Med. Micro Lecture 3, 2025 PDF

LECTURE 3 LECTURE 5 JAN., 23, 2025 LECTURE 3:  Overview:  Normal flora of the human body.  Host – microbe infectious process  Host defense system (Immunology)  Innate  PMNs  Soluble factors  Adaptive  T cells  B cells  Hypersensitivity r...

LECTURE 3 LECTURE 5 JAN., 23, 2025 LECTURE 3:  Overview:  Normal flora of the human body.  Host – microbe infectious process  Host defense system (Immunology)  Innate  PMNs  Soluble factors  Adaptive  T cells  B cells  Hypersensitivity reactions HOST- PARASITE RELATIONSHIP:  The normal flora:  Humans have ~ 1013 cells in the body and 1014 bacteria associated with them - the majority in the large bowel.  Viruses, fungi, and protozoa are also regularly found in healthy individuals, but form only a minor component of the total population of resident organisms.  Organisms occur in those part of the body that are exposed to, or communicate with the external environment:  Skin, nose and mouth, intestinal and urogenital tracts  Internal organs and tissue are normally sterile!!!  Normal flora is acquired rapidly during and shortly after birth and changes continuously throughout life.  Organisms present at any given time reflect the age, nutrition and environment of the individual. HOST- PARASITE RELATIONSHIP:  The normal flora:  Different regions of the skin support different flora.  Moist areas (axillae, between toes, etc.), support Staphylococcus epidermidis;  anaerobic bacteria (Cutibacterium acnes) occur below the skin surface in hair follicles, sweat & sebaceous glands;  Candida species occur on the scalp and around the nails  Both the nose and mouth are heavily colonized by bacteria.  Majority of bacteria are anaerobes.  Common colonizers include streptococci, staphylococci, diphtheroids an gram-negative cocci.  Potential pathogens include: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Candida. HOST- PARASITE RELATIONSHIP:  The normal flora (cont.,):  Dental caries is one of the most common infectious diseases in developed countries:  Streptococcus mutans is the etiological agent.  The pharynx and trachea carry their own normal flora:  Includes both  and  hemolytic streptococci, anaerobes, Staphylococcus aureus, Neisseria species  The lower respiratory tract (below the epiglottis) is relatively sterile despite the regular intake of organisms by breathing. The GI tract “gut”:  The density of microbes increases from the stomach to the large intestine. HOST- PARASITE RELATIONSHIP:  The normal flora (cont.,):  The GI tract “gut”:  Stomach harbors only transient bacteria due to acidic pH, an effective barrier, except for Helicobacter pylori, an agent that can cause gastric ulcers.  Small intestine start being colonized at the ileum where we see streptococci, lactobacilli, enterobacteriaceae and Bacteriodes (104 organism/g) to 1011 organism/g in the large bowel.  In the large bowel 95 - 99% of the organisms are anaerobes  We know now that at least 100 types of fungi reside in the intestine  And as many as a billion viruses are present per gram of feces. HOST- PARASITE RELATIONSHIP:  The normal flora (cont.,):  The urethra is lightly colonized in both sexes, but the vagina supports an extensive flora of bacteria and fungi.  Urethra: Staphylococcus epidermidis, diphtheroids, Enterococcus spp.  In the vagina, the composition of the bacterial and fungal flora undergo age-related changes:  Before puberty: S. epidermidis,  streptococci, Diphtheroids (ie., skin flora)  After puberty: Lactobacillus aerophilus predominates and maintains acid pH, which prevents overgrowth of other organisms. Small quantity of yeast is also present.  Menopause: S. epidermidis,  streptococci, Diphtheroids (ie., skin flora) HOST- PARASITE RELATIONSHIP:  The normal flora (cont.,):  Additional sites now thought to harbor at least some normal microbiota, based on nucleic acid detection & sequencing:  Lungs - lower respiratory tract;  Bladder and urine;  Amniotic fluid and fetus  Brain HOST- PARASITE RELATIONSHIP:  Advantages & Disadvantages of the normal flora:  Normal flora are beneficial to the host:  Normal flora prevent colonization by potential pathogens:  Skin flora produce fatty acid, which discourage other species from invading.  Gut flora produce a number of factors with antibacterial activity (bacteriocins & colicins) and metabolic waste prdts that help prevent other microbes from colonizing the same site.  The sheer number of organisms in the large bowel make it hard to establish a niche for new organisms..  Gut flora produce vitamin B and K.  Gut flora provide antigenic stimulation to ensure the normal development of the immune system.  Vaginal lactobacilli maintain an acid pH, which suppress growth of other species. HOST- PARASITE RELATIONSHIP:  Advantages & Disadvantages of the normal flora:  The generally antagonistic effect “good” microbes have against intruder microbes is called microbial antagonism.  Normal microbiota exist in a steady established relationship with the host and are unlikely to be displaced by incoming microbes.  This antagonistic protection is partly the result of a limited number of attachment sites.  This antagonism is also enabled by the chemical or physiological environment created by the resident microbiota, which is hostile to most other microbes.  HOST- PARASITE RELATIONSHIP:  Advantages & Disadvantages of the normal flora:  What happens when the normal flora is absent?  Germ-free animals tend to live longer, presumably because of the complete absence of pathogens. However, their immune system is less well developed and they are vulnerable to pathogens.  The disadvantage of the normal flora lie in the potential for spread into previously sterile parts of the body.  Members of the normal flora are important causes of hospital-acquired infections (HAI) when patients are exposed to invasive treatment or procedures.  Examples:  Yeast – transplant/immunosuppressed patients  CMV - transplant/immunosuppressed patients  Staphylococcus epidermidis – line infections HOST- PARASITE RELATIONSHIP:  Symbiotic associations:  All living animals are used as habitats by other organisms – none are exempt!  All association in which one species lives in or on the body of another can be grouped under the general term “symbiosis” (living together). Symbiosis has no overtones of benefit or harm and includes a wide diversity of relationships.  Three broad categories of symbiosis, based on the relative benefit obtained by each partner:  Commensalism,  Mutualism  Parasitism HOST- PARASITE RELATIONSHIP:  Symbiotic associations:  Commensalism: one species of organism lives harmlessly in or on the body of a larger species.  Skin flora and intestinal flora. They benefit the host by preventing colonization by more pathogenic species.  Mutualism: mutualistic relationships provide reciprocal benefit for the two organisms involved.  Not in humans; seen in domestic ruminants.  Parasitism: the relationship benefits only the parasite.  Note: parasites and parasitism do not just apply to protozoans and worms, but all pathogens are parasites.  Although in medicine we think of parasites as harmful, many actually establish quite innocuous associations with their natural host only becoming pathogenic once the host health changes or they infect an unnatural host. Example: N. meningitidis – nasopharynx vs bld/CSF HOST- PARASITE RELATIONSHIP:  Factors that weaken host defenses and increase susceptibility to infection include the following:  Extreme age (very old and exceptionally young – esp., prematurity)  Genetic defects in immunity and acquired defects in immunity ( such as AIDS/transplant pt)  Surgery and organ transplants  Underlying disease: cancer, liver malfunction, diabetes, chronic illness.  Chemotherapy/immunosuppressive drugs  Physical and mental stress  Pregnancy (an immunocompromised state) and  Other infections (ie., measles) HOST- PARASITE RELATIONSHIP:  Social and behavioral changes can be as important as ones genetic background in altering host-parasite relations.  Increase in tropical vacations may result in an increase in exposure to exotic organisms (malaria, yellow fever, etc)  Routine use of antibiotics in medicine, leads to emergence of antibiotic- resistant bacteria (MRSA, VRE, ESBL, CRO)  Use of immunosuppressive therapy, leads to development of opportunistic infections (Aspergillosis) HOST- PARASITE RELATIONSHIP:  Background to infectious diseases:  Microbes rapidly evolve characteristics/properties that enable them to overcome the host’s defenses.  Their key factor is their replication time ( ~ ½ hr).  The speed with which a host adaptive responses can be mobilized is crucial to the host’s ability to control and finally terminate the infection.  Whether disease result from an encounter between host and microbe is dependent on:  1. Microbe: its virulence, its infectious dose and its portal of entry.  Exogenous microbe - originating from a source outside the body  Endogenous microbe – already existing on or in the body – normal microbiota.  2. Host: genetic profile, previous exposure, and general level of health (any chronic illnesses – diabetes).. HOST- PARASITE RELATIONSHIP:  Obligatory steps for infectious microorganisms:  1. Attach & enter into body: (infection)  A microbe enters the tissues of the body by a characteristic route;  usually the skin or mucous membrane.  Infectious agent can be exogenous or endogenous.  Exogenous microbe - originating from a source outside the body  Endogenous microbe – already existing on or in the body – normal microbiota.  The majority of pathogens have adapted to a specific portal of entry - one that provides a habitat for further growth and spread.  HOST- PARASITE RELATIONSHIP:  Obligatory steps for infectious microorganisms:  1. Attach & enter into body: (infection)  Adhesion/attachment is a process by which a microbe gains a foothold on host tissue.  This is dependent on binding between specific molecules on both the host and pathogen.  Once attached, the pathogen is poised advantageously to invade the body compartments.  Another factor crucial to the course of an infection is the quantity of microbes in the inoculating dose. For most agents, infection will proceed only if a minimum number, called the infectious dose is present. HOST- PARASITE RELATIONSHIP:  Obligatory steps for infectious microorganisms:  2. Local or general spread in the body:  Evade natural protective cleansing mechanism of the host (host’s immediate local defenses).  Evade white blood cells – phagocytes, these cells ordinarily engulf and destroy pathogens by means of enzymes and antimicrobial chemicals  Antiphagocytic factors are a type of virulence factor used by some pathogens to avoid phagocytes  Examples:  Leukocidins – substance toxic to white blood cells,  capsule,  slime layer  3. Multiplication:  Increase numbers of microbes, this generally weaken the host. Accumulated damage by the microbe can lead to cell and tissue death, a condition called necrosis.  4. Evasion of host defenses:  Evade immune and other defenses long enough for the full life cycle in the host to be completed. HOST- PARASITE RELATIONSHIP:  Obligatory steps for infectious microorganisms:  5. Shedding from body/portal of exit:  Leave body at a site and on a scale that ensures spread to fresh hosts  AKA – transmission.  The pathogen is shed or released from the body through secretion, excretion, discharge, or sloughed tissue. Usually it involves very high number of infectious agents.  In many cases the portal of exit is the same as the portal of entry.  Ex.: Influenza.  Portal of exit concerns epidemiologists because it greatly influences the dissemination of infection in a population. HOST- PARASITE RELATIONSHIP:  Obligatory steps for infectious microorganisms:  6. Cause damage in host:  Not strictly necessary but often occurs.  Disease manifestation: pathology  It is uncommon for a microbe to cause exactly the same disease in all infected individuals, because the exact clinical picture depends upon many variables such as infecting dose and route, age, gender, presence of other microbes, nutritional status, and genetic back-ground.  The apparent recovery of the host does not always mean that the microbe has been completely removed or destroyed by the host defenses. After the initial symptoms in certain chronic infectious diseases, the infectious agent retreats into a dormant state called latency.  (Ex., chicken pox, HSV, EBV) HOST- PARASITE RELATIONSHIP  Obligatory steps for infectious microorganisms:  6. Cause damage in host:  Some diseases leave sequelae in the form of long-term or permanent damage to tissues or organs. Examples include:  Meningitis can result in deafness;  Strep throat can lead to rheumatic heart disease;  Lyme disease can cause arthritis;  Polio can produce paralysis.  Some diseases such as measles or cholera give a fairly consistent disease picture, but others such as syphilis causes such a wide spectrum of pathology.  Many individual are asymptomatic. HOST- PARASITE RELATIONSHIP  Four distinct phases of infection and disease:  1. Incubation period: the time from initial contact with the infectious agent (at the portal of entry) to the appearance of the first symptoms.  During the incubation period the agent is multiplying at the portal of entry but has not yet caused enough damage to elicit signs & symptoms. Incubation period is usually well defined and predictable for each microbe but it does vary according to host resistance, degree of virulence, and distance between the target organ and the portal of entry.  Sign: is any objective evidence of disease as noted by an observer.  Symptom: is the subjective evidence of disease as sensed by the patient.  Syndrome: when a disease can be identified or defined by a certain complex of signs and symptoms. HOST- PARASITE RELATIONSHIP  Four distinct phases of infection and disease (cont.,):  2. Prodromal stage: the short period when earliest notable symptoms of most infections appear.  Ex.: vague feeling of discomfort, such as head and muscle aches, fatigue, upset stomach and general malaise.  3. Period of invasion: a period where the microbe multiplies at high levels, exhibits its greatest virulence and becomes well established in its target tissue.  This period is marked by fever, and other signs & symptoms (cough, rash, diarrhea, swelling, discharge, etc). The length of this period is extremely variable. HOST- PARASITE RELATIONSHIP  Four distinct phases of infection and disease (cont.,): :  4. Convalescent period: the signs & symptoms decline, sometimes dramatically, other times slowly, the patient’s strength & health gradually returns owing to the healing nature of the immune response and treatment.  NOTE:  the transmissibility of the microbe during these 4 phases is different for each microbe.  A few agents are released mostly during incubation (measles), many are released primarily during the invasive period (Shigella) and others can be transmitted during all of these periods (Hepatitis B virus). HOST- PARASITE RELATIONSHIP:  How Virulence Factors contribute to tissue damage:  Virulence factors are structures or capabilities that allow a pathogen to cause infection in a host. They are adaptation the microbe uses to invade and establish itself in the host. The effects of a pathogen’s virulence factors on tissues vary greatly (ie., cold virus - local vs HIV virus - systemic).  Three major ways that microbes damage their host:  1. Directly through the action of enzymes:  mucinase – breaks down protective coating on mucous membranes;  Hyaluronidase – digests hyaluronic acid, the ground substance that cements cells together. (Staphylococcus, Streptococcus).  Coagulase – (an enzyme), that causes clotting of blood or plasma  Bacterial kinases (streptokinase, staphylokinase) dissolve fibrin clots and expedite the invasion of damaged tissue.  NOTE: we use streptokinase to dissolve blood clots. HOST- PARASITE RELATIONSHIP:  How Virulence Factors contribute to tissue damage (cont.,):  Three major ways that microbes damage their host:  2. Directly through the action of toxins (endotoxins and exotoxins).  A toxin is a chemical product of microbes that is poisonous to other organisms, and it is named according to its specific target of action, neurotoxin acts on nervous system; enterotoxins act on intestine; hemotoxin lyse RBC, etc.  Exotoxin are proteins with a strong specificity for a target cell and extremely powerful, generally affect cells by damaging the cell membrane or disrupting intracellular function.  Endotoxin refer to a single substance called the lipopolysaccharide, LPS, which is part of the outer membrane of gram-negative cell wall.  Endotoxin differ from exotoxin in having a variety of systemic effects on tissues and organs. Depending on amount present, endotoxin can cause fever, inflammation, hemorrhage, and diarrhea.  3. Indirectly by inducing the host’s defenses to respond excessively or inappropriately.  This means that pathogenicity is a consequence of the interplay between microbe and host. HOST- PARASITE RELATIONSHIP:  Definitions of infection types:  Localized infection: microbes enter the body, remain confined to a specific tissue. Ex.: boils, warts, fungal skin infections.  Systemic infection: Infections spreads to several sites and tissue/fluids (usually via the blood stream), but may travel by other means such as nerves (rabies), and cerebrospinal fluid (meningitis). Ex.: mumps, rubella, chicken pox, HIV, syphilis.  Focal infection: infectious agent spreads from a local site and is carried to other tissues. Ex.: tuberculosis, streptococcal pharyngitis.  Mixed infection: several agents establish themselves simultaneously at the infection site. Ex.: human bite infections, wound infections, HOST- PARASITE RELATIONSHIP:  Definitions of infection types:  Primary infection: the initial infection site.  Secondary infection: a second infection caused by a different microbe, which complicates a primary infection; often a result of lowered host immune defenses. Ex.: influenza complicated by pneumonia; common cold complicated by bacterial otitis media.  Acute infection: infection comes on rapidly, with severe but short-lived effect. Ex.: Influenza, common cold.  Chronic infection: infection that progresses and persists over a long period of time. Ex.: HIV, HBV, HCV) HOST- PARASITE RELATIONSHIP:  Some definitions to know:  Pathogen: a microbe that produces a disease.  Pathogenicity: the ability of a microbe to cause disease.  Infectivity: the ability of the microbe to establish a focal point of infection.  Infection: when a microbe is growing and multiplying within or on a host.  Disease: any change from a state of health in which, part or all of the body, is not properly adjusted or capable of carrying on its normal function due to the presence of microbe or its product.  Virulence: the degree or intensity of pathogenicity.  Invasiveness: the ability of the microbe to spread to adjacent or other tissues.  Toxigenicity: the microbe’s ability to produce toxins, chemical substances that will damage the host & produce disease. HOST- PARASITE RELATIONSHIP:  Some definitions to know:  Edema: the accumulation of fluid in an afflicted tissue.  Granulomas and abscesses: walled-off collections of inflammatory cells and microbes in the tissues  Lymphadenitis: swollen lymph nodes.  Leukocytosis: an increase in the level of white blood cells  Leukopenia: a decrease in the level of white blood cells.  Bacteremia/viremia: the presence of bacteria/virus in the blood stream.  Septicemia: a general state in which microbes are multiplying in the blood and are present in large numbers. This can rapidly deteriorate and cause shock/death.  Asymptomatic/subclinical infection: an infection which produces no noticeable symptoms, even though the microbe is active in the host tissue. HOST- PARASITE RELATIONSHIP:  Some definitions to know:  Reservoir: the primary habitat in the natural world from which a pathogen originates. Often it is a human or animal carrier, although soil, water, plants and the built environment are also reservoirs.  Infection transmitter: the individual or object from which an infection is actually acquired.  Carrier: an individual who inconspicuously shelters a pathogen and spreads it to others without any notice. The duration of the carrier state can be short or long term and it is important to remember that the carrier may or may not have experienced disease due to the microbe. HOST- PARASITE RELATIONSHIP:  Some definitions to know:  Examples of carrier states:  Asymptomatic carrier: infected but show no signs or symptoms of disease. Ex.: STI.  Incubating carrier: spread the infectious agent during the incubation period. Ex.: EBV – infectious mononucleosis.  Convalescent carrier: recuperating patient without symptoms; they continue to shed viable microbes and convey the infection to others. Ex.: Hep. A virus  Chronic carrier: individuals who shelter the microbe for a long period after recovery because of the latency of the infectious agent. Ex.: Tb, Hep. B virus)  Passive carrier: personnel who must constantly handle patient material that are heavily contaminated with patient secretions and blood risk picking up pathogens mechanically and accidently transferring them to other patients.  EX., clinical staff members- therefore hand washing is paramount!  Stethoscope, blood pressure cuff monitor HOST- PARASITE RELATIONSHIP:  Some definitions to know:  Communicable: an infectious disease that can be readily spread to others and cause disease in them.  Ex.: common cold, measles, Tb, dermatophytic infections, STI  Contagious: an agent that is highly communicable, especially through direct contact. Ex. measles  Noncommunicable: the infection does not arise through transmission of the infectious agent from host to host (person – to – person).  Noncommunicable infections occur primarily when a compromised person is invaded by his or her own microbes or:  when there is accidental contact with a microbe. (ie., anthrax, blastomycosis, pneumonia). HOST- PARASITE RELATIONSHIP:  Pattern of transmission in communicable diseases:  Vertical transmission is from parent to offspring via the ovum, sperm, placenta or milk.  Horizontal transmission: is spread through a population from one infected individual to another.  Direct contact transmission: involve physical contact – touching, kissing, sex, droplet contact, parenteral (intentional or unintentional injection into deep tissue)  Indirect contact transmission: infected individual contaminate objects through their activities.  Vector transmission:  Mechanical vector: insect carries microbes to host on its body parts.  Biological vector: insect injects microbe into host. HOST- PARASITE RELATIONSHIP:  Entry, exit and transmission:  Sites of entry:  Skin:  Pathogens gains entry via the skin; must overcome the inhibitory effects of the normal flora (competition), fatty acids produced by the host. Then entry may be through hair follicles, sebaceous glands, abrasions, wounds, or burns.  A few microbes are able to traverse the unbroken skin by their own activity: Leptospira, larvae of Ancylostoma and Schistosoma.  Some microbe penetrate the skin due to biting arthropods (ie., mosquitoes, ticks, fleas).  The conjunctiva: regarded as a specialized area of skin.  Decrease lacrimal gland secretion; eyelid damage; contaminated fingers, flies, towel carry microbes to the conjunctiva. HOST- PARASITE RELATIONSHIP:  Entry, exit and transmission:  Sites of entry:  Respiratory tract:  Some microbes can overcome the respiratory tract’s cleansing mechanisms.  ~10,000 microbes/day are introduced into the lungs, like other particles, they will be trapped in mucus, carried to the back of the throat by ciliary action, and swallowed.  Those that invade the normal healthy respiratory tract have developed specific mechanisms to avoid this fate.  Attach firmly to the surface of cells forming the mucociliary sheet.  Inhibit ciliary activity (ie. Bordetella pertussis).  Avoid phagocytosis by alveolar macrophages HOST- PARASITE RELATIONSHIP:  Respiratory:  Bordetella pertussis, Haemophilus influenzae, Pseudomonas aeruginosa and Mycoplasma pneumoniae all interfere with ciliary activity through the production of ciliostatic substances:  Viral infection impact ciliated cell dysfunction or destruction of cells ( Influenza/measles).  Chronic bronchitis, cystic fibrosis, chronically impairs mucocillary function. INFLUENZA VIRUS ATTACHMENT TO CILIATED EPITHELIUM. VIBRIO CHOLERAE TO BRUSH BORDER AND TO M CELLS. HOST- PARASITE RELATIONSHIP:  Entry, exit and transmission (cont.,):  Sites of entry:  Gastrointestinal tract:  Some microbes can survive the intestine’s defenses of acid, mucus, bile and enzymes.  There are no particular cleansing mechanisms in the intestinal tract, except insofar as diarrhea and vomiting - if you want to consider them a cleansing mechanism.  Normal transit time through the intestinal tract is 12 – 18 hrs. So microbes must attach themselves and multiply in large numbers within this time frame. HOST- PARASITE RELATIONSHIP: INTESTINAL TRACT PATHOGENS Microbe: Disease:  Poliovirus  Poliomyelitis  Rotavirus  Diarrhea  Cholera  Vibrio cholera  Diarrhea/HUS  Escherichia coli O157  Salmonella typhi  Enteric fever  Shigella species  Dysentery  Giardia lamblia  Diarrhea  Entamoeba histolytica  Dysentery HOST- PARASITE RELATIONSHIP:  Gastrointestinal tract (cont.):  Sites of entry:  Means of intestinal adherence by intestinal microbes:  Microbe will bind onto the microvilli (using specific receptors), or they may have sucker, or hooks/teeth (ie., tape worm, Giardia, hookworm);  Some penetrate into the intestinal mucosal wall (Trichuris).  Some microbes produce mucolytic agent so that the microbe can penetrate past the mucus layer.  Microbial exotoxin, endotoxin that expose underlying epithelial cells.  HOST- PARASITE RELATIONSHIP: Ex.: Tape worm, Giardia, & hookworm HOST- PARASITE RELATIONSHIP Property Examples Consequences Adhere to Poliovirus, Avoids expulsion; intestinal epith., V. cholerae est., infection Prod., of V. cholerae assist passage in mucinase mucous Acid resistance Helicobacter pylori Establish residence in stomach Bile resistance Salmonella, Infection & Shigella, shedding from Enteroviurses gut. Resist., to Salmonella, Infection & enzymes Shigella, shedding from Enteroviurses gut. HOST- PARASITE RELATIONSHIP:  Site of entry:  Urogenital Tract:  Microbes gaining entry via the urogenital tract can spread easily form one part of the tract to another:  Bind to cell receptors  Ex.: Vaginitis, urethritis, cystitis and pyelonephritis.  Vaginal defenses:  Lactobacilli metabolize the glycogen to produce lactic acid, pH ~4 – 5. This inhibits other colonizers except streptococci and diphtheroids.  Vaginal secretion contain up to 108 org/mL  No particular cleansing mechanisms. HOST- PARASITE RELATIONSHIP:  Site of entry:  Urogenital Tract:  Urethral and bladder defenses:  Length of urethra;  Females – generally short ~5 cm; not unusual for female to have UTI  Male - long, ~ 20 cm; uncommon for male to have UTI  Regular flushing action of urine is a major defense mechanism.  Bladder also has poorly understood intrinsic defense mechanisms.  Urogenital tract pathogens:  Escherichia coli. Klebsiella spp., Pseudomonas aeruginosa  Staphylococcus aureus, Staphylococcus saprophyticus and Enterococcus spp. HOST- PARASITE RELATIONSHIP:  Site of entry:  Oropharynx:  Pathogenic microbe must compete with normal flora.  Must bind to cell receptors (epithelial cells or tooth surface).  Must resist the flushing action of saliva and normal movement caused by mastication and other movement of the tongue, cheek and lips.  Must overcome other host substances such as secretory IgA (antibody), lysozyme, and leukocytes.  Microbes can invade the oropharynx when mucosal resistance is reduced.  Note: in dehydrated pts, salivary flow is greatly reduced and the mouth soon becomes overgrown with bacteria. Common in the elderly due to lack of water intake! HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Microbes have a variety of mechanisms to ensure exit from the host and transmission.  Nearly all microbes are shed from body. However, some are extracted from inside the body by vectors (blood sucking arthropods).  Transmission depends upon three factors:  1. Number of microbes shed:  The more number of microbes shed, the greater the chance of reaching a new/susceptible host. HOST- PARASITE RELATIONSHIP:  Exit and Transmission (cont.,):  Transmission depends upon three factors:  2. The microbe’s stability in the environment:  Microbes that resist drying spread more rapidly in the environment than those that are sensitive to drying.  Ex., nake viruses, Protozoan cyst, helminths eggs, bacterial endospores, fungal spores.  Microbes that resist drying also remain infectious longer.  Some microbes have developed spores to survive harsh environments.  NOTE: cyst and spores are dehydrated which accounts for their stability in harsh environments. HOST- PARASITE RELATIONSHIP: Exit and Transmission:  Transmission depends upon three factors: (cont.)  3. The number of microbes required to infect a new/susceptible host (the efficiency of the infection).  Efficiency of infection varies greatly between microbes, which explain many aspects of transmission.  Ex.: 10 Shigella dysenteriae microbe to become ill vs106 Salmonella microbes to become ill.  The route of transmission also impact efficiency of transmission.  EX.: 1 rhinovirus in nasal mucosa vs 200 viruses if inoculated in pharynx.  Other factors affecting transmission:  1. genetic factors in microbes also influence transmission  EX.: VRE isolates are much more sticky than the wild type Enterococcus.  2. activities of the host may increase the efficiency of shedding and transmission.  EX. Coughing and sneezing increase the spread of respiratory microbes.  EX.: diarrhea – an effective way of contaminating the environment. HOST- PARASITE RELATIONSHIP: Exit and Transmission:  Types of transmission between humans:  Microbes can be transmitted to humans by:  Humans, vertebrates and biting arthropods.  Transmission is most effective when it takes place directly from human to human.  The most common global infections are spread by:  the respiratory route,  fecal-oral route  or venereal route. HOST- PARASITE RELATIONSHIP: Exit and Transmission:  Types of transmissions between humans:  Transmissions from the respiratory tract:  Respiratory infections spread rapidly when people are crowded together indoors.  Increase in nasal secretion with sneezing and coughing promotes effective shedding from the nasal cavity.  One sneeze can produce 20,000 droplets, many of which will contain microbial particles.  Hundreds of microbes are expelled from the mouth, throat, and lungs during coughing (whooping cough, tuberculous).  Talking is a less important source of air-borne particles. HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from the respiratory tract:  Size of inhaled droplets determine their initial localization.  Particles that are 10 m in size can be trapped on the nasal mucosa.  Particles that are 4 m in size are kept suspended for an indefinite period by normal air movements and particles of this size can reach the alveoli.  Transmission from the intestinal tract:  Intestinal infections spread easily if public health and hygiene are poor.  In diarrhea there are large number of microbes present in stool – if there are susceptible individuals in the vicinity it can result in transmission. HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from the urogenital tract:  Urogenital tract infections are often sexually transmitted:  EX. Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, HIV, HBV.  Semen as a source of infection: Cytomegalovirus (CMV) is often present in semen and recoverable from the cervix. Ebola, Zika and Mpox viruses are recovered from semen.  Perinatal transmission:  Child can acquire infection during passage through the birth canal.  HSV 1 & 2  Grp B strep  Neisseria gonorrhoeae, Chlamydia trachomatis HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from the oropharynx:  Oropharyngeal infections are often spread in saliva.  EX.: Influenza, Herpes simplex virus (HSV), Cytomegalovirus (CMV), Human Herpes virus type 6, Epstein-Barr virus (EBV), Streptococcus pyogenes  Transmission from skin:  Skin infection can be spread by shedding or direct contact.  Ex.: Dermatophytic infections, Staphylococci infections  Transmission in milk:  Ex.: HIV, CMV and Human T-cell lymphotropic virus 1 (HTLV-1), HOST- PARASITE RELATIONSHIP: Microbe Type of milk Cytomegalovirus Human HIV Human HTLV-1 Human Brucella Cow, goat, sheep Mycobacterium bovis Cow Campylobacter jejuni Cow Salmonella spp Cow Yersinia enterocolitica Cow HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from blood:  Blood can spread infection via arthropods or needles.  EX.: malaria, hepatitis B, C, HIV.  Vertical transmission:  Vertical transmission takes place between parents and their offspring via sperm, ovum, placenta, milk or blood.  Note: horizontal transmission is when the infection is acquired from another person via contact, respiratory or fecal-oral spread.  Transmission from animals:  Two types: arthropod vector or zoonotic (directly from vertebrate vector)  Depends on the type of environment:  urban/rural;  Tropical/subtropical.  Contact made with animals HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from animals:  arthropod vectors:  Insect, ticks, and mites – the bloodsuckers are the most important vectors spreading infection.  Ex.:Flea and plague, mosquitoes and malaria  The distribution and epidemiology (the source) of these infections are determined by the climatic conditions that allow the vectors to breed and the microbe to complete its development in the bodies of the vector.  Insects may carry pathogens passively (passive carriage) on their mouth parts, on their bodies or within their intestines. Transfer onto food, or onto the host directly as a result of insect feeding, regurgitating or defecating.  Note: blood feeding arthropods have mouth parts adapted for penetrating skin in order to reach blood vessels or to create small pools of blood. HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from animals:  arthropod vectors:  Insect may be necessary host for the multiplication and development of the microbial pathogen (biologic transmission),  most common method of transmission.  Ex.: malaria, yellow fever.  Transmission from vertebrates:  Zoonotic: any infection transmitted to humans from infected animals, be it by direct contact or eating or indirect (via an invertebrate vector)  The epidemiology of zoonotic infection depends on the frequency and the nature of contact between the vertebrate and the human host.  Ex.: brucella, Q fever, dermatophytic infection HOST- PARASITE RELATIONSHIP:  Exit and Transmission:  Transmission from animals:  Transmission from vertebrates:  Domestic pets?  Ex.: toxocariasis from dogs; toxoplasmosis from cats.  Exotic pets: Salmonella from turtles; Chlamydophila psittaci from parrots HUMAN INFECTIONS TRANSMITTED DIRECTLY FROM VERTEBRATES: Pathogen Vertebrate Disease vector Viruses: Poxviruses Mammals Coxpox, ORF Rhabdoviruses Mammals Rabies Bacteria: Brucella Mammals Brucellosis Chlamydia Birds Psittacosis Salmonella Birds, mammals Salmonellosis  HUMAN INFECTIONS TRANSMITTED DIRECTLY FROM VERTEBRATES: Pathogens Vertebrate Diseases Vector Fungi: Cryptococcus Birds Meningitis Dermatophytes Mammals Ringworm Protozoa: Cryptosporidium Mammals Cryptosporidiosis Giardia Mammals Giardiasis Toxoplasma Mammals Toxoplasmosis Helminths: Echinococcus Mammals Hydatid disease Taenia Mammals Tapeworms HOST DEFENSES:  The immune system:  More than 1600 genes are involved in innate and adaptive immune responses.  The immune system is relatively immature at birth and has to evolve - a life of exposure to multiple foreign challenges through childhood, young adult and mature adulthood (including pregnancy), to the decline of old age.  Does surveillance of the entire body;  Recognition of foreign material and;  Destruction of entities deemed to be foreign. HOST IMMUNE DEFENSES:  Lymphatic tissue and organs:  Primary lymphatic organs/tissue:  Bone marrow  Thymus  Secondary lymphatic organs/tissue:  Lymph nodes  Spleen  Peyer’s patches  Tonsils  Appendix (??) HOST DEFENSES: LYMPHATIC SYSTEM DIAGRAM HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense.  First, there is a physical barrier to infection that is provided by the skin on the outer surfaces of the body, along with the mucous secretions covering the epidermal layers of the inner surfaces of the respiratory, digestive and reproductive tracts.  These surfaces are largely impermeable to microbes; this is why cuts and scrapes are often followed by infection.  Skin surfaces:  Tightly associated epithelial cells covered by a highly cross-linked keratin layer.  Fatty acids from sebaceous secretions are inhibitory to foreign microbes.  Antimicrobial peptides that directly kill microbes (ex., dermicidin, -defensins).  Continual desquamation of skin scales also aids in the elimination of microbes. HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense (physical barriers).  Mucous membrane:  Because of the inherent moisture with which they are associated, mucous membranes support a broader spectrum and larger number of microbes than does skin.  secretion of mucous acts as protective barrier as it inhibits adherence to epithelial cells. Once microbe are trapped they are removed by mechanical means.  Antimicrobial enzymes: lysozyme and N-aceylmuramyl-L- alanine amidase. Both substances are particularly effective against gram-positive bacteria – they hydrolyze the amino acid backbone of peptidoglycan.  Local secretions also contain immunoglobulins (sIgA).  Mucosal secretions also contain significant amounts of iron- binding proteins. Iron is a critical element for most microbes to grow.  Flushing action of tears, saliva, urine. HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense. (physical barriers cont.,)  Respiratory tract:  Filtration system of the upper airway and tracheobronchial tree. The airflow is turbulent causing large particles to come in contact with mucosal surfaces and face the full array of those defense mechanisms. Humidification aids in trapping hygroscopic particles/organisms.  90% of deposited material is cleared in less than 1 hr.  The mucociliary blanket transport the invading offender away from the lung.  Should a particle reach the lung it must overcome the alveolar macrophages and tissue histocytes.  All these defense mechanisms may be overcome by:  Introduction of large number of microbes;  Presence of air pollutant (cigarette smoke);  Mechanical respirators;  Tracheostomy;  Genetic defects (eg., cystic fibrosis) HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense. (physical barriers cont.,)  Intestinal tract:  Acid pH of the stomach and the antibacterial effect of the various pancreatic enzymes, bile, and intestinal secretions are effective nonspecific, antibacterial defense factors.  sIgA, -defensins, lysozyme, phospholipases  Peristalsis and normal loss of epithelial cells also act to purge the GI tract of harmful microbes.  Importance of symbiotic intestinal microbes (normal GI flora). HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense. (physical barriers cont.,)  Genitourinary tract:  Urine is bactericidal for some strains of bacteria mostly because of pH, hypertonicity urea and other solutes  Tamm-Horsfall protein, secreted by the kidneys acts like a sponge binds many bacteria preventing colonization and subsequent infection;  Urination, is a flushing mechanism (4 – 8 times/day);  Presence of lactobacilli in the vaginal of menstrual females inhibits other bacteria and also impact the pH, which hinders certain microbes.  Hormones – estrogen – impacts the lining of the vagina and T-cell function during pregnancy. HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense. (physical barriers cont.,)  Eye:  Constant bathing of the eye by tears is an effective means of protection.  They dilute and wash away microbes via the tear ducts into the nasal cavity.  Tears contain large amounts of lysozyme, lactoferrin and lipocalin, which bind iron.  Many bodily fluids/secretions contain microbicidal factors:  spermine and zinc in semen,  lactoperoxidase in milk, HOST IMMUNE DEFENSES:  NOTE: Host factors that impact the host-pathogen interaction (ie.,your immune response) is influence/impacted by:  Metabolic changes:  Stimulating hormones, vasopressin, insulin, and glucagon;  Shivering (to increase body temp.)  Decrease in serum iron (transferrin – an iron binding protein)  Zinc levels (aids lymphocytes response and wound healing  Nutrition:  Malnourished individuals have more severe infections.  Stress:  Inverse relation between stress and immune function.  Aging:  As we age our immune response decreases in activity. HOST IMMUNE DEFENSES:  The vertebrate immune system comprises three level of defense. (cont.,)  Commensal flora – competitive inhibitors to foreign microbes.  The second level of defense is provided by the innate immune system, a relatively broad-acting but highly effective defense system that is largely preoccupied with trying to kill infectious agents from the moment they enter the body. HOST IMMUNE DEFENSES:  The inflammatory response: A non-specific defensive response of the human body in response to injury, damage or infection, which involves a lot of soluble and cellular components of the body.  Types of damage:  Burns, radiation, microbial invasion, traumatic injury, and autoimmune response.  The inflammatory response is characterized by:  Redness,  Warmth,  Swelling and  Pain.  (One may add) loss of function as a fifth symptom.  Factors that can elicit inflammation include:  Trauma, tissue injury or necrosis due to physical or chemical agents, and  specific immune reactions,  Infection HOST IMMUNE DEFENSES:  Inflammation process is a complex reaction but can be summarized as:  To mobilize and attract immune components to the site of injury.  To set in motion mechanisms to repair damaged tissue and localize and clear away harmful substances.  To destroy microbes and block their further invasion. HOST IMMUNE DEFENSES:  Components of the innate immune system:  The key element of effective innate immunity are responses that are rapid, nonspecific, and of short duration. These features are the hallmark of the phagocytic process.  Phagocytic cells:  Polymorphonuclear granulocytes (PMNs)  Macrophages  Natural Killer cells  Soluble factors:  Acute phase proteins (C-reactive proteins)  Complement  Interferon HOST IMMUNE DEFENSES:  Components of the innate immune system:  Phagocytic cells:  Polymorphonuclear granulocytes: (professional phagocytic cells)  1. Neutrophil: normal in bld, 45-75%; generally seen in pyogenic (pus producing) infections  2. Basophil: normal in bld,