Module 4 - Immune Systems

• Pathogens - view our internal environment as a paradise, where the conditions are perfect for them to live and breed.
• the human body produced adaptations to protect itself from these pathogens – the immune system.
• The immune system is typically divided into two categories,

  • innate immunity
  • adaptive immunity
• Innate Immunity

  • refers to nonspecific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body.
  • mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body.
  • The innate immune response is activated by chemical properties of the antigen.
  • This is common to all animals and plants
• Invertebrates - Insects live in both terrestrial and aquatic environment which houses various pathogens, proving the effectiveness of their innate immunity

  • Exoskeleton provides a physical barrier for most pathogens;
  • Chitin lines the insect’s intestine to block pathogens in their food;
  • Lysozyme breaks down the bacterial cell walls;
  • Hemocytes are insects’ major immune cells which ingests microorganisms by phagocytosis;
  • Toll receptors, when bound with pathogen, activates the production and secretion of antimicrobial peptides to specifically kill the pathogen
• Vertebrates - they are similar with invertebrates. However, the unique aspect of it are natural killer cells, interferons, and the inflammatory response.

  1. Barrier defense
  2. Cellular innate defense
  3. Antimicrobial peptides and proteins
  4. Interferons
  5. Inflammatory response
• Types of phagocytic cells:

  Neutrophils - circulate in the blood, and are attracted by the signals from infected tissues. They engulf and destroy the infecting pathogen
• Types of phagocytic cells

  Macrophages - called as “big eaters” are mostly permanently residing in a tissue or organ (e.g. spleen) where they are likely to encounter pathogens.
• types of cells that play roles in the innate defense:

  Natural killer - cells release chemical that lead to cell death.
• Types of cells that play roles in the innate defense:

  Eosinophils - are often found in tissues underlying the epithelium to defend against multicellular invaders, such as parasitic worms. They discharge destructive enzymes to kill such parasites.
• Types of cells that play roles in the innate defense:

  Dendritic cells - mainly populate tissues that contact the environment (e.g. skin). They stimulate adaptive immunity against pathogens that they encounter and engulf.
• Vertebrates

  • Cellular innate defense - dedicated to detecting, devouring, and destroying invading pathogens. In doing so, these cells often rely on a Toll-like receptor (TLR), a mammalian recognition protein similar to the Toll protein of insects. Upon recognizing pathogens, TLR proteins produce signals that initiate responses tuned to the invading microorganism. This includes phagocytes.
• Vertebrates

  • Antimicrobial peptides and proteins - When pathogen recognition is triggered, production and release of a variety of peptides and proteins that impede their reproduction occur.
• Vertebrates

  • Barrier defense - includes the skin, saliva, tears, and mucous membranes. Lysozymes are also found in human saliva, tears, and mucous secretions. The acidic environment in the stomach (pH 2) and oil and sweat of the skin (pH 3- 5), also functions as a barrier defense
• Vertebrates

  • Interferons - are proteins that interfere with viral infections. The virus infected cells secrete interferon proteins that induce nearby cells to produce viral replication inhibiting substances. Thus, limits cell-to-cell spread of the virus.
• Vertebrates: Inflammatory Response

  • set of events triggered by signaling molecules released upon injury or infection.
  • Activated macrophages discharge cytokines, signaling molecules that recruit neutrophils to the site of injury or infection.
  • Mast cells, immune cells found in connective tissue, release the signaling molecule histamine at sites of damage.
  • Histamine triggers nearby blood vessels to dilate and become more permeable.
  • The result is an accumulation of pus, a fluid rich in white blood cells, dead pathogens, and debris from damaged tissue
• Adaptive immunity - refers to antigen-specific immune response, more complex than innate. The antigen first must be processed and recognized. Once an antigen has been recognized, the adaptive immune system creates an army of immune cells specifically designed to attack that antigen. Adaptive immunity also includes a "memory" that makes future responses against a specific antigen more efficient. This immunity is exclusive to vertebrates. The adaptive immune response is made possible because of the humoral response and cell mediated response.
• Adaptive Immunity

  Humoral response - production and secretion of antibodies or immunoglobulins against specific antigens. Antibodies are produced by cells that secrete them in the bloodstream or display them in the surface of some cells, ready to face and combat any antigen
• Adaptive Immunity

  Cell mediated response - occurs when cytotoxic cells defend the body against infection. The development of B and T cells, memory cells and plasma cells are important aspects of cell mediated immune mechanism
• B cells - are white blood cells that develop and mature in the bone marrow. They are activated when they encounter antigen in the lymph nodes. Activated B cells produce antibodies, proteins that recognize and bind to specific parts of antigens (any foreign body/structure- pollen, bacteria, virus, dust). Each B cell produces only one antibody which recognizes only one kind of antigen
• Human Antibodies

  IgG - most abundant antibody isotype in the blood (plasma), accounting for 70-75% of human immunoglobulins (antibodies). It detoxifies harmful substances and is important in the recognition of antigen-antibody complexes by leukocytes and macrophages. It is transferred to the fetus through the placenta and protects the infant until its own immune system is functional.
• Human Antibodies

  IgM - usually circulates in the blood, accounting for about 10% of human immunoglobulins. IgM has a pentameric structure in which five basic Y-shaped molecules are linked together. B cells produce this first in response to microbial infection/antigen invasion. Although it has a lower affinity for antigens than IgG, it has higher avidity for antigens because of its pentameric/hexameric structure. Avidity is the overall strength of binding between an antibody and an antigen. By binding to the cell surface receptor, also activates cell signaling pathways.
• Human Antibodies

  IgA - is abundant in serum, nasal mucus, saliva, breast milk, and intestinal fluid, accounting for 10-15% of human immunoglobulins. It forms dimers (i.e., two IgA monomers joined together). This in breast milk protects the gastrointestinal tract of neonates from pathogens.
• Human Antibodies

  IgE - is present in minute amounts, accounting for no more than 0.001% of human immunoglobulins. Its original role is to protect against parasites. In regions where parasitic infection is rare, It is primarily involved in allergy.
• Human Antibodies

  IgD accounts for less than 1% of human immunoglobulins. It may be involved in the induction of antibody production in B cells, but its exact function remains unknown.
• T cell - type of white blood cell that is of key importance to the immune system and is at the core of adaptive immunity, the system that tailors the body's immune response to specific pathogens. Are like soldiers who search out and destroy the targeted invaders.
• Immature T cells - After T cells are produced in the bone marrow, they migrate to the thymus gland in the neck where they mature and differentiate into various types of mature T cells and become active in the immune system. This is in response to a hormone called thymosin and other factors. T-cells that are potentially activated against the body's own tissues are normally killed or changed ("down-regulated") during this maturational process.
• There are three types of T cells:

  1. Cytotoxic T cells
  2. Helper T cells
  3. Regulatory T cells
• 5 Human Antibodies

  1. IgG
  2. IgM
  3. IgA
  4. IgE
  5. IgD
• Adaptive immunity was divided to two responses:

  1. Humoral response
  2. Cell mediated response
• Vertebrates has five defenses:

  1. Barrier defense
  2. Cellular innate defense
  3. Antimicrobial peptides and proteins
  4. Interferons
  5. Inflammatory response
• Types of cells that play roles in the innate defense:

  1. Dendritic cells
  2. Eosinophils
  3. Natural killer cells
• Two main types of phagocytic cells:

  1. Neutrophils
  2. Macrophages
• T Cells

  Cytotoxic T cells - have a co-receptor called CD8 on their cell surface. CD8 partners with the T cell receptor and with MHC class I molecules, acting as a sort of bridge. This bridge allows cytotoxic T cells to recognize normal cells that are infected by a pathogen. When the cytotoxic T cell recognizes the infected cell, it becomes activated and produces molecules that kill the infected cell, destroying the pathogen in the process.
• T Cells

  Helper T cells - have a different co-receptor called CD4 on their cell surface. CD4 also partners with the T cell receptor but interacts with MHC class II molecules instead of MHC class I molecules. This allows them to recognize pathogen peptides that have been displayed by antigen presenting cells. When it recognize a peptide on an antigen presenting cell, they become activated and begin to produce molecules called cytokines that signal to other immune cells.
• T Cells

  Regulatory Cells - also have CD4 on their surface, but they do not activate the immune system like helper T cells do. Instead, it play a protective role by shutting off the immune response when it is no longer needed. This prevents excessive damage to the normal cells and tissues in the body. The cells suppress the immune response in several ways, including:

  • Producing anti-inflammatory cytokines that suppress the immune response

  • Releasing molecules that kill activated immune cells

  • Changing the way dendritic cells behave so they can't activate T cell
• Where do T cell mature? Thymus
• What hormone matures T cells? Thymosin