1. HYPERSENSITIVITY REACTIONS AND AUTOIMMUNITY
BSc in Public Health
11th &12th week
2014

2. HYPERSENSITIVITY REACTIONS
Innocous materials can cause hypersensitivity in certain individuals
leading to unwanted inflammation  damaged cells and tissues
Non-proper reaction of the immune system to foreign substances
Mainly harmless substances – after second or multiple exposure
Type I.
„immediate”
Type II.
Type III.
Type IV.
„late”
Antibody mediated
T cell mediated

3. TYPES OF ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS
FcRIα)

4. TYPE I HYPERSENSITIVITY REACTION
ALLERGY

5. SENSITISATION PROCESS
Once sensitized (immunized), every following exposure to the allergen elicits the allergic reactions.

7. TYPES OF ALLERGIC REACTIONS
Pruritus

8. GENETIC/ENVIRONMENTAL PREDISPOSITION TO ALLERGY
Genetic factors
chromosome 11q
FcεRβ chain gene
IL-3-5 IL-9, IL-13 GMCSF
HLAII DRB1*015
Inproper immunregulation
Th1/Th2 inbalance
regulation of IgE synthesis
high eosinophil counts
allergy
Environmental factors
lack of tolerance

9. Prick test

10. Type II hypersensitivity
IgG type antibodies bound to cell surface or tissue antigens
cells expressing the antigen become sensitive to complement mediated lysis or to opsonized phagocytosis
frustrated phagocytosis  tissue damage
the antibody inhibits or stimulates target cell function no tissue damage

11. MECHANISMS OF TYPE II HYPERSENSITIVITY REACTIONS

12. FRUSTRATED PHAGOCYTOSIS MEDIATED BY IgG TYPE ANTIBODIES
Binding Opsonization Internalization Enzyme release
Extensive tissue damage
Opsonized surface Binding Frustrated Enzyme release
phagocytosis

13. DRUG INDUCED ANEMIA

14. MYASTHENIA GRAVIS GRAVES DISEASE
Autoantibodies against TSH receptors on thyroid cells causing stimulation and overproduction of thyroid hormones
Autoantibodies against ACh receptors in neuromuscular junction inhibiting transmission of nerve impulses to muscles
progressive muscle weakness
hyperthyroidism, goiter, protrusion of eyeballs

15. TYPE III HYPERSENSITIVITY
Antibodies binding to soluble antigens forming small circulating immune complexes which are deposited in various tissues
Depends on:
Size of immune complexes
Antigen-antibody ratio
Affinity of antibody
Isotype of antibody

16. TYPE III HYPERSENSITIVITY
symptoms caused by type III hypersensitivity reactions depend on the site of immune complex deposition
serum sickness – intravenous immunecomplexes (horse antiserum against snake/spider venom)
Arthus reaction – localized, skin
Farmer’s lung – localized, lungs

17. TYPE IV HYPERSENSITIVITY REACTION
T CELL MEDIATED PROCESS

18. TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY

19. TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY

20. TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY

21. DELAYED-TYPE HYPERSENSITIVITY (DTH) (e.g. tuberculin skin test)

22. TUBERCULIN SKIN TEST (MANTOUX TEST)
SCREENING PREVIOUS IMMUNIZATION (MEMORY T CELL RESPONSE)
Introduction of Ag
Ag = antigen:
Purified protein derivate (PPD) isolated from mycobacteria

23. CONTACT DERMATITIS
mediated by both helper and cytotoxic T cells recognizing peptide antigens originated from skin proteins that were modified by the contact sensitizing agents (e.g. cathecol of poison ivy, nickel)

24. CELIAC DISEASE gluten is recognized as non-self antigen by T cells
inflammation of the gut wall in the presence of gluten
tissue damage cause villous atrophy  malabsorption
gluten-free diet can solve the problem

25. AUTOIMMUNITY
Recognition of self-antigens by the cells of the adaptive immunity (B and T cells) normally induce tolerance
Tolerance is achieved by different mechanisms in the body:
elimination of auto-reactive (self-recognizing) lymphocytes in the bone marrow and thymus (the process is more strict regarding T cells)
limited access of lymphocytes to some tissues (CNS, eyes, testicles)
suppression by regulator T cells (CD4+ subtype)
induction of anergy (e.g. in the absence of costimulation)
normal tissue cells are not expressing MHC class II and/or costimulatory molecules
If any of these malfunction, activation of auto-reactive lymphocytes may provoke severe immune response against self tissues

26. AUTOIMMUNE DISEASES
The immune response against self-tissues is the same as against pathogens
Continuous presence of self-antigens maintain activation of auto-reactive cells  chronic inflammation
Tissue destruction surpasses tissue regeneration
Autoimmune responses can be categorized into type II, III or IV hypersensitivity reactions (the innocuous agent is the self-antigen in these cases)

27. GOODPASTURE SYNDROME (type II)
auto-antibody production against type IV collagen of the basement membrane
causing inflammation and tissue damage in the kidneys and lungs
localized / tissue-specific autoimmune disease

28. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) (type III)
characteristic dermal lesion in SLE patients: the malar rash or butterfly rash
fluorescent microscopic figure of immunecomplex depositions at the dermal-epidermal junction

29. RENAL FAILURE IN IMMUNECOMPLEX DISEASES
Glomerulus of a healthy individual. Relatively wide spaces between capillary loops.
One of the feared complications of the systemic autoimmune diseases is renal failure. This is most likely to occur in SLE. Here is a glomerulus in which the capillary loops are markedly pink and thickened such that capillary lumens are hard to see. This is lupus nephritis.

30. REUMATHOID ARTHRITIS (type III and IV)
cellular immune response against the synovial membranes of joints
CD4+ and
CD8+ T cells
B cells/plasma cells
neutrophils
macrophages
Rheumatoid factor: anti-IgG-Fc specific antibodies

31. MECHANISM OF AUTOIMMUNE INSULIN-DEPENDENT DIABETES (type IV)
AUTOREACTIVE CYTOTOXIC T CELLS KILL INSULIN SECRETING β-CELLS
Insulin
b cell
d cell
a cell
108 insulin secreting cells
glucagon
somatostatin
Pancreatic islet cells