Cell mediated immunity Chap15

Cell-Mediated Immunity

Overview

Cell-mediated immunity (CMI) is a crucial arm of the adaptive immune system, primarily involving specialized lymphocytes known as T cells. These cells respond to intracellular antigens (Ags), such as those presented by virus-infected or tumor cells.

• Differentiation and Migration: After their maturation and differentiation in the thymus gland, T cells circulate to various lymphoid tissues including lymph nodes and the spleen where they await activation.

• Mechanism of Action: T cells can identify antigens displayed on the surface of infected or abnormal cells via Major Histocompatibility Complex (MHC) molecules. Upon recognition, T cells engage directly in the destruction of these foreign cells and secrete cytokines that modulate the functions of other immune system cells, thus orchestrating a coordinated immune response.

• Memory T Cells: Once activated, sensitized T cells proliferate and differentiate into long-lasting memory T cells, which provide the immune system with the capability to respond more rapidly and effectively upon subsequent exposures to the same antigens.

Types of T Cells

T Helper Cells (CD4 or TH)

• Role: The most prevalent type of T cell, responsible for regulating immune reactions to various antigens by providing help to other immune cells, especially B cells and cytotoxic T cells.

• Activation: They activate macrophages, enhancing phagocytosis and increasing the innate immune response.

• Subtypes:

  • T Helper 1 (TH1): Specializes in boosting cell-mediated immune responses, particularly against intracellular pathogens.

  • T Helper 2 (TH2): Plays a key role in humoral immunity, facilitating the activation of B cells and the production of antibodies.

Cytotoxic T Cells (CD8 or TC)

• Function: These cells are pivotal in directly killing foreign or infected cells by releasing perforins, which are pore-forming proteins that result in the lysis of target cells.

• Mechanism: They require recognition of MHC class I molecules, which present endogenous antigens from within the cell.

Natural Killer Cells

• Characteristics: Unlike T cells, natural killer (NK) cells are part of the innate immune system and exhibit a broader range of action without prior sensitization. They circulate through the spleen, blood, and lungs, attacking virus-infected cells and tumors.

Other T Cell Subsets

• Delayed Hypersensitivity T Cells (TD): Involved in allergic responses and delayed-type hypersensitivity reactions, such as those seen with poison ivy and graft rejections.

• Suppressor T Cells (TS): Also known as regulatory T cells, they function to suppress or downregulate the immune response to maintain homeostasis and prevent autoimmunity when antigens are no longer present.

Characteristics of T Cell Subsets

Summary Table of T Cell Functions

Mechanism of Helper T Cells

• The interaction between helper T cells (especially TH1) and antigen-presenting cells (APCs) is essential for T cell activation. Upon recognizing an antigen bound to MHC II, helper T cells proliferate and release interleukin-2, which further stimulates specific immune responses and aids in the activation of B cells. This interaction underpins both cell-mediated immunity (against infected cells) and humoral immunity (antibody production by B cells).

Antibody-Dependent Cell-Mediated Cytotoxicity

• This process involves the activation of additional immune cells such as eosinophils and macrophages. Once activated, these effector cells release cytotoxic lytic enzymes that damage extracellular pathogens, thus enhancing the immune response to larger pathogens.

Nonspecific Cells in Cell-Mediated Response

• Activated Macrophages: When macrophages engulf and digest pathogens, they become activated and exhibit an increased capacity to present antigens and secrete pro-inflammatory cytokines.

• Natural Killer (NK) Cells: These cells provide rapid responses to viral infections and tumor formation, utilizing mechanisms that do not require prior sensitization to a specific antigen.

Superantigens and T Cell Activation

• Superantigens are a unique class of antigens that remarkably activate a large number of T cells by binding to T cell receptors (TCRs) and MHC molecules simultaneously. This can lead to a hyperactive immune response, resulting in systemic issues such as toxic shock and multi-organ damage due to excessive cytokine release.

Interrelationship Between Immunity Types

• The interplay between B cells and T helper cells is crucial, as B cells generally require T-dependent activation through cytokine signaling from TH cells. Additionally, antibody-dependent cell-mediated cytotoxicity (ADCC) mechanisms necessitate cooperation between antibodies, NK cells, and other nonspecific defense mechanisms to eliminate targeted pathogens and infected cells.

Immunization and Manipulating Immunity

Passive Immunity

• Involves the administration of immune serum globulin, offering immediate but temporary protection, typically lasting 2-3 months. Passive immunity is used in preventive measures for diseases like measles and hepatitis A, as well as in clinical settings to replace antibodies in immunodeficient patients.

Vaccination (Active Immunity)

• Purpose: Vaccination employs a deliberate exposure to non-pathogenic antigenic materials, thus priming the immune system for future encounters with pathogenic forms. This process stimulates both primary and secondary immune responses.

Vaccine Preparation

• Various preparations exist for vaccines, including:

  • Killed whole cells or inactivated viruses that cannot cause disease.

  • Live-attenuated organisms capable of inducing strong immune responses with fewer doses but may require special storage conditions.

  • Antigenic molecules derived from the microbes, such as capsular components or surface proteins.

  • Genetically engineered vaccines that use plasmid vectors for antigen production in host organisms, showing potential against diseases like AIDS and tuberculosis.

Effective Vaccine Characteristics

• Vaccines must be:

  • Safe with minimal side effects.

  • Effective against wild-type pathogens.

  • Capable of stimulating robust B-cell and T-cell-mediated responses.

  • Provide long-lasting immunity and stimulate memory formation.

  • Require few doses, have extended shelf-lives, and be simple to administer.

Types of Vaccines

• Killed or Inactivated Vaccines: Necessitate larger doses and multiple boosters to establish effective immunity.

• Live Attenuated Vaccines: Generate lasting immunity, mimicking natural infections while requiring careful handling.

• Antigenic Molecules Vaccines: Leverage known antigenic determinants for immune response induction.

• Genetically Engineered Vaccines: Utilize genetic manipulation to produce antigens, relevant in cutting-edge immunology research.

Route of Administration and Side Effects

• Most vaccines are given via injection. However, oral or nasal routes may be suitable for certain vaccines. Potential side effects may include localized reactions (swelling or redness), fever, and, in rare instances, serious adverse events. Adjuvants may be added to enhance the efficacy of vaccines, promoting a stronger and longer-lasting immune response.