Certain bacterial infections can induce an overwhelming systemic inflammatory response leading to a condition known as septic shock . Characterized by high fever and low blood pressure, septic shock is the most common cause of death in U.S. critical care units. Clearly, while local inflammation is an essential step toward healing, widespread inflammation can be devastating.
Major Histocompatability Complex (MHC): body cell surface antigens coded by a family of genes Class I MHC molecules: found on all nucleated cells Class II MHC molecules: found on macrophages, B cells, and activated T cells
----- Meeting Notes (11/25/12 20:21) -----
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.
The Immune SystemTopics 6.3 and 11.1
Immunity • Immunity – The ability of the body to fight infection and/or foreign invaders by producing antibodies or killing infected cells. • Immune System – The system in the body responsible for maintaining homeostasis by recognizing harmful from non-harmful organisms and produces an appropriate response. • Highly specific recognition of foreign antigens • Mechanisms for elimination of microbes bearing such antigens • A vast universe of distinct antigenic specifies • Immunologic memory • Tolerance of self-antigens
Key attributes of immune system • 4 attributes that characterize the immune system as a whole – specificity • antigen-antibody specificity – diversity • react to millions of antigens – memory • rapid 2° response – ability to distinguish self vs. non-self • maturation & training process to reduce auto- immune disease
Foreign Invaders • Called Pathogens – Viruses, bacteria or other living thing that causes disease/immune response. • Antigens – Toxins that pathogens produce that cause harm to an organism.
Avenues of attack• Points of entry – digestive system – respiratory system – urogenital tract – break in skin• Routes of attack – circulatory system – lymph system
Parts of the Immune System 1. Blood - White Blood Cells in particular. 2. Lymph nodes 3. Thymus Gland – Produces T Lymphocytes 4. Bone Marrow – Produces B Lymphocytes
Production & transport of leukocytesLymph system Traps foreign invaders lymph vessels (intertwined amongst blood vessels) lymph node
How does the body fight infection/foreign invaders? First Line of Defense – The Skin • Provides Physical and Chemical barriers • Physical – hard to penetrate, made of indigestible keratin • Chemical – tears, sweat
2nd Line – Nonspecific Immune Response These are defenses the body uses no matter what the invader may be. These defenses include: – Phagocytosis – done by Macrophages – Natural Cell Killers – Inflammation - caused by release of Histamine from leukocytes – Fever – caused by histamines. The fever (high temp) kills invaders by denaturing their proteins.
2nd line: Internal, broad range patrol • Innate, general defense leukocytes – rapid response • Patrolling cells & proteins – attack invaders that penetrate body’s outer barriers • leukocytes – phagocytic white blood cells • complement system – anti-microbial proteins • inflammatory response
Leukocytes: Phagocytic white blood cells (WBCs) • Attracted by chemical signals released by damaged cells – enter infected tissue, engulf & ingest microbes • lysosomes • Neutrophils – most abundant WBC (~70%) – ~ 3 day lifespan • Macrophages – “big eater”, long-lived • Natural Killer Cells – destroy virus-infected cells & cancer cells
Fever • When a local response is not enough – systemic response to infection – activated macrophages release interleukin-1 (IL-1) • triggers hypothalamus in brain to readjust body thermostat to raise body temperature – higher temperature helps defense • inhibits bacterial growth • stimulates phagocytosis • speeds up repair of tissues • causes liver & spleen to store iron, reducing blood iron levels – bacteria need large amounts of iron to grow
The Inflammatory Response• 1- Tissue injury; release of chemical signals~ • histamine (basophils/mast cells): causes Step 2... • prostaglandins: increases blood flow & vessel permeability• 2/3- Dilation and increased permeability of capillary~ • chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs• 4- Phagocytosis of pathogens~ • fever & pyrogens: leukocyte-released molecules increase body temperature
3rd line: Acquired (active) Immunity • Specific defense – lymphocytes • B lymphocytes (B cells) • T lymphocytes (T cells) – antibodies • immunoglobulins • Responds to… – antigens • specific pathogens • specific toxins • abnormal body cells (cancer)
3rd Line – Specific Immune Response This is a specific response to a specific pathogen/antigen. The response involves the creation of Antibodies.
Antibodies • Y-shaped protein molecule. • Made up of variable and constant regions. • Made up of Heavy and Light chains. • Produced by B- Lymphocytes • Function: Recognize antigens, bind to and deactivate them. – Note: Variable region recognizes the anitgens.
Antigens- recognition of invaders • Antigens – proteins that serve as cellular name tags • foreign antigens cause response from WBCs – viruses, bacteria, protozoa, parasitic worms, fungi, toxins – non-pathogens: pollen & transplanted tissue • B cells & T cells respond to different antigens – B cells recognize intact antigens • pathogens in blood & lymph – T cells recognize antigen fragments • pathogens which have already infected cells “self” “foreign”
How an antibody operates/works? Deactivation of a bacterium by an antibody.
How are cells tagged with antigens?• Major histocompatibility (MHC) proteins – antigen glycoproteins – MHC I – on all nucleated cells – MHC II – on macrophages, B-Ly, activated T-Ly• MHC proteins constantly carry bits of cellular material from the cytosol to the cell surface – “snapshot” of what is going on inside cell – give the surface of cells a unique label or “fingerprint” T cell MHC proteins displaying self-antigens
The Pathway of Specific Immune Response Step 1 Pathogens eaten by Macrophage Step 2 Displays portion of Pathogen on surface Step 3Pathogens Helper-T cell recognizes Pathogen
Cellular Immunity vs. Antibody Immunity Cellular Immunity Antibody or Humoral Immunity • Carried out by T-Cells • Carried out by B-cells • Infected cells are killed by • Antibodies are produced Cytotoxic T –Cells. and dumped into blood stream. • Antibodies bind to antigens and deactivate them.
Immune Response Explained 1. Antigen infects cells. 2. Macrophage ingests antigen and displays portion on its surface. 3. Helper T- Cell recognizes antigen on the surface of the macrophage and becomes active. 4. Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells. 5. Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory T – Cells. 6. Active Cytotoxic T-Cells kill infected cells. 7. At the same time, B-Cells divide into Plasma Cells and Memory B- Cells. 8. Plasma cells produce antibodies that deactivate pathogen. 9. Memory T and Memory B cells remain in the body to speed up the response if the same antigen reappears. 10. Supressor T-Cells stop the immune response when all antigens have been destroyed.
Immune Response Summary Displays copy of antigen on surface of cell Antigen Macrophage Helper T - Cell Antibody Immunity Cellular Immunity Active Cytotoxic T-Cell Active B - CellKills Infected Cells Memory T- Cell Plasma Cell Memory B-Cell Antibodies Deactivates Antigens
Primary .vs. Secondary Immune Response • Primary Immune Response – This is a response to an invader the 1st time the invader infects the body. • No measurable immune response for first few days. • Next 10 – 15 days antibody production grows steadily • Secondary Immune Response – A more rapid response to an invader the 2nd time it invades the body. • Antibody production increases dramatically and in a much shorter time period..
Induction of Immune Responses• Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen• Plasma cells: antibody-producing effector B-cells• Secondary immune response: immune response if the individual is exposed to the same antigen at some later time~ Immunological memory
Passive vs. Active Immunity 1. Active Immunity This is immunity where the body is “actively” producing antibodies to fight infection. Ex: You have a throat infection and you are actively creating antibodies to fight it. Vaccination: An injection of a weakened strain of an infectious microbe (pathogen) that causes the body to undergo active immunity (produce antibodies). 1. Passive Immunity This is immunity where antibodies are given to a person from the blood of another person or animal. This immunity only lasts for a short period of time. ex: Breastfeeding mothers pass antibodies to their children through the milk.
Autoimmune Disease • Autoimmune diseases are diseases where the immune system begins to attack itself. – Ex: • Rheumatoid Arthritis – crippling disease of the joints. • Lupus – disease of blood and organs. • Multiple Sclerosis – disease of nervous system • Cause(s): unknown • Cures/Treatments: No known cures.
Allergies Allergy - An exaggerated response by the immune system to an allergen. Allergen: a normally harmless substance that causes an allergic reaction. ex: dust, pollen, mould, food, insect stings Types of Allergic reactions There are two types of allergic reactions. a. Immediate – occurs within seconds and normally lasts for about 30 mins. b. Delayed – takes longer to react and can last for a much longer time.
What happens during an allergic reaction? • During an allergic reaction antibodies cause histamines to be released from certain cells. Histamines cause: a. Swelling of tissues b. Release of fluids (runny noses and eyes) c. muscle spasms (some cases) Anaphylaxis or anaphylactic shock: This is the sudden and severe allergic reaction to a substance that can cause death. Treatments for Allergies 1. Avoidance of material – especially food. 2. Epinephrine – “epi – pen” 3. Antihistamines -- benadryl
HIV & AIDS • Human Immunodeficiency Virus – virus infects helper T cells – helper T cells don’t activate rest of immune system: T cells & B cells • also destroy T cells • Acquired ImmunoDeficiency Syndrome – infections by opportunistic diseases – death usually from other infections • pneumonia, cancer
HIV • HIV is a virus that specifically attacks the lymphocytes. • This means the number of lymphocytes decreases. • Less antibodies are made. • Predict the consequences…
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• Caused by the HIV virus that selectively infects the immune system leaving the body open to infection by removing the specific immunity.
Social implications of AIDS • Cases of AIDS are not evenly distributed in the world, for example there are severe problems in Africa (some populations with 30% of their people are infected). • 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?