# Third Line of Defence - The Specific Defences This section details the body's *adaptive* or *specific immune system*, which targets particular pathogens that have bypassed the first and second lines of defence. It is characterized by specificity and memory. --- ## Antigen A substance, typically a protein on the surface of a pathogen (like a virus or bacterium), that stimulates a specific immune response. The name comes from **ANTI**-body **GEN**erating substance. ## Specific Defence Unlike the non-specific first and second lines, this defence system targets specific antigens, providing a powerful and tailored response to infections. ## Lymphocytes The primary white blood cells involved are **B-lymphocytes (B cells)** and **T-lymphocytes (T cells)**. ## Immune Response Types * **Humoral Immune Response:** Mediated by B cells and the antibodies they produce. * **Cell-Mediated Immune Response:** mediated directly by T cells. ## Role of Monocytes in Initiating the Response Monocytes are a type of white blood cell that act as a bridge between the non-specific and specific immune systems. * They circulate in the blood and then move into tissues, where they mature into larger cells called **macrophages** or **dendritic cells**. * **Phagocytosis:** These cells engulf and digest invading pathogens. * **Antigen Presentation:** After digesting a pathogen, they display the pathogen's antigens on their own cell surface. This turns them into **Antigen-Presenting Cells (APCs)**. * **Activation Signal:** APCs secrete a protein called **interleukin-1**, which activates T cells and promotes a general inflammatory response (e.g., fever). --- ## Cell-Mediated Immune Response (Role of T Cells) This response involves the direct action of T cells against infected body cells and pathogens. * *Origin and Maturation:* T cells originate from stem cells in the bone marrow and mature in the **thymus gland**, where they become "immunocompetent" (capable of an immune response). ### Activation of T Cells 1. **Antigen Presentation:** A macrophage (APC) presents a specific antigen on its surface, bound to its own protein called the **Major Histocompatibility Complex (MHC)**. 2. **Recognition:** A **Helper T cell** with a matching **T cell receptor (TCR)** binds to the antigen-MHC complex on the APC. 3. **Chemical Signaling:** The APC releases **interleukin-1**, stimulating the Helper T cell. 4. **Proliferation:** The activated Helper T cell releases **interleukin-2**, which triggers the rapid division (proliferation) of more Helper T cells, Cytotoxic T cells, and B cells. ### Types of T cells | T Cell Type | Surface Marker | Function | |-------------|----------------|----------| | **Helper T cell** | CD4 | Secretes **interleukin-2** to activate and promote the division of other T cells and B cells. They are the "generals" of the immune response. | | **Cytotoxic T cell** | CD8 | Directly kills infected body cells or pathogens by releasing proteins like **perforin** (creates holes in the cell membrane, causing lysis) or cytotoxins (destroy DNA). | | **Suppressor T cell** | CD8 | Inhibits the immune response once the infection is cleared, preventing excessive or autoimmune reactions. They "shut down" the response. | | **Memory T cell** | - | Long-lived cells that remain after an infection. They provide a rapid and strong response if the same antigen is encountered again in the future. | --- ## Humoral (Antibody-Mediated) Immune Response (Role of B Cells) This response involves the production of antibodies by B cells to fight pathogens circulating in body fluids (humors), like blood and lymph. * *Origin and Maturation:* B cells are produced and mature in the **bone marrow**. ### Activation of B Cells 1. **Stimulation:** Activated Helper T cells release **interleukin-2**. 2. **Antigen Binding:** A B cell with a specific **B cell receptor (BCR)** binds to its corresponding antigen. 3. **Differentiation and Proliferation:** The B cell is activated and divides into two main types of cells: * **Plasma Cells:** Antibody factories. They produce and secrete millions of antibody molecules per hour but live only for a few days. * **Memory B Cells:** Long-lived cells that remain in the body to provide a faster response to future infections by the same pathogen. ### Structure and Function of Antibodies Antibodies, also called *immunoglobulins (Ig)*, are Y-shaped proteins. * **Structure:** * Composed of four polypeptide chains: two identical **heavy chains** and two identical **light chains**. * **Constant Region (C):** The "stem" of the Y, which is the same for antibodies of a particular class. * **Variable Region (V):** The "tips" of the Y, with a unique amino acid sequence that forms the **antigen-binding site**. Each antibody has two identical antigen-binding sites. * **Modes of Action:** 1. **Neutralization:** Antibodies bind to toxins or viruses, preventing them from attaching to host cells. 2. **Opsonization:** Antibodies coat a pathogen, "marking" it for phagocytosis by macrophages. 3. **Complement System Activation:** The antibody-antigen complex activates a cascade of proteins that can form a **membrane attack complex**, bursting the pathogen's cell membrane. 4. **Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC):** Antibodies attach to infected cells, signaling Natural Killer (NK) cells to induce apoptosis (programmed cell death). --- ## Primary vs. Secondary Immune Response | Feature | Primary Immune Response | Secondary Immune Response | |---------|------------------------|---------------------------| | **Trigger** | First exposure to a specific antigen. | Subsequent exposure to the same antigen. | | **Speed of Response** | Slower (takes several days to become fully functional). | Faster and more rapid. | | **Strength** | Weaker response, lower antibody concentration. | Stronger response, higher antibody concentration. | | **Key Cells** | Naive B and T cells are activated. | Existing **Memory B and T cells** are activated. | | **Outcome** | Clears the infection and produces memory cells. | Rapidly clears the infection, often without symptoms. | --- ## Monoclonal Antibodies (mAbs) * **Definition:** Laboratory-engineered antibodies that are identical (clones) and designed to bind to a single, specific antigen. * **Impact and Applications:** * **Research:** Used to detect and quantify specific molecules, aiding in cancer research, protein analysis, and immunology. * **Diagnostics:** Key components in tests like **ELISA** and **Western blot**, and used as imaging agents (e.g., in PET scans). * **Therapy:** Used as targeted treatments for diseases like cancer, autoimmune disorders, and viral infections (e.g., COVID-19). --- ## Inborn (Innate) vs. Acquired (Adaptive) Immunity * **Inborn/Innate Immunity:** Non-specific defence mechanisms you are born with. Includes the first line (skin, mucous) and second line (inflammation, phagocytes) of defence. Found in all multicellular organisms. * **Acquired/Adaptive Immunity:** Highly specific protection developed after exposure to a pathogen. Includes the third line of defence (cell-mediated and humoral immunity). It is unique to vertebrates. --- ## Possible Questions/Answers **Q:** What is the difference between an antigen and an antibody? **A:** An **antigen** is a molecule (usually on a pathogen) that *triggers* an immune response. An **antibody** is a Y-shaped protein produced by plasma cells *in response* to an antigen, which binds to and helps neutralize the pathogen. **Q:** What is the primary role of a Helper T cell? **A:** A Helper T cell is the central coordinator of the adaptive immune response. It becomes activated by an antigen-presenting cell and then releases interleukin-2 to activate and promote the growth of both cytotoxic T cells (for cell-mediated immunity) and B cells (for humoral immunity). **Q:** Differentiate between cell-mediated and humoral immunity. **A:** **Cell-mediated immunity** involves T cells directly attacking and killing infected host cells. **Humoral immunity** involves B cells producing antibodies that circulate in the body's fluids (humors) to neutralize pathogens before they can infect cells. **Q:** What makes the secondary immune response so much faster and stronger than the primary one? **A:** The secondary response relies on **memory B and T cells** that were created during the primary response. These cells are already "primed" to recognize the antigen, allowing them to be activated much more quickly and mount a larger, more effective response upon re-exposure. --- ## References (Derived from FBISE textbook)