The organs of the immune system are color-coded on this slide. yellow = primary organs - bone marrow, thymus blue = response organs
Cells of the immune system are called lymphocytes.
Innate is a generalized, non-specific response. Adaptive is, just that, more customized. “Adaptive” is what used to be called “acquired”. Technically, this type of immunity is not acquired, as we are born with the capacity to mount this response. It adapts to the antigens it encounters.
NK cells are free-roving lymphocytes that identify, bind to, and lyse cancerous and virus-infected cells as part of the non-specific immune response. Lymphocytes are WBCs involved in antibody production and other aspects of the immune response.
Sweat, tears, saliva, stomach acids and urine contain chemical compounds and/or provide a flushing action that removes pathogens.
Bacteria release chemicals that act like a generalized announcement of their presence (see next slide, “Phagocyte Migration”). This signal attracts macrophages and neutrophils.
Note the ameboid movement of these cells. Seeing the fluidity of the cell membrane enables us to get a better idea of how one cell can engulf another. The above neutrophils were placed in a gradient of fMLP (n formyl methionine- leucine- phenylalanine), a peptide chain produced by some bacteria.
pink = macrophage yellow = bacteria; note rod-like structure of E. coli
During an oxidative burst, there is increased oxygen consumption, increased production of hydrogen peroxide and superoxide anion, and increased glucose oxidation. This results in the production of several microbicidal oxidizing agents in the lysosomes (which are the essentially the cell’s garbage disposal system), including superoxide anion, hydroxyl radical, singlet oxygen, and hydrogen peroxide. These will oxidize lipids, such as in the bacterial membranes causing lysis of the bacteria, and will oxidize or cross-link protein destroying their function. The primary enzyme involved in catalyzing the oxidation of foreign materials in the phagocytes is myeloperoxidase, which is contained in the lysosomes. Superoxide dismutase is also involved.
Streptococcus pyogenes , the pathogen that causes strep throat is the yellow, bead-like structure.
See teacher’s notes for slide number 13, entitled, “Macrophage Ingesting Yeast”.
The complement system plays an essential role in host defense against infectious agents and in the inflammatory process. It consists of about twenty plasma proteins that function either as enzymes or as binding proteins. Complement activation occurs with each component binding in a specific order. In addition to these plasma proteins, the complement system includes multiple distinct cell-surface receptors that are specific for the fragments of complement proteins and that occur on inflammatory cells and cells of the immune system. The complement system can be activated by two different pathways, the classical complement pathway and the alternative complement pathway. The classical pathway is activated by the binding of antibody molecules (specifically IgM and IgG1, 2 and 3) to a foreign particle. This pathway is antibody-dependent. The alternative pathway is of major importance in host defense against bacterial infection because, unlike the classical pathway, it is activated by invading micro-organisms and does not require antibody, and is therefore antibody-independent.
See teacher’s notes from the previous slide, number 17, entitled “Innate Immunity – Cellular Response”. Pore formation is important because w ith enough holes, the invader or infected cell will die, because water rushing inside the cell will induce osmotic swelling, and an influx of calcium may trigger apoptosis
The release of histamine by mast cells is induced by complement.
Fevers develop because macrophages release the cytokine interleukin–1 (IL-1), a chemical that acts on the hypothalamus, leading to increased body temperature. Bacterial growth requires iron, which is a component of cytochromes and certain non-heme iron proteins and a cofactor for some enzymatic reactions. The increase in temperature that occurs as the result of a fever may lead to bleeding or destruction of RBCs, so that blood iron levels are decreased . The length of a high temperature fever influences mortality due to fever. Prolonged fever influences mortality due to compromised enzyme activity.
Mast cells contain granules which store a variety of inflammatory mediators. These include: histamine, which causes the blood vessels to become “leaky and smooth muscle to contract enzymes that can destroy tissue or cleave complement components. heparin or chondroitin sulfate, which are both anticoagulants. chemotactic (attraction) factors for neutrophils and eosinophils, signalling them to move to the site of inflammation – eg. serotonin Normally, mast cells are found only in the tissues, not in circulation
Interferon is a protein produced by virus-infected cells that inhibits the synthesis of viral proteins, leading to decreased viral replication. It also can cause apoptosis (see info on next slide, 24, entitled “Apoptosis or Cell Death”) of virus-infected cells. An example of an acute phase protein is C-reactive protein, which fixes complement.
Apoptosis is the name given to the process of programmed cell death due to a chemical signal (an example would be interferon) that initiates a cascade of “suicide” proteins. Once the suicide proteins are activated, the cells shrink. As the DNA is chopped up, the nucleus condenses and nearby cells engulf the collapsing cells. During development, many cells die. In this situation, apoptosis provides a means of “getting rid of” cellular debris.
This focused attack is your second line of defense, adaptive immunity. It is “customized” to address the presence of a specific pathogen.
Use “enter” to advance each line in the animation.
THE IMMUNE SYSTEM We all get sick sometimes...but then we get better. What happens when we get sick? Why do we get better?
ANATOMY OF THE IMMUNE SYSTEM <ul><li>The immune system is localized in several parts of the body </li></ul><ul><ul><li>immune cells develop in the primary organs - bone marrow and thymus (yellow) </li></ul></ul><ul><ul><li>immune responses occur in the secondary organs (blue) </li></ul></ul>
ANATOMY OF THE IMMUNE SYSTEM <ul><li>Thymus – glandular organ near the heart – where T cells learn their jobs </li></ul><ul><li>Bone marrow – blood-producing tissue located inside certain bones </li></ul><ul><ul><li>blood stem cells give rise to all of the different types of blood cells </li></ul></ul><ul><li>Spleen – serves as a filter for the blood </li></ul><ul><ul><li>removes old and damaged red blood cells </li></ul></ul><ul><ul><li>removes infectious agents and uses them to activate cells called lymphocytes </li></ul></ul><ul><li>Lymph nodes – small organs that filter out dead cells, antigens, and other “stuff” to present to lymphocytes </li></ul><ul><li>Lymphatic vessels – collect fluid (lymph) that has “leaked” out from the blood into the tissues and returns it to circulation </li></ul>
PASSIVE IMMUNITY <ul><li>Antibodies ( Y ) are also found in breast milk. </li></ul><ul><li>The antibodies received through passive immunity last only several weeks. </li></ul>While your immune system was developing, you were protected by immune defenses called antibodies . These antibodies traveled across the placenta from the maternal blood to the fetal blood.
YOUR ACTIVE IMMUNE DEFENSES Innate Immunity - invariant (generalized) - early, limited specificity - the first line of defense Adaptive Immunity - variable (custom) - later, highly specific - ‘‘remembers’’ infection
INNATE IMMUNITY <ul><li>Innate immunity consists of: </li></ul><ul><li>Barriers </li></ul><ul><li>Cellular response </li></ul><ul><ul><li>phagocytosis </li></ul></ul><ul><ul><li>inflammatory reaction </li></ul></ul><ul><ul><li>NK (natural killer) and mast cells </li></ul></ul><ul><li>Soluble factors </li></ul>When you were born, you brought with you several mechanisms to prevent illness. This type of immunity is also called nonspecific immunity.
INNATE IMMUNITY Cellular response <ul><li>nonspecific - the same response works against many pathogens </li></ul><ul><li>this type of response is the same no matter how often it is triggered </li></ul><ul><li>the types of cells involved are macrophages , neutrophils , natural killer cells , and mast cells </li></ul><ul><li>a soluble factor, complement , is also involved </li></ul>
<ul><li>Phagocytic cells include: </li></ul><ul><li>Macrophages engulf pathogens and dead cell remains </li></ul><ul><li>Neutrophils release chemicals that kill nearby bacteria </li></ul><ul><ul><li>pus = neutrophils, tissue cells and dead pathogens </li></ul></ul>
Phagocyte migration Neutrophils and macrophages recognize chemicals produced by bacteria in a cut or scratch and migrate "toward the smell". Here, neutrophils were placed in a gradient of a chemical that is produced by some bacteria. The cells charge out like a "posse" after the bad guys. CELLS alive!
Macrophages <ul><li>WBCs that ingest bacteria, viruses, dead cells, dust </li></ul><ul><li>most circulate in the blood, lymph and extracellular fluid </li></ul><ul><li>they are attracted to the site of infection by chemicals given off by dying cells </li></ul><ul><li>after ingesting a foreign invader, they “wear” pieces of it called antigens on their cell membrane receptors – this tells other types of immune system cells what to look for </li></ul>
Macrophage ingesting yeast This human macrophage, like the neutrophil, is a professional "phagocyte" or eating cell (phago = "eating", cyte = "cell"). Here, it envelops cells of a yeast, Candida albicans . After ingestion, the white cell must kill the organisms by some means, such as the oxidative burst. CELLS alive!
Neutrophils <ul><li>WBCs – are phagocytic, like macrophages </li></ul><ul><li>neutrophils also release toxic chemicals that destroy everything in the area, including the neutrophils themselves </li></ul>
Neutrophil phagocytosing S. pyogenes, the cause of strep throat Human neutrophils are WBCs that arrive quickly at the site of a bacterial infection and whose primary function is to eat and kill bacteria. This neutrophil ingesting Streptococcus pyogenes was imaged in gray scale with phase contrast optics and colorized. CELLS alive!
Neutrophil killing yeast One way that neutrophils kill is by producing an anti-bacterial compound called “superoxide anion“, a process called oxidative burst. Here, an amoeboid human neutrophil senses, moves toward and ingests an ovoid yeast. In the next two panels, oxidation can be seen by using a dye, and is colorized here. YEAST NEUTROPHIL CELLS alive!
Complement <ul><li>complement is not a cell but a group of proteins </li></ul><ul><li>these proteins circulate in the blood </li></ul><ul><li>complement plays a role in inflammatory responses of both the innate and adaptive immune responses </li></ul>INNATE IMMUNITY Cellular response
Complement <ul><li>complement is not a cell but a group of proteins </li></ul><ul><li>these proteins circulate in the blood </li></ul><ul><ul><li>help to recruit phagocytes to site of inflammation and activate them </li></ul></ul><ul><ul><li>bind to receptors on phagocytes, helping to remove agent of infection </li></ul></ul><ul><ul><li>form pores in the invader or infected cell’s membrane (like the NKs do) </li></ul></ul><ul><ul><li>activate mast cells to release histamine and other factors </li></ul></ul><ul><li>complement plays a role in inflammatory responses of both the innate and adaptive immune responses </li></ul>INNATE IMMUNITY Cellular response
Inflammatory response Step 1. Circulation to the site increases tissue warm, red and swollen Step 2. WBCs leak into tissues phagocytes engulf and destroy bacteria <ul><li>chemical and cell response to injury or localized infection </li></ul><ul><li>eliminates the source of infection </li></ul><ul><li>promotes wound healing </li></ul>INNATE IMMUNITY Cellular response
Inflammatory response (cont’d) <ul><li>The release of histamine and prostaglandin causes local vessel dilation resulting in: </li></ul><ul><ul><ul><li>more WBCs to site </li></ul></ul></ul><ul><ul><ul><li>increased blood flow redness and warmth </li></ul></ul></ul><ul><ul><ul><li>increased capillary permeability </li></ul></ul></ul><ul><ul><ul><li>phagocytes move out of vessels into intracellular fluid (ICF) </li></ul></ul></ul><ul><ul><ul><li>edema (swelling) due to fluids seeping from capillaries </li></ul></ul></ul>INNATE IMMUNITY Cellular response
Inflammatory response (cont’d) <ul><li>POSITIVE </li></ul><ul><li>indicate a reaction to infection </li></ul><ul><li>stimulate phagocytosis </li></ul><ul><li>slow bacterial growth </li></ul><ul><ul><li>increases body temperature beyond the tolerance of some bacteria </li></ul></ul><ul><ul><li>decreases blood iron levels </li></ul></ul><ul><li>NEGATIVE </li></ul><ul><li>extreme heat enzyme denaturation and interruption of normal biochemical reactions </li></ul><ul><ul><li>> 39 ° C (103°F) is dangerous </li></ul></ul><ul><ul><li>> 41°C (105°F) could be fatal and requires medical attention </li></ul></ul>Fevers have both positive and negative effects on infection and bodily functions INNATE IMMUNITY Cellular response
Natural killer cells (NK cells) <ul><li>instead of attacking the invaders, they attack the body’s own cells that have become infected by viruses </li></ul><ul><li>they also attack potential cancer cells, often before they form tumors </li></ul><ul><li>they bind to cells using an antibody “bridge”, then kill it by secreting a chemical (perforin) that makes holes in the cell membrane of the target cell. With enough holes, the cell will die, because water rushing inside the cell will induce osmotic swelling, and an influx of calcium may trigger apoptosis. </li></ul>
Mast cells <ul><li>are found in tissues like the skin, near blood vessels. </li></ul><ul><li>are activated after antigen binds to a specific type of antibody called IgE that is attached to receptors on the mast cell. </li></ul><ul><li>activated mast cells release substances that contribute to inflammation, such as histamine. </li></ul><ul><li>mast cells are important in allergic responses but are also part of the innate immune response, helping to protect from infection. </li></ul>
INNATE IMMUNITY – Soluble factors <ul><li>Interferon </li></ul><ul><ul><li>a chemical (cytokine) produced by virus-infected cells that contributes to their death by apoptosis </li></ul></ul><ul><li>Acute phase proteins </li></ul><ul><ul><li>proteins in the plasma that increase during infection and inflammation </li></ul></ul><ul><ul><li>can be used diagnostically to give an indication of acute inflammation </li></ul></ul>
Apoptosis or cell death Human neutrophils released into the blood "commit suicide“ after only 1 day. A neutrophil (left) undergoes apoptosis, a series of changes including violent membrane blebbing and fragmentation of DNA. Apoptotic cells break into smaller pieces called apoptotic bodies that other body cells recognize and eat. CELLS alive!
<ul><li>Your mom’s antibodies were effective for just a short time at birth, but your innate immune system can be activated quickly. It is always your first line of defense during an infection, but it can’t always eliminate the germ. </li></ul><ul><li>When this happens, your body initiates a focused attack against the specific pathogen that is causing the infection. This attack may lead to long-term protection against that pathogen. </li></ul><ul><li>This type of immunity is called adaptive immunity , the customized second line of defense. </li></ul>
YOUR ACTIVE IMMUNE DEFENSES Innate Immunity - invariant (generalized) - early, limited specificity - the first line of defense Adaptive Immunity - variable (custom) - later, highly specific - ‘‘remembers’’ infection 1. Barriers - skin, tears 2. Phagocytes - neutrophils, macrophages 3. NK cells and mast cells 4. Complement and other proteins
This immunology curriculum and integrated laboratory modules were created by teachers and scientists working together through a grant from the National Science Foundation to the Nanobiotechnology Center in collaboration with the Cornell Institute for Biology Teachers, which is funded by the Howard Hughes Medical Institute. Collaborators for this project: Harriet Beck, Wellsville Central School Jim Blankenship, Cornell Institute for Biology Teachers Rita Calvo, Cornell University Jerrie Gavalchin, Cornell University Mary Kay Hickey, Dryden High School Susan Oliver, Dundee High School Jeanne Raish, Avoca Central School Anna Waldron, Nanobiotechnology Center This material is based upon work supported in part by the STC Program of the National Science Foundation under Agreement No. ECS-9876771. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.