Immunity and the Immune System

Immunity

The Immune System

  • The immune system's main components and their roles in immunity:
    • Skin
    • Macrophage
    • Helper T cell
    • B cell
    • Killer T cell
    • Suppressor T cell
    • Memory T cell

Pathogens

  • Pathogen: An organism that can cause disease in the host upon infection.
  • Cellular (living) pathogens:
    • Protozoa (e.g., plasmodia) → Malaria
    • Parasites (e.g., helminthes) → Tapeworm
    • Fungi (e.g., tinea) → Athlete's foot
    • Prokaryote (i.e., bacteria) → Leprosy
  • Acellular (non-living) pathogens:
    • Virus (e.g., HIV) → AIDS
    • Prion → CJD

Immune System

  • Innate Immunity:
    • Immediate response to a wide array of substances.
    • Non-specific internal defenses.
    • Includes:
      • Skin and mucosal membranes & barriers (prevent entry).
      • Cells (e.g., macrophages, NK cells).
      • Chemicals (e.g., interferon, complement).
      • Physiologic responses (e.g., inflammation, fever).
  • Adaptive Immunity:
    • Delayed response to specific antigen.
    • B-lymphocytes (humoral immunity).
      • Plasma cells (synthesize and release antibodies).
    • T-lymphocytes (cell-mediated immunity).

The Defence System

  • Three ways the body resists harm from pathogens:
    1. Physical and Chemical Barriers
    2. Non-specific defences
    3. Specific defences

Barriers (First Line of Defence)

  • Physical barriers:
    • Eyelashes, cilia in the respiratory tract, hairs in the nose, etc.
  • Chemical barriers:
    • Mucous, tears, and saliva (lysozyme), stomach acid, perspiration, etc.
  • Skin:
    • Hostile environment for microorganisms.
    • Outer layer: dry, thick, indigestible keratin.
    • Oil contains bactericides.
    • Sweat is acidic and contains lysozyme.
    • Stomach acid, Eyelashes and tears are also included.

Second Line of Defence: Non-Specific

  • Involves non-specific white blood cells known as phagocytes.
  • Phagocytes engulf and destroy foreign pathogens in the bloodstream.
  • Three types of phagocytes:
    • Monocyte
    • Macrophage
    • Neutrophil
  • Also referred to as the "inflammatory response," often resulting in swelling & a fever.

Phagocytosis

  • Ingestion of invading microbes by certain WBCs.

Non-Specific Defences (Second Line of Defence)

  • Neutrophils:
    • First to arrive.
    • Phagocytic; engulf and destroy harmful pathogens.
  • Monocytes (become macrophages):
    • Second to arrive.
    • Devour pathogens, dead tissue, and dead neutrophils.
    • Accumulation of pus.

2nd Line (non-specific) – Inflammatory Response

  • Tissue damage due to physical injury leads to inflammatory response.
  • Results in swelling, heat, and pain.
  • Histamine is released:
    • Capillaries swell and leak (vasodilation).
    • Phagocytes/WBC go to the wound.
    • Results in redness and swelling.
  • Clues to the second line of defence: pus and inflammation.
  • Neutrophils and macrophages digest invaders.
  • Release chemicals that reach the hypothalamus.
  • Reset body temperature to about 40∘C40^{\circ}C.
  • Fever makes it difficult for harmful bacteria to survive.
  • Fevers > 40∘C40^{\circ}C can be unsafe because enzymes start to denature.

Steps of the Inflammatory Response

  1. Damaged tissues release histamines, increasing blood flow to the area.
  2. Histamines cause capillaries to leak, releasing phagocytes and clotting factors into the wound.
  3. Phagocytes engulf bacteria, dead cells, and cellular debris.
  4. Platelets move out of the capillary to seal the wounded area.
    • The inflammatory response is a body's second line of defense against invasion by pathogens. Clotting factors from the circulatory system accessing the injured area are important.

Specific Defences (Third Line of Defence)

  • Antibodies are proteins that recognize the antigens displayed by foreign particles and trigger a series of events to quickly neutralize or destroy them.
  • Antibodies specific to different pathogens are generated AFTER white blood cells destroy said pathogens through phagocytosis.
  • Over time, exposure to various foreign substances leads to the development of an immune system unique to each individual.

Antibodies

  • Mechanisms:
    • Precipitation: Makes soluble antigens insoluble, aiding elimination.
    • Agglutination: Links cell-bound antigens together, causing clumping.
    • Neutralisation: Masks dangerous parts of pathogen (e.g. exotoxins, etc.).
    • Inflammation: Triggers histamine release, increasing immune mobility.
    • Complement: Complement protein perforates the cell membrane (cell lysis).
    • Opsonisation & Phagocytosis: Enhances cell lysis.

Specific Defences (Third Line of Defence)

  • Lymphocytic white blood cells or “lymphocytes” target pathogens according to the specific markers they present.
  • Two types of lymphocytes:
    1. B cells – mature in bone marrow (b as in bone)
    2. T cells – mature in thymus gland, near heart (t has in thymus)

Specific Defences (Third Line of Defence)

  • Specific defences (a.k.a. antibody-mediated immunity).
  • Lymphocytic white blood cells or “lymphocytes” target pathogens according to the specific markers they present.
  • Antigen receptors (same shape as antibodies) on B and T cells recognize foreign antigens and bind and neutralize.
  • Note: antibodies are specific (can only bind with one type of antigen).

Specific Defences (T cells)

  • After macrophage has engulfed pathogen, the pathogen’s antigens move to the macrophages membrane
  • Helper T-cells analyze pathogens after they have been broken down by phagocytes and recruit B-cells to help identify the foreign particles.
  • Types of T cells:
    • Helper T Cells
    • Killer T Cells
    • Suppressor T cells
    • Memory T cells

Specific Defences (Helper T cells)

  • Helper T cells recognize foreign antigen chemical signals released and stimulates more macrophages, B cells and T cells.

Specific Defences (Killer T cells)

  • Killer T cells recognize foreign antigen on infected cells and/or cancerous cells
  • Bind, puncture and destroy infected cells (lysis)

Specific Defences (Suppressor T cells)

  • Suppressor T-cells monitor killer T- cells to make sure they do not destroy healthy tissues.
  • Ends immune response and inhibit other T and B cells.

Specific Defences (Memory T cells)

  • Do not respond on first exposure, but remain in blood for future invasion.
  • Keeps record of the antigens on the invading particle for a quicker response.

Specific Defences (B cells)

  • Are recruited to the site of phagocytosis by T-cells.
  • Where they become activated and divided into two different types of B-cells:
    • Memory B-cells and
    • Plasma cells

B-Cells

  • Plasma cells produce antibodies that recognize and attach to the antigens of specific pathogens.
  • Essentially slowing the pathogen down and marking it for destruction by phagocytes.
  • Antibodies remain in the bloodstream so that next time the pathogen enters the bloodstream, phagocytes can quickly destroy it.
  • After infection is gone, stays in blood ready for the next attack à cellular immunity!

B-Cells

  • Memory B-cells display antibodies (proteins) that match the antigens (proteins) presented by that particular pathogen.
  • They remain in the bloodstream so that if they ever encounter that pathogen again, they can quickly call a phagocyte to the scene.
  • Both B and T lymphocytes are found in the lymph nodes of the lymph system!

The Actual Immune Response

  1. Pathogen enters the body
  2. Macrophages, neutrophils, and basophils are non- specific cells that kill invading bacteria
  3. Helper T cells recognize invaders and send a message to B cells to start making antibodies
  4. B cells make antibodies
  5. Antibodies attach to bacteria/virus and immobilize it
  6. If it is bacteria, macrophages will come along and engulf it (phagocytosis)
  7. If a virus, it will be found within a cell of the body (host). The killer T cells recognize it, and kills the cell and virus
  8. Macrophages come along and clean up the dead cells, viruses, and dead bacteria
  9. Suppressor T cell inhibit the T and B cells when the threat has been killed
  10. Memory T and B cells keep a record of the antigen, and these cells live for decades.
  11. Next time the same pathogen is encountered, the immune response will be even quicker because of Memory B and T cells.

The Immune Response

  • Phagocyte digests pathogen and displays the antigens specific to that pathogen on its surface.
  • Helper T-cells recognize the antigen and signal the action of B-cells.
  • B-cells arrive to the site of phagocytosis and bind with Helper T-cells, causing them to enlarge and divide to produce Memory B-cells and Plasma cells.
  • Helper T-cells also recruit Killer T-cells, or "Cytotoxic T-cells", which destroy any cells that have already been infected.
  • Suppressor T-cells monitor the activity of Killer T-cells so that they do not destroy healthy tissues.
  • Memory B-cells display antibodies specific to that particular pathogen on their surface. They remain in the bloodstream so that next time the pathogen is present, they can quickly bind to its antigen and recruit phagocytes to the scene.
  • Plasma cells produce large quantities of antibodies which match the antigen presented by the pathogen. These antibodies remain in the bloodstream so that next time the pathogen is present they can bind to the pathogen, essentially slowing it down and marking it for destruction by phagocytes.

Immunization

  • Based on principle of providing antibodies against specific antigens.
  • The injection of a “deactivated” harmless form of a virus or a dead virus. Contains antigen markers on the cells surface but can’t replicate
  • Body detects the antigen and launches an immune response. Helper T-cells recruit B-cells to produce antibodies against the antigens. The antibodies then make it so you can fight against the pathogen’s antigen.
  • Many require booster shots because the antibodies break down over time.

Antibodies & Vaccines

  • Illustrates the relationship between antibodies, antigens, and pathogens in the context of vaccines.
    • antibody
    • antigen
    • pathogen (deactivated)
    • MB
    • MB

Allergies

  • Exaggerated immune response to harmless material. Occurs when the immune system mistakenly recognizes harmless foreign particles as serious threats.
  • Two types:
    • Acute – within seconds; antibodies trigger the release of histamines à swelling, watery eyes, runny nose.
      • anaphylaxis
    • Delayed – slower, but lasts longer; triggered by memory T cells
      • E.g. Cosmetics, jewellery

Immune Disorders ~Acquired Immune Deficiency Syndrome - 1983~

  • “AIDS”- Caused by the Human Immunodeficiency Virus (HIV)
  • Specifically targets and kills T-cells
  • prevents immune system from working properly
  • HIV virus itself doesn’t kill you
  • cripples your immune system.

Immune Disorders

  • Mononucleosis – excess number of lymphocytes caused by the Epstein-Barr virus
  • Leukemia – a form of cancer characterized by excessive uncontrolled production of high levels of poorly developed white blood cells

Immune System Disorders

  • Autoimmune disorders – when T cells or antibodies mistakenly attack the body’s own cells.
  • Rheumatoid arthritis – chronic, inflammation of the joint linings
  • Celiac Disease - eating gluten triggers an immune response in your small intestine. Over time, this reaction damages your small intestine's lining and prevents it from absorbing some nutrients (malabsorption). The intestinal damage often causes diarrhea, fatigue, weight loss, bloating and anemia, and can lead to serious complications.
  • Type 1 Diabetes – body destroys insulin-producing cells in the pancreas