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MCMP 422: Immunology Class MWF 11:30-12:20 Instructors Objectives
Dr. Geahlen Dr. Harrison Dr. Hazbun (RHPH 406D, , Objectives Course Policies Grading
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The Immune System Second Edition
Peter Parham The Immune System Second Edition Chapter 1 Elements of the Immune System and their Roles in Defense Copyright © 2005 by Garland Science Publishing
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Chapter 1 Summarizes all of immunology
Read Chapter 1 for a complete foundation Before class: Read the textbook in general and try to understand all the terminologies in bold. During class: Take good notes because I will be adding information that will be tested The powerpoint slides are set-up so that you will have to fill in notes from the class.
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Lecture Concepts What components make up the immune system?
Cells, organs, cytokines and molecules involved in the immune system What is the goal of the immune system? To clear pathogens and cancer cells in our body How do we classify immune responses? Innate and adaptive immune responses What are the side effects of the immune system? Autoimmune diseases, Allergies, Transplantation Rejection
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Immunology: the science of how the body responds to foreign organisms (e.g. pathogens) or substances (e.g. allergen) Immune system: the organs, cells and molecules that defend and respond to pathogens/allergens 1. Tissues/organs 2. Cells 3. Blood borne proteins We will learn about the many cells and tissues of the immune system in the next few lectures.
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Origin of Immunology - individuals who survived a disease seemed to be untouched upon re-exposure
Vaccination/Immunization - procedure where disease is prevented by deliberate exposure to infectious agent that cannot cause disease. Polio?
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Figure 1-2 Pathogen - any organism that can cause disease
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How Clean are You? Part of body Bacteria Head (scalp) 1,000,000 /cm2
Surface of skin /cm2 Saliva ,000,000 /g Nose mucus 10,000,000 /g Faeces over 100,000,000 /g Faeces made of up to 30% live bacteria
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Diversity of Pathogens
Four Classes Opportunistic pathogens Pathogen-Host relationship Classes of pathogens: four classes of pathogens : Bacteria, Fungi, Viruses, and Parasites. Important because immune system responds to these classes in different ways. Opportunistic pathogen - e.g. Pneumocystis carinii - a fungal pathogen that causes disease in people with suppressed immune systems (due drugs or disease). This is an example of opportunistic growth in the lung of a monkey infected with simian virus equivalent to AIDS Host-pathogen relationship is complex - host and pathogen respond to each other in an ongoing war. This relationship can change at varying rates. New pathogens tend to cause more severe disease with associated high mortality. Common diseases - can be overcome by the immune system but not before they spread to a new host.
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Defenses against Pathogens
Physical Defenses 1. Skin 2. Mucosal surfaces Immune Defenses 1. Innate 2. Adaptive Skin - Important barrier against pathogens - tough, waterproof barrier that is continually making new cell that replace dead cells - most pathogens cannot penetrate the layer by themselves (with the exception of some fungi) - breached if physically broken by wound or mosquito Mucosal - surfaces: line cavities that enter the body (e.g. mouth, lungs) epithelial cells that line these cavities are covered in mucus Mucus: thick fluid layer containing (glycoproteins, proteoglycans, enzymes) that trap and remove microorganisms. - Lungs: Mucus in the lungs traps bacteria and fungal spores. Tiny hairs, called cilia, move the mucus to the back of the throat where it is swallowed - Nose: Mucus traps pathogens which are then swallowed or blown out in coughs and sneezes - Mouth: Friendly bacteria help to prevent the growth of harmful pathogens. Saliva cleans and removes bacteria.
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Figure 1-4 - Lungs: Mucus in the lungs traps bacteria and fungal spores. Tiny hairs, called cilia, move the mucus to the back of the throat where it is swallowed Nose: Mucus traps pathogens which are then swallowed or blown out in coughs and sneezes Mouth: Friendly bacteria help to prevent the growth of harmful pathogens. Saliva cleans and removes bacteria. Eyes: lysozyme in tears help limit bacterial growth Stomach: acid help to neutralize most pathogens Intestine: Friendly bacteria help to stop the growth of harmful pathogens Urogenital tract: Slightly acid conditions in the vagina and urethra help to stop the growth of pathogens
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Immunity: Basic Parts Pathogen Recognition (Binding event) (Foreign)
Signal Immune disorders (Self) Effector mechanisms Effector Cells Complement Basis of immunity is to recognize self from foreign organisms - this is usually initiated by a binding event - Binding molecules - Antibodies and receptors Effector cells - engulf bacteria, kill virus infected cells, attack parasites Complement - blood borne (serum) proteins that tag pathogens, attack in their own right Innate immunity is entirely determined by the genes a person has. It is the basic immunity that you already have in your genes Acquired immunity is the response to a specific pathogen Innate immunity - “naïve” everyday immunity Acquired immunity - “specialized” immunity
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Figure 1-5 part 1 of 2 How Immunity Works Complement Effector cell
Endocytosis
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Figure 1-5 part 2 of 2 One type of effector cell is the phagocyte
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Figure 1-6 Innate Immunity Cytokines Inflammation Phagocytosis
Cytokines - soluble proteins that transmit a signal that pathogen is present - local dilation of blood capillaries Vascular dilation (Vasodilation) introduces gaps between the endothelial cells allowing plasma to leak into the cells Change the adhesiveness of the endothelial tissue allowing white blood cell to attach State of Inflammation is induced - increased swelling, pain, heat and redness. Cytokines Inflammation Phagocytosis Inflammatory cells
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What if Innate Immunity is not Enough?
Innate immunity keeps us healthy most of the time Some pathogens escape the innate immune process Need a specific system to adapt to a specific pathogen Adaptive immune response Highly specialized defense against one pathogen that has little or no effect against other pathogens.
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Figure 1-7 Characteristics of Innate vs Adaptive Immunity
1. Innate Immunity a. present BEFORE the pathogen enters the body (rapid response) b. NOT specific for a unique pathogen c. Remains relatively constant during an infection Does NOT impart long term immunity Composed of cells (eg. NK cells) and proteins (eg. complement) circulating in the blood and cells present in tissues (eg., macrophages) 1. Adaptive Immunity a. develops AFTER the pathogen enters the body (slow response) b. IS exquisitely specific for a given pathogen c. Becomes more effective as the immune response progresses d. Imparts long term immunity (basis of vaccination/immunization) -Edward Jenner (1796) rural England doctor (cowpox to immunize against small pox; vaccine is the disease cowpox causes) e. Composed of cells and proteins circulating in the blood and present in tissues -lymphocytes (circulate in blood, lymph and found in tissues) -antibodies (circulate in blood) -cytokines (mostly act locally in tissues, few found in blood) Most of the time the innate response is sufficient to rid the body of daily, unwanted pathogens that normally enter the body (mouth is full of pathogens). Innate immune system functions silently. When it fails and an infection persists, the adaptive immune response (IR) develops with the accompanying symptoms (eg., fever, aches, congestion etc..). During an adaptive IR, the innate and adaptive responses work together to eliminate the pathog Effector mechanisms are similar - The important difference is in the cell surface receptors used by lymphocytes to recognize pathogen. The receptors used to recognize pathogen by the Innate response are There are many types of receptors of innate immunity but they are fixed and cannot be changed - encoded by conventional genes Adaptive immunity - receptors are of the same basic type that is specific for the pathogen. Lymphocytes - white blood cells that increase the immune response to ongoing infection
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Innate vs Adaptive Molecular Recognition
Most important difference: Receptors used to recognize pathogens Innate immunity: Receptors recognize conserved structures present in many pathogens Pathogen-associated Molecular Patterns: LPS, peptidoglycan, lipids, mannose, bacterial DNA and viral RNA Adaptive immunity: Receptors recognize a specific structure unique to that pathogen Effector mechanisms are similar - The important difference is in the cell surface receptors used by lymphocytes to recognize pathogen. The receptors used to recognize pathogen by the Innate response are a few highly conserved structures present in many different microorganisms pathogen-associated molecular patterns: LPS from the gram-negative cell wall, peptidoglycan, lipotechoic acids from the gram-positive cell wall, the sugar mannose (common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial DNA, N-formylmethionine found in bacterial proteins, double-stranded RNA from viruses, and glucans from fungal cell wall There are many types of receptors of innate immunity but they are fixed and cannot be changed - encoded by conventional genes Adaptive immunity - receptors are of the same basic type that is specific for the pathogen.
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Lymphocyte Amplification Each cell = one receptor
Millions of lymphocytes are generated Small subset will recognize a pathogen Proliferation and differentiation Acquired immunity - the adaptive immunity provided by immunological memory Acquired immunity can be present for decades but for some it may be short-lived: eg. Measles vs influenza Small lymphocyte - circulate in the blood in a dormant and immature form Encounter with pathogen activates a cell
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Figure 1-11 part 1 of 2 Flowchart of Hematopoiesis
How are the immune cells made? Common Progenitor to the cells of the immune system (leukocytes) and erythroid cells. Pluripotent hematopoietic stem cell gives rise to hematopoietic cells (hematopoiesis) Self renewal process: divide to give more hematopoietic stem cells Pluripotent stem cells also matures into three cell types Lymphoid, Myeloid, Erythroid
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Figure 1-11 Flowchart of Hematopoiesis
Several types of white blood cell (leukocytes) - we will study the function of each Leukocytes develop in the primary lymphoid organs - Bone marrow- B-lymphocytes (B-cells) - thymus - T-lymphocytes (T-Cells) Leukocytes - white blood cells
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Myeloid Lineage
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Figure 1-9 part 3 of 6 Granulocytes (Myeloid progenitor)
Polymorphonuclear leukocytes (PMLs) Figure 1-9 part 3 of 6 Neutrophils: Most abundant Phagocyte Effector cells of Innate Immunity Short-lived - Pus Eosinophils: Worms/intestinal parasites Amplify inflammation Bind IgE Very Toxic - Pathogen and host Chronic asthma Basophils: Rare Unknown function Bind to IgE Granulocytes - named due to their staining of cytoplasmic granules - also called PMLs due to the morphology of the Nucleus. Neutrophil - eosinophil bind to acid stain eosin - basophil binds to basic stain - neutrophil does not bind to either
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Figure 1-9 part 5 of 6 Monocytes - leukocytes that circulate in the blood Bigger than granulocytes All look the same - indented nucleus Circulate in the blood until needed - mature to macrophage Macrophage - main function is to phagocytose pathogens, dead cells and debris - secrete cytokines to recruit neutrophils and other leukocytes
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Dendritic cells: Star-shaped morphology
Resident in the tissue cellular messengers Cargo cells - carry pathogen materials Mast Cells - in all connective tissue - granules similar to basophil but a different unknown progenitor - degranulation major contributor to inflammation
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Figure 1-9 part 2 of 6 Lymphoid Lineage Cells Lymp
Two types - large lymphocytes with a granular cytoplasm and small with little cytoplasm Natural killer cell - Large granular lymphocyte effector cells of innate immunity - infected tissue and kill viral-infected cells - secrete cytokines that interfere with virus infections
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Figure 1-9 part 1 of 6 Small lymphocytes - responsible for the adaptive immune response - small because they are dormant and immature - Recognition of a pathogen drives their amplification and maturation - Two types - B cells and T-cell that can be distinguished by their cell surface receptors
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Figure 1-9 part 6 of 6
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Figure 1-11
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Figure 1-10
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Figure 1-11 part 2 of 2
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Figure 1-12
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Figure 1-13
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Figure 1-14
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Figure 1-15
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Figure 1-16
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Figure 1-17
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Figure 1-17 part 1 of 2
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Figure 1-17 part 2 of 2
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Figure 1-18
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Figure 1-19
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Figure 1-19 part 1 of 2
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Figure 1-19 part 2 of 2
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Figure 1-20
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Figure 1-21
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Figure 1-21 part 1 of 2
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Figure 1-21 part 2 of 2
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Figure 1-22
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Figure 1-23
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Figure 1-24
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Figure 1-24 part 1 of 2
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Figure 1-24 part 2 of 2
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Figure 1-25
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Figure 1-26
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Figure 1-26 part 1 of 2
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Figure 1-26 part 2 of 2
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Figure 1-27
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Figure 1-27 part 1 of 4
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Figure 1-27 part 2 of 4
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Figure 1-27 part 3 of 4
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Figure 1-27 part 4 of 4
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Figure 1-28
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Figure 1-28 part 1 of 3
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Figure 1-28 part 2 of 3
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Figure 1-28 part 3 of 3
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Figure 1-29
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Figure 1-29 part 1 of 2
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Figure 1-29 part 2 of 2
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Figure 1-30
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Figure 1-31
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Figure 1-31 part 1 of 3
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Figure 1-31 part 2 of 3
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Figure 1-31 part 3 of 3
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Figure 1-32
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Figure 1-34
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