Defence against infectious disease Antibodies and vaccination

What is a pathogen? Patho = disease Gen = Producer A pathogen is an organism or virus that causes a disease. Why aren’t viruses called organisms?? Organisms are living things. What are the characteristics of living things?

Characteristics of living things Properties of life Cellular Respiration Reproduction Metabolism Homeostasis Heredity Responsiveness Growth and development

Viruses infecting living cells

Viruses are not living organisms Viruses do not Grow Have homeostasis Metabolize Viruses do Infect cells and use the cell to make more viruses Cause disease in many organisms

Viruses Viruses are micro organisms consisting of a strand of DNA or RNA surrounded by a protein coat They enter cells and hijack the cells machinery to make more viruses. They then burst out of the host cell, destroying or damaging it.

Other pathogens Bacteria Fungi Protozoa Animals Prions (Work sheet) Bacteria – single celled organisms able to reproduce by themselves. Categorised based on their shape. Protozoa (larger and more complex than bacteria) Animals (e.g. flatworms, round worms) Prions are misformed proteins that get into organisms and cause cells to die, especially brain cells- ‘mad cow disease’, CJD in humans

Antibiotics Major medical improvement Produced by fungi and bacteria Work on bacteria but… Cannot be used on viruses antibiotics block specific metabolic pathways found in bacteria, but not eukaryotic cells because viruses reproduce using the host cell (eukaryotic) metabolic pathways, they are unaffected by antibiotics antibiotics have produced great benefits world-wide in the control of bacterial diseases Staphylococcus infections controlled STD's, such as gonorrhea and syphilis controlled antibiotic resistance has evolved in bacterial populations One of the most major advances in modern medicine has been the development of Antibiotics Produced by fungi and bacteria to inhibit growth of their competitors

Non specific immunity The body resists infection with general (non-specific) and specific methods. Non-specific immunity stops a wide variety of pathogens.

Non specific immunity Skin Mucous membranes Tears Sweat Hair Sebum Blood clots Cilia Stomach acid

Skin Unbroken skin provides a fantastic barrier against pathogens trying to enter the body Sebum (oil) waterproofing (The diagram of skin was first met in the context of homeostatic temperature control so, yes, you should be able to recall it.

Mucous Membranes (and other non-specific immunity) Anywhere on the body that is not protected by skin has its own method of protection. Eyes – tears contain lysozymes Vagina – mucous membranes and acid Anus – mucous membranes Lungs – Mucous membranes and cilia Stomach – Acid Urethra – mucus membranes + urine is sterile Mucous membranes secrete a physical barrier of mucus which traps pathogens. The mucus is then swept out of the throat and nose and into the stomach. Mucus is antiseptic (kills bacteria) due to lysozymes Lysozymes – destroy bacterial walls

Infection! This occurs if pathogens do get inside the body. The proteins on the surface of a pathogen are immediately recognised as “foreign”. Phagocytes (a type of leucocytes) will ingest the pathogen by phagocytosis.

Blood Clotting Clotting is the mechanism that prevents blood loss from broken blood vessels. It is a CASCADE reaction. Mechanism a) Platelets or damaged cells release a group of proteins called clotting factors. These clotting factors are released into the plasma at a wound site. b) Clotting factors activate the enzyme Thrombin from its inactive form prothrombin c) Thrombin turns the soluble plasma protein fibrinogen into its insoluble fibrous form Fibrin. d) Fibrin binds together platelets and blood cells to form a solid 'plug' for the wound. This plug is called a clot. Damaged cells release an enzyme called Thrombokinase. This as well as Factor X, Factor VII and Ca+ inos cause Prothrombin (inactive enzyme) to change to Thrombin (active enzyme) Thrombin will hydrolyse soluble fibrinogen into fibrin which is insoluble. Fibrin forms a network which traps erythrocytes and becomes a clot. Anti haemophilia factors are VIII and IX – these are important in step a above. http://biology-animations.blogspot.com/2008/01/hemophilia-video.html http://biology-animations.blogspot.com/2008/01/for-detailed-information-httpen.html

Blood Clotting

The lymph system and immunity

Phagocytosis

Phagocytes Phagocytes are found in the blood, the lymph and in body tissues such as the lungs. After phagocytes engulf pathogens, they destroy them with digestive enzymes found in lysosomes.

Phagocytosis Damage to tissues allows invasion across 1st line of defense microbes successfully invade body fluids or tissues damaged cells release histamine and other chemicals initiating inflammation Phagocytes attracted to site by chemotaxis toward histamine phagocytes recognize microbes as foreign by antigen recognition variety of phagocytic cells: neutrophils (small phagocytic & macrophages (large phagocytic) Phagocytes endocytotically engulf microbes,which are digested by enzymes held in lysosomes digested microbe fragments are displayed on cell membrane phagocytes with microbe fragments displayed = antigen-presenting cells

Phagocytosis

Phagocytosis animation

Distinguish between antigens and antibodies antigen: a molecule recognized as foreign by the immune system; it elicits an immune response antibody: =immunoglobulin a globular protein recognizes an antigen by its complementary shape and charge thus allowing it to attach to the antigen specifically marking it for attack by the immune system

Antigens Anything that elicits an immune response Most are proteins or large polysaccharides from a foreign organism. Microbes: Capsules, cell walls, toxins, viral capsids, flagella, etc. Nonmicrobes: Pollen, egg white , red blood cell surface molecules, serum proteins, and surface molecules from transplanted tissue. Lipids and nucleic acids are only antigenic when combined with proteins or polysaccharides. A cat and its dander, an allergen/antigen for many people 24

Antibodies SL Also known as immunoglobulins Globular glycoproteins The heavy and light chains are polypeptides The chains are held together by disulphide bridges Each antiboby has 2 identical antigen binding sites – variable regions. The order of amino acids in the variable region determines the shape of the binding site

Challenge and response antigens: substances foreign to the host which stimulate antibody production by B lymphocytes Response: antibodies: immunoglobulins produced during protein synthesis

How Antibodies work? Some act as labels to identify antigens for phagocytes Some work as antitoxins i.e. they block toxins for e.g. those causing diphtheria and tetanus Some attach to bacterial flagella making them less active and easier for phagocytes to engulf Some cause agglutination (clumping together) of bacteria making them less likely to spread

Number of ag binding sites Site of action Functions Type Number of ag binding sites Site of action Functions IgG 2 Blood Tissue fluid CAN CROSS PLACENTA Increase macrophage activity Antitoxins Agglutination IgM 10 IgA 2 or 4 Secretions (saliva, tears, small intestine, vaginal, prostate, nasal, breast milk) Stop bacteria adhering to host cells Prevents bacteria forming colonies on mucous membranes IgE Tissues Activate mast cells  HISTAMINE Worm response

ANTIBODIES Antibodies are actively released by lymphocytes when the body is infected by a pathogen. This is a natural process. The lymphocytes are activated by the antigen on the pathogens outer surface. HL- A vaccine can also be artificially injected into the body. Advantages/ Disadvantages?

Blood types

To Vaccinate or not? Vaccines: MMR = combined measles/mumps/rubella DPT = diphtheria, pertussis, typhoid polio Benefits: eradication of some diseases (e.g. small pox) reduced rate of infection; less illness and death reduced long-term disability Dangers: low percentage of vaccinations produce side effects, including symptoms of disease, sometimes serious or lethal artificial immunity not as effective at producing immune response as is active immunity excessive vaccination may reduce the ability of the immune system to respond to new diseases vaccination possibly implicated in autism

Active vs. Passive Immunity Active immunity: immunity acquired through individual immune response Catching a disease Passive immunity: immunity acquired through antibodies transferred from one person to another Mother’s milk

Active and passive immunity However, it takes time for the body to react to the infection and produce white (B and T) cells. During this time the disease can multiply and spread rapidly. Tetanus is an especially deadly disease that can kill in hours. Antibodies can be collected from people who have already been vaccinated against it. These can then be injected into people who may have caught the infection. Its only a temporary fix- the spleen and liver break them down. This is Passive Immunity. Mothers pass antibodies through the placenta during gestation. Colostrum is a liquid made in the mammary glands during the first few days after birth- it lines the gut and protects against bacteria and viruses.

Where do antibodies come from? = Lymphocytes Produce antibodies B-cells mature in bone marrow then concentrate in lymph nodes and spleen T-cells mature in thymus B and T cells mature then circulate in the blood and lymph Circulation ensures they come into contact with pathogens and each other

White Blood cells WBC (Lymphocytes) are made in the bone marrow. The cells divide and mature into 2 types: T Lymphocytes B Lymphocytes Develop in the thymus gland Develop in the lymph nodes The Cell-Mediated Resopnse The Humoral (Antibody) Response Plasma ɞ cells have a different shape receptor on its membrane. There are about 10 million kinds in your body at any one time! Each can detect any antigen of a pathogen. Once activated they divide very fast (clone) and start to secrete specific antibodies. Antibodies slowly removed from blood and lymph. Memory ɞ cells remember antigens and can turn into Plasma ɞ if re-infected. Foreign, mutant or infected cells are identified as ‘non-self’ by surface antigens. T helper cell recognises antigens and alerts the other T cells. Killer (Cytotoxic) cells attack with perforin or nitric oxide. T memory cells remember the antigen for a later attack. T suppressor cells switch off T and B cells after attack over.

How do B cells produce antibodies B cells develop from stem cells in the bone marrow of adults (liver of fetuses). After maturation B cells migrate to lymphoid organs (lymph node or spleen). Clonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells, which actively secrete antibodies. Each B cell produces antibodies that will recognize only one antigenic determinant.

B -Lymphocytes Challenge and Response The antibodies travel to the blood, lymph, lining of gut and lungs. The number of plasma cells goes down after a few weeks Antibodies stay in the blood longer but eventually their numbers go down too

Clonal Selection of B Cells is Caused by Antigenic Stimulation

Duality of Immune System I. Humoral (Antibody-Mediated) Immunity Involves production of antibodies against foreign antigens. Antibodies are produced by a subset of lymphocytes called B cells. B cells that are stimulated will actively secrete antibodies and are called plasma cells. Antibodies are found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells. Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells. Also cause certain reactions against transplanted tissue.

Immunological Memory Secondary Response: Subsequent exposure to the same antigen displays a faster and more intense antibody response. Increased antibody response is due to the existence of memory cells, which rapidly produce plasma cells upon antigen stimulation. Booster shots increase the number of memory cells

Production of monoclonal antibodies Extract B cell that can produce the required antibodies Hybridise with a tumour cell (capable of endless division) In culture the hybridoma can produce large quantities of antibodies

Production of monoclonal antibodies and their use Use in diagnosis – covered in 11.4.10 (pregnancy diagnostic) Treatment Diagnosis: HIV infection can be diagnosed through a blood test which assays for the presence of anti-HIV antibodies, antibody produced through monoclonal antibody production is an anti-anti-HIV antibody! Treatment: Rabies Virus monoclonal antibodies can be produced which selectively locate and adhere to cancer cells anti-cancer drugs can be attached to the monoclonal antibodies so that they deliver their effects directly to the targeted cancer cells

Immune System Abnormalities Allergies: Exaggerated immune response to antigens called allergens Autoimmune diseases: Body doesn’t recognize “self” and mounts immune response

HIV HIV is a virus that specifically attacks the lymphocytes. This means the number of lymphocytes decreases. Less antibodies are made. Predict the consequences… Click here for a complex video on how the virus enters the lymphocyte

Transmission of HIV Infected blood – blood transfusions, sharing needles, Infected semen and vaginal mucus – unprotected sex Infected mother’s milk – low risk Infected saliva – almost zero risk

AIDS Acquired Immuno-Deficiency Syndrome Caused by the HIV virus that selectively infects the immune system leaving the body open to infection by removing the specific immunity. AIDS: Acquired Immuno deficiency syndrome. Acquired relates the infectious nature of AIDS through the transmission of the HIV virus. Immuno deficient relates to the way diseases cannot be resisted. Syndrome relates to the variation in the way the disease manifest itself. People who develop AIDS can be a affected by quite different set of diseases.

HIV Progression

Social implications of AIDS The social implications of AIDS are well known. Cases of AIDS are not evenly distributed in the world for example there are severe problems in southern Africa. What cultural and economic reasons are there for differences in the prevalence of AIDS? Is there a moral obligation of those with the technology and the wealth to help others lacking these things in the fight against AIDS?