Immunology lecture Notes

lecture notes on immunology,how immunologic system works and immunology how vaccines work, how to increase immunology,how to improve immunology system
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Fundamentals of Immunology Alma Moon Novotny BIOC372x AMN 2014 1 Lecture L01 Introducing the Metaphor Infectious disease is one of the few genuine adventures left in the world. The dragons are all dead and the lance grows rusty in the chimney corner....About the only sporting proposition that remains unimpaired by the relentless domestication of a once free living human species is the war against those ferocious little fellow creatures, which lurk in the dark corners and stalk us in the bodies of rats, mice, and all kinds of domestic animals, which fly and crawl with the insects and waylay us in our food and drink and even in our love. Hans Zinsser, 1935 BIOC372x AMN 2014 3 Metaphor … is the lifeblood (ha) of good scientific prose.”– Matt Ridley, 2003 I. Welcome II. Staying Healthy A. Context 1. All organisms (including plants and fungi) have defense mechanisms. These are clearly derived from common ancestral forms, currently classified as innate. 2. Vertebrates have an additional particularly effective defense - acquired or adaptive immunity involving antibody production. 3. Insects, the group multicellular animals with the greatest number of species and probably the highest overall biomass, also have a form of immunity that allows for a flexible response. 4. The defenses are energetically expensive. (Figure 1.1) Figure 1.1: ATP 5. These defenses represent a serious threat to your own body, and you BIOC372x AMN 2014 4 control them to make sure that they don't wind up attacking the wrong cells, which certainly does happen. B. In Praise of Engineers - How We Stay Healthy 1. clean water 2. proper sewage disposal 3. mosquito (and other insect) discouraging buildings 4. communications and transportation infrastructure - allows delivery of preventive health care and distribution of food. 5. vaccination- OK the engineers didn't give us this one, but without the communications and transportation infrastructure, it’s hard to deliver vaccines. C. Disease Burden 1. Economic costs of being sick and having to tend to sick children. 2. Rates of infections disease and general ill health correlated with lowered IQ. (Figure 1.2) Figure 1.2: Happy Baby a) Correlation is about 67%, which suggests that this is not the only factor, but it does provide a possible explanation for the Flynn effect. b) Diarrheal diseases rob infant of nutrition at a period of critical brain growth. 87% of the nutritional energy in newborns goes to the brain. c) Cerebral malaria can damage the brain directly. BIOC372x AMN 2014 5 III. Pathogens and Immunity A. Types, with a few examples 1. Viruses: rhinovirus, flu, small pox, Ebola, polio (Figure 1.3) Figure 1.3: Viruses BIOC372x AMN 2014 6 2. Bacteria: Mycobacterium tuberculosis (TB), E. coli, anthrax, bubonic plague, strep, Clostridium difficile (Figures 1.4-1.7) Figure 1.4: Spirochetes Figure 1.5: Bacteria Structures Close up view BIOC372x AMN 2014 7 3. Fungi: Candida albicans (yeast), athlete’s foot, ringworm, Cryptococcus (Figure 1.8-1.11) Figure 1.8: Figure 1.9: Figure 1.10: Candida under Fungal organisms in Candida Tropicalis Microscope human tissue. 4. Unicellular eukaryotes: malaria, trypanosomes, amoebae, Giardia, Chagas (Figure 1.11-1.12) Figure 1.11: Malaria BIOC372x AMN 2014 10 5. Parasitic worms (Platyhelminthes and Nematoda): flukes, tapeworms, hookworms, heartworms (Figure 1.13-1.15) Figure 1.13: Schistoma Figure 1.14: Trichinella Figure 1.15: Hookworm Larvae B. Recognition – Two general strategies to identify and neutralize the threat. 1. Innate recognition: pattern of molecules characteristic of general category of pathogen. It does not require previous exposure to a pathogen. 2. Adaptive recognition: identifies molecules (usually specific proteins) found only in a specific strain of pathogen (like mug shots, fingerprints, DNA fingerprinting, facial recognition, text analysis.) Parallels: both are highly specific, require previous exposure and are more recent innovations. IV. Words of Advice A. Wash your hands 1. Hands are a big source of contamination. a) Fecal-oral – you pick up a bacterium and transfer it to your own mouth or someone else’s food - "employees must wash their hands…" b) colds and flu viruses - picked up by hands and transferred to eyes and nose c) Think about what you touch. d) Rub your eyes with the backs of your fingers. 2. Hand washing effectively prevents this. a) Soap and water BIOC372x AMN 2014 12 b) Gel alcohol 3. Doctors are a particularly lethal source of infections. a) Ignaz Semmelweis and the prevention of puerperal fever b) Hospital germs are much more likely to have multidrug resistance. B. Think before you have sex. C. If you're sick, stay in bed. 1. You'll keep your illness to yourself. 2. You'll force the virus into evolving strains that make everyone less sick. V. Metaphors if Power Politics A. Policing Functions 1. Expensive-Malnutrition is associated with chronic infection. 2. Necessary 3. Deployed frugally B. National Defense and the Defended Body 1. Variety of agents with complex interconnected controls and communication. 2. Different levels of defense and hostile engagement. a) All-out war: – T 1 (destruction) - all-out war. If this response H consumes a lot of energy and destroys many of the body’s own cells, so be it. The alternative is death and you risk all. b) Cold war: T 2 (containment) – diplomatic sanctions and trade H embargoes. This is the kind of response we make to chronic infections and to many helminth (worm) parasites. c) Non-Hostile or normal relations: T (peaceful coexistence): So reg you want some kind of signaling process that tells you to leave alone harmless bacteria. 3. Misdirected Defenses a) Allergy - immune response to non-pathogens b) Inflammatory tissue damage – collateral damage during attack on pathogen c) Autoimmunity- harm by “friendly fire” when the immune system attacks your own tissues. d) Against transplanted tissues VI. Innate versus Adaptive Immune Response A. Innate and Adaptive are parts if a whole 1. Innate evolved first 2. Adaptive later, in the vertebrates only 3. The two interact, cooperate and exchange information. B. Innate Characteristics – ready to go 1. Phagocytes (neutrophils and macrophages) and NK cells BIOC372x AMN 2014 13 2. Defensive proteins – complement, lysozyme 3. Barriers skin- mucus 4. Pattern recognition molecules – sense general characteristics of pathogens C. Adaptive Characteristics 1. Requires more time 2. Requires gene rearrangement Table 1.1: Innate Versus Adaptive Innate Fast (minutes) Always there Recognizes Phagocytes, patterns NK cells, proteins & barriers Adaptive Slower-weeks requires gene Recognizes B and T and H initially, 3 or rearrangement specific Tc cells more days proteins subsequently BIOC372x AMN 2014 14 D. Interactions in Action 1. T cells (adaptive) are at the heart of the immune response. H 2. Antigen presenting cells (innate) provide them with information. 3. T cells in turn chemically stimulate innate cells, such as macrophages. H E. B-cells 1. T cells will also stimulate B cells (adaptive) to develop and produce H antibodies. 2. Referred to as humoral immunity. 3. When stimulated they divide (clonal expansion). 4. After maturing, they secrete antibodies. F. T cells C 1. Stimulated sick cells, which present antigen (on MHC I) 2. Gets OK from T cells H 3. Begins attacking sick self cells VII. The More you Know: Optional Resources and Fun stuff (You don’t get tested on this) A. We cover T cells in the second session of this course. However, I can’t discuss B cells without mentioning T cells, so here’s a table (see next page) to help you sort out some T cell traits: BIOC372x AMN 2014 15 Table 1.2 Responding to Foreign Antigen (Inevitably simplified) Responding Cell T (Helper) Tc (Cytotoxic) H Response Coordinates immune Attacks and kills cell response Binds antigen with αβ T-cell receptor αβ T-cell receptor Co-receptor CD 4 CD 8 Antigen Class II MHC Class I MHC presented/displayed on Cells presenting/displaying Sentinel dendritic, All nucleated cells except macrophages, B cells sperm Source of antigen phagocytosis synthesized in cell Antigen hydrolyzed in phagolysosome proteosome Response Coordinates immune Attacks and kills cell response B. Also, if you’d like to follow up on some the issues raised in lecture, here’s some sources: 1. From a previous student on the death of a doctor who caught Nipah virus from a corpse (There weren’t proper handwashing station at the hospital. This is a horribly wasteful and tragic way to die.) 2. 3. Importance of sanitation: 4. Disinfecting patients prevents staph: 5. Low national average IQs linked with infectious diseases: and reported in The Economist, July 3, 2010, pages 75-76 BIOC372x AMN 2014 16 Lecture L02a Surveying the Cells & Organs of the Immune System, part a I can assure you that peace will not be built on poor nutrition and human suffering. - Norman Borlag, 11/19/01 (from talk at Rice University) BIOC372x AMN 2014 17 I. Orientation to Terminology A. Analogies- At the end of your lecture outline, you can find a table that summarizes the various cells and attempt to draw a parallel between their function and the function of some element of military or policing defense. B. Primary Classification Distinctions 1. Primary versus secondary organs: a. Primary organs are where cells divide, decide on a developmental fate and, if part of the plan, rearrange genes. b. Secondary organs are site of co-ordination of information about pathogens and the subsequent activation of cells. 2. Innate versus adaptive cells: innate cells don’t rearrange genes, adaptive ones do. 3. myeloid versus lymphoid cells: two general categories define by an early branching decision early in development. All adaptive cells are lymphoid, but some lymphoid cells (NK cells) are innate. Most of the cells in the lymph are lymphoid, but some of the cells in the blood plasma are lymphoid as well. C. “Cluster of Differentiation:” The Term from Hell 1. Immune cells differ in their surface markers, which are characteristic proteins extending from the plasma membrane. 2. Different cell surface properties cause a cell to sort differently during a process called flow cytometry. 3. Scientists have a collection of different monoclonal antibodies that attach to and identify these proteins. 4. Proteins are identified by a number preceded by CD, for “cluster of differentiation.” 5. Thus the names CD8 or CD25 simply indicate the relative order in which they were identified. II. The Source of It All – Hematopoiesis A. Hematopoietic Stem Cell (Figure 2A.1) 1. This is a pluripotent stem cell that can give rise to any type of blood cell. 2. It can divide to make more of itself - self-renew – or it can begin to differentiate by making a series of choices that narrows its options. 3. HSCs first form in the yolk sac membrane in the early embryo, migrate to the liver and spleen and most settle in the bone marrow before birth. BIOC372x AMN 2014 18 4. As few as 100 or so HSCs are enough to completely regenerate the whole hematopoietic system. 5. Isolate lin- stem cells from various types of lin+ cells. Figure 2A.1: Hematopoietic Stem Cell B. Signaling Differentiation (Figure 2A.2) 1. Bmi-1 (transcription factor) keeps the HSCs undifferentiated and continuing to divide and renew. 2. GATA-2 (transcription factor) triggers differentiation from the HSC into the general path of division and development into a specialized cell. 3. The first decision or branch point, is whether the cell will go myeloid or lymphoid: BIOC372x AMN 2014 19 a. CMP- If it turns into a common myeloid-erythroid progenitor, it may develop into a huge number of types including different types of white blood cells, red blood cells and platelet-producing megakaryocytes. b. LMP- If it turns into a common lymphoid progenitor, it expresses the transcription factor Ikaros, and can become the adaptive T and B cells, and also the innate NK and dendritic cells. The notch family of transcription factors decides the T- or B- cell choice. c. Dendritic cells (these are not nerve cells) – can arise from either myeloid or lymphoid lineages. Figure 2A.2: Signaling BIOC372x AMN 2014 20 C. Historical Baggage 1. red blood cells, or erythrocytes. (Figure 2A.3) 2. platelets, or cell fragments from the megakaryocytes. (Figure 2A.4) 3. white blood cells, or leukocytes, which include cells from both the myeloid and lymphoid lineages. Figure 2A.3: Erythrocyte Figure 2A.4: Platelet BIOC372x AMN 2014 21 III. Myeloid Cells A. Immune Involvement a Secondary Function 1. red blood cells – only extrude nuclei in mammals 2. megakaryocytes – pinch off platelets and cell fragments without nuclei. B. Granulocytes: These cells all have specific granules that compartmentalize potentially dangerous molecules. 1. neutrophils – the infantry of the system, in the most modern techie sense. a. strongly phagocytic – first responders to infection and population expands if they infection does not rapidly clear. (Figure 2A.5) b. typically live for only a day (in some ways, these guy resemble Kamikaze pilots) and remains accumulate in an infected region as pus. (Figure 2A.6) c. granules stain with both acidic and basic stains (different granules with different functions). d. nucleus multilobed (sometimes called a polymorphonuclear leukocytes) Figure 2A.5: Neutrophil Figure 2A.6: Neutrophil BIOC372x AMN 2014 22 2. basophils a. granules with histamines stain with methylene blue, a basic stain b. lobed nucleus (Figure 2A.7) c. not phagocytic d. respond to worms Figure 2A.7: Basophil 3. mast cells similar to basophils, only they associate with tissues instead of circulating. a. also basic granules with histamines (Figure 2A.8) b. non-lobed nucleus (Figure 2A.9) c. released as undifferentiated cells, maturing in their tissues. d. have other immune regulatory functions Figure 2A.8: Mast Cell Figure 2A.9: Mast Cell BIOC372x AMN 2014 23 4. eosinophils a. granules stain with eosin red, an acidic stain, have hydrolytic enzymes (Figure 2A.10) b. bilobed nucleus (Figure 2A.11) c. phagocytic, though less important d. target worms Figure 2A.10: Eosinophil Figure 2A.11: Eosinophil C. Myeloid Antigen-Presenting Cells, called mononuclear because the nuclei are unlobed and look like proper single nuclei. These cells are a little like cavalry or scouts: They both patrol and report back and may kill bad guys. 1. monocytes a. circulate in blood for about 8 hours (Figure 2A.12) b. enlarge and give rise to - macrophages (Figure 2A.13) BIOC372x AMN 2014 24

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