Immune System and Lymphatic System Lecture

Introduction to the Immune System

The immune system serves as the body's primary defense against pathogens, encompassing a complex network of biological structures and processes designed to protect the body. There are two main divisions of this system: nonspecific immunity and specific immunity. White blood cells (WBCs), which are large, nucleated blood cells, play a major role in protecting the body from foreign substances and microorganisms. While nonspecific immunity (also known as innate immunity) is not aimed at a specific pathogen and works against all invaders generally, specific immunity (adaptive immunity) is directed at specific pathogens and is the most effective immune response, involving the development of immunological memory. Nonspecific immunity helps to slow the progression of a disease, while the specific immune response provides a more tailored and powerful defense.

Non-specific Physical and Chemical Defenses (First Line of Defense)

The first line of defense consists of physical and chemical barriers that prevent microorganisms from entering the body. The skin is a physical barrier; it contains layers of dead skin cells that help protect against invasion. Furthermore, bacteria live symbiotically on the skin, digesting skin oils to produce acids that inhibit the growth of many pathogens. Chemical defenses include secretions like saliva, tears, and nasal secretions, which contain the enzyme lysozyme. This enzyme kills bacteria by breaking down bacterial cell walls. Mucus is another chemical and physical barrier found on the inner surfaces of the body; it acts as a protective layer that blocks bacteria from sticking to inner epithelial cells. In the respiratory system, the beating motion of cilia sends bacteria caught in mucus away from the lung. Additionally, the stomach secretes hydrochloric acid ($HCl$), which is highly effective at killing microorganisms found in food. The body also uses expulsion methods such as coughing, sneezing, vomiting, and diarrhea to remove pathogens.

Non-specific Cellular Defense and Regulatory Proteins (Second Line of Defense)

If pathogens get beyond the primary barriers, the body employs a second line of nonspecific defense, including cellular defenses and specific proteins. White blood cells, particularly neutrophils and macrophages, are phagocytic. Phagocytosis is the process by which these cells surround and internalize foreign microorganisms, subsequently releasing digestive enzymes and harmful chemicals from their lysosomes to destroy the invader. Neutrophils are blood cells that ingest bacteria (often viewed at magnification like $2150\times$), while macrophages are larger cells that ingest bacteria and remove dead neutrophils and other debris (often viewed at $380\times$).

Complement proteins consist of approximately $20$ different types of proteins found in the blood plasma. These proteins are activated by materials in the cell walls of bacteria and enhance phagocytosis by helping phagocytic cells bind better to pathogens and activating the phagocytes themselves. They can also form a complex in the plasma membrane of a foreign cell, causing fluid to rush into the cell until it bursts. Another crucial defense is provided by interferons, which are proteins secreted by virus-infected cells. Interferons bind to neighboring uninfected cells and stimulate them to produce antiviral proteins, thereby preventing viral replication within those cells ($\text{ISG induction and the creation of an antiviral state}$).

The Inflammatory Response

The inflammatory response is a complex nonspecific defense reaction to tissue damage caused by injury or infection. When a pathogen infects tissues, chemicals are released by both the pathogen and the body’s cells. These chemicals cause an increase in blood flow to the infected area and make blood vessels more permeable, allowing white blood cells to escape the capillaries and move toward the infected site. This process results in the symptoms typically associated with infection: pain, heat, redness, and swelling (edema). Once at the site, the white blood cells (phagocytes) engulf and destroy the bacteria to prevent further spread.

The Lymphatic System and Specific Immunity

Specific immunity is more effective and faster to develop upon secondary exposure than nonspecific immunity. It involves the lymphatic system, a network of organs and cells that filter lymph and blood and destroy foreign microorganisms. Lymph is the fluid that leaks out of capillaries to bathe body tissues and is collected by lymphatic vessels to be returned to the veins near the heart. Key components include:

• Lymph Nodes: These filter lymph fluid and remove foreign materials.
• Tonsils: These form a protective ring of lymphatic tissue between the nasal and oral cavities to protect against bacteria in the nose and mouth.
• Spleen: This organ stores blood and destroys damaged red blood cells; it also contains lymphatic tissue that responds to foreign substances in the blood.
• Thymus Gland: Located above the heart, this is where T cells mature and are activated.
• Bone Marrow: Both B cells and T cells are produced in the red bone marrow.
• Lymphocytes: A type of white blood cell including B cells and T cells. B cells are often considered "antibody factories" because they produce proteins designed to specifically react with foreign antigens.

Antibody Structure and Diversity

Antibodies are proteins produced by B lymphocytes that specifically react with foreign antigens. An antigen is any substance foreign to the body that causes an immune response. An antibody is composed of two types of protein chains: two heavy chains and two light chains. The molecular weight of an antibody can be calculated based on these components. For example, if the molecular weight of a light chain is $25,000$ and a heavy chain is $50,000$, the total molecular weight is $2(25,000) + 2(50,000) = 150,000$. Diversity in antibody production is achieved through DNA coding. If a B cell can make $16,000$ different kinds of heavy chains and $1,200$ kinds of light chains, the possible combinations result in $1,200 \times 16,000 = 192,000,000$ different types of antibodies.

Specific Immune Responses: B Cell and T Cell Pathways

The specific immune response pathways are divided into antibody-mediated and cytotoxic responses. In the antibody-mediated response, a macrophage engulfs an antigen and presents a processed portion of it on its surface. A helper T cell (often called CD4 because of its surface receptor) binds to this processed antigen, causing the helper T cell to divide. The activated helper T cell then presents the processed antigen to a B cell, which divides via mitosis. These daughter B cells produce antibodies or remain in the system as memory B cells.

In the cytotoxic T cell response, activated helper T cells present the processed antigen to cytotoxic T cells, activating them to divide and secrete cytokines. Cytokines are signaling molecules that stimulate immune cells to divide and recruit them to the area of infection. Activated cytotoxic T cells bind to and kill infected cells by causing them to lyse. While specific immunity is powerful, it takes time to develop during the primary response. The secondary response is much faster and stronger because of memory cells, which are long-living B and T cells that remain in the body after the first exposure to an antigen.

Active and Passive Immunity

Immunity can be acquired either actively or passively. Active immunity results from having an infectious disease (primary response) or through immunization (vaccination). Immunization involves injecting a person with a weakened or dead pathogen (antigen) to stimulate the production of memory cells and antibodies without causing the full disease. Passive immunity occurs when a person receives antibodies from another source, such as a mother passing antibodies to her fetus through the placenta or a child through breast milk, or through the injection of antibodies (e.g., to treat snakebites or scorpion stings). Passive immunity is temporary because the body does not create its own memory cells.

HIV and AIDS

Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV). HIV is an RNA virus that specifically infects and destroys helper T cells (CD4+ cells). As the virus replicates, the number of helper T cells decreases over time, which eventually causes the specific immune system to fail because both B cells and cytotoxic T cells require helper T cells for activation. The stages of HIV infection include an early phase ($6-12$ weeks) characterized by viral replication and symptoms like night sweats and fever. After seroconversion (the development of antibodies), the patient may enter an asymptomatic period that can last up to $10$ years. However, eventually, the CD4 count drops significantly ($\text{below } 200\, \text{cells/mm}^3$ is the threshold for AIDS). Patients with AIDS are highly susceptible to secondary infections, which are often the ultimate cause of death. Management involves antiviral drugs, though challenges like resistant strains, cost, and side effects exist.

Questions and Discussion

Q: What is the role of complement proteins?A: They enhance phagocytosis, activate phagocytes, and enhance the destruction of a pathogen's membrane by forming a complex that causes the cell to burst.

Q: Which white blood cells are the antibody factories?A: B cells (B lymphocytes).

Q: What substance kills pathogens by breaking down bacterial cell walls?A: Lysozyme.

Q: How does the secondary immune response differ from the primary?A: It is faster and more powerful because memory B cells and T cells are already present to respond to the antigen.

Q: What specific immune response is being enhanced when complement proteins form a complex in a cell membrane?A: Phagocytosis and the direct lysis (bursting) of the target cell.

Q: Why is the destruction of helper T cells by HIV so devastating?A: Because helper T cells are necessary to activate both the antibody-mediated (B cell) and cellular (cytotoxic T cell) specific immune responses.

Q: In the site of inflammation, what causes edema, redness, and heat?A: Increased blood flow and histamine release.

Q: What enables the secondary response to be more rapid than the primary?A: Memory B cells.