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Strategies of Pathogen Recognition
- Innate - detect molecular patterns common to groups of pathogens
- Different microbes = same receptors
- Adaptive - detect unique determinates of each pathogen
- Different microbes = different antibodies
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Virulence Theory
- Ability of a pathogen to cause disease
- Pathogen carry out replication and transmission > if its kills host before transmitted, it dies out > more hosts = more virulent > over time there's fewer hosts = less virulent
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Prions
- Proteinaceous Infectious Particle
- Made only of protein
- Abnormally-structure forms of a host protein, which convert normal molecules of the protein into the abnormal structure
- Ex. Mad cow disease
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Classes of Pathogens
- Virus - intracellular (HIV)
- Fungus - extraceluluar (Thrush-Candida albicans)
- Bacteria - intra and extra (Listeria)
- Parasite - intra and extra (Helminth worm)
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Tasks of Immune System
- Differentiation of self versus non-self
- Pathogen versus host
- infected versus healthy
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Innate Immunity
- All animals have an an innate immune system
- Basis is receptor recognition of molecular patterns in microbes, but not animals)
- Receptors limited in specificity and recognize classes of pathogens
- Receptors encoded in germline - idential receptors on all cells of a lineage
- Immediate response
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Innate Immunity Response
- Recognize a foreign presence
- Destroy (eat/chemical)
- Alarm
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Flaws of Innate Immunity
- Parasitic agents have a generation time orders of magnitude less than that of their hosts
- Only limited amplification of the response
- No memory
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Adaptive Immunity
- Adds to innate immune response
- HIghly specific response to unique components of the pathogen
- Provides long-lasting protection (immunological memory)
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Adaptive Immunity Response
- Recognize a foreign presence
- Destroy infected cells
- Neutralize/antibodies
- Activate/direct other cells to destry pathogens
- Form memory
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B cells
Antibody factories
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T Cells
Direct elimination of infected cells and direction of innate and lymphocyte responses
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Flaws of Adaptive Immunity
- Slow - requires 3-5 days to become effective
- Can be tricked and evaded by pathogens
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Graph of Innate and Adaptive
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Where is the innate system?
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Where is the adaptive system?
- Lymphoid organs
- Blood
- Tissue
- Bm
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Lymph node-like tissues
- GALT - gut associated lymphoid tissue
- BALT - bronchial
- MALT - mucosal
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Preventing Infection
- Skin is body's first defense
- Mechanical - epithelium, flow of fluid, mucus
- Chemical - sebum, enzymes, lysozyme, acidity
- Microbiological - normal flora
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Mucosal Surfaces
- Fluid layer that contains glycoproteins, proteoglycans, and enzymes
- Respiratory: mucus continuously removed through epithelial cells with cilia and secrete mucus by goblet cells
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Defensins
- Kill bacteria, fungi, and enveloped viruses
- Perturb their membranes
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Inflammation
- Cells and proteins in damaged tissue sense presence of bacteria and cells send out soluble protiens -> cytokines
- Cytokines react with other cells to trigger innate immune -> overall effect is inflammation
- Inflammation is immune system's response to the infection
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Cytokines
- Induce vasodilation -> increase blood flow (skin rred and warm)
- Permeable endothelium
- Leakage of blood plasma into tissue -> edema
- Change adhesive properties of vascular endothelium -> WBCs attach -> move from blood into tissue
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Clonal Selection
- During infection, only those lymphocytes bearing receptors that recognize the infecting pathogen are selected to participate in adaptive response
- These then proliferate and differentiate to produce lartge number of effector cells specific to that pathogen
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Leukocytes
White blood cells
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Hematopoiesis
- Generation of the cellular elements of blood
- WBC, RBC, and platelets
- Occurs in bone marrow - skull, ribs, sternum, vertebral column, pelvis, femurs
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Hematopoietic Stem Cells
- Any blood cell or its precursor cell types
- Divide to make more of its own - self-renewal OR
- Become mature stem cells > erythroid, myeloid, lymphoid
- Erythroid - platelets and erythrocytes
- Myeloid - granulocytes, monocytes, macrophages, dendritic, mast cell
- Lymphoid - NK, B-cells, T cells
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Platelets
- Non-nucleated
- Maintain integrity of blood vessels
- Intiate and participate in blood clotting reactions
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Megakaryocytes
- Nuclie containing multiple sets of chromosomes
- Permanent residents of bone marrow
- Produce platelets
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Granulocytes
- Have prominent cytoplasmic granules containing reactive substances that kill microorganism and enhance inflammation
- Irregular shpaed nuclei - 2 to 5 lobes
- Most abundant - neutrophil
- Also have eosinophil and basophil
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Neutrophil
- Specialized in the capture, engulfment, and killing of microorganisms
- Phagocytic
- Effector cells or innate immunity that rapidly mobilize to enter sites of infection
- Short lived and die at site of infection
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Monocytes
- Leukocytes that circulate in the blood
- Mobile progenitors of macrophages
- Travel in blood to tissues > mature into macrophages > take up residence
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Macrophage
- Phagocytic
- Extensive cytoplasm with many vacuoles
- Scavenger cells of the body
- Long-lived
- First phagocytic cell to sense invading microorganism
- Secrete cytokines
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Dendritic Cells
- Residnt in the body's tissues
- Act as cellular messengers that are sent to call an adaptive immune response
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Mast Cell
- Resident in all connective tissues
- Contribute to inflammation
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Natural Killer Cells (NK cells)
- Large granular lymphocytes
- Effector cells of innate immunity
- Enter infected tissue and prevent spread of infection > killing them and secreting cytokines
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Small Lymphocytes
- Responsible for adaptive immune response
- Circulate in an immature form that is functionally inactive
- Recognition of a pathogen drives a process of lymphocyte selection, growth, and differentiation
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B lymphocytes (B cells)
Cell surface receptors for pathogens are immunoglobulins
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T lymphocytes (T cells)
- T-cell receptors
- Cytoxic T cells and helper T cells
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Cytoxic T cells
Kills cells that are infected with viruses or bacteria
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Helper T cells
Secrete cytokines
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Primary Lymph Tissue
- Thymus - T cells
- Bone Marrow - B cells
- Lymphocytes develop and mature to the stage at which they are able to respond to pathogen
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Seondary Lymphoid Tissues
- Spleen, lymph nodes, tonsils, appendix
- Sites where mature lymphocytes become stimulated to respond to invading pathogens
- Also includes associated lymphoid - GALT, MALT, BALT
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What organ deals with pathogens that make it to the blood?
- Spleen - filter for the blood
- Remove damaged red cells
- Defend body against blod-borne pathogens
- Pathogens and lymphocytes enter and leave the spleen in the blood
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