Session 1 - Immunology, Immune System Disorders & Sepsis

• Immune system

  The body's means of detecting, protecting from, and responding to disease and threatening foreign bodies. It is balanced with mediators that limit these responses and initiate healing.

  
• Main parts of the immune system

  • White blood cells – phagocytes and lymphocytes and antigen-antibody system
  • Complement system
  • Lymphatic system
  • Spleen
  • Bone marrow
  • Thymus

  
• Immune system

  • There are two types: innate elements present at birth, and adaptive or acquired element that develops throughout life thereafter

  
• Innate immune elements

  • Mechanical and physical barriers of skin, mucus membranes, airway cilia and the cough/sneeze reflex
  • Chemical barriers including stomach acid, enzymes found in tears and skin oils
  • Fever to provide an intolerable environment for pathogens
  • Inflammatory responses to allow further immune system elements to respond

  
• Inflammatory response

  Non specific, providing similar response to a variety of attacks on the body including infection, physical injury and ischemia

  
• Inflammatory response

  1. Vasodilation to increase blood supply to an infected area

  2. Redness, heat, swelling and pain
• Innate immune elements perform a constant role and do not require any previous pathogen exposure

  
• Mast cell activation

  Histamine release from MAST cells causes local vasodilation and increased capillary permeability, leading to urticaria, rash, oedema, itchiness, increased peristalsis, vomiting, diarrhea, bronchoconstriction and mucosal oedema

  
• Mast cells

  • Found in connective tissue throughout the body, degranulate (break open) and release chemical mediators including histamine, bradykinin, cytokines, leukotrienes and prostaglandins to both stimulate and regulate subsequent immune system activities
  • Can partly degranulate and provide a smaller response or they can provide a more rapid and comprehensive total degranulation

  
• Triggers for mast cell degranulation

  • Physical injury and damage to cells and tissues
  • Microbes
  • Chemokines
  • Allergens as identified by immunoglobulins

  
• Cytokines

  Important messenger molecules to trigger other immune system cells, released by numerous immune system cells. Chemokines are the general group of such molecules and are released from cells near pathogen entry. Interleukins are a group of cytokines secreted by many immune system cells to trigger other cells into response action.
• Leukotrienes

  Released by MAST cells (and leukocytes) to augment the innate responses of increased vascular permeability and bronchospasm, even stronger than histamine release
• Immune response following mast cell degranulation

  1. Complement system is activated to fight infection before it can proliferate and includes cytokine messengers to attract other white blood cells

  2. Clotting system of localised platelet aggregation and coagulation to limit blood loss and movement of any antigen away from the site

  3. Kinin system which works to augment some of the histamine responses including vasodilation and capillary permeability increases, particularly in the later phases of response

  
• Leukocytes (white blood cells)

  Formed in bone marrow, there are several different types stored in the thymus, spleen and lymph nodes. They circulate through blood and lymph, monitoring for pathogens including bacteria, viruses, parasites and fungi. Upon detection, they trigger further immune responses.

  
• Main types of leukocytes

  • Neutrophils
  • Monocytes
  • Basophils
  • Eosinophils
  • Lymphocytes
• Phagocytes

  Surround and engulf pathogens, absorb and break down the pathogen within, and aid in identifying the pathogen and trigger the specific lymphocyte antibody response

  
• Major types of phagocytes

  • Neutrophils
  • Monocytes
• Other immune response white blood cells

  • Macrophages
  • Basophils
  • Eosinophils
  • Dendritic cells
• The immune system develops a memory of previous pathogens encountered
• Leukocytes

  White blood cells
• Other immune response white blood cells

  • Macrophages - primary cells for removing dead and dying cells
  • Basophils - key part of the allergy-antigen response. Their role is to also release histamine (vasodilator) and heparin (anticoagulant) to increase blood flow to injured tissue allowing better access for other white cells. Also attack parasites.
  • Esonophils - primarily for response to parasitic infections, capable of dealing with invaders too large for phagocytosis. Mostly found in the mucous membranes of the respiratory, digestive and urinary tract. These are major elements in the diseases of hay fever and asthma.
  • Dendritic cells are macrophage like cells found in the skin and mucous membranes where outside world contact occurs. Formed in bone marrow, they are part of the innate system and present pathogens to T cells in the lymph system

  
• The immune system develops a memory of invaders encountered throughout life allowing effective response if they reappear. Some diseases, particularly viruses, must be responded to many times. This is the adaptive part of the immune system.
• Lymphocytes chiefly responsible for remembering previous pathogens and initiating appropriate response upon subsequent contact

  • B lymphocytes (B cells) - produce antibodies and activate T- cells
  • T lymphocytes (T cells) destroy compromised cells (T cells as they are primarily thymus matured
  • Natural killer cells - (cytotoxic T cells) don't attack pathogens directly; rather they destroy virus infected and cancerous cells to stop spread and infection

  
• Antigens

  The parts of a pathogen or their toxin that B cells recognise. In response, B cells then differentiate into specific plasma cells with the role of manufacturing proteins to fight against the pathogen - antibodies.
• Antigens can enter the body from outside (e.g. ingested, inhaled) or form from metabolic processes within. Vaccines are a form of antigen.
• Antibodies (immunoglobulins)

  • IgG
  • IgM
  • IgA
  • IgD
  • IgE
• Fever (pyrexia)

  A normal immune system response. It is an elevated body temperature and can vary throughout the course of the illness.
• Fever in contrast is an intentional resetting of the 'temporary normal' body temperature. Fever is NOT hyperthermia, a medical emergency
• Pyrogens

  Anything that triggers fever, either external organisms or chemicals or result from the immune response components such as some white blood cells.
• Infection (Urinary, GIT, respiratory) is the most common fever cause but so to can cancer and other inflammatory reactions. Infection fever tends to be shorter duration (<4 days) than the other two causes
• Fever is therapeutic and can kill some microbes and inhibit pathogen reproduction.
• Older people are less able to mount a high fever response. Their immune system has many competing co-morbidities and diseases it is constantly responding to. This depletes the elements normally available for mounting fever response.
• Interleukin1

  A pyrogen that triggers the hypothalamus to raise the body temperature and cause fever by slowing heat sensitive neurones and causing increased metabolic activity and muscle shivering to generate heat.
• Immunity

  The state where a person is protected from disease from a pathogen due to previous exposure/infection and subsequent recovery.
• Immunisation

  A process where people are artificially protected against a particular pathogen before exposure occurs naturally within the community
• Vaccine

  The medicinal material administered to provide for the immunisation.
• Vaccination

  The term used to describe the act of vaccine administration.
• Key variables influencing need for and types of immunisation (HALO)

  • Health - Individuals who are particularly vulnerable to diseases, perhaps because of genetic predisposition or immunocompromise
  • Age - Immunisation typically follows an age related schedule beginning with babies and continuing through childhood development
  • Lifestyle - Individual specific choices can dictate immunisation needs including international travel, sexual or drug practices
  • Occupation - Roles that increase risk of exposure can warrant increased attention to immunisation
• Types of vaccines

  • Live attenuated viruses (e.g. measles/mumps/rubella)
  • Live attenuated bacteria (e.g. BCG tuberculosis)
  • Killed or inactivated viruses (e.g. hepatitis)
  • Killed or inactivated bacteria (e.g. Q fever)
  • Subunits of a pathogen (e.g. hepatitis B)
  • Toxoids (bacterial toxins made non toxic (e.g. tetanus/diptheria)
• Vaccines aim to stimulate the adaptive arm of the immune system to create specific antibodies for the selected pathogen (just as the immune system would do if confronted by the virus)