THE
ADAPTIVE IMMUNE SYSTEM
V.
HYPERSENSITIVITY
B.
Immediate Hypersensitivity
3.
Type III (Immune
Complex-Mediated)
Fundamental Statements for this Learning Object:
1. Type III (immune complex-mediated) hypersensitivity is caused when soluble antigen-antibody (IgG or IgM) complexes, which are normally removed by macrophages in the spleen and liver, form in large amounts and overwhelm the body.
2. These small complexes lodge in the capillaries, pass between the endothelial cells of blood vessels - especially those in the skin, joints, and kidneys - and become trapped on the surrounding basement membrane beneath these cells.
3. The antigen/antibody complexes then trigger excessive activation of the classical complement pathway leading to a massive inflammatory response, influx of neutrophils with extracellular killing of body tissue, MAC lysis of tissue, and aggregation of platelets and macrophages.
4. Examples include Serum sickness, autoimmune acute glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus.
LEARNING
OBJECTIVES FOR THIS SECTION
When the immune systems cause harm
to the body, it is referred to as a hypersensitivity (def).
There are two categories of adaptive hypersensitivities: immediate hypersensitivity
and delayed hypersensitivity. Immediate hypersensitivities (def)
refer to humoral immunity (antigen/antibody reactions) causing harm;
delayed hypersensitivities (def)
refer to cell-mediated immunity (cytotoxic T-lymphocytes. macrophages,
and cytokines) leading to harm.
There are 3 types of immediate
hypersensitivities that depend on the interaction of antigens (def) with antibodies (def):
Type I, Type II, Type III, and Type V. In this section we will look at Type
III immediate hypersensitivities.
3. Type III
(Immune complex-mediated) (def)
Mechanism:
This is caused when soluble antigen-antibody
(IgG or IgM) complexes, which are normally removed by macrophages in
the spleen and liver, form in large amounts and overwhelm the body
(see Fig. 1). These small complexes lodge
in the capillaries, pass between the endothelial cells of blood vessels
- especially those in the skin, joints, and kidneys - and become trapped
on the surrounding basement membrane (def)
beneath these cells (see Fig. 2). The antigen/antibody
complexes then activate the classical complement pathway (def)
(see Fig. 3). This may cause:
a. Massive inflammation, due to complement protein C5a triggering mast cells to release inflammatory mediators;
b. Influx of neutrophils (def), due to complement protein C5a , resulting in neutrophils discharging
their lysosomes and causing tissue destruction through extracellular killing and causing further inflammation
(see Fig. 4 and Fig.
5);
c. MAC lysis (def)
of surrounding tissue cells, due to the membrane attack complex, C5b6789n;
d. Aggregation of platelets, resulting in more inflammation and the formation of microthrombi
that block capillaries; and
e. Activation of macrophages (def), resulting in production of inflammatory cytokines and extracellular killing causing tissue destruction.
This can lead to tissue death
and hemorrhage.
Examples include:
- serum sickness, a combination
type I and type III hypersensitivity;
- autoimmune acute glomerulonephritis;
- rheumatoid arthritis;
- systemic lupus erythematosus;
- some cases of chronic viral
hepatitis; and
- the skin lesions of syphilis
and leprosy.
Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.
Last updated: Feb., 2020
Please send comments and inquiries to Dr.
Gary Kaiser