Cellular Immunity: T Cells and Immune Regulation (Part 2: Part 2)

Cytokines

Definition and Function

Cytokines are chemical messengers of the immune system that mediate cell development, differentiation, and responses within the immune system. They play a crucial role in coordinating both innate and adaptive immune responses.

• Types: Include interferons and interleukins.

• Interleukin 1 (IL-1): Released by macrophages; co-stimulates bound T cells to:

  • Release interleukin 2 (IL-2)

  • Synthesize more IL-2 receptors

Additional info: Cytokines can act in an autocrine, paracrine, or endocrine manner, affecting the behavior of the same cell, nearby cells, or distant cells, respectively.

Roles of Helper T (TH) Cells

Central Role in Adaptive Immunity

Helper T cells (TH cells) are essential for the activation and regulation of both humoral and cellular immune responses.

• Activate both humoral (B cell-mediated) and cellular (T cell-mediated) arms of adaptive immunity.

• Once primed by antigen-presenting cell (APC) presentation of antigen, TH cells:

  • Help activate T and B cells

  • Induce proliferation of T and B cells

  • Release cytokines that recruit other immune cells

• Without TH cells, there is no effective immune response.

Example: TH cells are required for B cells to undergo class switching and for cytotoxic T cells to become fully activated.

Mechanisms of Helper T Cell Action

• In humoral immunity, TH cells bind to B cells presenting antigen and release interleukins as co-stimulatory signals.

• In cellular immunity, TH cells interact with dendritic cells and CD8 T cells, releasing IL-2 to promote CD8 T cell activation.

Additional info: TH cells are classified into subsets (e.g., TH1, TH2, TH17) based on the cytokines they produce and their roles in immunity.

Cytotoxic T (TC) Cells

Direct Attack on Infected or Abnormal Cells

Cytotoxic T cells (TC cells) are specialized lymphocytes that directly attack and kill other cells displaying specific antigens.

• Activated TC cells circulate in blood, lymph, and lymphoid organs searching for target cells.

• Targets include:

  • Virus-infected cells

  • Cells with intracellular bacteria or parasites

  • Cancer cells

  • Foreign cells (e.g., from transfusions or transplants)

Mechanism of Action

• TC cells recognize antigens presented by MHC I molecules on target cells.

• Release perforin and granzymes:

  • Perforin forms pores in the target cell membrane.

  • Granzymes enter through these pores and trigger apoptosis (programmed cell death).

Example: TC cells are responsible for killing virally infected cells and tumor cells, as seen in the provided electron micrograph of a TC cell attacking a cancer cell.

Regulatory T (TReg) Cells

Immune Suppression and Tolerance

Regulatory T cells (TReg cells) are crucial for maintaining immune system balance and preventing autoimmune reactions.

• Dampen immune responses by direct contact or by releasing inhibitory cytokines such as IL-10 and TGF-β.

• Suppress self-reactive lymphocytes in the periphery (outside lymphoid organs).

• Important in preventing autoimmune diseases and maintaining tolerance to self-antigens.

• Research is ongoing into using TReg cells to induce tolerance to transplanted tissues.

Additional info: Deficiency or dysfunction of TReg cells can lead to autoimmune diseases.

Organ Transplants

Types of Grafts

• Autografts: Transplanted from one body site to another in the same person.

• Isografts: Between genetically identical individuals (identical twins).

• Allografts: Between individuals who are not identical twins.

• Xenografts: From another animal species.

Prevention of Rejection

• Success depends on tissue similarity, especially ABO, other blood antigens, and MHC antigens.

• After surgery, patients are treated with immunosuppressive therapy:

  • Corticosteroid drugs to suppress inflammation

  • Antiproliferative drugs

  • Immunosuppressant drugs

• Many immunosuppressive drugs have severe side effects, including increased risk of infection and cancer.

Immunodeficiencies

Congenital Immunodeficiencies

• Severe Combined Immunodeficiency (SCID) Syndrome: Genetic defect resulting in marked deficit of B and T cells.

• Often due to defective adenosine deaminase (ADA) enzyme, leading to accumulation of toxic metabolites lethal to T cells.

• Fatal if untreated; treated with bone marrow transplants.

Acquired Immunodeficiencies

• Acquired Immune Deficiency Syndrome (AIDS): Caused by HIV, which cripples the immune system by interfering with helper T cell activity.

• Characterized by severe weight loss, night sweats, swollen lymph nodes, and opportunistic infections (e.g., pneumocystis pneumonia, Kaposi's sarcoma).

Autoimmune Diseases

Loss of Self-Tolerance

Autoimmune diseases occur when the immune system loses the ability to distinguish self from foreign antigens, leading to the production of autoantibodies and sensitized T cells that destroy body tissues.

• Examples include:

  • Multiple sclerosis

  • Myasthenia gravis

  • Graves' disease

  • Type 1 diabetes mellitus

  • Systemic lupus erythematosus (SLE)

  • Glomerulonephritis

  • Rheumatoid arthritis

Mechanisms of Autoimmune Disease

• Weakly self-reactive lymphocytes may be activated by:

  • Foreign antigens resembling self-antigens (molecular mimicry)

  • Antibodies against foreign antigens cross-reacting with self-antigens

  • New self-antigens appearing due to:

    • Gene mutations

    • Changes in self-antigens by hapten attachment or infectious damage

    • Release of novel self-antigens by trauma to barrier tissues

Additional info: Treatments for autoimmune diseases often involve immunosuppressive drugs to reduce immune system activity.