THE ADAPTIVE IMMUNE SYSTEM

V. HYPERSENSITIVITY

C. Delayed Hypersensitivity (Type IV)

Fundamental Statements for this Learning Object:

1. During delayed hypersensitivity,T8-lymphocytes become sensitized to an antigen and differentiate into cytotoxic T-lymphocytes (CTLs) while effector T4-lymphocytes become sensitized to an antigen and produce cytokines.
2. CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit.
3. Examples include the cell or tissue damage done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections, candidiasis, and histoplasmosis, the skin test reactions seen for tuberculosis and other infections, contact dermatitis like poison ivy, type-1 insulin-dependent diabetes where CTLs destroy insulin-producing cells, multiple sclerosis, where T-lymphocytes and macrophages secrete cytokines that destroy the myelin sheath that insulates the nerve fibers of neurons, and Crohn’s disease and ulcerative colitis.

 

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.

In this section we will look at Type IV or delayed hypersensitivity.

C. Delayed Hypersensitivity (Type IV) (def)

Delayed hypersensitivity is cell-mediated rather than antibody-mediated.

Mechanism: Delayed hypersensitivity is the same mechanism as cell-mediated immunity. T8-lymphocytes (def) become sensitized to an antigen and differentiate into cytotoxic T-lymphocytes (def) while effector T4-lymphocytes become sensitized to an antigen and produce cytokines (def). CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit (see Fig. 1 and Fig. 2).

1. CTLs use their TCR/CD8 to bind to peptide epitopes bound to MHC-I (def) on infected cells or normal cells having cross-reacting epitopes and kill them through apoptosis (def).

2. T_H1 cells (def) activate macrophages (def)causing the production of inflammatory cytokines and extracellular killing by the macrophages leading to tissue damage.

3. T_H2 cells (def) produce interleukin-4 (IL-4) and interleukin-5 (IL-5) to promote extracellular killing by eosinophils (def) and causing tissue damage.

Examples include:

• the cell or tissue damage done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections, candidiasis, and histoplasmosis;
• the skin test reactions seen for tuberculosis and other infections;
• contact dermatitis like poison ivy;
• type-1 insulin-dependent diabetes where CTLs destroy insulin-producing cells;
• multiple sclerosis, where T-lymphocytes and macrophages secrete cytokines that destroy the myelin sheath that insulates the nerve fibers of neurons;
• Crohn’s disease and ulcerative colitis; and
• psoriasis.

Delayed hypersensitivity also plays a major role in chronic transplant rejection as a result of CTL destruction of donor cells (host versus graft rejection) or recipient cells (graft versus host rejection). Immunosuppressive drugs such as cyclosporin A or FK-506 (Tacrolimus) are given in an attempt to prevent rejection. Both of these drugs prevent T-lymphocyte proliferation and differentiation by inhibiting the transcription of IL-2.

For More Information: TH1 and TH2 cells from Unit 6

For More Information: CTLs from Unit 6

• QUIZ YOURSELF ON THIS SECTION

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.