A STEP-BY-STEP GUIDE TO UNDERSTANDING CELL-MEDIATED IMMUNE RESPONSE

Introduction

The cell-mediated immune response is a crucial component of the immune system that plays a vital role in defending the body against intracellular pathogens, such as viruses, certain bacteria, and parasites. It involves the activation and coordination of various types of immune cells to eliminate infected or abnormal cells.

T cells, also known as T lymphocytes, are the central players in the cell-mediated immune response. They are produced in the bone marrow and mature in the thymus gland. T cells express unique antigen receptors on their surface called T cell receptors (TCRs), which allow them to recognize specific antigens presented by antigen-presenting cells (APCs).

The process of cell-mediated immune response begins when APCs, such as dendritic cells, macrophages, or B cells, capture and process antigens derived from pathogens. These antigens are then presented on their surface in association with major histocompatibility complex (MHC) molecules. MHC class I molecules present antigens derived from intracellular pathogens to CD8+ T cells, while MHC class II molecules present antigens derived from extracellular pathogens to CD4+ T cells.

When a TCR on a T cell recognizes its specific antigen-MHC complex, it triggers a series of signaling events that lead to T cell activation. This activation process involves co-stimulatory signals provided by interactions between molecules on the surface of APCs and T cells. Once activated, T cells undergo clonal expansion, resulting in the generation of a large population of effector T cells specific for the antigen.

There are two main subsets of effector T cells involved in cell-mediated immunity: cytotoxic T lymphocytes (CTLs) and helper T lymphocytes. CTLs express CD8 molecules on their surface and are responsible for directly killing infected or abnormal cells. They recognize antigens presented by MHC class I molecules and induce apoptosis in target cells through the release of cytotoxic molecules, such as perforin and granzymes.

Helper T lymphocytes, on the other hand, express CD4 molecules on their surface and play a crucial role in coordinating the immune response. They recognize antigens presented by MHC class II molecules and secrete cytokines that regulate the activity of other immune cells. Helper T cells can be further divided into two subsets: Th1 cells and Th2 cells.

Th1 cells primarily produce interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which activate macrophages to enhance their phagocytic and microbicidal activities. They also promote the differentiation of B cells into antibody-producing plasma cells. Th1 responses are typically associated with intracellular pathogens.

Th2 cells, on the other hand, produce interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), which stimulate B cells to produce antibodies, particularly immunoglobulin E (IgE). Th2 responses are typically associated with extracellular parasites and allergies.

In addition to CTLs and helper T cells, other immune cells also contribute to the cell-mediated immune response. These include natural killer (NK) cells, which can directly kill infected or abnormal cells without prior sensitization, and macrophages, which phagocytose pathogens and present antigens to T cells.

The cell-mediated immune response is tightly regulated to prevent excessive inflammation and tissue damage. Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis by suppressing the activation of effector T cells. They express a molecule called Foxp3 and secrete anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β).

Overall, the cell-mediated immune response is a complex and coordinated process involving various immune cells working together to eliminate intracellular pathogens and abnormal cells. It plays a crucial role in maintaining the body’s defense against infections and preventing the development of certain diseases.

 

Types of T Cells and Their Functions

T cells, also known as T lymphocytes, are a crucial component of the immune system that plays a central role in protecting the body against invading pathogens. There are several types of T cells, each with distinct functions and characteristics. In this answer, we will discuss the different types of T cells and their functions in detail.

1. CD4+ (T helper) cells:

CD4+ T cells, also known as T helper cells, are the most abundant type of T cell. They are responsible for activating other immune cells, such as B cells and macrophages, to fight off infections. CD4+ T cells recognize antigens presented on the surface of infected cells by major histocompatibility complex (MHC) class II molecules. Once they have recognized the antigen, they release cytokines that activate other immune cells. CD4+ T cells can be further divided into several subtypes, including Th1, Th2, Th17, and Treg cells, each with distinct functions.

2. CD8+ (cytotoxic) cells:

CD8+ T cells, also known as cytotoxic T cells, are responsible for directly killing infected cells or tumor cells. They recognize antigens presented on the surface of infected cells by MHC class I molecules. Once they have recognized the antigen, they release granzymes and perforin, which cause the death of the infected cell. CD8+ T cells are important for controlling viral infections and cancer.

3. Th1 cells:

Th1 cells are a subtype of CD4+ T cells that specialize in fighting intracellular bacteria and viruses. They produce cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ), which activate other immune cells and promote the production of antiviral proteins. Th1 cells are important for protecting against diseases such as tuberculosis and leprosy.

4. Th2 cells:

Th2 cells are another subtype of CD4+ T cells that specialize in fighting parasites and allergies. They produce cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10), which activate other immune cells and promote the production of anti-parasitic proteins. Th2 cells are important for protecting against diseases such as worm infections and allergies.

5. Th17 cells:

Th17 cells are a subtype of CD4+ T cells that specialize in fighting extracellular bacteria and fungi. They produce cytokines such as interleukin-17 (IL-17) and interleukin-22 (IL-22), which activate other immune cells and promote the production of antimicrobial peptides. Th17 cells are important for protecting against diseases such as skin infections and respiratory infections.

6. Treg cells:

Treg cells, or regulatory T cells, are a subtype of CD4+ T cells that specialize in suppressing the activity of other immune cells. They produce cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which inhibit the activation of other immune cells and prevent autoimmune diseases. Treg cells are important for maintaining immune homeostasis and preventing diseases such as asthma and autoimmune disorders.

In conclusion, T cells play a crucial role in protecting the body against invading pathogens and maintaining immune homeostasis. The different types of T cells, including CD4+ and CD8+ T cells, Th1, Th2, Th17, and Treg cells, each have distinct functions and characteristics that help to defend the body against various types of infections and diseases. Understanding the functions of these different types of T cells is essential for developing effective treatments for immune-related diseases and infections.

 

Antigen processing and presentation

Antigen processing and presentation is a crucial step in the immune response, where the immune system recognizes and responds to foreign substances, such as viruses, bacteria, and other microorganisms. The process involves the breakdown and presentation of these foreign substances to T-cells, which then trigger an immune response.

There are several key steps involved in antigen processing and presentation:

1. Antigen capture: The foreign substance, or antigen, is captured by immune cells called antigen-presenting cells (APCs), such as dendritic cells and macrophages.

2. Antigen processing: The antigen is broken down into smaller pieces, called epitopes, which are then loaded onto MHC (major histocompatibility complex) molecules.

3. MHC presentation: The MHC molecules, which are present on the surface of the APCs, display the epitopes to T-cells.

4. T-cell recognition: T-cells recognize the epitopes displayed on the MHC molecules and trigger an immune response.

 

Method of Activation of T Cells

1. Antigen Presentation: The process of activation of T cells begins with the presentation of an antigen (a specific molecule) to a T cell by an antigen-presenting cell (APC) such as a dendritic cell or a macrophage. The APC engulfs the pathogen or a dead cell and breaks it down into small pieces called epitopes. These epitopes are then presented to the T cell on the surface of the APC through major histocompatibility complex (MHC) molecules.

2. T Cell Recognition: The T cell recognizes the antigen presented by the APC through its surface receptors called T cell receptors (TCRs). The TCRs bind to the epitopes on the surface of the APC, which triggers the activation of the T cell.

3. Co-stimulation: After recognition of the antigen, the T cell needs to receive co-stimulatory signals to become activated. Co-stimulation is provided by the interaction of the T cell with other immune cells such as dendritic cells, B cells, and other T cells. This interaction leads to the production of cytokines, which are signaling molecules that help to activate the T cell.

4. Activation: Once the T cell has received both the antigenic and co-stimulatory signals, it becomes activated. Activation involves changes in the expression of genes and proteins that allow the T cell to proliferate, produce cytokines, and differentiate into effector T cells.

5. Effector Functions: Activated T cells can perform various effector functions such as producing cytokines, killing infected cells, or directly killing cancer cells.

In summary, the method of activation of T cells involves the recognition of an antigen presented by an antigen-presenting cell, followed by co-stimulation and activation of the T cell. This complex process is essential for the proper functioning of the immune system.

 

Method of activation of macrophages

Macrophages are a type of immune cell that play a crucial role in the body’s defense against pathogens and foreign substances. They are responsible for engulfing and destroying invading microorganisms, as well as presenting antigens to other immune cells to initiate an immune response. Macrophages can be activated through various mechanisms, including exposure to pathogens, cytokines, or other immune cells.

One of the main methods of macrophage activation is through the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) on the surface of macrophages. PAMPs are unique molecules found on the surface of pathogens that are recognized by PRRs, such as toll-like receptors (TLRs). When a macrophage encounters a pathogen, TLRs on its surface bind to specific PAMPs, triggering a signaling cascade that leads to the activation of the macrophage. This activation results in the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6), which help recruit other immune cells to the site of infection and promote inflammation.

In addition to PAMP recognition, macrophages can also be activated by cytokines released by other immune cells. For example, interferon-gamma (IFN-γ), which is produced by T cells and natural killer cells, can stimulate macrophages to become more efficient at killing intracellular pathogens. IFN-γ activates macrophages by binding to specific receptors on their surface and inducing the expression of genes involved in antimicrobial activity.

Another important method of macrophage activation is through interaction with T cells during delayed type hypersensitivity (DTH) reactions. DTH is a type IV hypersensitivity reaction that occurs when T cells recognize antigens presented by macrophages and mount an immune response. In this process, macrophages act as antigen-presenting cells (APCs) by engulfing and processing antigens derived from pathogens or other foreign substances. The processed antigens are then presented on the surface of macrophages in complex with major histocompatibility complex class II (MHC-II) molecules.

When T cells encounter these antigen-MHC-II complexes on macrophages, they become activated and release cytokines, such as IFN-γ and interleukin-2 (IL-2). These cytokines further stimulate the activation of macrophages, leading to increased phagocytic activity and the production of inflammatory mediators. The activated macrophages, in turn, recruit more immune cells to the site of inflammation and contribute to the destruction of the antigen.

Overall, the activation of macrophages is a complex process that involves recognition of PAMPs, interaction with cytokines, and antigen presentation to T cells. These mechanisms ensure that macrophages are able to mount an effective immune response against pathogens and foreign substances.

 

Overview of Major Histocompatibility Complex

Major Histocompatibility Complex (MHC) is a group of proteins that play a crucial role in the immune system’s ability to distinguish between the body’s own cells and foreign substances like viruses and bacteria. MHC molecules are responsible for presenting pieces of these foreign substances (antigens) to T-cells, which then trigger an immune response.

A) Classification of MHC:

There are three main classes of MHC molecules:

1. MHC class I: These molecules are expressed on the surface of all nucleated cells and present fragments of intracellular proteins to CD8+ T-cells (cytotoxic T-cells).
2. MHC class II: These molecules are expressed on the surface of antigen-presenting cells (APCs) such as dendritic cells and macrophages, and present fragments of extracellular proteins to CD4+ T-cells (helper T-cells).
3. MHC class III: These molecules are involved in the immune response to parasites and are not well understood.

B) Structure of MHC:

MHC molecules consist of two subunits, alpha and beta, which are non-covalently linked to form a heterodimer. The alpha subunit is responsible for binding to the antigen, while the beta subunit is responsible for binding to the T-cell receptor (TCR).

C) Expression of MHC:

MHC molecules are expressed in the endoplasmic reticulum (ER) and are transported to the cell surface via the Golgi apparatus. The expression of MHC molecules can be influenced by a variety of factors, including the presence of certain microorganisms and the activation of immune cells.

D) Gene Defects:

Defects in MHC genes can lead to a range of immunological disorders, including:

1. MHC class II deficiency: This can lead to a condition known as bare lymphocyte syndrome (BLS), which is characterized by a severe impairment of the adaptive immune response.

2. MHC class I deficiency: This can lead to a condition known as mycosis fungoides, which is a type of cancer that affects the skin and mucous membranes.

In conclusion, Major Histocompatibility Complex (MHC) molecules play a crucial role in the immune system’s ability to distinguish between the body’s own cells and foreign substances. There are three main classes of MHC molecules, each with a specific function in the immune response. Defects in MHC genes can lead to a range of immunological disorders.