Cell Mediated Immunity

Cell-mediated immunity represents a vital aspect of the adaptive immune system, primarily involving T cells that directly attack and destroy infected or dysfunctional cells. This branch of immunity does not rely on antibodies but instead employs T cells to identify and eliminate cells harboring intracellular pathogens like viruses or certain bacteria. Essential for combating diseases where pathogens reside within cells, cell-mediated immunity also plays a crucial role in tumor suppression and transplant rejection, highlighting its importance in maintaining robust immune health and preventing disease.

Definition of Cell-Mediated Immunity

Cell-mediated immunity refers to an immune response that does not involve antibodies but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. This type of immunity is primarily mediated by T cells and is crucial for defending the body against pathogens that survive inside cells, such as viruses, some bacteria, and cancer cells. Cell-mediated immunity plays a vital role in recognizing and eliminating cells infected by pathogens, as well as tumor cells, through direct cell-to-cell contact and the release of cytokines, which are signaling molecules that aid in the immune response.

How Cell-Mediated Immunity Works?

• T Cells: Central to cell-mediated immunity, these cells originate from bone marrow and mature in the thymus. They are differentiated into several types, primarily helper T cells (CD4+) and cytotoxic T cells (CD8+).
• Macrophages: These are large phagocytic cells that can engulf and digest pathogens and cellular debris. They also act as antigen-presenting cells (APCs) that display pieces of the pathogen to T cells, initiating an immune response.
• Dendritic Cells: Similar to macrophages, dendritic cells capture antigens and present them to T cells, thereby serving as a bridge between the innate and adaptive immune systems.

1. Antigen Presentation:
   • The process begins when a macrophage or dendritic cell ingests a pathogen and processes its antigens. These antigens are then presented on the cell surface bound to major histocompatibility complex (MHC) molecules.
2. T Cell Activation:
   • Helper T cells recognize these antigen-MHC complexes through their T cell receptors (TCRs). The interaction, along with additional signals (like those from co-stimulatory molecules), fully activates the helper T cells.
   • Activated helper T cells release cytokines, which are signaling molecules that modulate the immune response and activate other immune cells, including cytotoxic T cells and more macrophages.
3. Targeting Infected Cells:
   • Cytotoxic T cells are activated either directly by antigens presented by infected cells or indirectly by cytokines from helper T cells.
   • Once activated, cytotoxic T cells recognize and bind to infected cells displaying the antigen-MHC complex. They release perforins and granzymes, which create pores in the target cell’s membrane and induce apoptosis (cell death), respectively.
4. Regulation and Memory:
   • After the pathogen has been cleared, regulatory T cells help to shut down T cell-mediated immunity to avoid excessive immune responses that might lead to tissue damage.
   • Memory T cells are formed and remain in the body, providing a quicker and more robust response if the same pathogen attempts to infect the body again.

Importance of Cell-Mediated Immunity

Cell-mediated immunity is essential for controlling infections by intracellular pathogens, such as viruses and some bacteria, which hide inside the cells where antibodies cannot reach them. It is also crucial in tumor suppression and plays a significant role in the rejection of transplanted organs, as the immune system recognizes the transplanted tissue as foreign.

Functions of Cell-Mediated Immunity

Defense Against Viral Infections

Cell-mediated immunity specifically targets and destroys cells infected by viruses, preventing the spread of the virus within the body.

Defense Against Bacterial and Parasitic Infections

It is crucial for eliminating intracellular bacteria and parasites that evade other components of the immune system by hiding within cells.

Cancer Surveillance

Cell-mediated immunity plays a key role in identifying and destroying cells that have undergone malignant transformation, thereby preventing the development and spread of cancer.

Transplant Rejection

This function involves recognizing and attacking transplanted organs or tissues that do not match genetically, leading to rejection.

Regulation of Autoimmune Responses

Regulatory T cells within the cell-mediated immune response help prevent autoimmune diseases by maintaining tolerance to the body’s own antigens and suppressing excessive immune responses.

Immune System Modulation

Cell-mediated immunity modulates the overall immune response by activating and directing other immune cells through the secretion of cytokines and other signaling molecules.

Tissue Repair and Regeneration

Beyond its defensive roles, cell-mediated immunity also contributes to tissue repair and regeneration by orchestrating the removal of dead cells and supporting the renewal of tissues after an immune response or injury.

Types of Cell-Mediated Immunity

1. Cytotoxic T Cell Immunity

Cytotoxic T cells (CTLs) or CD8+ T cells are perhaps the most critical players in cell-mediated immunity. These cells recognize and destroy infected cells, cancer cells, and cells of transplanted tissues. They are particularly effective against viral infections. The process involves CTLs recognizing foreign or abnormal peptides presented by MHC class I molecules on the surface of infected cells. Once engaged, CTLs release perforins and granzymes, which induce apoptosis in the target cell, effectively eliminating the threat.

2. Helper T Cell Immunity

Helper T cells, or CD4+ T cells, do not directly kill infected cells. Instead, they support other cells in the immune system through the secretion of cytokines, which enhance the response of B cells (for antibody production), cytotoxic T cells, and macrophages. Helper T cells are crucial in both cell-mediated and humoral immune responses and are subdivided into various types, including Th1, Th2, Th17, and Treg cells, each with distinct functions and cytokine profiles.

3. Delayed-Type Hypersensitivity (DTH)

Delayed-type hypersensitivity is a type of immune response mediated by T cells, which occurs several hours to days after exposure to the antigen. It is typically seen in response to bacterial infections, fungal infections, and contact allergens (like poison ivy or nickel). In DTH, activated Th1 cells release cytokines that recruit and activate macrophages. The macrophages increase in size and number, leading to inflammation and tissue damage at the site of antigen exposure.

4. Natural Killer (NK) Cell Activity

While NK cells are part of the innate immune system, their functions overlap significantly with cell-mediated immunity. NK cells can kill virus-infected cells and tumor cells without prior sensitization, which distinguishes them from cytotoxic T cells that require activation. NK cells detect stressed cells in the absence of MHC (missing self) and kill these cells by releasing cytotoxic granules.

5. Macrophage Activation

Macrophages are versatile cells involved in both innate and adaptive immunity. In cell-mediated immunity, macrophages are activated by cytokines produced by helper T cells (especially Th1 cells). Once activated, macrophages become highly phagocytic and produce various cytotoxic substances that are effective against bacteria, fungi, and tumor cells. They also play a crucial role in antigen presentation and cytokine production, further promoting the immune response.

Components of Cell-Mediated Immunity

Cell-mediated immunity involves several key components that work together to defend the body against pathogens that are not accessible by antibodies alone. Here are the primary elements of this critical immune response system:

T Lymphocytes (T Cells)

T cells are the central figures in cell-mediated immunity. They originate in the bone marrow and mature in the thymus. There are several types of T cells, each serving a distinct function:

• Helper T Cells (CD4+ T Cells): These cells coordinate the immune response by secreting cytokines that activate other immune cells.
• Cytotoxic T Cells (CD8+ T Cells): These cells directly attack and destroy cells infected by viruses or transformed by cancer.
• Regulatory T Cells: These cells help maintain immune tolerance by preventing overactive immune responses that could lead to autoimmune diseases.

Antigen-Presenting Cells (APCs)

APCs, including dendritic cells, macrophages, and B cells, play a crucial role in the immune response. They capture antigens, process them, and present them on their surface in a form that T cells can recognize. This process is vital for the activation of T cells.

Major Histocompatibility Complex (MHC) Molecules

MHC molecules are essential for immune function. They are cell surface proteins that display bits of processed antigen to T cells. There are two classes of MHC molecules:

• MHC Class I molecules are present on almost all nucleated cells and are recognized by CD8+ cytotoxic T cells.
• MHC Class II molecules are present on the surface of APCs and are recognized by CD4+ helper T cells.

Cytokines

Cytokines are signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis. In cell-mediated immunity, cytokines direct the immune response by signaling between the cells of the immune system, helping to activate or suppress various immune responses.

Natural Killer (NK) Cells

Although not T cells, NK cells are included in cell-mediated immunity because they play a similar role to cytotoxic T cells but do not require antigen stimulation to kill. NK cells target and destroy virally infected cells and cancer cells through mechanisms that do not always require MHC presentation.

Stages of Cell-Mediated Immunity

Antigen Presentation

• Antigen Capturing: Antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells capture antigens from pathogens or damaged cells.
• Antigen Processing: APCs process the captured antigens into peptide fragments.
• Antigen Presentation: Processed antigens are displayed on the surface of APCs bound to Major Histocompatibility Complex (MHC) molecules. MHC Class I molecules present to CD8+ T cells, while MHC Class II molecules present to CD4+ T cells.

T Cell Activation

• T Cell Recognition: T cells recognize the antigen-MHC complex through their T cell receptors (TCR). The interaction is highly specific to the antigen presented.
• Co-stimulation: Additional signals from co-stimulatory molecules on APCs and T cells (e.g., CD28 and B7) are required for full activation of T cells.
• Clonal Expansion: Once activated, T cells proliferate and differentiate into effector cells tailored to address the specific pathogens or abnormal cells.

Effector Functions

• Helper T Cells (CD4+): These cells secrete cytokines that enhance the immune response by activating macrophages, influencing B cell antibody class switching, and further stimulating the proliferation of T cells.
• Cytotoxic T Cells (CD8+): These cells directly attack and kill infected or abnormal cells. They release cytotoxic substances such as perforin and granzymes, which induce apoptosis in the target cells.
• Regulatory Functions: Regulatory T cells modulate the immune response to prevent overactivity and autoimmunity by inhibiting the function of T cells and other immune cells.

Resolution and Memory

• Resolution: After the pathogen has been cleared or the abnormal cells have been destroyed, most of the activated effector T cells undergo apoptosis, reducing the immune response to prevent unnecessary tissue damage.
• Memory Formation: Some of the activated T cells convert into memory T cells, which remain in the body long-term. These cells can rapidly activate upon re-exposure to the same antigen, providing quicker and more effective responses in future encounters.

Example of Cell-Mediated Immunity

Cell-mediated immunity is exemplified by the body’s response to the Varicella zoster virus, which causes chickenpox. Initially, when the virus infects cells, it is recognized by cytotoxic T cells (CD8+ T cells), which are activated to destroy virus-infected cells, limiting the virus’s spread. Concurrently, helper T cells (CD4+ T cells) are activated by antigen-presenting cells and help by producing cytokines that boost cytotoxic T cell function and stimulate antibody production by B cells. After the infection, memory T cells are formed, providing long-lasting immunity and a rapid response to future exposures. This response showcases the crucial role of cell-mediated immunity in fighting viral infections and forming the basis for vaccines like those against chickenpox and shingles.

FAQs

What is an Example of a Cell-Mediated Immune Response?

T-cells attacking infected cells directly is a prime example of a cell-mediated immune response, crucial for targeting viruses and cancer cells.

What is the Difference Between Humoral and Cell-Mediated Immunity?

Humoral immunity uses antibodies in body fluids, while cell-mediated immunity involves T-cells that directly attack pathogens.

What Does Cell-Mediated Immunity Protect Against?

Cell-mediated immunity is essential for protecting against viruses, fungi, and some bacteria, and plays a key role in tumor surveillance.

Is Cell-Mediated Immunity Innate or Adaptive?

Cell-mediated immunity is a part of the adaptive immune system, involving specialized cells that learn to recognize specific pathogens.

Why is Cell-Mediated Immunity Considered Adaptive Rather Than Innate?

Cell-mediated immunity is adaptive as it develops memory of specific pathogens, enabling a faster response on subsequent exposures.