Molecular and cellular immunology, 7.5hp Schedule on homepage www.his.se/mb321g (and more info) Lectures Lecture Work with questions Summary 45 min 15 min 30 min 15 min Andreas Jansson, email: firstname.lastname@example.org
Labs 30 Sep & 2 Oct (ELISA Lab) - A short exam on the first day (30 Sep). You must answer all questions correct in order to do the lab <ul><li>You must study before coming to the labs </li></ul><ul><li>(see homepage for more info) </li></ul>15 & 16 Oct – Computer Lab (modeling HIV infection).
Grades on the lab In order to get the grade pass (G) on the lab, You need to pass both the wet-Lab and the computer Lab (ECTS: G = C/D/E). In order to get the grade pass with distinction (VG) on the lab, you need to have the grade pass with distinction on both the wet-Lab and the computer Lab. (ECTS: VG = A/B).
Grades on the course In order to get the grade pass (G) on the course, you need to pass both the labs and the main exam. In order to get the grade pass with distinction (VG) on the course, you need to have the grade pass with distinction on both the labs and the main exam. Main exam: 60-80% (G), 80-100% (VG), 60-65% (E), 65-70% (D), 70-80% (C), 80-90%(B), 90-100%(A)
My background <ul><li>Did my PhD at University of New South </li></ul><ul><li>Wales (UNSW), Australia 2003-2006. </li></ul><ul><li>Investigated experimentally how a certain </li></ul><ul><li>pathogen influenced T helper cell development </li></ul><ul><li>(Th1/Th2). </li></ul><ul><li>2. Mathematical modeling of T cell activation </li></ul><ul><li>(costimulation) </li></ul><ul><li>3. Computational modeling Th cell development </li></ul>
Current research Develop mathematical models for parameter estimation of T cell development and T cell homeostasis to understand its role in Ulcerative Colitis (in collaboration with Prof. Elisabeth Hultgren-Hörnquist, Örebro University) Developing software tools (PathwayLab) for simulating biological systems, in collaboration with Prof. Mats Jirstrand (Fraunhofer-Chalmers Research Centre). Are involved in a large EU-network for mathematical modeling of immunological systems.
<ul><li>Pathogens are biological agents that cause disease to its host. </li></ul><ul><li>The immune system protects the host from pathogens, but also from cancer cells. </li></ul><ul><li>“ Friendly" bacteria present in the human body's normal flora also protect the host from pathogens. </li></ul>
<ul><li>Sometimes the immune system fail. E.g. HIV. </li></ul><ul><li>… and sometimes it work to well </li></ul><ul><li>- Allergy </li></ul><ul><li>- Autoimmune diseases (e.g. Diabetes type 1) </li></ul>
The immune system is VERY complex. Why? <ul><li>Pathogens vary a lot and there are thousands of different pathogens </li></ul><ul><li>The immune system must differ between self and non-self substances. If activated against our own cells or proteins = autoimmune disease. If activated against harmless substances (e.g. food or pollen) = allergy. </li></ul><ul><li>Must find the pathogen in the body </li></ul><ul><li>Must respond fast. </li></ul>
<ul><li>Infection – foreign species colonize (populate an area) the body and utilize the host’s resources to multiply. However, an infection may not cause important clinical symptoms or impair host function. </li></ul><ul><li>infectious disease is a clinically evident disease resulting from the presence of pathogens. </li></ul><ul><li>Pathogens – viruses, bacteria, fungi, parasites (e.g. Malaria – caused by protozoan parasites) </li></ul><ul><li>Some pathogens live and multiply within our own cells (different pathogens infect different cells, e.g. Hepatitis virus infect liver cells, whereas HIV infect Th cells). Such pathogens are called intracellular pathogens. </li></ul><ul><li>The immune system therefore needs to kill the infected cell and thereby kill our own cells (which are infected). </li></ul><ul><li>Cytotoxic T cells (killer cells) eliminate intracellular pathogens by killing the infected cells. </li></ul>
<ul><li>Other pathogens live and multiply outside our cells within the body (tissues and blood stream). Such pathogens are called extracellular pathogens. </li></ul><ul><li>Antibodies are produced by B cells which bind and mark extracellular pathogens. Other immune cells (or proteins) can then bind to the antibodies attached on the pathogen and then kill it. </li></ul>
<ul><li>Incubation period - is the time elapsed between exposure to a pathogen and when symptoms and signs are first apparent. </li></ul><ul><li>Examples: </li></ul><ul><li>Influenza 1-3 days </li></ul><ul><li>Chicken pox (“SWE: vattenkoppor”) 14-16 days </li></ul><ul><li>Measles (“SWE: mässling”) 9-12 days </li></ul>
Viruses (e.g. HIV) A figure of the HIV structure. Check the chapter of HIV in the book to find this figure
Viruses 1. Attachment- certain viruses attach to certain receptors specific for a certain cell type (e.g. HIV binds CD4 which is only expressed by macrophages and Th cells) 2. DNA/RNA is released within the host cell, which carry genetic information about the virus components 3. Synthesis of the virus RNA/DNA and proteins 4. Assembly of the virus particles 5. Release from the host cell by lysis – kills the cell.
Bacteria Can multiply on their own as long there is nutrition Host cell Intracellular bacteria Extracellular bacteria
Pathogen infection Infection of pathogens can usually be divided into 4 steps: 1. Invasion: the pathogen invades the host through wounds on the skin, through airways or follow the food we eat 2. Multiplication 3. Spread: the pathogen finds new areas in the body to colonize. 4. Pathogenesis – causing disease by damage the host. Note: Not all pathogens follow this route.
How do we protect us from invasion? <ul><li>Anatomic barrier (skin) </li></ul><ul><li>Skin consists of two layers: </li></ul><ul><li>Epidermis (outer layer) </li></ul><ul><li>Dermis (inner layer) </li></ul><ul><li>Cells form the dermis are pushed outward into the epidermis and produce large amount of keratin and die (the dead keratinocytes constitute the surface of the skin). </li></ul><ul><li>Wounds (E.g. S.aureus) </li></ul><ul><li>Burns (E.g. P. aeruginosa) </li></ul><ul><li>Insects (E.g. Malaria, Y. pestis) </li></ul><ul><li>*We also have friendly bacteria on the skin that protect the host. </li></ul>
How do we protect us from invasion? <ul><li>Anatomic barrier (skin) </li></ul><ul><li>Skin: Keratinocytes are shed continuously, which make bacteria to fall off </li></ul><ul><li>Skin is dry and acidic </li></ul><ul><li>Temperature is 35 degrees </li></ul><ul><li>Contain lysozyme, an enzyme that degrades cell wall of bacteria </li></ul><ul><li>Pathogens must compete with already established ”friendly” bacteria strains </li></ul>
How do we protect us from invasion? Anatomic barrier (mucus membranes) - Mucous membrane (epithelial cells), protects respiratory, gastrointestinal and genito-urinary tracts by secreting mucus. Mucus secretion increase during infection (e.g. in respiratory tracks) Anatomic barrier (cilia) - Cilia prevent attachment of the pathogen to the host’s membranes and tissues. Results show an increased pneumococcal adherence in smokers compared to that of non-smokers, since tobacco smoke kills cilia.
How do we protect us from invasion? Physiologic barrier Temperature: the immune system can trigger a fever. Such high temperature can kill pathogens. pH: The low pH in the stomach kills most pathogens (some like it, e.g. H.pylori).
Cells of the immune system are called white blood cells (leukocytes). <ul><li>The are divided into two large classes depending on their morphology: </li></ul><ul><li>Polymorphonuclear (PMN) cells </li></ul>Neutrophils (50-70%) Eosinophils (3-4%) Basophils (0.5-1%) * Note that percentages come from blood cell count. It is hard to say the percentage within the tissues.
2. Mononuclear cells Lymphocytes (B and T cells), 25-45% Monocytes (3-8%) Macrophages (tissues) Dendritic cells (tissues) Mast cells (tissues) etc. NK-cells
All white blood cells are produced and derived from hematopoietic stem cells within the bone marrow (red marrow). Red marrow is found mainly in hip bone, breast bone, skull, ribs, shoulder blades, and the long bones. Leukocytes are found throughout the body, including the blood and lymphatic system.
Immunogens are those substances that elicit a response from the immune system Antigens are all substances that can be recognized by the adaptive immune system (B and T cells). Self-antigens – antigens from the host that can bind receptors of the adaptive immune system. Antigens are usually proteins or polysaccharides. This includes parts (coats, capsules, cell walls, flagella, or toxins) of bacteria, viruses, or other microorganisms. When we say antigens we “immunologists” usually mean foreign substances that can induce a immune response (the same as immunogens) .
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