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THREE LEVELS OF DEFENCE (:STAR:LEVEL 2:STAR: Innate immune response Non…

- - - - MHC class I
        • As proteins in normal cells are broken down, some small peptides (antigens) are loaded into the MHC class I proteins and presented on the surface
        • If the cell is normal, these antigens tell lymphocytes the cell is a normal ‘self’ cell
        • Due to genetic differences, every person will have different MHCI self signals so everyone’s MHCI signal is unique to that person (unless you have an identical twin)
        • If the cell mutates (tumour) or is infected by a virus, the proteins presented (and so destroyed) will change and the MHCI signal will be ‘non-self’
      - MHC Class II
        • Only on Antigen Presenting Cells (APC) - cells that phagocytose foreign material
        • APCs present digested antigens from foreign material to alert and activate other immune cells
        • APCs include: Macrophages , Dendritic cells and B Cells
  - - - Antibodies
        • Antibodies (Ab): Proteins, called Immunoglobulins (Ig)
        • Produced by B Lymphocytes
        • Made in response to an Antigen and can recognise and bind Antigen
        • Highly specific (One Antigen = One Antibody)
        • Each antibody has at least two sites that can bind antigen – the Antigen Binding Site (variable regions)
        • Antigen binding sites are identical on each Antibody - requires complementary shape
        
        Antibodies act by:
        
        Neutralisation
        • Antibodies bind to viral binding sites or coat bacterial toxins
         Particles cannot bind to host cell (and cannot enter in the case of viruses)
        
        Limits mobility
        
        Sticking Together Particulate Antigens
        • Foreign organisms are clumped together (Agglutination)
        • Enhances phagocytosis
        
        Opsonisation
        • Antibodies stuck to an antigen target it for destruction and make it easier for phagocytes to find the antigen
        • Enhances phagocytosis
        
        Isotypes (types of antibodies)
        • 5 different types (outlined on p196)
        • Different types are found in different areas of the body
        • Main ones of note are - IgE - involved in allergic reactions and IgG - released by effector and memory cells, most commonly passed from mother to child in breast milk
      - Humoral Immune Response
        • Each B cell can produce Antibodies against one specific Antigen
        • A mature B lymphocyte may carry ~100,000 Antibody molecules on the surface (identical)
        • Can bind to intact (non-processed/presented) Antigen
        • B cells can also act as APC to activate TH cells (see the Cell mediated response)
        • Acts on bacteria and viruses outside the cell
        • Toxins produced by bacteria
        • B cells need to be activated by an antigen
        • Of the millions of different immature B cells, only a few will be able to bind to the antigen (lock and key model to bind)
        • B cells can also engulf ‘foreign’ material and act as APC to activate the cell mediated response
        • Once bound, that B cell starts to rapidly divide and the numbers of that clone will increase
        • Multiplication is more effective with assistance by TH cells
        • These B cells will differentiate into either Plasma cells or Memory cells
        
        Plasma Cells
        • Secrete Antibodies against a specific Antigen
        • Live a few days but produce ~2000 Ab molecules/second
        
        Memory Cells
        • Long lived
        • Rapidly differentiate into Ab-producing plasma cells when same Antigen encountered
      - Activation of Complement
        
        Presence of a pathogen (non-specific)
        
        Antibody-Antigen Interactions (specific)
        • Proteins form a pore in cell membrane  Cell rupture (lysis)
        • Enhances Phagocytosis
        • Enhances inflammation
      - Advantage of the Humoral Response?
        • Plasma cells take care of the immediate infection - Antibodies typically persist for about 28 days
        • Memory cells stay dormant in the body for months or years holding antibodies on their plasma membrane, waiting for an antigen to bind
        • If months later a second exposure occurs B memory cells rapidly divide and differentiate into plasma cells
        • Response much faster than initially (more memory B cells present than the original naive B cell pool) and often attack disease before symptoms occur
    - - • Involves directly killing virally infected and cancerous cells by TC lymphocytes
        • Distinguish self from non-self by membrane bound cell receptors
        • Do not bind antigens directly but instead recognise MHC Class I signals to identify targets
        • Release powerful cytotoxins when they encounter a target cell - These include perforin and granzymes that work to induce apoptosis in the target cell
        • There is a great variety of different T cells, as with B cells
        • When activated (by binding an antigen and being activated by TH cells) they rapidly bind and differentiate into memory T cells and effector cells
        • Skin graft experiments in mice demonstrate that memory T cells exist
        • Memory T cells cause problems in organ transplants - Donor and recipients must be as closely matched as possible, Difficult as blood type must be compatible and 6 different MHC types should be as close a match as possible (with many alleles for each MHC type), Unless of course you have an identical twin…
        • Organ transplant recipients must take anti-rejection drugs for the rest of their life to ‘dumb down’ their immune system enough to not recognise the foreign cells (but still fight off diseases!)
        • TH cells act as helpers for both B cells and T cells (Release cytokines and other chemicals to cause activated (bound to a compatible antigen) B or T cells to multiply)
        • Regulatory T cells (Treg) modulate the immune response and may enhance or suppress the actions of other lymphocytes or phagocytes (Prevents the immune system overreacting to a stimulus)