious anemia, hemolytic
anemia, idiopathic thrombocytopenia and
leukopenia
• Endocrine: insulin dependent diabetes,
thyrotoxicosis and Hashimoto’s thyroiditis
• Musculoskeletal: mixed connective tissue
diseases, rheumatoid arthritis, systemic lupus
erythematosus, myasthenia gravis
• Dermatology: dermatomyositis and
scleroderma

20. Rejection of Tissue Transplants
• Mechanisms of recognition:
- Class I molecules are expressed on
all nucleated cells. Class I molecules
bind peptide fragments derived from
endogenous proteins
- Class II molecules are confined to
APC including dendritic cells,
macrophages, B cells and activated T
cells

21. - Class II molecules bind peptide
fragments derived from exogenous
proteins and presents these processed
antigens to CD4+ T lymphocytes
• Host T cells recognize either by direct or
indirect pathways

22. Rejection of solid organs:
• Following lymphocyte activation, rejection
is mediated by the following:
- direct CTL-mediated parenchymal
and endothelial cytolysis
- macrophage mediated damage
- cytokine mediated vascular and
parenchymal dysfunction
- microvasccular injury
- antibody mediated responses

23. • Rejection:
- hyperacute
- acute
- chronic

24. Immunodeficiency Syndrome
• Primary immunodeficiencies
- are usually hereditary and manifest
between 6 months and 2 years of life
as maternal protection is lost
• Secondary immunodeficiencies
- result from altered immune function
due to infections, malnutrition, aging,
immunosuppression, irradiation,
chemotherapy and autoimmunity

25. • Acquired immunodeficiency syndrome
- retrovirus human immunodeficiency
virus (HIV) characterized by profound
suppression of T cell mediated
immunity leading to opportunistic
infections, secondary neoplasms and
neurologic disorders

26. Amyloidosis
• Amyloid is a heterogenous group of
fibrillar proteins that share the ability to
aggregate into an insoluble, cross-beta
pleated sheet tertiary conformation
• Amyloid fibrils accumulate extracellularly
in tissues due either to excess synthesis
or resistance to catabolism

27. • As amyloid accumulates, it produces
pressure atrophy of adjacent parenchyma
• Depending on tissue distribution and
degree of involvement, the clinical effects
of amyloid can range from life threatening
to an asymptomatic incidental finding at
autopsy

28. Do you have any questions?