# Second Line of Defence - Nonspecific Defence The second line of defence is a set of *nonspecific internal defences* that are activated when microbes penetrate the primary barriers of the skin or mucous membranes. It acts rapidly against a wide variety of pathogens and consists of killing cells, protective proteins, inflammation, and fever. ## Killing Cells of Blood These are white blood cells (leukocytes) that directly attack foreign invaders or abnormal body cells. ### Phagocytes - ***Phagocytosis*** is the process by which a cell engulfs and destroys other cells, such as microorganisms or cancerous cells. - The main types of phagocytic white blood cells are: - Macrophages - Dendritic Cells - Neutrophils | Feature | **Macrophages** | **Dendritic Cells (DCs)** | | :--- | :--- | :--- | | **Origin** | Develop from *monocytes* in the bone marrow. | Develop from *monocytes* in the bone marrow. | | **Location** | Found in organs like lungs, liver, spleen, and lymph nodes. | Found in tissues with contact to the external environment (e.g., skin). | | **Primary Function** | Patrol tissues, trap and destroy microbes via *phagocytosis*. Remove dead cells and debris, aiding in wound healing. Function as **Antigen Presenting Cells (APCs)**. | Primary role is to act as **Antigen Presenting Cells (APCs)**. Capture, process, and present antigens to T-cells to initiate the *adaptive immune response*. | | **Secretions** | Secrete proteins like *interleukin-1* which can induce fever. | | ### Neutrophils - A type of *granulocyte* (a class of WBCs). - **Highly mobile** and can squeeze through capillary walls to reach infected tissues. - Move in an *Amoeba-like* fashion. - **Short-lived**, often dying after a single phagocytic event. - Can release *lysosomal enzymes* and *Neutrophil Extracellular Traps (NETs)* to kill microbes externally. ### Natural Killer (NK) Cells - A type of *lymphocyte* that provides innate immunity. - They do **not** attack microbes directly. - **Target:** They attack the body's own cancerous cells or virus-infected cells. - **Mechanism of Action:** 1. NK cells release proteins called ***perforins***, which create pores in the target cell's membrane. 2. Other proteins called ***granzymes*** enter through these pores. 3. Granzymes trigger ***apoptosis*** (programmed cell death) in the target cell. 4. Macrophages then engulf the dying cell. ## Protective Proteins These are circulating proteins that support the immune response. ### Complement System - Consists of over 50 small proteins synthesized by the liver, normally inactive in the blood. - Activated by the presence of foreign particles, leading to a cascade effect where one protein activates the next. - **Functions:** - **Opsonization:** Enhances (complements) the ability of antibodies and phagocytes to clear microbes. - **Promotes inflammation** to attract more phagocytes. - Forms a ***Membrane Attack Complex (MAC)*** that punches holes in the pathogen's plasma membrane, causing it to swell and burst (lysis). ### Interferons - A class of proteins known as ***cytokines*** (chemical messengers for immune cells). - Released by virus-infected cells to "interfere" with viral replication. - **Functions:** - Warn neighboring uninfected cells to resist viral entry. - Signal infected cells to undergo apoptosis. - Stop viral replication and prevent viruses from leaving an infected cell. - Activate other immune cells like macrophages and NK cells. ## Inflammatory Response A localized response to tissue damage caused by injury or infection. - **Process:** 1. Damaged cells release chemical alarms like ***histamine***. 2. Histamine causes nearby blood vessels to *dilate* (widen) and become more *permeable* (leaky). 3. Increased blood flow brings more defensive cells to the area. 4. Plasma leaks into the tissue, causing swelling (edema). - **Classical Signs of Inflammation:** - Heat - Pain - Redness - Swelling - Loss of function - **Function:** To contain the infection, eliminate the cause of injury, clear out dead cells, and initiate tissue repair. ## Temperature Response (Fever) A systemic (widespread) increase in body temperature, also known as *pyrexia*. - **Cause:** Chemicals called ***pyrogens*** are released by microbes or by the body's own white blood cells (*endogenous pyrogens*). These pyrogens raise the temperature set point in the brain's *hypothalamus*. - **Defensive Benefits:** - **Slows microbial growth:** Higher temperatures can inhibit bacterial reproduction (partly by reducing available iron) and inactivate some viruses. - **Enhances immune response:** Increases the activity of phagocytic cells and the production of interferons. - **Risk:** Very high fevers can be dangerous and damage the body's own metabolic systems, which is why *antipyretic* (fever-reducing) drugs are sometimes used.