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LECTURE Chapter 16: Introduction to the Immune System
Overview: The immune system is incredibly complex, and we could spend an entire year discussing its mechanisms. For ease of study, we divide the immune system into branches. However, the immune system functions as a unified system. In this chapter, we will focus on the innate immune system , which you're born with. Later, in Chapter 17, we'll cover the acquired immune defense. Immune System Divisions:
- Innate Immunity (born with) : o This includes your first and second lines of defense, which are non-specific responses to any pathogen.
- Acquired Immunity (develops over time) : o This involves specific mechanisms, like B cells and T cells, which respond to specific pathogens.
First Line of Defense (Physical, Chemical, and Genetic Factors)
Physical Barriers: Skin : Your body's primary physical barrier. It prevents microbes from entering, unless the skin is broken. Mucous Membranes : These trap microbes, preventing them from entering the body through the lungs or nose. Ciliary Escalator : Cilia in your trachea trap microbes and push them out when you cough. Lacrimal Apparatus : This helps to flush out microbes from the eyes. Saliva : Washes microbes from the mouth. Urine : Flows out and washes pathogens from the urinary tract. Vaginal Secretions : Prevent microbes from going further inside the body. Blood-Brain Barrier : Prevents most microbes from entering the brain. Genetic Factors: The presence of normal flora (microorganisms that naturally live on your body) helps prevent pathogenic organisms from thriving due to competitive exclusion.
Chemical Factors:
Sebaceous Glands : Release chemicals that alter the pH of the skin, making it inhospitable for pathogens.
Lysozyme : Found in sweat, tears, and tissues, lysozyme breaks down the cell walls of bacteria. Gastric Juice : Its acidic nature helps to inhibit most pathogens. Antimicrobial Peptides : These proteins break down various microbes.
Second Line of Defense (Internal Mechanisms)
This involves more complex mechanisms that are activated when pathogens bypass the first line of defense. These include phagocytosis , inflammation , and the complement system.
Key Cellular Components of the Immune System
Blood Components: Blood is divided into plasma (liquid portion) and formed elements (cells). o Plasma contains proteins, gases, hormones, and electrolytes. o We focus on the formed elements , particularly white blood cells (WBCs) , as they are crucial to immune defense. White blood cells include: o Neutrophils o Eosinophils o Basophils o Monocytes (which differentiate into macrophages) o Lymphocytes (B cells, T cells)
Types of White Blood Cells (WBCs)
- Granulocytes (have granules in their cytoplasm): o Neutrophils : High numbers in the blood. Phagocytize pathogens and release enzymes to destroy them. Can form NETs (Neutrophil Extracellular Traps) to trap bacteria. Primary component of pus. o Eosinophils : Attack eukaryotic pathogens (e.g., fungi, parasites). Release toxic compounds but rarely phagocytize. Associated with allergies and inflammation. o Basophils : Similar to eosinophils but their role is less understood. Can differentiate into mast cells involved in allergic reactions by releasing histamine.
- Agranulocytes (lack granules): o Monocytes : Differentiate into macrophages once they enter tissues. Major phagocytic cells.
Lymph is similar to blood but lacks red blood cells. The lymph nodes clean the lymph and are important for detecting infections. o Swollen lymph nodes often indicate an infection.
Conclusion
Chapter 16 focuses on the innate immune system with its first and second lines of defense. The main mechanisms discussed are phagocytosis and cytokine release. Blood cells like neutrophils , monocytes , and macrophages are key to defending against a broad range of pathogens. The lymphatic system helps to circulate immune cells and remove pathogens. In the next chapter, we’ll explore the acquired immune response , including the role of B cells and T cells in specific immunity.
Lecture Part 2: The Mechanisms of the Innate Immune System
There are six primary mechanisms that function for the innate immune system. These mechanisms include:
- Inflammation
- Phagocytosis
- Fever
- Complement
- Chemical Mediators
- Natural Killer Cells We will focus on each of these mechanisms, starting with inflammation.
Inflammation
Inflammation is the body’s response to trauma, which can arise from various causes, such as mechanical injury (e.g., broken bones), chemical irritants, or infections caused by pathogens. In this class, we will focus on inflammation caused by pathogen infections. Purpose of Inflammation: Mobilize and attract immune cells to the site of infection. Aid in tissue repair. Localize and remove harmful substances. Prevent the pathogen from spreading further into the body. Four Primary Signs of Inflammation: Redness
Heat Swelling Pain In clinical healthcare settings, these four signs are essential indicators of inflammation. Although each of these signs has a Latin term (which you'll learn in more advanced courses like nursing or PT school), for this class, it's enough to remember the basic four: redness , heat , swelling , and pain. The Mechanism of Inflammation: When a pathogen infects the body (e.g., bacteria from a dirty knife wound), it sets off a series of events:
- Initial Response : The skin barrier is breached, and bacteria enter the dermis.
- Immune Cells Activation : Macrophages and neutrophils, which are already present in the tissues, respond to the infection.
- Cytokine Release : These immune cells release cytokines —chemical messengers that include histamine, kinins, prostaglandins, and leukotrienes. For this class, just remember that cytokines are enzymes that help activate other immune processes. Key Processes in Inflammation: Vasodilation : Cytokines cause blood vessels to dilate, bringing more blood (and immune cells) to the area. Margination and Diapedesis : This is the process through which immune cells (like neutrophils and macrophages) leave the bloodstream and enter the tissues. o Margination : As blood flow slows, immune cells cling to the blood vessel walls. o Diapedesis : The immune cells squeeze through the blood vessel walls into the tissues, aided by selectins (special receptors produced by the blood vessel lining). The increased cytokine concentration and the action of selectins help white blood cells move toward the site of infection. Long-Term Inflammation: While short-term inflammation is beneficial in fighting infection, long-term inflammation can lead to serious health problems, such as: Rheumatoid arthritis Coronary heart disease (atherosclerosis) Alzheimer’s disease Certain cancers Long-term cytokine release can also result in septic shock , a condition where the body is overwhelmed by a widespread infection and massive cytokine release, leading to organ failure and dangerously low blood pressure.
Phagocytosis involves immune cells, particularly macrophages, engulfing and destroying pathogens. Chemical mediators such as cytokines and chemokines coordinate the immune response and guide immune cells to the site of infection. In the next parts of the course, we’ll explore additional mechanisms like fever , complement , and natural killer cells.
Lecture Part 3: Mechanisms of the Innate Immune System
1. Fever as an Immune Response Fever is an important part of the immune system's response to infection. It is typically a sign of an immune system at work, trying to create an environment less hospitable to pathogens. Treatment of fever often aims to control discomfort, but it also plays a role in enhancing the immune response. 2. Interferon: The Antiviral Protein Interferon is an antimicrobial protein that plays a critical role in defending against viral infections. Types of Interferon : There are several types of interferons produced by the body depending on the type of viral infection. We will focus on interferon produced in response to viral infections. Mechanism of Interferon: During a viral infection, the virus enters the host cell and begins replicating. This triggers the infected cell to produce interferon, which is then released into the extracellular space. The interferon binds to receptors on neighboring cells and activates a cascade that leads to the production of antiviral proteins in those cells. These antiviral proteins protect neighboring cells by preventing viral replication. Interferon also: o Activates T cells and B cells. o Stimulates natural killer cells. o Inhibits cancer cells. o Enhances macrophage function. Summary : Interferon is critical for creating an antiviral state in neighboring cells and boosting overall immune responses, particularly against viral infections. 3. The Complement System The complement system involves over 26 proteins in the blood that are normally inactive but can be activated to assist in immune defense.
The classical pathway of complement activation is the primary mechanism to focus on for this class. Activation Process (Classical Pathway): The complement system is activated when an antibody binds to a pathogen, such as a bacterium. The Fc region of the antibody becomes activated and binds to C1 , the first complement protein. C1 cleaves C2 and C4 , which form a complex ( C4bC2a ) that cleaves C. Activated C3 forms a complex with C4bC2a , and together they cleave C. C5 then binds to the pathogen and forms a membrane attack complex (MAC) by recruiting proteins C6 , C7 , C8 , and C9. This complex forms a channel in the pathogen’s membrane, causing it to rupture. Functions of Complement Proteins: C3b enhances phagocytosis, making it easier for phagocytes to engulf pathogens. C3a and C5a act as chemoattractants to attract immune cells to the site of infection. C3a and C5a also bind to mast cells, triggering degranulation and further promoting inflammation. Key Outcome : The complement system causes lysis of pathogens and enhances phagocytosis and inflammation.
4. Natural Killer (NK) Cells Natural Killer (NK) cells are part of the innate immune system and play a crucial role in identifying and eliminating infected or cancerous cells. NK cells are activated when they detect cells that are missing MHC (Major Histocompatibility Complex) or have an altered MHC. Mechanism of NK Cell Activation: NK cells look for cells with altered or absent MHC markers (which are normally displayed on healthy cells to signal "self"). If an NK cell detects a cell with an abnormal or missing MHC marker, it releases: o Perforins : Proteins that create holes in the target cell membrane. o Granzymes : Enzymes that enter the target cell and induce apoptosis (programmed cell death). o Interferons : These can further activate immune responses, such as antiviral proteins in neighboring cells. Summary : NK cells are crucial in defending against viral infections and tumor cells by inducing cell death in compromised cells.
