Immune System

Page 1: Immune System

Page 2: Lymph Nodes and Immune System

• Lymph Nodes:

  • Contain lymphocytes, the cells of the immune system that recognize and eliminate invading pathogens.

• Respiratory System:

  • Cilia line the airway and move mucus and contaminants upward and out of the respiratory tract.

• White Blood Cells:

  • How they attack pathogens in the blood and other tissues.

• Spleen:

  • Protects the body against bacterial infections.

• Functions of the Immune System:

  • Protect the body from foreign pathogens (bacteria, viruses, parasites).

• Skin:

  • Acts as a barrier against invading pathogens.

• Stomach and Intestines:

  • Stomach acid kills most harmful bacteria.

  • Antibodies from intestinal cells attack viruses and pathogens in the intestinal tract.

Page 3: Overview of Foreign Pathogens

• Infectious Agents (Pathogens):

  • Can damage or kill host organisms.

  • 6 major categories of infectious agents:

    1. Prions

    2. Bacteria

    3. Viruses

    4. Fungi

    5. Protozoans

    6. Multicellular Parasites

Page 4: Overview of Infectious Agents (Prions)

• Prions:

  • Infectious proteins found in the brain.

  • Accumulate over time in nervous tissue and misfold normal proteins (plaques).

Page 5: Overview of Infectious Agents (Viruses)

• Viruses (NOT A CELL):

  • Composed of pieces of RNA or DNA in a protein shell (capsid).

  • Obligate intracellular parasites: requiring a host cell to reproduce.

  • Host cell may be killed by the virus or immune response.

  • Examples: Common cold, Ebola, Chickenpox, HIV, Flu, coronavirus.

Page 6: Overview of Infectious Agents (Bacteria)

• Bacteria:

  • Single-celled prokaryotes.

  • Most are harmless; skin is covered with protective bacteria.

  • Virulent bacteria can release toxins and cause damage.

  • Examples: Tuberculosis, Staph, Lyme disease, Syphilis, strep throat, Chlamydia.

Page 7: Overview of Infectious Agents (Fungi)

• Fungi:

  • Eukaryotic cells (molds, yeasts, multicellular fungi).

  • Release digestive enzymes for extracellular digestion.

  • Can cause superficial diseases in the integument and mucosal linings.

  • Examples: Yeast infections, athlete’s foot, ringworm.

Page 8: Overview of Infectious Agents (Protozoans)

• Protozoans:

  • Eukaryotic cells without a cell wall.

  • Can be intracellular and extracellular parasites.

  • Examples: Malaria, Giardia.

Page 9: Overview of Infectious Agents (Multicellular Parasites)

• Multicellular Parasites:

  • Take nourishment and live inside hosts.

  • Examples: Tapeworms, roundworms.

Page 10: Immune Cells

Page 11: Bone Marrow and Immune Cell Lineages

• Bone Marrow:

  • Hematopoietic stem cells (HSC) differentiate into two major lineages:

    1. Myeloid Lineage:

       • Mature Cells: Neutrophils, Eosinophils, Basophils, Mast cells, Macrophages, Dendritic cells.

    2. Lymphoid Lineage:

       • Thymocytes, NK cells, B cells, T cells.

Page 12: Immune Cells (Granulocytes)

• Granulocytes:

  • Myeloid immune cells with granules containing enzymes, released during infections, allergic reactions, and asthma.

  • Types: Neutrophils, Eosinophils, Basophils.

Page 13: Immune Cells (Neutrophils)

• Neutrophils:

  • Neutral colored cytoplasm, polymorphonuclear (PMN).

  • Most abundant granulocyte (40-70% of all WBCs).

  • First responders to infection; phagocytize pathogens.

Page 14: Immune Cells (Eosinophils)

• Eosinophils:

  • Primarily in mucous membranes, with deep red granules and a bilobed nucleus (5% of all WBCs).

  • Attack multicellular parasites and release cytotoxic chemicals.

Page 15: Immune Cells (Basophils)

• Basophils:

  • Present in blood vessels; also known as mast cells in tissues (0.5% of all WBCs).

  • Involved in inflammation and allergic reactions.

Page 16: Immune Cells (Basophils / Mast Cells)

• Basophils and Mast Cells:

  • Release chemicals that cause inflammation:

    • Histamine: Vasodilator, increases capillary permeability.

    • Heparin: Anticoagulant.

Page 17: Immune Cells (Agranulocytes)

• Monocytes:

  • Circulate in blood for 1-3 days, then enter tissues and become:

    • Macrophages

    • Dendritic cells (epithelium)

    • Dust cells (lungs)

    • Kupffer cells (liver).

Page 18: Immune Cells (Phagocytosis by Macrophages)

• Phagocytosis Process:

  1. Bacterium engulfed by a macrophage, encased in a vacuole.

  2. Lysosomes fuse with the vacuole and digest the bacterium.

  3. Antigens from the digested bacterium presented with MHC II on the cell surface.

  • Immune Role: Antigen Presenting Cell (APC), activates receptors on other immune cells.

Page 19: Immune Cells (Lymphocytes)

• Lymphocytes:

  • Three types: B-lymphocytes (B-cells), T-lymphocytes (T-cells), and Natural Killer cells.

  • Essential for adaptive immunity and destruction of infected cells.

Page 20: Immune Cells (B-Cells and T-Cells)

• B-lymphocytes (B-cells) and T-lymphocytes (T-cells):

  • Found in lymphatic organs and tissues, become activated to manage the adaptive immune response.

Page 21: Immune Cells (Natural Killer Cells)

• Natural Killer Cells (NK cells):

  • Also known as cytotoxic T cells, located in lymphatic organs, lymphatic tissue, lymph, and blood.

  • Function: Destroy virally infected cells.

Page 22: Innate and Adaptive Immunity

• Innate Immunity:

  • Immediate response to a wide variety of substances, includes:

    • Skin and Mucosal Membranes: Prevent entry of pathogens.

    • Internal Defenses: Macrophages, NK cells, chemicals (e.g., interferons, complement).

    • Physiological Responses: Inflammation, fever.

• Adaptive Immunity:

  • Delayed response to specific antigens, involving:

    • T-lymphocytes: Cell-mediated immunity.

    • B-lymphocytes: Humoral immunity, plasma cells produce antibodies.

Page 23: Innate Immunity

• Innate Immunity:

  • Present at birth, nonspecific, responds immediately to potentially harmful agents.

Page 24: Adaptive Immunity

• Adaptive Immunity:

  • Acquired immunity; involves T & B cells. Specific responders to an antigen take days to become effective and develops memory for future exposures.

Page 25: Innate Immunity - 1st Line of Defense (Skin)

• Cutaneous Membrane:

  • Epidermis and dermis serve as physical barriers, tightly linked cells prevent microbial entry.

  • Dermis produces hyaluronic acid to slow microbial migration.

Page 26: Innate Immunity - 1st Line of Defense (Skin pH)

• Skin pH:

  • Healthy skin has a pH of 5.5; alkaline pH results in skin issues.

Page 27: Innate Immunity - 1st Line of Defense (Skin Microflora)

• Skin Microflora:

  • Nonpathogenic commensal microflora help prevent growth of pathogenic microorganisms.

Page 28: Innate Immunity - 1st Line of Defense (Glands)

• Glands:

  • Sweat Glands: Release antimicrobial substances (salt- solute).

  • Sebaceous Glands: Secrete sebum to lower skin pH.

Page 29: Innate Immunity - 1st Line of Defense (Mucosal Membranes)

• Mucosal Membranes:

  • Line body openings (respiratory, gastrointestinal, urinary, reproductive tracts), form barriers.

Page 30: Innate Immunity - 1st Line of Defense (Respiratory Tract)

• Respiratory Tract Defense:

  • Nasal hairs (vibrissa) trap microbes; mucin with antimicrobial substances secreted.

  • Cilia sweep mucus towards pharynx; coughing and sneezing expel microbes.

Page 31: Innate Immunity - 1st Line of Defense (GI Tract)

• Gastrointestinal Tract Defense:

  • Saliva contains antimicrobial substances.

  • Stomach acid (~pH 2) destroys bacteria.

  • Defecation and vomiting remove microbes before they enter the bloodstream.

  • Intestinal commensal microflora inhibit pathogen growth.

Page 32: Innate Immunity - 1st Line of Defense (Urogenital Tract)

• Urogenital Tract Defense:

  • Urine flushes microbes; lactate secretion lowers pH.

Page 33: Innate Immunity

• Innate Immunity:

  • Immediate response; involved skin and mucosal membranes, internal defenses, cells (macrophages, NK cells), chemicals (interferon, complement), and physiological responses (inflammation, fever).

Page 34: Innate Immunity - 2nd Line of Defense

• 2nd Line of Defense:

  • Immune cells recognize foreign microbes through surface molecules and glycocalyx (sugar coat). Pattern recognition receptors identify non-self cells for targeting.

Page 35: Innate Immunity - Phagocytic Cells

• Phagocytic Cells:

  • Include neutrophils, macrophages, and dendritic cells that engulf unwanted substances.

  • Neutrophils undergo apoptosis, contributing to pus.

Page 36: Innate Immunity - Phagocytic Function

• Dendritic Cells:

  • Destroy particles and present antigen fragments to T-lymphocytes; serve as APCs.

    • Adaptive immunity

    • Macrophages are also APC

Page 37: Innate Immunity - Eosinophils

• Eosinophils:

  • Attack multicellular parasites through degranulation (release of enzymes and toxic substances).

Page 38: Innate Immunity - Basophils and Mast Cells

• Basophils and Mast Cells:

  • Promote inflammation; basophils circulate in blood, mast cells are located in tissues.

Page 39: Innate Immunity - Histamine and Chemical Release

• Basophils/Mast Cell Granules:

  • Contain chemicals like histamine and heparin, promoting inflammation and anticoagulation.

    • Eicosanoids- increase fluid movement

Page 40: Innate Immunity - Natural Killer Cells

• Natural Killer Cells:

  • Destroy unwanted cells via chemical agents; essential for immune surveillance against viruses, bacteria, tumors, and transplanted cells.

Page 41: NK Cell Mechanism

• Destruction Mechanism:

  1. NK cells release perforin, forming pores in unwanted cells.

  2. Granzymes enter pores, causing targeted cell apoptosis.

Page 42: Innate Immunity - Interferons

• Effects of Interferon:

  • A class of cytokines targeting intracellular pathogens, interfering with pathogen replication.

Page 43: Innate Immunity - Complement System

• Complement System:

  • Comprises over 30 plasma proteins synthesized by the liver; released in inactive form and acts alongside antibodies.

Page 44: Complement System Activation

• Complement Activation:

  • Classical Pathway: Antibody attaches to foreign substances, activating complement proteins.

  • Alternative Pathway: Complement binds to polysaccharides of certain bacteria and fungi.

Page 45: Complement System Functions

• Functions:

  • Opsonization, inflammation, cytolysis.

Page 46: Opsonization

• Opsonization:

  • Complement protein (C3b) tags bacteria, attracting phagocytic cells (macrophages).

Page 47: Inflammation Response

• Inflammation Promotion:

  • C3a and C5a promote histamine release from basophils, attracting phagocytes to infection sites.

Page 48: Cytolysis

• Cytolysis Mechanism:

  • Complement protein components form pores within pathogenic cells (protein channel), compromising integrity and causing cell lysis.

Page 49: Physiologic Responses - Inflammation

• Inflammation:

  • Immediate, local, nonspecific response to injury-causing stimuli in vascularized tissues.

Page 50: Inflammatory Events

• Events of Inflammation:

  1. Release of chemicals promoting inflammation.

  2. Vascular changes (vasodilation, increased permeability) facilitating leukocyte adhesion.

  3. Recruitment of leukocytes through margination, diapedesis, and chemotaxis.

Page 51: Margination and Diapedesis

• Margination:

  • Cell adhesion molecules (CAMs) adhere leukocytes in the blood.

• Diapedesis:

  • Leukocytes squeeze between endothelial cells to reach infection sites.

Page 52: Plasma Protein Delivery

• Delivery of Plasma Proteins:

  • Antibodies and other proteins increase capillary permeability and CAM production at infection sites.

Page 53: Signs of Inflammatory Response

• Signs:

  • Redness, heat, swelling, pain, and potential loss of function.

  • Typically resolves in 8-10 days.

Page 54: Fever (Pyrexia)

• Fever:

  • Abnormal body temperature elevation (>2°F from normal 98.6°F) induced by pyrogens.

Page 55: Fever Mechanism**

• Fever Stages:

  1. Onset: Temperature rises as hypothalamus constricts blood vessels and muscles shiver.

  2. Stadium: Elevated temperature maintained, increasing metabolic rate to eliminate harmful substances.

  3. Defervescence: Body temperature returns to normal.

Page 56: Risks of High Fever

• High Fever:

  • Considered high above 100°F (>103°F in children); can alter metabolic pathways and damage proteins.

  • Risks of brain damage over 106°F and potential death above 109°F.

• Benefits of Fever:

  • Inhibits pathogen reproduction, enhances adaptive immunity, accelerates tissue repair.

Page 57: Overview of Innate Immunity**

• Immediate Responses: Nonspecific, involving barriers and internal defenses against pathogens.

• Adaptive immunity: Delayed responses to specific antigens using T and B lymphocytes.

Page 58: Adaptive Immunity**

• Antigen Detection:

  • T-lymphocytes and B-lymphocytes recognize pathogens based on (adaptive) antigens present on their surfaces.

  • Examples of antigens include viral protein capsids, bacterial cell walls, toxins, and tumor cells.

Page 59: Lymphocyte Structure**

• Lymphocytes:

  • Each contains approximately 100,000 receptor complexes specifically binding to one specific antigen such as TCR for T-lymphocytes and BCR for B-lymphocytes.

Page 60: Activation Requirements**

• T-lymphocytes: Cannot directly bind with an antigen without the help of an APC (Antigen Presenting Cell).

• B-lymphocytes: Can bind directly to antigens.

Page 61: T-lymphocytes and Coreceptors**

• Coreceptors:

  • T-lymphocytes possess additional receptors allowing interaction with APCs; helper T-cells (CD4) and cytotoxic T-cells (CD8).

Page 62: MHC Binding**

• MHC: Major Histocompatibility Complex on APCs that bind with TCR (T-Cell receptors) for recognition.

  • MHC I: Present on all cells (except RBCs); recognized by CD8 T-cells.

  • MHC II: Present on professional APCs; recognized by CD4 T-cells.

Page 63: T-Cell Activation**

• Activation and Clonal Selection:

  • Helper T-cells release interleukin 2 upon signaling, stimulating their activation and proliferation into memory T-cells for future infections.

Page 64: Cytotoxic T-Cell Activation**

• Cytotoxic T-Cells:

  1. First signal: Interaction between CD8 protein and MHC I on APC.

  2. Interleukin 2 released by Helper T-lymphocytes further activates and clones Cytotoxic T-cells.

Page 65: B-Cell Activation**

• B-Cell Activation:

  • B-lymphocytes contact antigens directly and present them on MHC II, obtaining help from a Helper T-lymphocyte for full activation.

Page 66: Second Signal for B-Cell Activation**

• Second Signal: The Helper T-lymphocyte releases interleukin 4, further stimulating the B-lymphocyte's activity.

  • Activated B-cells clone, producing plasma cells that synthesize antibodies and memory B-cells for re-exposure.

Page 67: B-Cell Clonal Expansion**

• B-Cells Clone: Activated B-lymphocytes differentiate into specific clones for rapid antibody production and memory formation.

Page 68: Antibody Structure**

• Antibody Structure:

  • Y-shaped molecules consisting of light and heavy polypeptide chains.

  • Contains antigen-binding sites crucial for pathogen neutralization.

Page 69: Antibody Mechanism - Neutralization**

• Neutralization:

  • Antibodies coat pathogens or toxins, rendering them ineffective for infection.

Page 70: Antibody Mechanism - Agglutination**

• Agglutination:

  • Cross-linking of pathogens by antibodies creates mass clumps for easier elimination by immune cells.

Page 71: Antibody Mechanism - Precipitation**

• Precipitation:

  • Antibody cross-linking forms insoluble complexes that deposit in tissues, allowing for engulfment by immune cells.

Page 72: Constant Region Functions**

• Constant (Fc) Region:

  • Determines how the antigen is disposed through mechanisms such as complement fixation, opsonization, and NK cell activation.

Page 73: Innate vs Acquired Immunity**

• Innate Immunity: Born with it; provides resistance to certain pathogens (e.g., humans resist wheat rust).

• Acquired Immunity: Develops immunity; body produces its own antibodies.

Page 74: Acquired Immunity - Types**

• Types of Acquired Immunity:

  • Naturally Acquired: Pathogens enter naturally; disease develops.

  • Artificially Acquired: Weakened or dead pathogens introduced via vaccines.

Page 75: Immune Response - Primary vs Secondary**

• Immune Response:

  • Primary Response: Initial exposure generates antibodies (IgM followed by IgG) over time.

  • Secondary Response: More rapid response upon re-exposure due to memory cells.

Page 76: Passive Immunity**

• Passive Acquired Immunity:

  • Antibodies are received from another source, do not require pathogen exposure.

Page 77: Passive Immunity Types**

• Types of Passive Immunity:

  • Naturally acquired: Antibodies transferred from mother to baby.

  • Artificially acquired: Antibodies injected (e.g., snake antivenom).