Lecture (4) Hypersensitivity

●Type III (Immune Complex)

● Type IV (Cell Mediated)
Reactions
 Type III (Immune Complex) Reactions
• Involve antibodies directed against antigens which
are not part of host cells, but soluble antigens
circulating in the serum.
• In contrast, type II immune reactions are directed
against antigens located on cell or tissue surface.
• The antigen-antibody complexes are deposited on
organs (precipitate and lodge in basement
membranes) and cause inflammatory damage.
• These immune complexes insert themselves into
small blood vessels, joints, and glomeruli, causing
symptoms.
 Type III (Immune Complex) Reactions

• Immune complexes form only when certain

ratios of antigen and antibody occur.
• The antibodies involved are usually IgG.
• A significant excess of antibody leads to the
formation of complement- fixing complexes
that are rapidly removed from the body by
phagocytosis. When there is a significant excess
of antigen, soluble complexes from that do not
fix complement and do not cause inflammation.
 Type III (Immune Complex) Reactions

• When a certain antigen-antibody ratio exist,

usually with a slight excess of antigen, the
soluble complexes that form are small and
escape phagocytosis leads to inflammation
and cell lysis.
• Large complexes can be cleared by
macrophages but, comparatively macrophages
have difficulty in the disposal of small immune
complex.
 Type III (Immune Complex) Reactions
• Example: Glomerulonephritis
• Is an immune complex condition, usually resulting
from infection, that cause inflammatory damage to
the kidney glomeruli, which are site of blood
filtration.
 Type III (Immune Complex) Reactions
• Occurs as a sequel to a beta-hemolytic streptococcal
infection (group A).
• Antigen-antibody complexes circulate in the blood, pass
between endothelial cells of the blood vessels, and become
trapped in the basement membrane beneath the cells. In
this location, they may activate complement and cause a
transient (temporary)inflammatory reaction: attracting
neutrophils that release enzymes.
• Repeated introduction of the same antigen can lead to more
serious inflammatory reaction, causing damage to the
basement membrane’s endothelial cells within 2-8 hours.
Type III (Immune Complex) Reactions
Glomerulonephritis
Type III (Immune Complex) Reactions
 Type IV (Delayed- Cell Mediated) Reactions

• Up to this point we have discussed humoral immune

responses involving IgE, IgG or IgM.
• Type IV reactions involved cell-mediated immune
responses and are caused mainly by T cells.
• Delayed-type hypersensitivity (TDTH) reactions are due
primary to T-cells proliferation.
• Delayed-type hypersensitivity are not apparent for a
day or more.
• Transplant rejection is most commonly mediated by
cytotoxic T-lymphocytes.
 Causes of Delayed- Cell Mediated
Reactions
• When certain antigens, particularly those that bind to tissue cells,
are phagocytized by macrophages and then presented to receptors
on the T-cell surface.
• Contact between the antigenic determinant sites and the
appropriate T cell, causes the T cell to proliferate into mature
differentiated T cells and memory cells. (time)
• When reexposure occur memory cells will activate T cells
• Sensitized T-cells secrete lymphokines (cytokines) in their
interaction with the appropriate antigen.
• Lymphokines attract and activate macrophages and initiate tissue
damage.
• Examples of delayed hypersensitivities:
• Tuberculin skin test
• Allergic contact dermatitis
 Delayed- Cell Mediated Hypersensitivity
Reactions of the Skin
• One delayed hypersensitivity reaction that involves
the skin is the familiar screening skin test for
tuberculosis.
• The tuberculosis skin test is a test used to determine
if someone has developed an immune response to
the bacterium that causes tuberculosis (TB).
• The tuberculin skin test is based on the fact that
infection with M. tuberculosis bacterium produces a
delayed-type hypersensitivity skin reaction to certain
components of the bacterium.
Delayed- Cell Mediated Hypersensitivity Reactions of the Skin

1-The components of the organism are contained in extracts of

culture filtrates PPD (known as purified protein derivative).
2-This PPD material is used for skin testing for tuberculosis.
3-Reaction in the skin to tuberculin PPD begins when
specialized immune cells, called T cells, which have been
sensitized by prior infection, are recruited by the immune
system to the skin site.
4- Where they release chemical messengers called
Lymphokines.
5- Lymphokines induce induration (a hard, raised area with
clearly defined margins at and around the injection site).
6- Lymphokines attract and activate macrophages and other
types of inflammatory cells to the area. initiate tissue
damage.
Delayed- Cell Mediated Hypersensitivity
Reactions of the Skin
 Allergic contact Dermatitis
• Another common manifestation of delayed
cell-mediated hypersensitivity, is usually
caused by haptens that combine with proteins
in the skin of some people to produce an
immune response.
• Reaction to poison ivy, cosmetics, metals in
jewelry and latex surgical gloves are
examples.
Allergic Contact Dermatitis - Reaction to Latex Surgical Gloves
 Allergic Contact Dermatitis – Reaction to
Catechols from the Poison ivy plant
• Catechols are oils secreted by the plant that
dissolve easily in skin oils and penetrate the
skin. In the skin Catechols function as hapten-
that is, they combine with skin proteins to
become antigenic and provoke an immune
response.
• The first contact with poison ivy sensitizes the
susceptible person, and subsequent exposure
results in contact dermatitis.
Development of an Allergy to Catechols from Poison Ivy
• THE END