מבוא לאימונולוגיה

Introduction to Immunology

• The immune system protects the body from various microorganisms attempting to enter.
• It also acts against cancerous cells.
• Failures in the immune system can lead to allergies or autoimmune diseases. Understanding these failures allows for prevention.
• The immune system makes organ transplantation more challenging.
• Microorganisms enter to find nutrients for growth and reproduction, and the immune system protects these nutrients.

Potential Immune Responses to Microorganisms

• The immune system has three possible responses when a microorganism enters the body:
  • Eliminate the microorganism and restore homeostasis.
  • Control the microorganism (without elimination).
  • Fail to control the microorganism, leading to the organism's death.
• Homeostasis after an infection is not identical to pre-infection homeostasis.

Threats to the Immune System

• External factors: Fungi, parasites, bacteria, viruses, toxins (like snake venom), and trauma.
• Internal factors: Cancerous cells, cells that die naturally, and need to be eliminated.
• Organism death from infection can occur due to uncontrolled pathogen proliferation or self-damage by the immune system's fight.
• Self-damage from the immune system can include high fever, harmful chemicals produced against pathogens that mistakenly target the body's own cells, killing infected cells, and reacting against harmless or beneficial bacteria.
• LPS (lipopolysaccharide) on gram-negative bacteria signals the immune system, even if the bacteria do not cause harm. High LPS levels can still cause serious harm leading to organism death.

Successful Immune Response

• A successful immune response ensures the organism's well-being and survival.
• The immune system comprises cells and organs capable of generating responses ensuring survival and integrity.
• Inflammation is the body's way of maintaining integrity.

Historical Developments in Immunization

• Variolation was a process of scratching a healthy person with infected material to develop a milder form of the disease, not a vaccination.
• Edward Jenner observed cowpox lesions similar to smallpox lesions. Milkmaids who had cowpox lesions never contracted smallpox.
• Jenner hypothesised that exposure to cowpox protected against smallpox, developing a cowpox-based smallpox vaccine.

Immune System Characteristics

• An experiment with one normal and one immunodeficent mouse exposed to a bacteria showed that a fully functional immune system effectively removes bacteria.
• An absent immune system function results in bacterial overgrowth and death.
• The immune response depends on pathogen load and the harm caused.

Innate and Adaptive Immunity

• Innate immunity: Pre-existing components of the immune system that rapidly respond to pathogens. Reaches peak activity within 24 hours.
• Adaptive immunity: Takes longer to function. Reaches peak activity between one and two weeks after pathogen entry.
• Mice lacking innate or adaptive immunity failed to successfully combat the infection and eventually died.
• Innate immunity is frequently active, but adaptive immunity might not be as frequently active.

Immune System Memory

• Innate immunity lacks immunological memory. Each infection starts from scratch.
• A theory suggests innate immunity has epigenetic memory.

Self-Tolerance (Experiment)

• Experiment with genetically identical mice revealed that skin grafts between identical mice were successfully accepted, but skin grafts from different strains were rejected. This demonstrates the body's ability to distinguish self from non-self.
• A new experiment with yellow and pink mice demonstrated that it takes about a week or two for a recipient's immune system to reject a foreign skin graft. This means the adaptive immune system is responsible for the tissue rejection.
• Repeating the graft showed a faster rejection of the graft from the pink mouse, indicating immunological memory in the adaptive system.

Antigens and Antibodies

• An antigen is a substance that stimulates the immune system, activating it and causing antibody production.
• Antibodies are proteins produced by the adaptive immune system. They are effector mechanisms.
• Antibody production and graft rejection are distinct effector mechanisms of the immune system.
• Adaptive immunity is divided into: Humoral (antibodies in body fluids) and Cellular (cells directly involved in elimination).
• The adaptive immune system generates antibodies when an antigen is introduced, and the antibody levels decrease after infection but maintain a certain level in the blood.
• A secondary exposure to antigens (such as A and B) results in a faster and more robust antibody response, demonstrating immunological memory.
• Shared antigens between pathogens allow a response against both if the body is exposed to one.

Active and Passive Immunity

• Active immunity: Introducing a weakened or inactivated pathogen to stimulate the adaptive immune system to produce antibodies, creating immunological memory.
• Passive immunity: Administering pre-formed antibodies, quick response but no immunological memory.
• Prolonged presence of an antigen can lead to the development of memory in passive immunity.

Immune System Cells and Organs

• Immune cells: Cells primarily dedicated to identifying antigens and responding during inflammation.
• Hemopoietic Lineage: Cells developing in bone marrow with the capacity to differentiate.
• Differentiation leads to lymphoid and myeloid lineages.
• Myeloid Lineage: Red blood cells, platelets (not involved in the Immune system). Other myeloid lineage cells involved in innate immunity are Mast cells, basophils, eosinophils, monocytes, dendritic cells, and neutrophils.
• Lymphoid Lineage: Natural killer cells, B & T lymphocytes (adaptive immunity), and ILCs (functions are unclear).

Morphological Analysis of Immune Cells

• Immune cells are larger than red blood cells and platelets.
• White blood cells have diverse nuclei (single or multi-lobed).
• Granules with different colors are present within white blood cells.
• Granule colour depends on pH: acidic=red, basic=dark purple, neutral=light/transparent.
• Cells can be categorized based on nucleus and granules:
  • No nucleus: Platelets, Red Blood Cells
  • Multi-lobed nucleus, granules: Eosinophils, Basophils, Neutrophils (myeloid lineage)
  • Single nucleus: Monocytes, Lymphocytes (lymphoid lineage).

Immune Cell Markers (CD)

• Cluster of Differentiation (CD): transmembrane glycoproteins.
• CD expression can vary dynamically.

Specific Immune Cells: Macrophages

• Originate in bone marrow, release into bloodstream, then differentiate in tissues for roles within the immune response
• Function: Phagocytosis, inflammatory regulation, antigen presentation, tissue repair, and pathogen killing.
• Two types: M1 (pro-inflammatory) and M2 (anti-inflammatory/repair). Fetus macrophages can also become specific macrophages like microglia (brain), Kupffer cells (liver), and alveolar macrophages (lungs). Fetal/Embryonic macrophages maintain a consistent number throughout life. Mature macrophages that result in inflammatory response are renewed during adulthood .

Specific Immune Cells: Dendritic Cells

• Originate in bone marrow, enter bloodstream and differentiate in tissues.
• Function: Antigen presentation, activating adaptive immune cells (lymphocytes).
• Engulf pathogens, process them, and display them on their surface to activate lymphocytes in lymphoid organs.

Specific Immune Cells: Granulocytes

• Multiple types (eosinophils, basophils, neutrophils) with granules.
• Function: Primary function is degranulation (release of granule contents).
• Neutrophils: Neutral pH granules with enzymes and substances for pathogen killing. Phagocytosis, substance release, degranulation, and killing of extracellular bacteria. Chemotaxis (cell movement towards gradient) allows them to pursue and eliminate bacteria.

Specific Immune Cells: Eosinophils and Basophils

• Eosinophils: Acidic pH granules, primarily degranulate to kill helminths (worms).
• Basophils: Release inflammatory substances (histamine, cytokines) like Mast cells (separate lineages) to communicate immune status to the immune system. Granules exhibit a basic pH (purple).

Specific Immune Cells: Natural Killer (NK) Cells

• Single nucleus, similar to lymphocytes but myeloid lineage origin.
• Function: Cytotoxic activity, kill cancerous or infected cells by inducing cellular death (apoptosis) via the release of chemicals.
• If resistance occurs, NK cells will induce necrosis.
• NK cells are not responsible for breaking down infected cells they kill.

Specific Immune Cells: Lymphocytes

• Single nucleus, adaptive immunity origin.
• Function: B (antibody production), T helper cells (cytokine production), and T cytotoxic cells (killing).
• B lymphocytes mature in the bone marrow; T lymphocytes mature in the thymus. Both then circulate to secondary lymphoid organs.
• Recognize and respond to specific antigens.

Immune System Organs

• Bone Marrow: Primary lymphoid organ for hematopoiesis & B-lymphocyte maturation. Located in the interior of long and flat bones.
• Thymus: Located above the heart, involved in T-lymphocyte development & maturation and size decreases with age.
• Secondary Lymphoid Organs: Lymphatic system, including lymphatic vessels and lymph nodes, circulating lymph fluid containing lymphocytes. Acts as a transport system.
• Lymph Nodes: Contain many lymphocytes and supporting tissues.
• Spleen: Filters blood, removing old red blood cells. White and red pulp contain lymphocytes for antigen recognition similar to lymph nodes.
• Mucosal Lymphoid Tissues: Crucial for preventing foreign bodies from entering tissues. Located in the intestines, bronchi, lungs, nose, and reproductive system etc.

Immune Systems Response

• Innate Immune Response: Initial response to pathogens. Very quick, peaking within 24 hours.
• Adaptive Immune Response: Later response, peaking between 1-2 weeks. Requires antigen presentation to lymphocytes.
• Immune System Memory: The body retains information about previous encounters with pathogens; faster, more effective response upon subsequent exposures.

Important Immune Defense Mechanisms

• Barriers: Physical barriers (skin, mucous membranes), chemical barriers (pH, enzymes), and microbially mediated barriers (normal flora).
• Inflammation: Response to injury or infection, involving the recruitment of immune cells, blood vessel dilation, increased permeability, and cytokine release to help eliminate pathogen.

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