CELLS AND THE IMMUNE SYSTEM

• OVERVIEW OF THE IMMUNE SYSTEM

  the immune system works through a system of recognition mechanisms which enable it to distinguish native cells (cells) from pathogen (foreign bodies), and subsequently eliminate these pathogens.
• PATHOGENS: microorganisms that cause disease
• PHAGOCYTES: macrophages or neutrophils are involved in phagocytosis which is immediate.
• LYMPHOCYTES: B and T cells involved in longer responses
• T-CELL: cell-mediated response
• B-CELL: humoral response
• ANTIGEN: specific molecules (proteins, glycoproteins etc.) found on the surface all cells. When these molecules are recognised as foreign by the immune system, they can stimulate an immune response and lead to the production of antibodies. 


  They allow the body to identify:

  • pathogens
  • abnormal body cells
  • toxins and cells from other individuals of the same species
• ANTIGENS

  • antigens vary hugely
  • this is because proteins have enormous variety and a highly specific tertiary structure.
  • It is this variety of specific 3D structure that distinguishes one cell from another.
  • proteins have a specific tertiary structure / shape allowing different proteins to act as specific antigens.
• 1, ANTIGENS ARE SO SPECIFIC SO ALLOW THE IMMUNE SYSTEM TO IDENTIFY:


  • PATHOGENS: these are organisms that cause disease eg. Bacteria, virus and fungi. All pathogens have antigens on their surface - these are identified as foreign by immune system cells, which then respond to destroy the pathogen.
  • ABNORMAL BODY CELLS: cancerous or pathogen-infected cells have abnormal antigens on their surface, which trigger an immune response.
• 2. ANTIGENS ARE SO SPECIFIC SO ALLOW THE IMMUNE SYSTEM TO IDENTIFY:

  • TOXINS: poisons - also molecules, not cells. Some toxins are produced by bacteria eg. Clostridium botulinum releases a protein toxin that affects the nervous system, causing symptoms of botulism. the immune system can respond to toxins, as well as the pathogens that release them.
• 3. ANTIGENS ARE SPECIFIC SO ALLOW THE IMMUNE SYSTEM TO IDENTIFY:


  • CELLS FROM OTHER INDIVIDUALS OF THE SAME SPECIES: when you receive cells from another person, eg. Organ transplant / blood transfusion, those cells have antigens that are different to your own - unless donor is genetically identical to you. The forge in antigens trigger an immune response which leads to rejection of transplanted organs if drugs aren’t taken to suppress the recipients immune system.
• BLOOD GROUPS


  • Your blood type depends on the genes you inherit from your parents. In the ABO system there are 4 blood groups: A, B, AB and O.
  • BLOOD TYPE A = A antigens = Anti-B antibodies in plasma
  • BLOOD TYPE B = B antigens = Anti-A antibodies in plasma
  • BLOOD TYPE AB = A and B antigens = no antibodies in plasma
  • BLOOD TYPE O = no antigens = Anti-A and Anti-B antibodies in plasma
• BLOOD GROUPS 


  BLOOD GROUP STATISTICS

  • Blood group O is the most common blood group.
  • Almost half of the UK population (48%) has blood group O.
  • About 85% of the UK population is RhD positive (36% of the population has O+, the most common type).
• BLOOD GROUPS 


  THE RhD ANTIGEN (1)

  • Red blood cells can sometimes have another antigen called a RhD antigen.
  • This is a protein on the surface of red blood cells. If this is present, your blood group is RhD positive. If it's absent, your blood group is RhD negative. This means that your blood type can be the positive or negative version of each of the blood groups in the table above depending on whether the RhD antigen is present.
• BLOOD GROUPS 


  THE RhD ANTIGEN (2)

  • Whether you're RhD positive or negative depends on how many copies of the RhD antigen you've inherited. You can inherit one copy of the RhD antigen from your mother or father, a copy from both of them, or none at all. You'll only have RhD negative blood if you don't inherit any copies of the RhD antigen from your parents as it is dominant.
• 1, BLOOD TRANSPLANTS AND REJECTION 


  • A blood transfusion is when you're given blood from someone else (a donor) that could be lifesaving.
  • You may need a blood transfusion if you have a shortage of red blood cells, cancer, severe bleeding or a condition which affects the way your blood cells work.
  • A blood transfusion can replace blood you have lost, or just replace the liquid or cells found in blood (such as red blood cells, plasma or cells called platelets).
• 2. BLOOD TRANSPLANTS AND REJECTION

  • However, there are risks with a blood transfusion.
  • If the donor blood type doesn’t match the receiver and the antigens on the red blood cells are not recognised by the recipient, the immune system will generate an immune response as they reject the foreign cells and attack them.
• 3. BLOOD TRANSPLANTS AND REJECTION 


  • An allergic reaction may occur resulting in an anaphylactic shock.
  • Your body will produce antibodies to destroy the donor’s blood cells.
  • When a blood transfusion needs to happen, the blood type of the doner needs to be taken into account. Bloodborne diseases also need to be acknowledged including diseases like human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV).
• ANTIGENIC VARIATION

  • DNA in a pathogen mutates frequently.
  • if mutation occurs in gene that codes for the antigen the primary strcytyre of the antigen will change.
  • this alters the tertiary structure of the antigen causing it to change shape.
  • as the antigens are a new shape, previous natural / artificial immunity to this pathogen is no longer effective as memory cells are specific to only one type of antigen.
  • this is why a new flu vaccine is created every year as the influenza virus mutates and changes its antigens very quickly.
• INFLUENZA AND ANTIGENIC VARIABILITY

  • the pathogen may mutate frequently, so that its antigens change suddenly rather than gradually.
  • This means that vaccines suddenly become ineffective because the new antigens on the pathogen are no longer recognised by the immune system.
  • as a result, the immune system doesn’t produce the antibodies to destroy the pathogen.
  • This antigenic variability happens with the influenza virus, which changes its antigens frequently.
  • immunity is therefore short lived and individuals may develop repeated bouts of influenza during their lifetime.
• HOW LYMPHOCYTES RECOGNISE CELLS (1)

  1. 10 million different types of B lymphocyte in body - each recognises a specific antigen.
  2. lymphocytes are made when you’re a foetus which is only exposed to self cells.
  3. lymphocytes complementary to antigens on self cells will die or the production of them will be suppressed.
  4. this is to prevent your body from attacking your own cells.
  5. the only remaining lymphocytes are complementary to non-self cells or pathogens.
  6. This process repeats after birth in the bone marrow.

  • any new lymphocytes made which are complementary to the self cells are destroyed.
• HOW LYMPHOCYTES RECOGNISE CELLS (2)


  • sometimes this process doesn’t work and the lymphocytes attack self cells.
  • attacking normal cells can lead to disastrous consequences, and diseases of the immune system which cause the immune system to target normal cells are known as autoimmune diseases.
  • these autoimmune disorders can often be fatal for an organism.
• 1, SELF AND NON-SELF CELLS

  • the immune system doesn’t want to attack self cells.
  • Attacking normal cells can lead to disastrous consequences, and diseases of the immune system which cause the immune system to target normal cells are known as autoimmune diseases.
  • These autoimmune disorders can often be fatal for an organism.
• 2. SELF AND NON-SELF CELLS


  • MAJOR HISTOCOMPATIBILITY COMPLEX (MHC): is a protein marker on self cells that are used to distinguish native cells (self) from foreign bodies (non-self). MHC proteins enable the immune system to be able to specifically attack foreign pathogens as well as abnormal cells, while sparing normal cells.
  • THERE ARE 2 TYPES:
  • MHC I
  • MHC II
• 3. SELF AND NON-SELF CELLS 


  MHC I: molecules are found on normal body cells. They bind to endogenous antigens (normal antigens produced in normal cells) and display them on the cell surface membrane so that they can be identified as self-cells to the immune system. MHC class I molecules are also found on immunological cells and allow them to recognise each other and communicate with each other.
• 4. SELF AND NON-SELF CELLS 


  MHC II: molecules are found on immune system cells. MHC II is found specifically in immunological cells such as macrophages, neutrophils, and dendritic cells. MHC class II molecules bind to foreign antigens to activate an immune response against a particular invading pathogen.
• TRANSMISSIBLE CANCER 


  Devil facial tumour disease (DFTD) is an aggressive non-viral, transmittable parasitic cancer that affects Tasmanian Devils. Small lesions or lumps, in and around the mouth, quickly develop into large tumours on the face and neck (and sometimes other parts of the body). Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Tasmanian devils are genetically close to each other which causes genetic bottlenecking. They develop facial tumours as their immune system cannot tell which cells belong to itself or are new ones.
• DEFENCE MECHANISMS

  The human body has a range of defences to protect itself from pathogens. Some are general and immediate defences like the skin forming a barrier to the entry of pathogens and phagocytosis. Other are more specific, less rapid but longer-lasting.
• DEFENCE MECHANISMS

  NON-SPECIFIC:

  • physical barrier
  • phagocytosis
• DEFENCE MECHANISMS

  SPECIFIC RESPONSE:

  • cell-mediated response
  • humoral responses involving B lymphocytes
• ANTIGEN PRESENTING CELLS (APC)

  • they are any cell that presents a non-self antigen on their surface.
  • they are the hosts own cells.
  • they can be: phagocytes, abnormal self-cells, cancer cells, non-self cells from a transplant, infected body cells.
  • they can trigger cell meditated response.
• PHAGOCYTES

  • phagocytes are white blood cells that are produced continuously in the bone marrow.
  • they carry out phagocytosis (engulfment of pathogens).
  • they are the first cells to respond to an immune system trigger inside the body.
  • they carry it a non-specific immune response.
  • they are stored in the bone marrow before being distributed around the body in the blood.
  • they are responsible for removing dead cells and invasive microorganisms.
  • there are two main types of phagocyte, each with a specific mode of action: neutrophils and macrophages.
• NEUTROPHILS: a type of phagocyte. short acting, initiate immediate response. Travel throughout the body and often leave the blood by squeezing through capillary walls to ‘patrol’ the body tissues. During an infection, they are released in large numbers from their stores.
• MACROPHAGES: a type of phagocyte. Adaptive immune response. Larger than neutrophils and are long-lived cells. rather than remaining in the blood, they move into organs including the lungs, liver, spleen, kidney and lymph nodes. After being produced in the bone marrow, macrophages travel in the blood as monocytes, which then develop into macrophages once they leave the blood to settle in the various organs listed Above.
• PHAGOCYTES

  as both neutrophils and macrophages are both phagocytes, they both carry out phagocytosis (the process of recognising and engulfing a pathogen) but the process is slightly different for each type of phagocyte.
• PHAGOCYTOSIS (1)

  1. the phagocyte is attracted to the pathogen by chemical products of the pathogen. It moves towards the pathogen along an increasing concentration gradient of chemoattractants (the movement is called chemotaxis).
  2. a phagocyte (macrophage) recognises the foreign antigen on a pathogen. Pathogens have unique antigens called Pathogen Associated Molecular Patterns (PAMPs). Phagocytes can recognise these PAMPs through specialised receptors on their cell surface membrane known as Pathogen Recognition Receptors (PRRs). They are complementary to each other.
• PHAGOCYTOSIS (2)

  3. When the PRRs recognise and bind to a PAMP, it activates the phagocyte. Signalling molecules such as interferons may also help in phagocyte activation.

  4. The pathogen may be coated in molecules which coat the pathogen so that phagocytes can easily bind to called opsonins.

  5. The phagocyte grows cytoplasmic extensions to engulf the pathogen, and internalises it into its cytoplasm by endocytosis.

  6. The pathogen is now contained in a phagocytotic vacuole / phagosome in the middle of the cytoplasm.

  7. A lysosome fuses with the phagosome.
• LYMPHOCYTES 


  • lymphocytes are another type of white blood cell.
  • they play an important part in the specific immune response.
  • these are slower in action at first, but they can provide long-term immunity.
  • they are smaller than phagocytes.
  • they have a large nucleus that fills most of the cell.
  • they are produced in the bone marrow by stem cells.
• TWO TYPES OF LYMPHOCYTES

  Two types of lymphocytes, both with different modes of action:

  • T-lymphocytes (T-cells)
  • b-lymphocytes (B-cells)
• T-CELLS (1)

  • a t-cell is a type of white blood cell.
  • involved in cell-mediated response.
  • it has receptor proteins on its surface that bind to complementary antigens presented to it by phagocytes.
  • this activates the T-cell.
  • secondary defence after pathogen into blood stream, specific.
  • made in the bone marrow, then T-cells leave the bone marrow to mature in the thymus.
  • mature T-cells have specific cell surface receptors called T cell receptors which are specific to one antigen.