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Host Defenses Microbiology 2314 A Healthy Host Has a Variety of Defenses to Prevent Infection Definitions • Resistance - Ability to ward off disease. • Susceptibility - Lack of resistance. Two Types of Resistance Nonspecific Resistance / Defense Against All Invaders • First Line of Defense 1. Skin 2. Mucus Membranes • Second Line of Defense 1. Phagocytes 2. Inflammation 3. Fever Specific Resistance / Defense Against Specific Microorganisms • Antibodies • Lymphocytes (B and T Cells) Skin Structure and Composition (Waterproof Keratin) Provide Resistance to Infection. It is not a great place for bacteria to live… Dries Sheds Secretes Epidermis of the Skin • Epidermis consists of four layers. • Top layer is dead • 15-40 Rows of Dying Cells • Keratin a waterproof protein • pH of 3-5 Symbiotic bacteria living on the skin decompose dead skin cells. The process results in a strong odor as the number of bacteria increase. Fungus Can Penetrate Keratin to Cause Infection When Excessive Moisture is Present Best Areas for Organisms to Occupy are Scalp Ears Underarms Genital Regions Why? Lachrymal Apparatus Protects the eyes from irritating substances and microorganisms. The conjunctiva has only a small number of bacteria present due to continuous blinking and lachrymal secretions which contain bactericidal substances. The lacrimal glands underneath the skin of the upper eyelids make a fluid that is mostly salt and water. This salty water gets to the eye through small openings inside the upper eyelids. When the eyelid blinks, the watery liquid is spread across the eye. There are other glands on edges of the eyelids that make oils. The most important of these glands are called the meibomian glands. The oils from these glands actually float on top of the watery fluid in the tears. This keeps the water from evaporating too quickly. Some of the oils stay along the edge of the eyelid, and they help keep the tears from "leaking" over the eyelashes. If there is not enough of these oils, tears will keep overflowing from the eyes. Oddly enough, a problem with the meibomian glands can lead to overflowing tears and dry eye syndrome at the same time Salivary Glands Produce Saliva Saliva Washes Microorganisms from Teeth and Gums Saliva isn’t always enough. S. mutans Secretes Sticky Polysaccharide Plaque Tooth decay (dental caries) was not a major problem before the fateful year of 1886. Do you remember why 1886? That was the year that Coca Cola was first invented and marketed. European Teeth Teeth in skulls from Europeans prior to the 1500’s showed remarkably wellreserved teeth. Once sugar was introduced into the European diet, teeth deteriorated quickly and tooth decay became a widespread disease. Defensive Body Secretions • • • • • • • Tears Saliva Mucus Vaginal Secretions Nasal Secretions Sebum Perspiration Mucus traps many microorganisms that enter the respiratory and gastrointestinal tracts. Snotty noses are a result of the body trying to rid the system of the trapped microorganisms. The nostrils are heavy with bacteria but the sinuses and lungs are usually sterile. The flow of urine moves microorganisms out of the urinary tract. The kidney and bladder are usually sterile. What is Sebum? Sebum is an oily/fatty substance secreted from the sebaceous glands (unsaturated fatty acids) that inhibits the growth of pathogenic bacteria. Constituent % by weight Glycerides and free fatty acids 57.5 Wax esters 26.0 Squalene 12.0 Cholesteryl esters 3.0 Cholesterol 1.5 Unfortunately, Some Bacteria Have Adapted and Now Metabolize Sebum Perspiration • Washes Microorganisms Off Skin • Maintains Body Temperature • Eliminates Cellular Wastes • Contains Lysozyme • Lysozyme is Most Effective Against Gram Positive Bacteria Increased Perspiration Does Increase the Growth of Some Bacteria. Lysozyme • Found In 1. Tears 2. Salava 3. Nasal Secretions 4. Perspiration The Acidity of Gastric Juice Prevents Most Microbial Growth in the Stomach • Mucus, HCl, Enzymes • pH 1.2 - 3.0 • No effect on Clostridium botulinum • No effect on Staphylococcus aureus Helicobacter pylori and Ulcers Ulcers • 4 Million Americans Have Ulcers Annually • H. pylori is Found in Almost 50% of the Population • That 50% Could Either Have Gastritis or Ulcers Why is H. pylori able to survive in the acidic environment of the stomach if it isn’t an acidophil? Phagocytosis The Ingestion of Microorganisms or Particulate Matter by a Cell We frequently see this when WBC’s engulf bacteria. Phagocytosis 1. Attraction (Chemotaxis) 2. Attachment (Opsonization / Coating with Protein) 3. Ingestion 4. Digestion (Lysosomal Enzymes and Oxidizing Agents) 5. Expulsion The Mechanism of Phagocytosis Chemotaxis is the process by which phagocytes are attracted to microorganisms. Pus is the accumulation of damaged tissue and dead microbes and white blood cells. Removing Pus From an Infected Liver An accumulation of pus in the front of the eye. In this image, the pus is seen as a pool of whitish fluid between the iris and cornea. Blood is a Fluid with Formed Elements White Blood Cells (Leukocytes) Macrophages are Mature Monocytes that are Phagocytic in Nature Histiocytes are a special type of macrophage fixed in a particular tissue 1. Kupffer Cells / Liver 2. Alveolar macrophages / Lungs WBC - Neutrophils • Increased / Bacterial Infection • Normally 50-70 • Two Types 1. Segmented (Mature) 2. Banded (Less Mature) WBC - Basophils • Allergic Reactions • Leukemias • Normally 0-1 WBC - Eosinophils • • • • Worm Infections Skin Disorders Scarlet Fever Normally 1-5 WBC - Lymphocytes • • • • • Viral Infections German Measles Whooping Cough Syphilis Normally 20-30 WBC - Monocytes • Recovery from Infections • Fungal, Rickettsial, Protozoal, Infections • Normally 2-6 Differential WBC Count (100 Cells) • • • • • Neutrophils Lymphocytes Monocytes Eosinophils Basophils 50-70 20-30 2-6 1-5 0-1 Wright's stain is a technique that is used to make the differences between cells visible under light microscopy. It is used in the examination of peripheral blood smears and bone marrow aspirates. Avoid areas in which the blood cells are clumped or unevenly dispersed. Also avoid areas where the blood cells are jumbled together and touching one another Concentrate your examination in areas where the cells are individually separated from one another and fairly uniformly dispersed (Segmented) Neutrophils Banded Segmented Lymphocyte Monocyte Eosinophil Basophil Mononucleosis Leukemia Sickle Cell Anemia Can We Diagnose From a Blood Smear? Slits / Alcoholic Liver Disease Target Cells / Decreased Iron Thorn Cells / Severe Burns Stippling / Heavy Metal Poisoning Teardrops / Bone Marrow Malfunction WBC Hypersegmentation / Chronic Infection or Liver Disease WBC Ringed Nucleus / Acute Myeloid Leukemia Holes in Cytoplasm of Granulocytes / Toxic Effect of Ethanol • Acanthocytes are red blood cells with irregularly spaced projections. These projections vary in width but usually contain a rounded end. They may be found in abetalipoproteine mia and certain liver disorders. • Auer rods are elongated, bluish-red rods composed of fused lysosomal granules, seen in the cytoplasm of myeloblasts, promyelocytes and monoblasts and in patients with acute myelogenous leukemia. • Bacteria in the smear. This image was taken from a patient with Streptococcus pnemoniae infection. Sickle Cell Anemia Döhle Bodies – Small pale blue cytoplasmic inclusions / Tuberculosis • Hairy cells are characterized by their fine, irregular pseudopods and immature nuclear features. They are seen only in hairy cell leukemia. • Howell-Jolly bodies are spherical blue-black inclusions of red blood cells seen on Wright-stained smears. They are nuclear fragments of condensed DNA, 1 to 2m in diameter, normally removed by the spleen. They are seen in severe hemolytic anemias, in patients with dysfunctional spleens or after splenectomy. • Nucleated red blood cells, (nrbcs or normoblasts), represent the stages of a red blood cell before it matures. Cells of this stage are usually seen in newborn infants, and in patients with iron deficiency anemia. Case Study 1 • This 16 year old male came to the emergency room complaining of severe abdominal pain in the right lower quandrant. He had a fever of 101 F. On physical examination, he had a rigid, board-like abdomen and rebound tenderness in the right lower quandrant. There were no other abnormalities. What is the predominant white blood cell present? What does this indicate? Case Study 2 • This 15 year old female was sent home from summer camp because of weakness, lassitude, and sore throat. As her family physician, you found that on physical examination she had an inflamed pharynx, enlarged tonsils, several enlarged and slightly tender lymph nodes in the neck, a palpable spleen, and a tender palpable liver edge. What is the predominant white blood cell type? What is your diagnosis in this case? Case Study 3 • This 65 year old male was in good health except for mild hypertension. At his last checkup, a CBC showed a markedly elevated white blood cell count and physical examination revealed several slightly enlarged lymph nodes in the neck and the axillae, and the spleen was palpable. What is the predominant white blood cell type present? What is the differential diagnosis? Case Study 4 This 52 year old male had gradually increasing fatigue together with discomfort in the left upper quandrant. Physical examination revealed an easily palpable spleen and liver edge. A few slightly enlarged lymph nodes were palpable in the neck. Inflammation is a bodily response to cell damage. Inflammation 1. 2. 3. 4. 5. Redness Pain Heat (Local Fever) Swelling Possible Loss of Function • Vasodilation Increase in blood vessel diameter to increase blood flow 1. Histamine / Body Cells 2. Kinins / Blood Plasma 3. Prostaglandin / Damaged Cells • Margination Adherence of phagocytes to vessel walls. • Emigration Phagocytes leaving blood vessels and entering tissues. • Pus Accumulation of damaged tissue, dead microbes, and white blood cells (phagocytes). Tissue Repair 1. Stroma (Supporting Tissue) 2. Parenchyma (Functioning Tissue) Fever • Abnormally High Body Temperature • Can Be Induced by Bacterial Endotoxins • Chills Increased Temperature • Crisis Decreasing Temperature • Temperature is Controlled by the Hypothalamus How Do We Treat a Fever? • Do not force food. If diarrhea is present, limit the intake of fruits and juice. • Sponging the body with a wet compress, especially keeping it on the forehead, temples and the feet is a very effective method of bringing down the temperature. Use lukewarm water; cool water may cause shivering, which actually raises body temperature. Don't use rubbing alcohol, since it can be toxic. Sponging can be repeated as often as required. • Overheating due to overdressing can aggravate the fever so dress lightly, and make sure bedclothes too are light. • Temperatures lower than 102 degrees F (38.9 degrees C) usually do not require medication. • Give acetaminophen or ibuprofen based on the package recommendations for age or weight. If you don't know the recommended dose call your doctor. Aspirin is not recommended for children under age 12. The Complement System The complement system consists of a group of serum proteins that activate one another to destroy invading microorganisms. The complement system helps clear pathogens from an organism. It is derived from many small plasma proteins that form the biochemical cascade of the immune system. Activation of this system leads to cytolysis, chemotaxis, opsonization, immune clearance, and inflammation, as well as the marking of pathogens for phagocytosis. The complement system consists of more than 35 soluble and cell-bound proteins, 12 of which are directly involved in the complement pathways Interferons • Antiviral Proteins Produced in Response to Viral Infection • Alpha • Beta • Gamma