T Cell Mediated Hypersensitivity

1. T CELL-MEDIATED
HYPERSENSITIVITY
(TYPE IV)
DR. HASNI MAHAYIDIN (hasnim_7@yahoo.com)
IMMUNOLOGY UNIT
PATHOLOGY DEPARTMENT
FACULTY OF MEDICINE AND HEALTH SCIENCES
UNIVERSITI PUTRA MALAYSIA

2. RECAP
• Hypersensitivity reaction:
▫ Excessive / inappropriate immune response

3. RECAP
• Classification of hypersensitivity:
▫ Coombs and Gell (1963)
TYPES IMMUNE
COMPONENT
CLINICAL
I (immediate) IgE, mast cells,
eosinophils
Allergic reactions
II Antibodies (IgG,
IgM)
Antibody-mediated cell
reactions
III Antibodies Immune complex-
mediated reactions
IV T cells Cell-mediated reactions

4. T cell-mediated immune response
Immunity
Innate
Adaptive
Humoral
Cell-
mediated

5. Type IV hypersensitivity
• aka:
▫ Delayed-type hypersensitivity (DTH)
▫ T cell-mediated hypersensitivity
▫ Cellular-mediated hypersensitivity
• T cell-mediated inflammatory response

6. T cell-mediated HS
• Involved antigen specific CD4+ T cells
• CD4+ T cells are normal component of adaptive
immunity
• Essential for control of pathogens, particularly
intracellular organisms
• May also response to chemicals and self antigens
• However, if the response is excessive  damage
to host

8. • 2-phase:
▫ Sensitization phase
▫ Effector phase
• >12hrs to develop (according to the Coombs and
Gell classification)
• Three variants of DTH:
▫ Contact Hypersensitivity
▫ Tuberculin-type Hypersensitivity
▫ Granulomatous Hypersensitivity

9. • The 3 types of DTH were originally
distinguished according to the reaction they
produced when the antigen was directly applied
to the skin (epicutaneously) or injected
intradermally.
• The degree of response is usually assessed by
measuring thickening of the skin.

10. Phases of DTH
• Primary contact
• Sensitization (1-2 weeks)
 Antigen presentation by APC
 Occur in regional lymph nodes
 Priming of antigen specific CD4 cells
• Effector phase due subsequent exposure to the
antigens (peaks 48-72 hrs)
 Recruitment of antigen specific CD4 cells
 Influx of macrophages
 Secretion of pro-inflammatory cytokines

14. • Three variants of DTH:
▫ Contact Hypersensitivity
▫ Tuberculin-type Hypersensitivity
▫ Granulomatous Hypersensitivity

15. Contact hypersensitivity
• aka contact dermatitis
Nickel watch Nickel pendant

16. Nickel ear ring
Rubber slippers

17. Rubber gloves
Contact dermatitis due
rubber gloves

18. Contact dermatitis
• Occur at the point of contact with an allergen
(usually haptens)
• Hapten: a small molecule that can not elicit an
immune response on its own
• Haptens bind to carrier (tissue) protein to form neo-
antigen (immunogenic)
• Uptake by Langerhans’ cells  stimulation of
keratinocytes & pro-inflammatory cytokines
• Present to T cells at regional lymph nodes
• Recruitment of effector T cells and macrophages
• Dermatitis (eczema)

21. Patch test

22. Tuberculin hypersensitivity
• Seen following tuberculin skin test (TST) or
Mantoux test
• Induced by soluble antigens from a variety of
organism
• Originally developed by Koch in 1890
• Current technique in use was described in 1912
by Charles Mantoux, a French physician

23. • Soluble antigens introduced intradermally
• Characteristic skin-test reaction (induration)
that peak after 24 hours
• Skin induration is thickening of the skin due to
migration of lymphocytes and macrophages into
the dermis, the proliferation of cells in the
dermis in response to cytokines, and the
deposition of new extracellular matrix.

24. Mantoux test

25. • Positive reaction shows existence of antigen
specific T cells (previous exposure)
 Due pathogenic form of M. tuberculosis
 BCG vaccination
• Can be done for other infections as well

27. Granulomatous hypersensitivity
• Due to intracellular pathogens that resist
macrophage killing
• Chronic/ continuous T cell stimulation leads to
cytokine secretion (IL-3, IFN-γ & GM-CSF)
• Recruit & activate macrophages
• Failure of eradicating intracellular pathogens
induces epithelioid cell transformation
• Epithelioid cells secretes TNF-α and induce cell
fusion to form giant cells

28. Granuloma • Granuloma is composed of
a core of infected (and
uninfected) macrophages,
epithelioid cells, multi-
nucleated giant cells
(fusion of activated
macrophages), along with
peripheral accumulation
of T lymphocytes, plasma
cells, maybe a few
neutrophils and
fibroblasts with collagen;
with or without central
necrosis.

29. • Many chronic diseases manifest granulomatous
hypersensitivity
• Most are due to infectious agents
▫ Tuberculosis (TB)  M.tuberculosis
▫ Leprosy  M.leprae
▫ Schistosomiosis  worm schistosomas
• In some, no infectious agents has been
established
▫ Sarcoidosis
▫ Crohn’s disease

30. Pulmonary
tuberculosis

31. Leprosy
• A chronic infection by
bacteria M.leprae and
M.lepromatosis
• Initially infections are
without symptoms and for
5 - 20 years. Symptoms
that develop include
granulomas of
the nerves respiratory
tract, skin, and eyes.

32. • This may result in a
lack of ability to feel
pain and thus loss of
parts of extremities
due to repeated
injuries.

33. Reference
• Immunology 7th edition, David Male et al.,
Mosby Elsevier, Canada. 2006.