Defense against disease © 2016 Paul Billiet ODWS

INFECTIOUS DISEASE Caused by microbes which invade the body and upset it’s homeostasis Microbes that cause diseases = pathogens E.g. viruses, bacteria, fungi, protozoans. © 2016 Paul Billiet ODWS

Antibiotics Only useful against bacteria Inhibit growth of prokaryote but do not affect eukaryotes Viruses use their host cell’s metabolism Viruses a unaffected by antibiotics. © 2016 Paul Billiet ODWS

Penecillin Alexandre Fleming 1928 Florey & Chain 1939-1940 © 2016 Paul Billiet ODWS

Fleming Zone of Mould inhibition colony Plate of staphylococcus bacteria contaminated by mould The mould inhibited bacterial growth Toxicity tests seemed good on mice & rabbits But the active component seemed to disappear rapidly from the blood Fleming though it might be useful as an antiseptic. Bacteria © 2016 Paul Billiet ODWS

Florey & Chain 1940 Purified penicillin Not an enzyme 8 mice injected with a streptococcal infection 4 experimental 4 controls 16.5h later the control mice were dead Scaled up testing on hundreds of mice. © 2016 Paul Billiet ODWS

Skin – primary defense © 2016 Paul Billiet ODWS www.agen.ufl.edu/.../lect/lect_19/lect_19.htm. © 2016 Paul Billiet ODWS

Skin Skin consists of the epidermis Dead, waterproof layer prevents microbes from entering the skin Continually replaced from below Skin flora act as commensals Blood clotting seals cuts. © 2016 Paul Billiet ODWS

Mucus membranes – primary defense www.lab.anhb.uwa.edu.au/.../Images/sto040pa.jpg © 2016 Paul Billiet ODWS

Mucus membranes Mucus membranes cover the inner compartments of the body Cells being constantly renewed from below Not waterproof These membranes secrete mucus (mucopolysaccharide), and sugars Mucus traps materials in the airways A commensal flora grows there too feeding on the secretions. © 2016 Paul Billiet ODWS

Other defences HCl is secreted from the stomach mucosa = an anti-microbial agent Secretions of lysozyme produced by glands such as tear and salivary glands. © 2016 Paul Billiet ODWS

Phagocytic leucocytes Leucocytes (white blood cells) can act directly upon microbes by PHAGOCYTOSIS (Cell Mediated Immunity) Phagocytes recognise and engulf foreign (non-self) material Pus forms when large numbers of phagocytes die from engulfing microbes. © 2016 Paul Billiet ODWS

Phagocytosis library.thinkquest.org/.../phagocytosis.gif

Antibodies Antibodies are proteins produced by B-cell lymphocytes Antibodies recognise non-self molecules called antigens They call up phagocytes They have two or more antigen binding sites They are very specific: One antibody recognises one antigen molecule The different binding sites can bind to two or more cells clumping them together = AGGLUTINATION. © 2016 Paul Billiet ODWS

Agglutination www.vet-lyon.fr/.../ENV_immuno_1A/immun1-04.htm.

Antibodies = immunoglobulins www.science-projects.com/IgG.GIF imgt.cines.fr/.../_UK/PosterIGH/imagesIgH.png © 2016 Paul Billiet ODWS

Antigens www.okc.cc.ok.us/.../plasmamembrane2.jpg Antigens are molecules found on the surface of non-self cells (e.g. microbes infecting the body or transplants) They are usually complex molecules (e.g. glycoproteins). © 2016 Paul Billiet ODWS

Antibody production Each type of antibody is produced by a specific lymphocyte B-cell B-cells are produced by the red bone marrow The body produces a vast range of B-cells capable of producing different antibody molecules (cf What is a gene?) Early on in development the body learns to recognise the difference between self (belonging to the body) and non-self (foreign material) Only non-self recognising lymphocytes are retained. © 2016 Paul Billiet ODWS

The Lymophocyte B-Cell www.visualsunlimited.com/.../188/188898.jpg

The T-cells depts.washington.edu/tumorvac/MultiMedia/Imag... Macrophages capture pathogens and present their antigens to helper T-cell lymphocytes Helper T-cell lymphocytes stimulate the appropriate B-cells to multiply forming a clone. © 2016 Paul Billiet ODWS

Immunisation These B-cells produce the antibodies to fight that particular microbe Antibodies are found in the blood plasma (Humoral Immunity) When the infection is overcome memory cells remain so the immune response is faster the second time the body is infected (natural immunity) The body can be stimulated into producing the memory cells by vaccination/immunisation (artificial immunity). © 2016 Paul Billiet ODWS

HIV attacks the immune system HIV (Human Immunodeficiency Virus) is the virus that causes AIDS (Acquired Immune Deficiency Syndrome) HIV infects the body through transfer of body fluids (blood, blood products, semen) or across the placenta HIV infects one type of the T-cell lymphocyte, helper T-cells. Antibody production cannot be stimulated. © 2016 Paul Billiet ODWS

AIDS The immune system fails to respond to an infection by certain bacteria (e.g. pneumonia) and fungi (e.g. Candida) which are normally easily resisted The disease may take 8-10 years to reveal itself This gives time for several cross infections There is no vaccine yet Drugs may stop the disease progressing but do not cure it. © 2016 Paul Billiet ODWS

THE IMMUNE SYSTEM Challenge & Response Infection = Challenge Reaction of immune system = Response Self & Non-self Molecules which belong to the body = Self Antigens which are foreign = Non-self © 2016 Paul Billiet ODWS

THE IMMUNE SYSTEM Bone marrow Stem cells B-cells T-Cells Macrophages © 2016 Paul Billiet ODWS

Specific antibody produced B-cells Antigen presented independently B-cell primed Helper TH-cells Plasma cell clone Specific antibody produced Memory cells Agglutination of toxins and pathogens Attraction of macrophages Activation of complement enzymes in the plasma © 2016 Paul Billiet ODWS

Stimulate specific B-cell to develop Switch off immune response T-Cells Thymus gland Cytotoxic TE-cells Helper TH-cells Suppressor TS-cells Stimulate specific B-cell to develop Switch off immune response Lyse cancer cells and cells infected by viruses © 2016 Paul Billiet ODWS

Macrophages Phagocytose pathogens and present antigen to T-cell along with Class II MHC protein Cytotoxic TE-cells Suppressor TS-cells Helper TH-cells Phagocytosis © 2016 Paul Billiet ODWS

Humeral response Agglutination Chemicals in the plasma respond For pathogens in the blood stream, lungs, skin and gut. © 2016 Paul Billiet ODWS

Cell-mediated response Phagocytosis and cytotoxic cells White blood cells directly involved For pathogens inside cells (e.g. viruses) and cancerous cells The lymphocyte must recognise both SELF (MHC) proteins and NON-SELF antigen. © 2016 Paul Billiet ODWS

Allergies An immune response to a substance that is normally harmless Results from the response of a mast cell B-cells produce IgE antibodies in response to antigens Mast cells are activated by IgE.

Mast cells Mast cells are leukocytes that patrol to body cavities Mast cells protect against parasite infection Mast cells release histamine protein. © 2016 Paul Billiet ODWS

Histamine Histamine provokes increase blood flow to and permeability of blood vessels in an infected region (inflammatory response) Histamine also increases smooth muscle contraction to expel parasites. © 2016 Paul Billiet ODWS