Immune System

Immune System A functional system rather than an organ system in an anatomical sense Its “structures” are a diverse number of immune cells and molecules that are involved in the immune response.

Pathogens Pathogen = any living organism or virus that is capable of causing disease. Includes: Bacteria, Viruses, Protozoa, Fungi, some worms Most don’t result in disease because of our defense system

Before antibiotics Between 1345 – 1350, approx. 25,000,000 people in Europe died from ‘the plague’. Most people thought it was from breathing ‘bad air’, so treatments included burning nice-smelling incense. Disease was actually caused by a bacteria carried by rats.

Before antibiotics People would either get better on their own, or get worse and die Ex. 40% of people with pneumonia died Home ‘cures’ would sometimes hurt more than help. Example: leeches!

How antibiotics work against bacteria Antibiotics take advantage of the differences between prokaryotic and eukaryotic cells There are many classes of antibiotics each with their own method of destroying bacteria selectively blocks protein synthesis (aminoglycosides, macrolides, tetracyclines) some inhibit new cell wall production, blocking their ability to grow and divide (penicillins, cephalosporins), includes amoxicillin, ampicillin, cefalexin Some damage cell membranes (polymixins) Some interfere with bacterial enzymes (quinolones, sulfonamides)

Immune System: 2 major kinds of defense First kind is Innate immunity largely nonspecific, responding to a broad range of microbes. - external barriers: skin and mucus membranes - internal barriers: cellular and chemical defenses that defend against microbes that get past the external barrier (macrophages and other phagocytic cells that ingest and destroy pathogens)

Immune System: 2 major kinds of defense Second kind is Acquired immunity: Develops after exposure to microbes or other foreign substances Highly specific White blood cells (lymphocytes). 2 responses: Humoral response – cells derived from B-lymphocytes secrete antibodies that bind to microbes and target them for elimination Cell-mediated response – cytotoxic lymphocytes directly destroy infected body cells, cancer cells, or foreign tissue

Overview of innate and cell-mediated responses Surface barriers Skin Mucus membranes Innate defenses Internal defenses Phagocytes NK cells Inflammation Antimicrobial proteins Fever Adaptive Defenses (Acquired Immunity) Humoral immunity B cells Cellular immunity T cells

Ways we prevent pathogens from entering the body Skin: 2 primary layers: Dermis (underlayer) has sweat glands, capillaries, sensory receptors, and dermal cells that give strength and structure to skin Epidermis (top layer) – layer of mostly dead cells. Good barrier because its not truly alive. Stomach acid: if pathogens come in with food or liquid, stomach acid helps to kill most of them

Ways we prevent pathogens from entering the body Mucus Pathogens enter in the air we breathe (mouth or nose) Mucus is produced by cells lining entryways (trachea, nasal passages) to trap incoming pathogens. The cells that secrete mucus also secrete the enzyme lysozyme which digests bacterial cell walls Some mucus membranes are lined with cilia, which also help move pathogens up and out

What happens when they do get in? (pt.1) Role of phagocytic leukocytes Leukocytes = white blood cells, many different types, they are the main cells in bloodstream that help fight off pathogens that enter our bodies - they also provide us with immunity for returning pathogens Macrophages – large WBC’s that can change their shape and squeeze their way in and out of small blood vessels. They surround invaders and ingest them by phagocytosis.

If its “self”? they leave it alone When a macrophage finds a cell, it determines whether its “self” or “not-self” based on surface protein receptors on the cell If its “self”? they leave it alone If its “not-self”? they engulf by phagocytosis and chemically digest it with lysosomes Non-specific; just determined to be “not-self”

Macrophages phagocytosing bacteria

4 types of phagocytic leukocytes 1) Macrophages 2) Neutrophils 60-70% of all WBC’s Attracted to and enter infected tissue, engulfing and destroying microbes there Self-destruct in only a few days

3) Eosinophils Critical for defense against multicellular parasites like blood flukes. Instead of engulfing them, they position themselves against the parasite’s body and then discharge destructive enzymes that kill them

4) Dendritic cells Can ingest by phagocytosis, But primary role is to stimulate the development of acquired immunity

What happens when they do get in? (pt.2) Antibody Production Antibodies = proteins that we produce in response to a specific type of pathogen -Y-shaped Each antibody is different because each type has been produced in response to a different pathogen Antigens = foreign substances that stimulate the production of antibodies

Each type of antibody recognizes one specific antigen Antibodies have binding sites specifically for those antigens

How are antibodies produced When antigens are found, the body gears up to produce large amounts of antibodies needed Each type of lymphocyte recognizes one specific antigen and responds by dividing to form clones These clones then secretes specific antibodies against the antigen

How are antibodies produced A B-cell´s recognition of a target structure quickly leads to the production of numerous antibodies ready to attack this target. Memory cells ensure a quick response in case the target reappears at a later time. B-cells which don’t recognize the target (here the cells 1 and n), don’t produce antibodies

Immune Response animation http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation__the_immune_response.html

Immune Response A macrophage discovers an antigen When it determines it to be “not-self”, it engulfs it by phagocytosis, but pieces are purposely left on the cell membrane of the macrophage Helper T cells chemically recognize the antigen being presented and become activated Helper T cells then chemically communicate with (activate) the specific B cell that is able to produce the antibody needed

Immune Response (B lymphocytes are the leukocytes that produce antibodies) B cells are activated to clone themselves by mitosis to make many more of themselves - (antibody-secreting plasma cells and memory cells) The newly formed ‘army’ begins antibody production Antibodies circulate in the blood until they find their antigen match Antibodies destroy the pathogens Some of the cloned lymphocytes stay in bloodstream and give immunity from a second infection by the same pathogen. (they are called memory cells)

HIV HIV infects cells in the immune system, specifically helper T cells Once helper T cells are destroyed, there is no longer communication between cells and antibodies are not produced, so the individual cant fight off pathogens HIV can be dormant in host cells for years before becoming active Once active, secondary infections occur, and symptoms of AIDS begin to appear

Issues related to AIDS What are some cultural and economic reasons for differences in the prevalence of AIDS?

Principles of Immunity Challenge and response: The immune system must be challenged by an antigen during the first infection in order to develop an immunity. All the cellular events (involving macrophages, helper-T cells, and B cells) are part of the response which leads to immunity to this pathogen

Principles of Immunity Clonal selection: when B cells encounter a specific antigen to which their antibody binds, they multiply many times to form clones. Memory cells: These are the cells that provide long-term immunity. You must experience a pathogen once in order to produce these and be truly immune.

Active vs. Passive Immunity Active immunity: Immunity due to the production of antibodies after the body’s immune cells have been stimulated by antigens. Passive immunity: when one organism acquires antibodies which were produced in another organism. Only the organism which produced the antibodies has the memory cells and so has long-term immunity. Getting antibodies from somewhere else acts only short-term.

Examples of Passive Immunity Antibodies passed from mother to fetus through the placenta Antibodies passed from mother to baby through the colostrum. Colostrum is the breast milk produced in late pregnancy and first few days after birth; high antibody concentration. Injection of antibodies in antisera. Ex. antivenom if you’ve been bitten by a poisonous snake

Production of monoclonal antibodies Process by which large quantities of antibodies (targeted against a particular antigen) can be produced A mouse (or other laboratory animal) is injected with a specific antigen Then the animal is given time to go through an immune response The mouse’s body will stimulate the production of antibodies against the antigen

Production of monoclonal antibodies The spleen is taken out as a source of many B cells B cells are fused with tumor (cancer) cells to produce hybridomas

Production of monoclonal antibodies Each hybridoma proliferates and produces mass quantities of antibodies called monoclonal antibodies

Uses of monoclonal antibodies: Diagnosis One common use: pregnancy testing. Early in pregnancy, the embryo starts to produce a hormone called HCG (Human Chorionic Gonadotrophin). Only pregnant women would have this hormone which shows up in blood and urine. Hybridomas are produced by injecting a mouse with HCG, the B cells produced secrete antibodies which recognize HCG as an antigen. These anti-HCG antibodies are bonded to an enzyme which shows a color change when the antibody encounters HCG. why pregnancy tests change color when positive

Uses of monoclonal antibodies: Treatment Cancer cells produce cancer-cell specific antigens on their cell membranes One possible treatment for cancer is to produced monoclonal antibodies that target those antigens Big advantage is that they target the cancer cells directly

Vaccination A vaccine is developed by weakening a virus by heating it or chemically treating it, then injecting it into the body The body will recognize it as ‘not-self’ and the primary immune response takes place (including formation of memory B cells for quick response if needed later)

Note that a second infection of the same pathogen results in a faster response with more antibodies produced

Benefits of vaccination Possible total elimination of the disease, as has occurred with smallpox Decrease in spread of pandemics (worldwide infections) and endemics (local infections). Increased international travel has made this very important: an infection started on one side of the world could be on other side of the world in < 1 day Preventative medicine is cheaper than treating diseases Prevention of harmful side-effects of diseases

Dangers of vaccination Possible toxic effects of mercury; prior to 1999, a mercury-based preservative was used Multiple vaccines in a short period of time may ‘overload’ the immune system Possible links to autism (?)