Health and Disease Exam Notes PDF

Health and Disease Colonization, infection, and disease Colonization ○ Microbes living in or on human body Bacteria, fungi, protozoa, viruses ○ Resident microbiota (normal flora) → don’t cause disease Fend off other pathogens...

Health and Disease Colonization, infection, and disease Colonization ○ Microbes living in or on human body Bacteria, fungi, protozoa, viruses ○ Resident microbiota (normal flora) → don’t cause disease Fend off other pathogens Ex: Vitamin K ○ Transient microbiota → come and go Infection ○ Pathogenic microbes penetrate host defenses, enter tissues, and multiply Disease ○ Deviation from normal health ○ Disruption of body Disease Factors that cause disease ○ Infections ○ Genetics and aging ○ Environmental agents / chemicals ○ Malfunctions of systems or organs Infectious disease ○ Disruption of tissues or organs caused by microbes or their products Pathogen ○ Microbe capable of causing disease Pathology ○ Study of disease Etiology ○ Cause of disease Pathogenesis ○ Development of disease Normal microbiota Some microbes may cross placenta Microbes are picked up when baby passes through birth canal Gut is colonized by ingestion of microorganisms Skin, eyes, respiratory system, mouth, intestines, urogenital system (urethra, vagina) ○ Microbes are in tissues previously thought to be sterile Lungs, bladder, breast milk, placenta Human microbiome project Sequencing biota of humans Human cells contain 21,000 protein encoding genes ○ Microbes that inhabit humans contain 8 million All healthy people harbor potentially dangerous pathogens, but in low numbers Can study changes in microbiome due to disease Benefits of normal microbiota Influence development of organs Aid digestion Make products for use by humans ○ Ex: Vitamin K → gut bacteria Prevent overgrowth of harmful microorganisms ○ Microbial antagonism Microbes in a steady, established relationship are unlikely to be displaced by incoming microbes Outcompete pathogens that try to come in and take over Pathogens True pathogens ○ Capable of causing disease in healthy persons w/ normal immune systems Opportunistic pathogens ○ Cause disease when Host’s defenses are compromised When they become established in a part of the body that is not natural to them Virulence Virulence ○ Degree of pathogenicity Indicated by microbe’s ability to establish itself in the host and cause damage ○ Comparing one microbe to another to determine intensity ○ May be enhanced by rapid passage through susceptible hosts ○ Can be weakened by growth in lab → attenuation Ex: vaccines Virulence factor ○ Any characteristic or structure of microbe that contributes to toxin production or induction of an injurious host response Microbes w/ smaller infectious does have greater virulence Infectious dose (ID) and lethal dose (LD) ID50 → number of microorganisms required to produce demonstrable in 50% of test host population LD50 → lethal dose for 50% of inoculated hosts within a given period ○ How many it takes to kill you ○ Potency of toxin Which organism is more virulent? (lower the number = causes diseases more easily) ○ Organism A LD50 = 2 ○ Organism B LD50 = 20,000 Causing disease 1. Entrance 2. Attachment / adhesion 3. Establishment → evading host defenses 4. Causing disease → pathogenesis 5. Exiting Step 1: Entrance Usually through skin and mucous membranes ○ Parenteral route Microbes deposited directly beneath skin Ex: punctures, injections, bites, cuts, wounds, surgery ○ Ingestion Adapted to survive digestive enzymes and abrupt pH changes ○ Inhalation (airborne) Extent to which an agent is carried into respiratory tree is based on its size Small cells and particles are inhaled more deeply than larger ones ○ Sexually transmitted Urogenital tract Portals of entry Skin, ears, eyes, nose, mouth, mammary glands, urethra, vagina, anus Few microbes can penetrate unbroken skin Entry ≠ disease One microbe gained entrance to body → do not necessarily cause disease Host defenses, normal flora, and the ID may not allow organism to become established or cause disease ○ Ex: In order to cause infection in normal large intestine, Salmonella needs 1,000 bacterial cells present ID50 = 1,000; for Shigella, ID50 = 10 Step 2: Attaching to host (becoming established) Adhesion → microbes attach to host tissues ○ Specificity → binding b/t specific molecules on both host and pathogen Particular pathogen is limited to limited types of cells and organisms Can only reside to certain parts in body ○ Once attached → pathogen can invade body compartments Quorum sensing  ○ Chemical communication b/t nearby bacteria ○ Critical to establishment of infection Microbes attach to host cells Bacteria, fungi and protozoa most often use surface molecules ○ Adhesions or ligands Specific proteins, glycoproteins or lipoproteins Located on pili, fimbriae, flagella or glycocalyx (capsule) Viruses use spikes Step 3: Surviving host defenses (becoming established) Phagocytes ○ White blood cells that engulf and destroy pathogens using enzymes and antimicrobial chemicals Antiphagocytic factors ○ Virulence factors used by pathogens to avoid phagocytes ○ Capsules → resist phagocytosis Not being able to grab onto ○ Leukocidins → chemicals that kill WBCs ○ Some can survive inside phagocytes Use WBC as incubator Step 4: Causing disease Microbes secrete enzymes and toxins Host defenses damage healthy tissue Microbes induce epigenic changes in host cells ○ Turn genes on / off Direct damage via enzymes Exoenzymes ○ Secreted by pathogenic bacteria, fungi, protozoa, and worms ○ Break down and inflict damage on tissues ○ Dissolve host’s defense barriers and promote the spread of microbes into deeper tissues ○ Ex: Mucinase → breaks down mucus to maneuver around wherever Keratinase → breaks down keratin of skin and go deeper in body Refer to microbial metabolism lecture Toxins: Potent sources of cellular damage Toxin ○ Specific chemical product of microbes, plants, and some animals that is poisonous to other organisms Exotoxin → secreted by living bacteria ○ Many types Ex: hemolysins (protein) → break down red blood cells Endotoxin → not actively secreted  ○ Shed from outer membrane when organism dies ○ Only found in gram-negative bacteria Ex: lipopolysaccharide (LPS) → stays in membrane until dying Exotoxins Water soluble substances secreted into host tissues Soluble in body fluids ○ Quickly spread via bloodstream ○ Can be carried through circulatory system Destroy specific parts of host cells ○ Ex: membrane, proteins, interfere w/ protein synthesis Among most lethal substances Body produces antitoxins (antibodies) against toxins Origins and effects of circulating exotoxins and endotoxins Naming exotoxins Type of host cell attacked ○ Neurotoxins → act on nervous tissue ○ Hepatotoxins → liver cells ○ Enterotoxins → act on enteric tissue (gut) Type of disease caused ○ Diphtheria toxin, tetanus toxin Type of bacteria ○ Botulinum toxin → Clostridium botulinum ○ Vibrio enterotoxin → Vibrio cholerae Endotoxin production Part of bacterial cell wall ○ Ex: LPS → gram-negative cell walls Released into tissues when organisms die Weak toxins compared to exotoxins Cause phagocytic WBCs to produce cytokines Can activate blood clotting Can lead to necrosis (death) of tissues Pyrogenic (fever causing) Do not have specific method of action Produce same effect no matter what the organism Exotoxins vs endotoxins Exotoxins → mostly gram-positive Endotoxins → only gram-negative Pathogenesis Step 5: Vacating the host - Portals of exit Portal of exit ○ Avenue for pathogens to exit host ○ Secretion ○ Excretion ○ Discharge ○ Sloughed tissue (shedding) Respiratory and salivary portals Escape media for pathogens that infect upper and lower respiratory tract ○ Mucus ○ Sputum ○ Nasal drainage ○ Other moist secretions Skin scales Outer layer of skin and scalp is constantly being shed into environment Household dust is composed of skin cells Ex: ○ Dermatophytes (fungi) → athlete’s foot ○ Viruses → warts, herpes, smallpox ○ Bacteria → syphilis, impetigo Fecal exit Some intestinal pathogens cause irritation in the intestinal mucosa that increases motility of bowel Resulting diarrhea provides rapid exit for pathogen Helminth worms release eggs and cysts through feces Feces containing pathogens are public health problem when allowed to contaminate drinking water or when used to fertilize crops Urogenital tract Agents involved in STDs leave host in vaginal discharge or semen Source of neonatal infections that infect infant as it passes through birth canal ○ Herpes simplex ○ Chlamydia (bacterial) ○ Candida albicans (yeast infection) Pathogens that affect kidney are discharged in urine Removal of blood or bleeding Blood has portal of exit when removed or released through vascular puncture Blood-feeding insects are common transmitters of pathogens ○ Ticks ○ Fleas ○ Mosquitos Infections and Epidemiology Localized infection Microbe enters body and remains confined to specific tissue ○ Boils ○ Fungal skin infections ○ Warts Systemic infection When infection spreads to several sites and tissue fluids, usually in bloodstream ○ Viral → measles, rubella, chickenpox, AIDS ○ Bacterial → anthrax, typhoid fever, syphilis ○ Fungal → valley fever, cryptococcosis Infectious agents can also travel by means of nerves (rabies) or cerebrospinal fluid (meningitis) Focal infection Can be local in one, but spread in another Exists when infectious agent breaks loose from local infection and is carried to other tissues Examples: ○ Tuberculosis ○ Streptococcal pharyngitis (strep throat → scarlet fever) ○ Toxemia (infection remains localized → toxins carried through blood to target tissue) Mixed infection Several agents establish themselves simultaneously at infection site Polymicrobial diseases ○ Wound infections, dental caries, human bite infections Primary and secondary infections Not at the same time Primary infection ○ Initial infection Secondary infection ○ Occurs when primary infection is complicated by another infection caused by different microbe Acute vs. chronic infections Acute infections ○ Come on rapidly ○ Often have short-lived effects ○ Ex: flu Chronic infections ○ Progress and persist over a long period of time ○ Ex: Valley fever (fungal) Signs and symptoms: Warning signals of disease Sign ○ Objective changes that can be observed and measured by someone other than patient ○ More precise than symptoms ○ Ex: tachycardia, heart murmur, fever Symptom ○ Subjective evidence of disease as sensed by patient ○ Only patient can describe ○ Ex: stomachache, headache Syndrome ○ Disease identified or defined by a certain complex of signs and symptoms Common signs and symptoms of infectious diseases Signs ○ Fever ○ Septicemia (bacteria multiplying in blood) ○ Microbes in tissue fluids ○ Chest sounds ○ Skin eruptions ○ Leukocytosis (high WBC count) / leukopenia (low WBCs) ○ Swollen lymph nodes ○ Abscesses ○ Tachycardia (increased heart rate) ○ Antibodies in serum Symptoms ○ Chills ○ Pain, ache, soreness, irritation ○ Tiredness, brain fog Malaise  Fatigue ○ Chest tightness ○ Itching ○ Headache ○ Nausea Infections that go unnoticed Asymptomatic, subclinical, or inapparent infections ○ Carriers Host is infected but does not manifest disease ○ Patient experiences no symptoms or disease and does not seek medical attention ○ Most infections are intended by some sort of sign Long-term infections & long-term effects Latency ○ Dormant state of infectious agent ○ During this state, microbe can periodically become active and produce recurrent disease ○ Agents of syphilis, typhoid fever, tuberculosis, and malaria also enter into latent stages Sequelae ○ Long-term or permanent damage to organs and tissues Meningitis → deafness Strep throat → rheumatic heart disease Lyme disease → arthritis Polio → paralysis Course of an infection Incubation period ○ Time from initial contact w/ infectious agent to appearance of first symptoms Prodromal period ○ When the earliest notable symptoms of infection appear Acute period ○ Infectious agent multiplies at high levels, exhibits its greatest virulence, and becomes well established in its target tissue Convalescent stage ○ Patient responds to infection and symptoms decline Stages in the course of infection and disease Some diseases have 5th phase ○ Continuation period Patient experiences sequelae Reservoirs: Where pathogens persist Reservoir ○ Primary habitat in natural world from which a pathogen originates ○ Human or animal carrier; soil, water, or plants ○ Ex: giardia → body of water Source ○ Distinct from reservoir ○ Individual or object from which an infection is acquired ○ Ex: giardia → Lake Pleasant Living reservoirs Animals (other than humans and arthropods) ○ Can be directly transmitted to humans ○ Can be transmitted to humans via vectors ○ Can be transmitted through vehicles (ex: water) Actively ill humans ○ Indirect transmission Person w/ a cold contaminates a pen, which is then picked up by a healthy person  ○ Direct transmission Sick person sneezing on healthy person Human carriers ○ Person who is fully recovered from hepatitis but is still shedding hepatitis A virus in feces uses suboptimal hand-washing technique and then contaminates food which a healthy person ingests ○ Incubating carrier of HIV, who doesn’t know she is infected, transmits virus through sexual contact Arthropods ○ Fleas, mosquitoes, flies, ticks, etc. ○ Host (and reservoir) of pathogen can also be the most of transmission Carrier states Asymptomatic carriers ○ Infected but show no symptoms ○ Ex: gonorrhea, genital herpes w/ no lesions Incubating carriers ○ Infected but show no symptoms ○ Ex: infectious mononucleosis Convalescent carriers ○ Recuperating patients w/o symptoms ○ Continue to shed viable microbes and infect others (Hepatitis A) Chronic carriers ○ Individuals who shelter infectious agent for long period after recovery due to latency of agent ○ Ex: tuberculosis, typhoid fever Passive carriers ○ Medical / dental personnel who handle patient materials that are contaminated w/ patient secretions / blood ○ Ex: risk picking up pathogens mechanically and accidentally transferring them to other patients Vectors Epidemiology ○ Live animal that transmits infectious agent from one host to another Majority of vectors are arthropods Biological vector ○ Actively participates in pathogen’s life cycle, serving as site in which pathogen can multiply or complete its life cycle  ○ Communicates infectious agent to human host by biting, aerosol formation, or touch ○ Ex: mosquito transmitting malaria, chicken, bats Mechanical vectors ○ Not necessary to life cycle of infectious agent ○ Merely transport pathogen w/o being infected ○ Ex: cockroaches, flies Zoonosis Infection indigenous to animals but also transmissible to humans Human is dead-end host and does not contribute to natural persistence of microbe Spread of disease is promoted by close associations of humans w/ animals People in animal-oriented or outdoor professions are at greatest risk Ex: rabies, hantavirus, West Nile virus, anthrax, plague, ringworm, toxoplasmosis, tapeworm Nonliving reservoirs Microbes have adapted to nearly every habitat in biosphere Soil, water, air, built environment Types ○ Most are saprobic (decomposers) and cause little harm to humans ○ Some are opportunists ○ Few are regular pathogens Ex: TB bacterium can be directly transmitted to humans when they come in contact with contaminated soil, water, or air Acquisition and transmission of infectious agents Communicable disease ○ Occurs when infected host can transmit infectious agent to another host and establish infection in that host ○ Ex: giardia, malaria, lyme disease Contagious ○ Agent is highly communicable, especially through direct contact ○ Ex: COVID-19, flu, common cold Noncommunicable ○ Does not arise through transmission of infectious agent from host to host ○ Ex: Valley fever, tetanus Horizontal vs vertical transmission Horizontal transmission ○ Disease is spread through population from one infected individual to another ○ Direct (contact) transmission Kissing, sex ○ Indirect transmission Fomites, vehicles, parenteral (via injection into deeper tissues) ○ Vector transmission Vertical transmission ○ Transmission from parent to offspring via ovum, sperm, placenta, or milk ○ Congenital disease Born w/ it Indirect transmission Vehicle ○ Natural, non-living material ○ Air, water, soil, food Fomite ○ Inanimate object that harbors and transmits pathogens ○ Not continuous source of infection Oral-fecal route ○ Fecal carrier w/ inadequate personal hygiene contaminates food during handling, and an unsuspecting person ingests it Droplet nuclei and aerosols Droplet nuclei ○ Dried microscopic residues created when microscopic pellets of mucus and saliva are ejected from mouth and nose Aerosols ○ Suspensions of fine dust or moisture particles in air that contain live pathogens Healthcare-associated infections (HAI) Nosocomial infections ○ Infectious diseases that are acquired or develop during hospital stay or stay in another health-care facility Rates of HAIs can range from 0.1 - 20% of all admitted patients Iatrogenic infections ○ Due to medical treatment ○ Antibiotics that are used to treat bacterial infection, may result in yeast infection Control of nosocomial infections Reduce number of pathogens Aseptic techniques ○ Medical asepsis Practices that lower microbial load in patients, caregivers, and hospital environment ○ Surgical asepsis Ensuring all surgical procedures are conducted under sterile conditions Handle contaminated materials carefully Frequent and thorough hand washing ○ Single most important means of prevention Isolation rooms and wards Disinfect or sterilize materials and equipment Using Koch’s Postulates to determine etiology Essential aim of study of infection and disease → determining etiologic agent (causative agent) Series of proofs that established classic criteria for etiologic studies 1. Same pathogen must be present in every case of disease 2. Pathogen must be isolated from diseased host and grown in pure culture 3. Pathogen from pure culture must cause disease when it is inoculated into healthy, susceptible laboratory animal 4. Pathogen must be isolated from inoculated animal and must be shown to be original organism Exceptions to Koch’s Postulates Unique culture requirements ○ Some microbes cannot be cultured on artificial media ○ Treponema pallidum, Mycobacterium leprae ○ Rickettsia and many viruses (multiply only within cells) One pathogen can cause different disease states ○ Mycobacterium tuberculosis → lungs, skin, bones, etc. ○ Streptococcus pyogenes → sore throat, scarlet fever, skin infections Similar symptoms caused by several different pathogen ○ Pneumonia → fluid in lungs ○ Nephritis → inflammation of kidneys Idiopathic disease ○ Cause unknown Epidemiology: Study of disease in populations Epidemiology ○ Effects of diseases on community ○ Involves study of frequency and distribution of disease and distribution of disease and other health-related factors in defined populations Reportable diseases ○ Notifiable diseases ○ By law, some diseases must be reported to authorities ○ Other diseases are reported on voluntary basis Centers for Diseases Control and Prevention (CDC) Responsible for keeping track of infectious diseases nationwide Part of the U.S. Public Health Service Morbidity and Mortality Report ○ Weekly notice of diseases published by CDC CDC shares stats on disease w/ World Health Organization (WHO) for worldwide tabulation and control Epidemiological Statistics Prevalence of disease ○ Total number of existing cases w/ respect to entire population Incidence of disease ○ Measures number of new cases over certain time period ○ Aka case or morbidity rate Mortality rate ○ Measures number of deaths in population due to certain disease Epidemics Point-source epidemic ○ Infectious agents came from single source Common-source epidemic ○ Common exposure to single source of infection that can occur over period of time Propagated epidemic ○ Infectious agent that is communicable from person to person and is sustained over time in population Pandemic ○ Spread of epidemic across continents Index case ○ First patient found in epidemiological investigation  Endemic ○ Infectious disease that exhibits relatively steady frequency over long time period in particular geographic locale ○ Ex: Valley fever in South America Sporadic disease ○ Occasional cases are reported at irregular intervals in random locales Patterns of infectious disease occurrence Global issues in epidemiology Emerging Infectious Diseases (EIDs) ○ Newly identified microbes ○ COVID-19, HIV, SARS, novel strains of influenza Re-emerging diseases ○ Dengue fever, tuberculosis, yellow fever Contributing factors ○ Widespread antibiotic use ○ Climate change leads to distribution changes in microbe habitats ○ Modern transportation ○ Natural disaster, construction, expanding settlement ○ Animal control → loss of “balance” ○ Public health measure failures The Immune System Major components of the immune system Circulatory and lymphatic systems Lymphoid organs Primary lymphatic organs ○ Red bone marrow Makes all kinds of WBCs, including T-cells  ○ Thymus House of T-cells Lymph nodes Spleen ○ Can live without, highly vascular, best to have removed at older age if needed SALT, MALT, GALT, BALT ○ Skin, mucosa, gut, breast- associated lymphatic tissue Loose connective tissue framework that houses aggregations of lymphocytes Leukocytes (white blood cells - WBCs) First line of defense: Barriers Skin ○ Hairs, sweat glands Mucous membranes Blinking and tears Flow of saliva Secretions have lysozyme Urination Vaginal secretions Acronyms and terminology Markers → antigens ○ Proteins, glycoproteins, lipoproteins ○ Found on all cells and microbes ○ Can be recognized by immune system ○ “Self” and “non-self” antigens PAMPs → pathogen-associated molecular patterns ○ Antigens that many microbes have in common PPRs → pattern recognition receptors ○ Host cell receptors that recognize PAMPs MPS → mononuclear phagocyte system ○ Phagocytes throughout connective tissues that surround organs Second line of defense: Phagocytosis and inflammation Activities of phagocytes Survey tissue compartments and discover ○ Microbes ○ Debris ○ Injured / dead cells Ingest and eliminate these materials Recognize antigens Recognition of pathogens by innate immune system Mononuclear phagocyte system Chemotaxis and ingestion Pathogen-associated molecular patterns (PAMPs) ○ Recognized by phagocytes and other defensive cells ○ Serve as signal molecules on surfaces of microbes ○ Not present in mammals Examples of PAMPs: (specifically used for foreign antigens of microbes) ○ Peptidoglycan ○ Lipopolysaccharide (gram-negative bacteria, endotoxin) ○ Double-stranded RNA found in viruses Pattern recognition receptors (PRRs) Found on surfaces of phagocytes, dendritic cells, endothelial cells, and lymphocytes Recognize and bind PAMPs Found on surface at all times, regardless of whether they have encountered a PAMP Toll-like receptors and collectins Toll-like receptors (TLRs) ○ Type of PRR ○ Recognize PAMPs ○ Orchestrates a defense response to pathogen  Collectins ○ Exogenous proteins (secreted by cells) Not part of cell membrane ○ Roam blood and tissues Destruction and elimination systems Oxygen-dependent system ○ Myeloperoxidase forms halogen ions (OCl-) ○ Other oxygen products → superoxide anion, singlet oxygen, and hydroxyl free radical Release of lactic acid, lysozyme, and nitric oxide Cationic proteins that injure bacterial cell membranes Proteolytic and hydrolytic enzymes Major events in inflammation Signs & benefits of inflammation Signs ○ Redness → erythema ○ Swelling → edema ○ Pain ○ Heat → temperature Benefits ○ Influx of fluid dilutes toxic substances ○ Fibrin clot can trap microbes and prevent further spread  ○ Neutrophils actively phagocytose and destroy bacteria, dead tissue, and particulate matter Chronic inflammation Symptoms usually more subtle ○ Range from mild to severe and last for several months or years Inflammatory response can eventually damage healthy tissues ○ DNA damage, tissue death, and internal scarring Chronic inflammation increases risk of serious diseases ○ Cancer, heart disease, rheumatoid arthritis, type 2 diabetes, obesity, asthma, neurodegenerative diseases (Alzheimer’s) Variety of foods have anti-inflammatory properties ○ Foods that are high in antioxidants and polyphenols Olive oil, leafy greens, tomatoes, fatty fish, nuts, fruits Third line of defense: Specific immunity Mediated by T and B lymphocytes Principal stages of immunologic development and interaction Stages of lymphocyte development and function I Characteristics of antigens Must be perceived as foreign: ○ Whole microbes or their parts  ○ Cells or substances that arise from other humans, animals, plants, and various molecules ○ Molecules of complex composition are more immunogenic than repetitious polymers composed of single unit Effects of molecular size Substance must be large enough to catch the attention of surveillance cells to initiate an immune response Generally, large antigens are better than small antigens Epitope ○ Portion of antigen molecule recognized and responded to by a lymphocyte ○ An epitope of antigen that is recognized Haptens ○ Too small by themselves to elicit an immune response ○ If linked to a carrier group, the combined molecule develops immunogenicity Hapten-carrier phenomenon Alloantigens Proteins and other molecules of one person that are antigenic to another Cell surface markers that occur in some members of same species but not in others Bases for an individual’s blood group and major histocompatibility profile Responsible for incompatibilities that occur in blood transfusion or organ grafting Superantigens Bacterial toxins Potent stimuli for T cells ○ Activate T cells at a rate 100 times greater than ordinary antigens ○ Can result in overwhelming release of cytokines and cell death  Toxic shock syndrome and certain autoimmune diseases are associated w/ these antigens Role of antigen processing and presentation Antigens must be further acted upon and formally presented to antigen-presenting cells (APCs): ○ Macrophages, B cells, dendritic cells The Lymphatic System Introduction Body harbors ~ 10,000 times as many bacterial cells as human cells ○ Some beneficial ○ Some potentially pathogenic (disease-causing) Immune system → not an organ system, but a cell population that inhabits all organs and defends body from agents of disease ○ Lymphatic system → especially concentrated in the true organ system Network of organs and vein-like vessels Functions of the lymphatic system Fluid recovery → fluid continually filters from blood capillaries into the tissue spaces ○ Blood capillaries reabsorb 85% ○ 15% (2 - 4 L/day) of water and ~½ the plasma proteins enter lymphatic system and then are returned to blood ○ Interference w/ lymphatic drainage can lead to severe edema Immunity → excess filtered fluid picks up foreign cells and chemicals from tissues ○ Passes through lymph nodes where immune cells stand guard against foreign matter Lipid absorption ○ Lacteals in small intestine absorb dietary lipids that are not absorbed by blood capillaries Defenses against pathogens Pathogens → agents capable of producing disease ○ Infectious organisms, toxic chemicals and radiation Three lines of defenses against pathogens ○ First-line: external barriers, skin, mucous membranes ○ Second-line: nonspecific defense mechanisms Leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever Effective against a broad range of pathogens ○ Third-line: the immune system Defeats a pathogen and leaves the body w/ a “memory” of it so it can defeat it faster in the future Nonspecific defenses ○ Broadly effective, no prior exposure ○ External barriers  ○ Inflammation, fever Specific defenses ○ Results from prior exposure ○ Protects against only a particular pathogen ○ Immune system External barriers Skin → dry and nutrient-poor ○ Toughness of keratin ○ Defensins → peptides (from neutrophils) attack microbes ○ Lactic acid (acid mantle) → component of sweat Many microbes cannot survive in acidic environment Mucous membranes ○ Stickiness of mucus ○ Lysozyme → enzyme destroys bacterial cell walls Subepithelial areolar tissue ○ Tissue gel is viscous barrier of hyaluronic acid Hyaluronidase → enzyme used by pathogens to circumvent the hyaluronic acid defense Leukocytes and macrophages Phagocyte → cell (like WBCs) that engulfs and absorbs waste material, microorganisms or other foreign bodies in bloodstream and tissues 5 types of leukocytes ○ Neutrophils ○ Eosinophils ○ Basophils ○ Monocytes ○ Lymphocytes Neutrophils and eosinophils Neutrophils ○ Wander in tissues and phagocytize bacteria ○ Create a killing zone Degranulation → lysozymes discharge into tissue fluid, which triggers a respiratory burst Toxic chemicals are created (O2-, H2O2) Eosinophils ○ Found especially in mucous membranes  ○ Phagocytize antigen-antibody complexes, allergens and inflammatory chemicals ○ Block excess inflammation, limit action of histamine ○ Antiparasitic effects → aggregate and release enzymes onto parasites Other leukocytes Basophils and mast cells ○ Aid mobility and action of WBC’s by the release of Histamine (vasodilator) ↑ blood flow to infected tissue Heparin (anticoagulant) prevents immobilization of phagocytes Leukotrienes activate and attract other leukocytes Lymphocytes ○ Blood contains 80% T-cells, 15% B-cells, 5% NK cells ○ T-cells and B-cells are part of specific immune response ○ Natural killer (NK) cells are non-specific Large lymphocytes that attack and destroy bacteria, transplanted tissue, host cells infected w/ viruses or have turned cancerous Monocytes and macrophages Monocytes → move from blood into connective tissues and transform into macrophages Macrophages → phagocytic cells ○ Wandering macrophages Actively seek pathogens Widely distributed in loose connective tissue ○ Fixed macrophages Only phagocytize pathogens that come to them Microglia → in central nervous system Alveolar macrophages (dust cells) → in lungs Hepatic macrophages → in liver Antimicrobial proteins Proteins that inhibit microbial reproduction and provide short-term, nonspecific resistance to pathogenic bacteria and viruses Two families of antimicrobial proteins ○ Interferons ○ Complement system Antimicrobial proteins – Interferons Interferons → polypeptides secreted by cells invaded by viruses ○ Antiviral effect  Do not benefit cell that secretes them Interferons diffuse to neighboring cells and stimulate them to produce antiviral proteins Activate natural killer (NK) cells and macrophages Destroy infected host cells ○ Anticancer effect Activated NK cells can destroy cancer cells Complement system Group of 30+ proteins that contribute greatly to both nonspecific resistance and specific immunity ○ Synthesized mainly by liver ○ Circulate in blood in inactive form ○ Activated by presence of pathogen Induce 4 methods of pathogen destruction ○ Inflammation ○ Immune clearance ○ Phagocytosis ○ Cytolysis Three routes of complement activation ○ Classical, alternative and lectin pathways Mechanisms of complement action Inflammation ○ C3a stimulates mast cells and basophils to secrete histamine and other inflammatory chemicals ○ Activates and attracts neutrophils and macrophages ○ Speeds pathogen destruction in inflammation Immune clearance ○ C3b binds w/ antigen-antibody complexes to RBCs ○ These RBCs circulate through liver and spleen ○ Macrophages of those organs strip off and destroy Ag-Ab complexes leaving RBCs unharmed ○ Principal means of clearing foreign antigens from bloodstream Phagocytosis ○ Neutrophils and macrophages cannot phagocytize “naked” bacteria, viruses, or other pathogens ○ C3b assists them by opsonization Coats microbes – serves as binding sites for phagocyte attachment  Cytolysis ○ C3b splits other complement proteins ○ Bind to enemy cell and attracts more complement proteins ○ Membrane attack complex (MAC) forms Create hole in target cell Electrolytes leak out, water flows in rapidly → cell ruptures Membrane Attack Complex Complement proteins form ring in plasma membrane of target cell causing cytolysis Immune Surveillance Phenomenon in which natural killer (NK) cells continually patrol body on lookout for pathogens and diseased host cells Fever Defense mechanism that can do more good than harm ○ Promotes interferon activity ○ Accelerating metabolic rate and tissue repair ○ Inhibiting pathogen reproduction Inflammation Cardinal signs ○ Redness (erythema) caused by hyperemia (↑ blood flow) ○ Swelling (edema) caused by ↑ capillary permeability and filtration ○ Heat caused by hyperemia  ○ Pain (-algia) caused by inflammatory chemicals secreted by damaged cells, pressure on nerves Specific immunity Specificity ○ Immunity directed against particular pathogen Memory ○ When re-exposed to same pathogen, body reacts so quickly that there is no noticeable illness Humoral immunity ○ Antibody mediated Cellular immunity ○ Cell-mediated Types of immunityFp Cell-mediated immunity → T-cells ○ Lymphocytes directly attack and destroy foreign cells or diseased host cells ○ Means of ridding body of pathogens that reside inside human cells, inaccessible to antibodies ○ Kills cells that harbor them Humoral (antibody-mediated) immunity → B-cells ○ Mediated by antibodies that don’t directly destroy pathogen ○ Indirect attack where antibodies neutralize pathogen ○ Can only work against extracellular stage of infectious microorganisms Passive and active immunity Natural active → produces memory cells ○ Production of one’s own antibodies or T cells as a result of infection or natural exposure to antigen Artificial active → produces memory cells ○ Production of one’s own antibodies or T cells as a result of vaccination Natural passive → through placenta, milk ○ Fetus or infant acquires antibodies from mother ○ Temporary Artificial passive → injection of immune serum from another individual / organism ○ Snakebite, rabies, tetanus ○ Temporary Types of T cells Cytotoxic T (TC) cells → killer T cells (T8, CD8, or CD8+) ○ “Effectors” of cellular immunity Carry out attack on enemy cells Helper T (TH) cells → T4, CD4, CD4+ ○ Help promote TC cell and B cell action and nonspecific resistance Regulatory T (TR) cells → T-regs ○ Inhibit multiplication and cytokine secretion by other T cells Limit immune response Memory T (TM) cells ○ Responsible for memory in cellular immunity Two classes of MHC MHC-I proteins → only TC cells respond ○ Occur on every nucleated cell in body ○ Normal self-antigens that do not elicit T cell response ○ Foreign proteins or abnormal cancer antigens do elicit a T cell response ○ Infected or malignant cells are then destroyed before they can do further harm to body MHC-II proteins (human leukocyte antigens - HLAs) → only TH cells respond ○ Occur only on APCs ○ Display only foreign antigens Classes of antibodies IgG: monomer, constitutes 80 % of circulating antibodies ○ Crosses placenta, secondary immunity, complement fixation IgM: pentamer in plasma and lymph ○ Primary immunity, agglutination, complement fixation IgE: monomer, transmembrane protein on basophils and mast cells ○ Stimulates release of histamine - mediates inflammation and allergy Attracts eosinophils to parasitic infections Produces immediate hypersensitivity reactions IgA: monomer in plasma, dimer in mucus, saliva, tears, milk, intestinal secretions ○ Prevents pathogen adherence to epithelia ○ Provides passive immunity to newborns IgD: monomer, B cell transmembrane antigen receptor ○ Thought to function in B cell activation by antigens Practical Applications of Immunology – Immunization Immunizations 2 artificial methods to make an individual immune to a disease ○ Active immunization Vaccine Patient actively mounts an immune response Can be long lasting ○ Passive immunization Transfer of antibodies formed by an immune individual or animal Temporary History of immunization The Chinese noticed that children who recovered from smallpox did not contract the disease a second time Infected children with material from a smallpox scab to induce immunity ○ Variolation Variolation was eventually stopped due to the risk of death It was observed that protection against smallpox could be induced by inoculation with material from an individual infected with cowpox ○ A similar but much milder disease Since cowpox was also called vaccinia this process was called vaccination The inoculum was termed a vaccine Practice of transferring protective antibodies was developed when it was discovered that vaccines protected through the action of antibodies Principles of vaccine preparation Vaccine considerations: ○ Antigen selection ○ Effectiveness ○ Ease in administration ○ Safety ○ Cost Requirements for an effective vaccine Low level of adverse side effects or toxicity and not cause serious harm Protect against exposure to natural, wild forms of pathogen Stimulate both antibody (B-cell) response and cell-mediated (T-cell) response  Long-term, lasting effects (produce memory) Not require numerous doses or boosters Inexpensive, have a relatively long shelf life, and be easy to administer Vaccination problems Socioeconomic and political problems prevent many developing nations from receiving vaccines Inability to develop effective vaccines for some pathogens Vaccine-associated risks discourage investment in developing new vaccines Routes of administration Traditional routes of vaccine administration: ○ Subcutaneous ○ Intramuscular ○ Intradermal ○ Oral or nasal vaccines Available for only a few diseases Vaccine types 4 general types of vaccines ○ Whole agent Attenuated (live, weakened) Killed (inactivated) ○ Subunit ○ Toxoid ○ DNA NOW A 5TH → mRNA Whole agent: Attenuated vaccines Modified live / active vaccines ○ MMR, chicken pox Uses pathogens that are living/active but have reduced virulence so they don’t cause disease Attenuation → process of reducing virulence (weakening natural form) ○ Viruses Raise them in tissue culture cells for which they aren’t adapted Lose the ability to produce disease ○ Bacteria Culture under unusual conditions  Genetic manipulation Benefits of attenuated vaccines Confer long-lasting protection Usually require fewer doses and boosters than other types of vaccines Are particularly effective at inducing cell-mediated immune response dominated by TH and cytotoxic T cells Contain replicating microbes that can stimulate a strong immune response due to the large number of antigen molecules Can infect those around them, providing herd immunity Problems w/ attenuated vaccines Attenuated microbes may retain enough virulence to cause disease ○ Especially in immunosuppressed individuals Pregnant women should not receive live vaccines due to the risk of the modified pathogen crossing the placenta Modified viruses may occasionally revert to wild type or mutate to a virulent form Whole agent: Inactivated vaccines Deactivated whole microbes Safer than live/active vaccines since ○ Cannot replicate or mutate to a virulent form When microbes are killed must not alter the antigens responsible for stimulating protective immunity Formaldehyde is commonly used to inactivate microbes ○ Cross-links proteins and nucleic acids Recognized as exogenous antigens Stimulates a TH response that promotes antibody-mediated immunity Problems w/ inactivated vaccines Whole agent vaccines may stimulate an inflammatory response due to non-antigenic portions of the microbe Antigenically weak ○ Microbes don’t reproduce and don’t provide many antigenic molecules to stimulate the immune response Subunit vaccines Antigenic fragments of microbes (actual or synthetic)  ○ HPV, pertussis (whooping cough) Recognized as exogenous antigens Stimulates a TH response that promotes antibody-mediated immunity Antigenically weak compared to attenuated vaccines Making inactivated and subunit vaccines more effective Administration in high or multiple doses (boosters) ○ May produce allergic reactions Incorporation of an adjuvant ○ A special binding substance added to some vaccines ○ Any compound that enhances immunogenicity and prolongs antigen retention at the injection site ○ Precipitates the antigen and holds it in the tissues so that it will be released gradually ○ Facilitates contact with APCs and lymphocytes ○ May also stimulate local inflammation Toxoid vaccines Chemically or thermally modified toxins Useful for some bacterial diseases ○ Tetanus, diphtheria Stimulate antibody-mediated immunity Require multiple doses because they possess few antigenic determinants DNA vaccines Microbial DNA is inserted into a plasmid vector and inoculated into a recipient Human cells take up the plasmid and express the microbial DNA in the form of proteins ○ DNA doesn’t have to be incorporated into the human genome in order to be expressed Studies have shown that levels of incorporation are lower than that of spontaneous mutations These foreign proteins will be recognized by the immune system and sensitize both B and T lymphocytes COVID-19 Moderna and Pfitzer → mRNA vaccines that code for SARS-CoV-2 virus spike ○ 95% efficacy ○ Pfitzer vaccine initially had to be stores at -70℃  AstraZeneca and Johnson&Johnson → DNA viruses that use an adenovirus that has been modified to include genetic material from SARS-CoV-2 virus so that it introduces the immune system to the spike protein, which sits on the exterior of the virus ○ 65 - 70% effective overall Vaccine side effects Common side effects: ○ Local reactions and pain at the injection site ○ Allergies ○ Fever ○ Symptoms associated with being sick are actually the immune system response Relatively rare side effects: ○ Panencephalitis - 1 in 220,000 vaccinations from the measles vaccine ○ Back-mutation to a virulent strain: old polio vaccine ○ Neurological effects of unknown cause: pertussis and swine flu vaccinations ○ Anaphylactic shock – a severe allergic reaction ○ Blood clots – may be from cross-reactivity J&J COVID-19 vaccine → 6 women in US b/t ages 18 - 48 6.8 million doses administered, so that is < 1 in 1 million Herd immunity Each microbe requires a certain density of susceptible individuals in a population (herd) to maintain the chain of transmission With a sufficient number of immune individuals, the microbe does not spread Collective immunity through mass immunization confers indirect protection on non immune members Maintenance of herd immunity through immunization prevents epidemics Passive immunity Administration of preformed antibodies to a patient Used when protection against a recent infection or an ongoing disease is needed quickly Serum from human or animal donors that have been infected with the disease or immunized against it Serum used for passive immunizations is called antiserum Limitations of antisera Contain antibodies against many antigens ○ Not just the ones of interest!  Repeated injections of antisera collected from a different species can trigger allergic reactions May be contaminated with viral pathogens Antibodies are degraded quickly Many of these limitations have been overcome through the development of hybridomas