Meditaliano IMAT Prep

Part 1: The Immune System: A Detailed Exploration

The immune system is a remarkably complex network of cells, tissues, and organs that collaborate to defend the body against a constant barrage of harmful invaders (pathogens) like bacteria, viruses, fungi, and parasites.

1.1 Innate vs. Adaptive Immunity

The immune system has two main, interconnected branches:

1.2 Cells of the Immune System (Leukocytes)

The "soldiers" of the immune system are the white blood cells, or leukocytes, which originate from hematopoietic stem cells in the bone marrow.

1.3 Organs of the Immune System (Lymphoid Organs)

Immune cells are produced, mature, and are activated in specialized lymphoid organs.

• Primary Lymphoid Organs: Where lymphocytes are created and mature.
  • Bone Marrow: Origin of all blood cells, including all leukocytes. Site of B cell maturation.
  • Thymus: Gland located behind the sternum. Site of T cell maturation and "education" (learning self-tolerance through positive and negative selection).
• Secondary Lymphoid Organs: Where mature lymphocytes encounter antigens and are activated.
  • Lymph Nodes: Bean-shaped structures that filter lymph fluid. They are packed with lymphocytes and macrophages, acting as strategic sites for initiating adaptive immune responses.
  • Spleen: Filters blood, removing old red blood cells and pathogens. Contains areas of white pulp rich in lymphocytes.
  • Mucosa-Associated Lymphoid Tissue (MALT): Diffuse clusters of lymphoid tissue in mucous membranes (e.g., tonsils, Peyer's patches in the intestine).

1.4 Key Processes of the Immune Response

The Inflammatory Response (Innate)

When tissues are injured, mast cells release histamine, which causes local blood vessels to dilate (vasodilation) and become more permeable. This allows plasma fluid and phagocytes like neutrophils and macrophages to move from the blood into the tissue (extravasation) to destroy pathogens and clean up debris. The four cardinal signs are rubor (redness), calor (heat), tumor (swelling), and dolor (pain).

Cytokines: The Chemical Messengers

Cytokines are a broad category of small proteins that are crucial for cell signaling in the immune system. They are produced by a wide range of cells and act as messengers, allowing different parts of the immune system to coordinate their actions.

• Interleukins (ILs): A large group of cytokines produced mainly by leukocytes. They mediate communication between white blood cells (e.g., IL-1 promotes inflammation, IL-2 activates T cells).
• Interferons (IFNs): Released by virus-infected cells. They don't save the infected cell, but they signal to neighboring cells to increase their anti-viral defenses, thus interfering with viral replication.
• Chemokines: A type of cytokine that induces directed cell movement (chemotaxis). They create a chemical trail that attracts immune cells like neutrophils to the site of infection.

Antigen Presentation: Linking Innate and Adaptive Immunity

T cells cannot recognize free-floating antigens. Antigens must be processed and "presented" to them by other cells on proteins called Major Histocompatibility Complex (MHC) molecules.

• MHC Class I: Found on all nucleated body cells. They present endogenous antigens (peptides from within the cell, e.g., from a virus) to Cytotoxic T cells (CD8+). This is a "kill me" signal if the antigen is foreign.
• MHC Class II: Found only on professional Antigen-Presenting Cells (APCs) like macrophages, dendritic cells, and B cells. They present exogenous antigens (from phagocytosed pathogens) to Helper T cells (CD4+). This activates the Helper T cell to "sound the alarm" and coordinate a wider immune response.

Clonal Selection: The Basis of Specificity and Memory

Clonal selection is the central theory of adaptive immunity. The body generates a vast population of B and T cells, each with a unique antigen receptor. When a lymphocyte encounters its specific antigen, it is selected and activated to proliferate (divide rapidly) and differentiate. This creates a large clone of cells specific to that antigen. Most become short-lived effector cells (plasma cells or cytotoxic T cells) to fight the current infection, while a few become long-lived memory cells, ready for future encounters.

Antibody Function: More Than Just Binding

Antibodies (immunoglobulins, Ig) disable pathogens through several mechanisms:

• Neutralization: Antibodies bind to toxins or surface proteins on viruses, preventing them from harming the body or entering host cells.
• Opsonization: Antibodies coat pathogens, marking them for destruction by phagocytes like macrophages. The constant (Fc) region of the antibody acts as a handle for the phagocyte to grab.
• Agglutination: Each antibody has at least two antigen-binding sites, allowing them to clump pathogens together. This immobilizes them and makes them easier for phagocytes to clear.
• Complement Activation: The binding of antibodies to a pathogen can trigger the complement cascade, leading to the formation of the Membrane Attack Complex and cell lysis.

Primary vs. Secondary Immune Response

The first exposure to an antigen triggers a slow, weak primary response which takes several days to peak. However, this creates long-lived memory B and T cells. A second exposure to the same antigen triggers a much faster (hours), stronger, and longer-lasting secondary response. This is the fundamental principle behind vaccination.

Active vs. Passive Immunity

Part 2: Homeostasis: The Body's Balancing Act

Homeostasis is the active maintenance of a stable, relatively constant internal environment despite fluctuations in the external world. This "dynamic equilibrium" is crucial for the optimal functioning of cells, enzymes, and organ systems.

2.1 Negative vs. Positive Feedback

Homeostasis is primarily controlled by negative feedback loops. In these loops, the response generated by the control center counteracts the original stimulus, bringing the variable back to its set point. In contrast, positive feedback loops are rare; they amplify the stimulus, driving a physiological process to a rapid completion (e.g., uterine contractions during childbirth, blood clotting cascade).

2.2 Example 1: Thermoregulation

The hypothalamus in the brain acts as the body's thermostat, maintaining a core temperature set point of around 37°C (98.6°F).

2.3 Example 2: Blood Glucose Regulation

The pancreas (specifically the Islets of Langerhans) maintains blood glucose homeostasis (set point ~90 mg/dL) via an antagonistic pair of hormones in a classic negative feedback system.

• High Blood Glucose (after a meal): Beta (β) cells in the pancreas release insulin. Insulin signals body cells (especially muscle and fat) to take up glucose from the blood and signals the liver to store glucose as glycogen. This lowers blood glucose.
• Low Blood Glucose (during fasting): Alpha (α) cells in the pancreas release glucagon. Glugacon signals the liver to break down glycogen (glycogenolysis) and synthesize new glucose (gluconeogenesis), releasing it into the blood. This raises blood glucose.

2.4 Example 3: Blood Calcium Regulation

Blood calcium levels are vital for nerve transmission, muscle contraction, and blood clotting. They are tightly controlled by two antagonistic hormones.

• High Blood Calcium: The thyroid gland releases calcitonin. Calcitonin inhibits osteoclast activity (cells that break down bone) and stimulates osteoblast activity (cells that build bone), causing bones to absorb Ca²⁺ from the blood. It also increases Ca²⁺ excretion by the kidneys.
• Low Blood Calcium: The parathyroid glands release Parathyroid Hormone (PTH). PTH stimulates osteoclasts to release Ca²⁺ from bones, increases Ca²⁺ reabsorption in the kidneys, and promotes activation of Vitamin D, which enhances dietary Ca²⁺ absorption in the intestines.

2.5 Example 4: Osmoregulation (Water Balance)

The body must maintain a stable water and salt concentration (osmolarity) in the blood. This is mainly controlled by the hormone ADH.

• Stimulus: Dehydration / High Blood Osmolarity: Detected by osmoreceptors in the hypothalamus.
• Response: The hypothalamus stimulates the posterior pituitary gland to release Antidiuretic Hormone (ADH). ADH travels to the kidneys and makes the collecting ducts more permeable to water. More water is reabsorbed back into the blood, producing small volumes of concentrated urine. The hypothalamus also triggers the sensation of thirst.
• Result: Blood osmolarity decreases back to the set point, and ADH release is inhibited (negative feedback).

2.6 Example 5: Blood Pressure Regulation

Maintaining stable blood pressure is critical for ensuring adequate blood flow to all tissues. This involves both rapid, short-term nervous system responses and slower, long-term hormonal responses.

• Short-Term (Baroreceptor Reflex): Baroreceptors in the aorta and carotid arteries are stretch receptors that monitor blood pressure. If pressure drops, they signal the medulla oblongata in the brainstem, which increases heart rate and causes vasoconstriction to raise pressure back to normal.
• Long-Term (Renin-Angiotensin-Aldosterone System - RAAS): If blood pressure or blood flow to the kidneys drops, the kidneys release the enzyme renin. Renin initiates a cascade that produces angiotensin II, a potent vasoconstrictor. Angiotensin II also stimulates the adrenal cortex to release aldosterone, which promotes sodium and water reabsorption in the kidneys, increasing blood volume and thus blood pressure.

2.7 Example 6: Blood pH Regulation

The pH of human blood is tightly maintained between 7.35 and 7.45. This is crucial as even small deviations can denature proteins. The main regulatory systems are the chemical buffers, lungs, and kidneys.

• Bicarbonate Buffer System: The main chemical buffer in the blood. CO₂ reacts with water to form carbonic acid (H₂CO₃), which can dissociate into H⁺ and bicarbonate (HCO₃⁻). The reaction is reversible: CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻. This system can absorb or release H⁺ to resist pH changes.
• Respiratory Control: The brainstem monitors blood pH. If pH drops (acidosis), breathing rate increases to exhale more CO₂, pulling the equilibrium to the left and reducing H⁺. If pH rises (alkalosis), breathing slows. This is a rapid response.
• Renal Control: The kidneys are the most powerful, but slowest, regulators. They can selectively excrete H⁺ or reabsorb HCO₃⁻ to adjust pH over hours to days.

Interactive Practice Quiz (30 Questions)

Test your comprehensive understanding of immunity and homeostasis. Choose the best answer for each question (A-E) and then submit to see your results.