I Immune System A) Important historical events demonstrating importance of immunity, disease and human populations 1) Romans (165-180AD), "disease of Antoninus", smallpox epidemic that killed many Romans, caused by the trade link between Rome, Northern Africa and Asia 2) Europe (1340's) - "Black Death" = bubonic plague, happened after trade routes were established with China, traders brought back flea infested furs which were carriers of the disease (70% death toll) 3) Colonization of North America (15th, 16th Centuries), Spanish explorers brought over measles, typhus, influenza and others (95% death toll) 4) Bioterrorism and Anthrax - anthrax is currently being used as a biological weapon a) 3 Types Inhalation Cutaneous Intestinal b) Natural history - naturally occuring bacterium, found throughout the world but concentrated in agricultural regions (associated with domesticated animals) c) Transmission - inhalation of spores from animals or animal products, uncooked food, handling infected animals or animal products, human to human is extremely rare d) Symtpoms - inhalation, flu-like symptoms followed by shock and death e) Symptoms - cutaneous, small rash similar to insect bite, develops into larger rash with necrotic center, can be fatal in some cases f) Symptoms - intestinal, inflammation of the intestinal tract, nausea, loss of appetite, vomiting, fever are followed by abdominal pain, vomiting of blood, and severe diarrhea, can be fatal g) How does it affect hosts - after infection, bacteria multiplies and releases toxins which are the poisons that affect the host h) Treatments - vaccination, antibiotics ( ciprofloxacin, doxycycline, chloramphenicol, clindamycin, tetracycline, rifampin, vancomycin and others) i) For additional information see Centers for Disease Control web sites FAQs on Anthrax Anthrax Fact Sheet j) Other agents of bioterrorism Smallpox virus Plague - bacterium Botulinum toxin - produced by botulism bacteria (Clostridium botulinum) 5) The flu shot - vaccination for the influenza virus (overview from CDC) caused by a virus that attacks the respiratory tract symptoms - headache, fever, cold, sore throat, fatigue What is the flu shot? - vaccine made from inactivated viruses Who should get the flu shot individuals over 50 yrs old residents of nursing homes healthcare workers women pregnant for 3 months or more adults and young with CV disease B) Immune System - Function 1) protection against invasion - fight disease 2) Common routes of infection intimate contact inhalation (e.g., sneezing) insect bites contaminated food contact with domesticated animals C) Immune System - Components 1) Non-specific defense system - fights all invaders 2) Specific defense system - works on specific types of invaders which it identifies and targets for destruction D) Non-specific Defense System 1) Components a) Physical barriers 1)skin 2) mucus secretions - trap b) Chemical responses 1) skin secretions (salts, acids) 2) Inflammatory response - release of histamine which stimulates swelling in the infected area, vasodilation and increases permeability of vessels 3) Release of pyrogens by WBC's (macrophages) - causes local heating 4) Gastric secretions of the stomach 5) Complement proteins - come into contact with invaders, results in production of more proteins that attack and lyse invading cells, or attract WBCs c) Cellular component 1) Phagocytes Neutrophils - kill bacteria Eosinophils - kill worms Basophils - secrete histamine and leads to inflammatory response Macrophages - involved in phagocytosis, release interferon and interleukin (stimulates production of cells of the Specific Defense System) 2) NK cells (natural killer) - used to combat tumor cells or virus-infected cells E) Specific Defense System Components 1) Mode of operation a) identify, destroy, remember b) cellular components - lymphocytes (WBCs) B cells Effector B cells - produce antibodies Memory B cells - ready for the next invasion T cells helper T cells cytotoxic T cells 2) How does this occur? a) Recognition - antigens on microbes' cell membranes (antigen = protein license plate), b) Presentation - alert lymphocytes about an invasion, macrophage, virgin B cell or cell infected by microbe displays the antigen on its membrane c) Presentation is an antigen-MHC complex, MHC is a protein marker on the body's cell, binds with the antigen of a foreign microbe d) B cells and antibody-mediated immunity 1) virgin B cell comes into contact with antigen on microbe 2) process antigen and becomes an antigen-presenting B cell with antigen-MHC complex 3) activated by Helper T cell that binds to the complex, cells disengage and Helper T secretes interleukin that stimulates mitosis in B cells 4) B cells undergo mitosis, some become effector cells, some become memory cells 5) Effector B cells produce antibodies - antibodies - clump microbes for destruction, mark microbes for destruction by phagocytes, activate complement proteins that rupture/lyse microbe cell membrane or infected host cells e) T cells and cell mediated immunity 1) virgin cytotoxic T cells contact antigen presenting cells and undergo mitosis, mature and directly kill foreign invaders 2) virgin Helper T cells antigen presenting cells and undergo mitosis, mature and secrete interleukin that stimulates mitosis of T and B Cells 3) both types of T cells also produce memory T cells for future use 4) Suppressor T cells - call off the fight, suppress all of the above F) Summary of events occurring during invasion of microbes 1) invasion into the body Primary followed by Secondary Response 2) Primary response - activation of non-specific and specific defense systems a) active destruction of microbes 3) Secondary Response - based on memory B cells with antibodies, body is already prepared for invasion based on the previous encounter G) Practical Applications 1) Problems with the system a) allergies - overreaction to substances that are not harmful (peanut butter, shellfish, tree/weed pollen, leaf mold) Allergic reaction - people with allergies are sensitized to allergens because they have higher levels of antibodies for certain substances, when sensitized individual is exposed to an allergen, this sets off the inflammatory response Examples Allergic rhinitis - hay fever Eczema - allergy of the skin Asthma - allergens in the respiratory system - sets off inflammatory response Anaphylactic shock - inflammatory response and swelling occurs throughout the entire body (may be caused by allergies to shellfish, peanuts, stinging insects, latex, other)
Allergic Reaction - An Overview b) autoimmunity - when the immune system can't recognize differences between self versus non-self (MHC recognition) 2) Listing of Immunologic diseases Immunologic Diseases from the Karolinska Institute 3) AIDS and HIV (overview from JAMA) a) How the AIDS virus work Retrovirus action HIV virus attacks phagocytes and Helper T cells b) attacks Helper T cells (prevents activation of more B and T cells) c) transmission - intimate contact (exchange of bodily fluids) 1) Sex - enters through the lining of the mouth, vagina, penis, rectum - anal sex (breaks skin) 2) Infected blood 3) IV drug use 4) Transmission to the fetus by infected pregnant mothers 5) Transmission to a baby through breast feeding d) Early symptoms - flu-like symptoms, headache, enlarged lymph nodes followed by an asymptomatic phase (virus begins to infect and spread to other cells) e) Later symptoms - rapid weight loss, swollen nodes, susceptibility to infection (pneumonia), yeast infections of the mouth, f) AIDS - most advanced stage, defined as CD4 T cell count of 200 or less, opportunistic infections, bruising due to blood vessel cancer - Kaposi's Sarcoma, various cancers (lymphomas, cervical cancer g) causes of death - overwhelming infection, pneumonia cancerous side effects h) Who is at risk (US)? 1) IV drug users (needle programs) 2) Homosexual community 3) High incidence among prostitutes 4) Increasing rate among heterosexuals i) Testing - antibody test for the HIV (blood, urine, saliva samples), performed at Doctor's office, health clinic and home kits j) Treatment - cure is unknown, 1) Transcriptase inhibitors - interrupts early stages of viral replication (AZT) 2) Protease inhibitors interrupts later stages k) Behavior - avoid situations where one might come in contact with the virus l) controversies - distribution programs (e.g., sterile needles, condoms, etc...) II Lymph System A) Function - pick up fluid that leaks out of capillaries and bring it back to the circulatory system B) Components 1) Lymph capillaries, vessels - pick up fluids 2) Lymph nodes - cleaning stations for fluids, WBC's destroy invaders, cell debris a) important nodes - tonsils, spleen, thymus gland
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