Microbiology Final Study Guide

Inflammation process

1.Brief vasoconstriction minimizes blood loss 2.Vasodilation by histamine increases permeability 3.Influx of phagocytes release proinflammatory chemicals 4.Complement system is activated, produces anaphylatoxin 5.Bradykinin dilates capillaries, causing edema 6.Neutrophils arrive, degranulate - pus forms 7.In a few days macrophages clear out pus; tissue repair begins

Classes of cytokines

1.Interleukins - modulates almost every function of immune system 2.Chemokines- chemotactic factors that recruit leukocytes to sites of infection, tissue damage, inflammation 3.Interferons - produced & released by cells infected with viruses, inhibits transcription & translation

Infected person capable of transmitting disease without showing signs or symptoms

asymptomatic carrier

Negative selection to remove self-reactive thymocytes in the thymus gland

central tolerance

Class of parasitic worms that are flat, ribbon-like, multisegmented

cestode

Urogenital infection caused by Haemophilus ducreyi

chancroid

Major symptom of septic shock

drop in blood pressure

Inanimate object that transmits infections between people

fomite

Benzimidazoles and avermectins are used to treat which type of infection?

helminths

how clean should it be

iMost microbes are transferred through... Fomites- Inanimate items, highest transmission risk How clean shout it be? Based on these two things ●Item use ●Resistance level to antimicrobials Biological safety levels (BSL) - Established by CDC ○Agent's infectivity ○Ease of transmission ○Potential disease severity Type of work being done in lab

chromosomal theory of inheritance

●1800s -chromosome replication observed ●Mendel's work re-examined. re-evaluated ●Sutton & Boveri proposed Chromosomal Theory of Inheritance (1902) ●Identified chromosomes as genetic material ●Scientific demonstration of theory in 1915 by Thomas Hunt Morgan with fruit flies

DNA: molecule of heredity

●1944- Avery, McLeod, & McCarty identified Griffith's "transforming principle" was DNA ●DNA - genetic material - only 4 different nucleotides- structurally too simple? ●Not scientifically accepted; thought to be protein contamination

Innate Non specific Immunity

●1st & 2nd lines of defense ○Physical defenses ○Chemical defenses Cellular defenses

Primary response

●At 1st exposure to a protein Ag, T cell-dependent primary antibody response occurs (ONLY T CELL DEPENDANT) ●Initial stage - lag/latent period ~10 days, no antibody can be detected in serum ●At end of lag period IgM levels rise ●IgM peak ~ 14 days after exposure, T helper cells stimulate antibody class switching ●IgMs decline, IgGs increase, peaking at 3 weeks ●Some cloned B cells become memory B cells

Mycoplasma Pneumonia (Walking Pneumonia)

●Atypical pneumonia by Mycoplasma pneumoniae - lacks cell wall, pleomorphic, fastidious ●Not part of microbiota; causes epidemics ●Walking pneumonia- common in crowded environments (college campuses, military bases) ●Spread by aerosols from coughing or sneezing ●Mild disease compared to others - low fever, persistent cough ●micro plasma Attaches to bind ciliated cells, hinders function ●Infection is self-limiting; responds well to macrolide antibiotic therapy

Vacciniation

●Deliberate inoculation with less virulent pathogen -safer ●Invented by Edward Jenner ●Inoculated patients with infectious materials from cowpox lesions to prevent smallpox ●Prevention is the best form of treatment ●Vaccination - artificial active immunity ●Artificially stimulates adaptive immune defenses ●Triggers memory cell production similar to primary response ●Patient can mount strong secondary response upon exposure—but without suffering through initial infection ●Deliberate exposure to weakened/inactivated pathogens, or key pathogen antigens

Normal Microbiota of the skin

●Derives nutrition from skin & secretions ●Protects, competes for resources, produces antimicrobials ●Composition depends on location ●Dry, moist, sebum-rich regions -Propionibacteria ●Sebaceous regions- Betaproteobacteria ●Moist regions- Corynebacterium, Staphylococcus ●Viruses -Circoviridae, Papillomaviridae, Polyomaviridae ●Fungi -Malassezia

Treatments of hypersensitivities

●Desensitization - (hyposensitization) therapy, reduce sensitivity with repeated injections of diluted allergens ●For insect stings, environmental allergies ●Production different interleukins & IgG instead of IgE ●Excess IgG bind to allergen, as blocking antibodies to neutralize before it can bind IgE on mast cells ●For serious allergic reactions -emergency systemic anaphylaxis ○Epinephrine injection to counteract BP drop, followed by antihistamines, corticosteroids ●Milder allergy- antihistamines, anti-inflammatories ●Type III & Type IV - Avoidance of allergen ○Anti-inflammatory corticosteroid inhalers diminish inflammation, allow lungs to heal

Diagnosis of hypersensitivities

●Diagnostic tests + well-documented patient history ●Prick puncture skin test -introduction of allergens in superficial skin pricks ●Intradermal test - injection with tuberculin needle ●Both tests observed for 15-20 min for wheal-flare reaction ●Measurement of wheal (raised, itchy bump), flare (redness) within minutes indicates a type I ●Larger wheal-flare reaction, greater sensitivity ●Type III hypersensitivities- often misdiagnosed because of nonspecific inflammatory nature ●Symptoms easily visible, but may be associated with many diseases ●Comprehensive patient history is crucial for diagnosis

Coccidioidomycosis

●Dimorphic fungus Coccidioides immitis ●Endemic to San Joaquin Valley of California (Valley fever) ●Spores inhaled, forms spherules filled with endospores ●Mostly asymptomatic, self-limiting but serious for immunocompromised patients ●Endospores transported in blood, disseminate infection, lead to granulomatous lesions on face, nose ●In severe cases, major organs are infected, leading to complications such as fatal meningitis ●Diagnosed by culturing clinical samples, but culturing is dangerous- very infectious, capable of causing laboratory-acquired infections ●Select bioterrorism agent- BSL-3 microbe ●Mild cases not treated, disseminated infections with iv antifungals

Mendel law

●Diploid garden pea- self-fertilizes, highly inbred, produces "true-breeding" pea plant lines ●Mendel discovered basic principles of heredity ●When purebred plants cross-breed, offspring resembles one or other of the parents, not a blend ●Theory of blending of traits in continuous variation

alcohols (chemical)

●Disinfectant, antiseptic ●Denatures proteins, disrupts membranes ●Used at concentrations of ~ 70% aqueous solution ●Bactericidal, fungicidal, virucidal (enveloped viruses only) ●Not sporicidal but inhibit sporulation, germination ●Degerming skin before injection ●Active ingredients in instant hand sanitizers; will not work effectively in presence of visible dirt ●Inexpensive, highly volatile, limits effectiveness (does not work after alcohol is dried)

different levels / methods of control

●Disinfection - inactivates microbes on fomite ●Disinfectant- fast acting, stable, easy to prepare, inexpensive, easy to use chemical NON LIVING ●Does not sterilize; endospores remain (vinegar, bleach) ●Antiseptic- antimicrobial safe for use on living skin ●Selectively effective against microorganisms ●Able to penetrate tissue deeply without causing damage

Noncoding DNA

●Do not encode proteins or stable RNA products ●Found prior to start of coding sequences & in between genes ●Prokaryotes ~12% genome is noncoding ●Eukaryotes ~ 98% genome is noncoding (in humans) ●Varies between species ●Once referred to as "junk DNA"

Antigen Presentation with MHC I Molecules

●Done by all nucleated cells including APCs ●Proteins from cytoplasm are degraded & presented through MHC ●When normal - NK cells move on ●When abnormal, activates NK cells & APCs ●APCs cross present antigens on MHC I to activate cytotoxic T cells

Desiccation / drying (physical)

●Drying/dehydration- will not kill all microbes, endospores; ●Lyophilization - Freeze drying - rapidly frozen, placed under vacuum ○Combines cold temp & desiccation ○For foods, long-term storage of microbes ●Water activity lowered without physical drying- adding salts/ sugars to increase osmotic pressure (jams, jelly, brine)

DNA replication

●E. coli -4.6 million bp in single circular chromosome ●Replicates every 42 minutes starting at single origin ●Proceeds bidirectionally adding 1k nucleotides per second ●Rapid process, few errors ●Main enzyme- DNA polymerase (DNA pol.) ●3 types of DNA polymerases (DNA pol I, DNA II, and III) ○DNA pol III -DNA synthesis ○DNA pol I & DNA pol II -for repair

Great oxygenation EVENt

●Earliest earth - highly reducing conditions with no free O2 ●Levels increased only after cyanobacteria ●Oxygen Revolution, caused massive extinction ●Most organisms harmed by powerful oxidative properties of reactive oxygen species (ROS) ●ROS - highly unstable ions, molecules that damage virtually anything they come in contact with

Nonspecific innate immune response

●Early defense- 1st & 2nd line of defenses ●Immediate, rapid responses ●Not specific -defends against a range of pathogens ●Innate- built-in mechanisms born with ●Not acquired over time ●Does not improve after repeated exposures to specific pathogens (no "memory") ●Physical, chemical, and cellular

Acute Inflammation

●Early response to tissue injury ●Dilutes toxins and bacterial products at site ●Contributes to 5 observable signs- ○erythema (redness) ○edema (swelling) ○heat ○pain ○altered function

Cellular defences

●Formed elements -found in non-fluid portion of blood ●Formed from pluripotent hematopoietic stem cells (HSCs) in bone marrow (basic military training center) ●HSC replicate in marrow and cells receive different cues to differentiate into different elements ●Process of differentiation is called hematopoiesis ●RBCs - Erythrocytes -carry oxygen ●Platelets - Thrombocytes - clot blood, repair tissue ●WBCs - Leukocytes- part of innate and adaptive immunity ○Granulocytes ○Agranulocytes

Griffith

●Frederick Griffith - showed HGT ●Used smooth(S) and rough(R) strains of Streptococcus pneumoniae in rats ●R strain- nonpathogenic (no capsule)- colonies are rough ●S strain- pathogenic (capsule) -allows it to escape phagocytosis; colonies are smooth ●Genetic information can be transferred from DNA in dead bacteria to other bacteria nearby

Acanthamoeba

●Free-living protozoan amoebae in soils, unchlorinated water; rare parasitic species ●Travels & affect other body systems ●Skin infections -abscesses, ulcers, nodules ●Acanthamoeba keratitis - inflammation of cornea ○Can lead to damage, vision impairment, or blindness ○Greater risk to wearers of contact lenses ○Lenses should be properly disinfected prior to use, and never be worn while swimming or using a hot tub ●Diagnosed by symptoms, microscopic examination ●Difficult to treat, prompt treatment is necessary ●Requires 3-4 weeks of intensive treatment ●Topical antiseptics, painkillers or corticosteroids ●Advanced cases require corneal transplant to prevent blindness ●Can enter through skin wounds, respiratory tract; causing disease only in the immunocompromised Rarely spreads to CNS, causes fatal encephalitis

Cancer

●From loss of cell-cycle regulation & subsequent cell proliferation ●Loss of ability of cells to control their cell cycle ●Affected cells rapidly divide; lose ability to differentiate ●Lose contact inhibition; grow on top of each other

Neonatal Herpes

●From mother to newborn during birth or before (can cross placenta) ●Can occur even when no lesions are present in birth canal ●Infection is limited to skin, mucous membranes, eyes ●If virus spreads to Central Nervous System, motor function deficits or death may occur ●Before birth -causes complications in fetal development causing spontaneous abortion or severe disability ●Expectant mothers screened with TORCH panel ●Systemic acyclovir is used for treatment

Mast cells

●Functionally similar to basophils ●Unlike basophils, mast cells leave circulating blood & reside in tissues

Chlamydial Pneumonias & Psittacosis

●Chlamydophila pneumoniae, Chlamydophila psittaci Chlamydia trachomatis all cause pneumonia & bronchitis ●Chlamydophila pneumoniae-most common, transmitted via respiratory droplets or aerosols ●C. psittaci-psittacosis, rare zoonotic disease, affects domesticated birds, can be transmitted to humans, kissing disease from kissing birds ●Chlamydia trachomatis, causes STD chlamydia, can cause pneumonia in infants soon after birth Fastidious, PCR for diagnosis, tetracycline & macrolides for treatment

Molecular Koch's Postulates

Steps used to identify gene responsible for pathogenicity

Disease caused by Naegleria fowleri

ameobic menengitis

monomer of protein

amino acid

Change in viral strains due to point mutations that accumulate

antigenic shift

Layers of the skin

1st layer -Epidermis - thin outermost layer ●Stratum corneum - mostly dead cells ●Rich in keratin - tough, waterproof, dry ●Desquamation- normal shedding, peeling of skin- may be accelerated when infected 2nd layer -Dermis - thicker in-between connective tissue ●Embedded with blood vessels, nerves, muscles, hair follicles 3rd layer - Hypodermis -fibrous, adipose connective tissue ●Sweat & sebaceous glands ●Perspiration provides moisture & antimicrobial substances -salts, lysozyme, antimicrobial peptides ●Sebum protects skin, reduces water loss

Antimicrobial for use on living tissue

antiseptic

Net ATP gain in aerobic respiration vs fermentation

38:2

Direction in which DNA pol III adds bases

5-3

Respiratory fungal pathogens

ubiquitous, most people have antibodies -symptomatic infections rare in healthy individuals

Capsules, adhesions, toxins etc

virulence factors

prions

Acellular pathogen that is the causative agent of Kuru

Type of microbes that are obligate intracellular pathogens

viruses

IgM

Antibody class that is produced first

Antigen

Antibody generator

Multiole Sclerosis

Autoimmune disease with damage to the myelin sheaths of nerve cells; possible symptoms include muscle weakness, numbness, and problems with memory

difference between

B cells - attack invaders outside the cell T cells - attack infected cells

Neosporin

Bacitracin, neomycin, polymyxin B

Streptococcal Infections

Bacterial ●Streptococcal pharyngitis (strep throat)- Streptococcus pyogenes, gram +ve cocci in chains ●Mucosal membranes of pharynx are damaged by exoenzymes, exotoxins ●Many strains of S. pyogenes degrade connective tissues using hyaluronidase, collagenase, streptokinase Signs and symptoms ●Fever > 38 °C (100.4 °F) ●Intense pharyngeal pain, erythema ●Swollen, dark-red tonsils, with pus ●Petechiae (microcapillary hemorrhages) ●Swelling of submandibular lymph nodes beneath jaw ●Strep strains may produce erythrogenic toxin ●Toxin attacks plasma membranes of endothelium ●Leads to scarlet fever- red rash on skin, strawberry tongue, red rash on tongue ●Severe cases lead to toxic shock syndrome from massive superantigen production ●Spreads easily by direct contact or droplet transmission ●Diagnosed quickly using a rapid enzyme immunoassay ●Culture identification is best for confirmation ●S. pyogenes is catalase-negative, beta hemolytic, susceptible to bacitracin Sequelae of S. pyogenes Infections ●Strep throat is aggressively treated with antibiotics ●Can lead to serious sequelae (later clinical consequences of a primary infection) ●1%-3% of untreated strep infections can develop sequelae 1-3 weeks after acute infection ●Acute rheumatic fever & acute glomerulonephritis ●Acute rheumatic fever- due to molecular mimicry & autoimmunity to heart tissue ●Leads to carditis- damage, inflammation of heart ●Acute glomerulonephritis -immune response to pharyngitis & cutaneous infections ●Develops within 6-10 days after pharyngitis, or 21 days after cutaneous infection ●Antigen mimicry & autoimmunity ●Primary mechanism- hypersensitivity type III ●Leads to damage, inflammation

Bacterial infection of eye

Bacterial Conjunctivitis ●Pinkeye -inflammation with sticky fluid (acute purulent conjunctivitis) ●Affects 1 eye or both; does not affect vision permanently ●Caused by Haemophilus influenzae or Moraxella catarrhalis, S. pneumoniae, S. aureus ●Identified by cultures, staining, biochemical, antigenic, or NA tests ●Secretions are very contagious, but self-limiting ●Topical antibiotics sometimes prescribed ●Contact lenses use should be discontinued during infection ●Blurred vision, eye pain, light sensitivity, if serious, requires medical attention Neonatal Conjunctivitis ●Contracted through exposure to pathogens during birth in mothers with sexually transmitted infections ●Gonococcal ophthalmia neonatorum- Neisseria gonorrhoeae ●Inclusion conjunctivitis - Chlamydia trachomatis -anaerobic, obligate, intracellular parasite ●Silver nitrate ointment or erythromycin routinely applied to all infants at birth (required by law) ●If untreated, spreads to cornea, causing ulceration, perforation, vision loss or permanent blindness ●Treated aggressively with oral or IV antibiotics to stop spread Identified by cultures, Gram stain, biochemical, antigenic, or NAprofile tests Trachoma ●Granular conjunctivitis-cause of preventable blindness ●Caused by different serovars of same species as neonatal inclusion conjunctivitis, Chlamydia trachomatis ●Transmitted through fomites, flies, infected mucous ●Chronic conjunctivitis- forms necrotic follicles, scarring of upper eyelid ●Scars turn eyelashes inward (trichiasis)- mechanical abrasion of the cornea leads to blindness ●Azithromycin is effective Bacterial Keratitis ●Caused by Staphylococcus epidermidis, Pseudomonas aeruginosa ●Contact lens users at risk- reduced by proper care of contact lenses, avoiding wearing lenses overnight ●Infection quickly leads to blindness ●Prompt, aggressive treatment with antibiotics is important ●Identified using cultures, Gram stain, biochemical, antigenic, or NA profile tests

Mast Cells

Cell responsible for hypersensitivity type 1 reactions

Specific Adaptive Immunity

Cell-mediated/ Cellular Immunity ●T Lymphocytes (T cells) ●Matures in thymus ●Destroys cells infected with intracellular pathogens Humoral Immunity ●B lymphocytes (B cells) ●Matures in bone marrow ●Produces immunoglobulins (antibodies) against pathogens & toxins in extracellular environment

Epigenetic Change

Change in gene expression without changing base sequence

Chemical Defences

Chemical mediators -substances in body fluids and tissues ●Work alone or in conjunction to inhibit microbial colonization & infection ●Endogenous -produced by human body cells ●Exogenous - produced by microbiome ●Some are produced continually, bathing area in the antimicrobial substance ●Others are activated in response to stimuli

Histamine

Chemical responsible for increasing blood flow to wound site

gas gangrene

Clostridium perfringens

Septicemia

Condition in which bacteria are actively dividing in the blood

diptheria

Disease associated with the production of an exotoxin that causes the formation of a pseudomembrane that impairs breathing

bacterial menengitis

Disease caused by Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Cryptococcus neoformans

Addison's disease

Disease that causes damage to the adrenal gland; possible symptoms include weakness, hypotension, fatigue, kidney failure

cyctic fibrosis

Disease that has been controlled by gene therapy

sterilization by heat

Dry-heat ●Inoculating loops using BB / microincinerator, dry-heat sterilizer (ovens) heat until red hot ●Can be applied for long time - 2 h at temps to 170 °C Moist / wet-heat ●Most effective than dry heat, penetrates better ●Autoclaves & Retorts (industrial autoclave restaurants)

Mitochondria and chloroplasts were derived from uptake of bacteria

Endosymbiotic theory

Most dangerous type of E.coli that produces a shiga-like toxin

Enterohemorrhagic E. coli (EHEC)

ATP synthase

Enzyme complex responsible for oxidative phosporylation

cytochrome oxidase

Enzyme required for bacteria to grow aerobically

Exons and introns

Eukaryotic genes have ●Coding sequences - exons (ex-on = expressed) ●Intervening sequences - introns (int-ron = intervening) ●Introns do not encode proteins -removed from during processing ●Exons joined together to code for functional protein ●Single nucleotide error, sequences will shift; protein will be nonfunctional

superantigen

Exotoxin that triggers a cytokine storm

cross matching

Final check in haemovigilance system before blood transfusion

Histoplasmosis

Fungal disease of the lungs that shows symptoms similar to TB

Most common bacterial genus found in plaque on teeth

Fusobacterium

Gram negative has thin peptidoglycan layer

Gram positive has thick layer

Staining procedure that helps select antibiotic

Grams stain

Stationary phase

Growth phase of Bacteria when they are most resistant to antibiotics

Central dogma

DNA ->(transcription) RNA ->(translation) Protein

DNA replication -semiconservative

DNA doubles on replication, each having 1 parental strand + 1 new strand

Hershey & Chase

DNA is the genetic material

microbial death curve

Decimal reduction time (DRT) or D-value - time taken to kill 90% of microbial population

Nucleases

Degrades DNA released by dying cells (bacteria and host cells) that can trap the bacteria, thus promoting spread

Proteases

Degrades collagen in connective tissue to promote spread

glycohydrolases

Degrades hyaluronic acid that cements cells together to promote spreading through tissues

phospholipases

Degrades phospholipid bilayer of host cells, causing cellular lysis, and degrade membrane of phagosomes to enable escape into the cytoplasm

Hämmerling

Hämmerling - Microbial model Acetabularia- genetic information in a eukaryotic cell is within nucleus Confirmed presence of nucleus in foot & showed it was the location of genetic material in a cell ●Beadle & Tatum- red bread mold- relationship between genes, encoded proteins ●Proposed one-gene, one-enzyme hypothesis, revised to "one gene-one polypeptide"

Biofilm

IOFILM●Environment influences structure ●Filamentous biofilms (streamers) form in flowing water ●In still or slow-moving water, biofilms have a mushroom-like shape ●Clusters of microbes embedded in a matrix with open water channels ●Extracellular matrix - extracellular polymeric substances (EPS) secreted by organisms - 50-90% of total dry mass BIOFILM FORMATION ●Planktonic cells - free-floating microbes in aquatic environment ●Attach to substrate, becomes sessile

Eoisinophils

Leukocytes that are produced in response to parasites & helminths

BSL levels

Level 1 - Basic aseptic technique, doors to the lab (nonpathogenic escherchia coli) Level 2 - Level 1 precautions + PPE with face shield, biological safety cabinets, self-closing doors, eyewash station, autoclave (staphlocccus) Level 3 - Level 2 precautions + vaccinations, respirator, biological safety cabinet, hands-free sink, eyewash station near exit, 2 sets of self-closing & locking doors, directional airflow (nothing to escape lab) Level 4 - Level 3 precautions + ●Change clothing to enter, shower & decontaminate to exit ●Full-body protective suit with designated air supply or work within biological safety cabinet with (HEPA)-filtered air supply & double HEPA-filtered exhaust ●High pressure full-body suit ●Lab in separate building or isolated with own air supply, exhaust & decontamination system (most risky organisms ex. Ebola)

Localized Autoimmune diseases

Localized Autoimmune Diseases ●Celiac Disease ●Affects small intestine, in people aged 30-40 ●Reaction to proteins like gluten in wheat, barley, rye etc ●On exposure to gluten, autoantibodies are produced in digestion tract ●Inflammation reduces depth of microvilli mucosa; hinders absorption (supposed to be long but get flattened) ●Weight loss, anemia, diarrhea, abdominal pain ●Poorly understood genetic, environmental causes ●Often misdiagnosed as IBS ●Diagnosed by screening for IgA antibodies to gluten components ●Followed up by endoscopy, biopsy of duodenal mucosa ●Treated by complete removal of gluten from the diet ●Graves Disease ●Most common cause of hyperthyroidism ●TSH (thyroid stimulating hormone)-receptor antibodies target, binds receptor for TSH produced by pituitary gland ●Can cause conflicting symptoms by stimulating gland too much or too little ●Symptoms - heat intolerance, irregular heartbeat, weight loss, goiter - swelling of thyroid, exophthalmia (bulging eyes) ●Hashimoto thyroiditis ●Chronic lymphocytic thyroiditis ●Most common cause of hypothyroidism ●Can develop other autoimmune diseases like addison's disease, Type 1 diabetes (T1D), rheumatoid arthritis (RA), celiac disease ●Thyroid gland is attacked by cytotoxic lymphocytes, macrophages, autoantibodies ●Symptoms- goiter- swelling of thyroid, cold intolerance, muscle weakness, painful, stiff joints, depression, memory loss ●Type 1 Diabetes ●Juvenile diabetes- in children and young adults ●T-cell-dependent autoimmune disease ●Selective destruction of β cells of islets of Langerhans in pancreas- leads to lack of insulin ●By CD8 T cells, anti-β-cell antibodies, macrophages ●β-cell destruction takes years but symptoms are sudden ●Hyperglycemia, extreme thirst, urination, fatigue, weight loss ●Goes unnoticed until most β cells have been destroyed Addison's Disease ●Destruction of adrenal glands -primary adrenal insufficiency (PAI) ●Disruption of adrenal function leads to impaired metabolic processes ●Both humoral & T-cell-mediated ●Autoimmune destruction of other endocrine glands (pancreas, thyroid) ●Collectively referred to as autoimmune polyendocrine syndromes (APS) ●Adrenal cortex cells destroyed; replaced by fibrous tissue ●Sometimes 90% of cells are destroyed before symptoms become diagnostic ●Diagnosed by detecting antibodies to key enzymes for steroid synthesis ●Symptoms - Weakness, nausea, decreased appetite, weight loss, hyperpigmentation, hyperkalemia (elevated blood potassium levels), hyponatremia (decreased blood sodium levels), hypoglycemia (decreased levels of blood sugar), hypotension (decreased blood pressure), anemia, lymphocytosis (decreased levels of wbcs), fatigue ●Under extreme stress, adrenal crisis - vomiting, abdominal pain, back/ leg cramps, severe hypotension, shock

Denatruation

Loss of tertiary structure of protein

tools of genetic engineering

MOLECULAR CLONING: ●Construct recombinant DNA & incorporate into host ●Molecular tools from microbes ○Restriction enzyme - natural enzymes in microbes ○Ligase - enzyme that pastes DNA fragments ○Introduction of recombinant DNA into host ●Restriction endonucleases- enzymes bacteria produce to cut, destroy foreign DNA from bacteriophage infection RESTICTION ENZYMES ●Cuts DNA at recognition site, (4-6 bp palindrome sequence) ●Some cut with sticky ends - complementary overhangs ●Others cut with blunt ends ●Complementary sticky ends easily anneal ●Blunt ends attach together less efficiently ●Ligation by DNA ligase PLASMIDS ●Circular, extrachromosomal dsDNA ●Using restriction digestion, genes are inserted into plasmids (vectors) ●Combined with genes for antibiotic resistance to locate plasmid ●Plasmid vectors have polylinker site, or multiple cloning site- unique restriction enzyme sites for inserting DNA●Polylinker site often has a reporter gene ●Reporters -artificially engineered to locate recombinant plasmids ●E.g. bacterial lacZ gene encoding beta-galactosidase- enzyme that degrades lactose & colorless synthetic analog X-gal (produces blue colonies on X-gal-media) ●Gene is disabled upon splicing - X-gal is not degraded; produces white colonies

what cells do not express MHC

Mature RBC lacks nucleus

Halophile

Microbe that grows in environment with high salt concentration

Biofilm

Microbial community with higher antibiotic resistance that makes some wound infections harder to treat

Ghonorrhea

Most common STD in the US among 15-24 years

Mycoses of the skin

Mycoses - classified based on invasiveness ●Cutaneous mycoses - superficial infections of epidermis, hair, nails ●Subcutaneous - penetrate epidermis, dermis; infect deeper tissues ●Systemic mycosis - spread throughout body ●Normal fungal microbiota - opportunistic in immunocompromised) or when they enter through wound ●Unusually moist environments- sweaty shoes, communal showers, locker rooms

Antigen-Antibody Interactions

Neutralization ●Binding of certain antibodies (IgG, IgM, or IgA) to epitopes on pathogens or toxin ●Prevents their attachment to cells Opsonization for phagocytosis ●Coating a pathogen with molecules ●Assists in phagocyte binding to facilitate phagocytosis ●IgG antibodies are excellent opsonins Agglutination (aggregation) ●Abs cross-link pathogens to creates large aggregates ●Fab sites bind to separate pathogens, clump them ●When multiple Abs bind, large aggregates develop ●Easier for kidneys, spleen to filter from blood, for phagocytes to ingest ●Pentamer IgM most efficient for agglutination - 10 Fab sites Activation of complement ●Classical pathway- requires binding of IgG or IgM to surface of pathogen ●Allows for recruitment, activation of the C1 complex Antibody-dependent cell-mediated cytotoxicity (ADCC) ●Helps kill pathogens too large to be phagocytosed ●Fab region of an IgG binds to a large pathogen ●Fc region binds to NK cells, bringing them close ●NK cells then secrete powerful cytotoxins

Chemical & Enzymatic Mediators in Body Fluids

On skin - endogenous & exogenous ●Sebum - oil secreted by sebaceous glands (endogenous) ●Seals off pore of hair follicle ●Microbiome use lipase enzymes to consume sebum, produce oleic acid (exogenous) ●Creates mildly acidic environment inhospitable to pathogens In digestive tract ●Saliva - lactoperoxidase enzymes ●Mucus from esophagus - antibacterial enzyme lysozyme ●In stomach, highly acidic gastric fluid kills microbes ●In lower digestive tract- pancreatic & intestinal enzymes, antibacterial peptides (cryptins) ●Liver - produces bile In urinary tract ●Urine flushes microbes out ●Slight acidity of urine (avg pH6) inhibits growth In female reproductive system ●Glycogen in vagina - used by Lactobacilli to make lactate ●Lactate (exogenous mediator) inhibits microbial growth In eyes ●Tears- lysozyme, lactoferrin eliminate microbes ●Lysozyme cleaves bond in peptidoglycan ●Lactoferrin binds & sequesters iron, starving microbes of iron In ears - Cerumen (earwax) lowers pH, inhibits microbes In respiratory tract- Mucus - mix of antimicrobial molecules

Erythrocytes

Only cells that cannot present MHCs

Prokaryotes and Eukaryotes

P:●Transcription, translation occur concurrently, forming polyribosomes ●Both occur in cytoplasm ●RNA transcript not processed after transcription ●Cell responds quickly to environment needing new protein E:●Simultaneous transcription & translation not possible ●Processing required before transport to cytoplasm

causative organism of malaria

Plasmodium falciparum

Problematic bacteria causing nosocomial infections due to ability to form biofilm

Pseudomonas aeruginosa

Kidney Infections

Pyelonephritis ●Inflammation by bacteria from other parts of urinary tract or from bloodstream ●In lower urinary tract, fecal bacteria like E. coli ●Acute- back pain, fever, nausea or vomiting; hematuria in 30-40% of women, rare in men ●Can lead to life-threatening bacteremia ●Scarring can occur and persist after infection leading to dysfunction ●Diagnosis by microscopic examination, culture of testing for enzymes, nitrite levels ●Imaging of kidneys in high-risk patients (diabetes, immunosuppression, elderly, renal damage) or to rule out obstruction ●Treated with either oral or IV antibiotics Glomerulonephritis ●Glomeruli damaged from inflammation; acute or chronic ●Commonly a post-streptococcal sequelae associated with Streptococcus pyogenes throat & skin infections

Tissue trophism

Reason why viruses can only grow in a specific type of tissue

replication of extrachromosomal DNA

Rolling circle replication- rapid unidirectional DNA synthesis in some plasmids, bacteriophages, some viruses

superinfection

Secondary infection that can develops when antibiotics kill much of the patient's normal flora

surfactants

Soaps ●Lowers surface tension of water ●Mechanical method -creates emulsions- loosen, lift away dirt, microbes (scrub 20-40 seconds) (scrubbing cleans not soap) ●Not antiseptics or disinfectants- only degerming ●Can contain bactericidal, bacteriostatic agents Detergents ●Works in hard water, no residue ●Anionic detergents - used for laundry ●Cationic detergents- Quaternary ammonium salts (Quats) ●Inserts into membrane,disrupts integrity ●Stable, nontoxic, inexpensive, colorless, odorless, tasteless ●Kills bacteria, fungi, protozoans, enveloped viruses, but not endospores ●Antiseptics & disinfectants in clinical settings ●Household cleaners, disinfectants

Causative organism of folliculitis

Staph aureus

Causative organism of pharyngitis

Streptococcus pyogenes

Rubella

Teratogenic virus that pregnant women should guard against

Merozoites

The synchronous release of this parasitic form is responsible for the symptoms of malaria

tetanus

Toxin that blocks the release of neurotransmitter GABA that stops muscles from relaxing

Horizontal Gene Transfer

Transfer of genetic material between two organisms that are not related as parent and offspring

Uptake of DNA by a plasmid

Transformation

Causative organism of Syphilis

Treponema pallidum

Bacterial conjunctivitis

Type of highly infectious conjunctivitis with thick sticky discharge

Transfection

Uptake of DNA by eukaryotic cell

Sporotrichosis

VERY RARE ●Subcutaneous mycoses spread from skin to deeper tissues ●Sporothrix schenkii (rose gardener's disease) ●Contracted after working with soil, plants, or timber- fungus enters through a small wound ●Avoided by protective clothing, promptly cleaning and disinfecting wounds ●Starts as small ulcers in skin, spreads to lymphatic system ●Nodules appear, become necrotic, may ulcerate ●As more lymph nodes become affected, abscesses & ulceration develop over a larger area (arm or hand) ●Diagnosed upon histologic examination of tissue ●Macroscopic morphology on potato dextrose agar ●Microscopic morphology by staining with lactophenol cotton blue ●Treatment with itraconazole

GENITAL herpes

Viral infection caused by HSV-2

Endotoxin released from Gram-negative bacteria

lipopolysaccharide LPS

Reason why acid fast bacteria will not stain with Gram's stain

membrane has waxy mycolic acids

Reason why Clostridium tetani grows well in deep tissue

obligate anaerobe

chemostat

opening to feed nutrients, outlet to remove effluent; adjusted to maintain culture in log phase of growth

Process of coating of a pathogen by chemical substance to increase recognition by immune cells

opsonization

Disease caused by Yersinia pestis

plague

Type of microbe that uses pseudopodia for locomotion

protazoa

RNA function

protein synthesis ●Transcription & translation - information in DNA is accessed by creating RNA ●Messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA) ●DNA is complete library of cellular information, mRNA is a photocopy of specific information

Viral form of a retrovirus after it has integrated with host DNA

provirus

Enzyme produced by retroviruses to produce cDNA from RNA

reverse transcriptase

Infection caused by Tinea corporis

ringworm

Borrelia burgdorferi

spirochete that causes lyme disease

Process bacteria undergo when there is insufficient nutrients

sporulation

Cleaning protocol for critical medical items

sterilization

Mechanism of drug resistance against vancomycin & beta lactums

target modification

Digestive infection caused by roundworm (nematode) in undercooked pork

trichinosis

Heavy Metals (chemical)

●1st chemical disinfectants, antiseptics- all heavy metals ●Binds to proteins, inhibits enzymes ●Oligodynamic -only very small concentrations required ●Ions bind to amino acids, denatures proteins ●Not selectively toxic ●main toxic used are... (dont use)Mercury, (use)silver, copper, nickel, zinc ●Topical antiseptic (silver, zinc) ●Treatment of wounds and burns (silver) ●Prevention of eye infections in newborns ●Antibacterial material in catheters, bandages (copper) ●Mouthwash (zinc) ●Algicide for pools and fish tanks (copper, nickel, zinc) ●Long-term water storage (silver, copper) ●Hg (mercury) - toxic in high concentrations, bioaccumulates in fish

DNA structure

●2 strands twisted to form a right-handed helix ●Strands are antiparallel - 3ʹ end of one strand faces 5ʹ end of the other ●Sugar + phosphate form the backbone ●Nitrogenous bases - stacked, interact through base pairing ●Approx 10 bases per turn in DNA

Transcription in eukaryotes

●3 polymerases - RNA pol. I, II, & III ●mRNAs are monocistronic- encode only 1 polypeptide ●mRNA needs to be transported to cytoplasm ●Processed before transport to protect from degradation ●Eukaryotic mRNAs last several hours, prokaryotic 5 sec ●Primary transcript (pre-mRNA) coated with RNA-stabilizing proteins ●Processing begins during synthesis ●Nucleotide called 5' cap, is added to 5' end of transcript -for protection & recognition to initiate translation ●After elongation, string of ~200 adenine nucleotides added to 3' end - poly-A tail ●Further protects & signals readiness for export

Specific Adaptive immunity

●3rd line of defense ○Humoral immunity ■B cells and antibodies ○Cell-mediated immunity ■T cells

T-cell subtypes

●3rd step - APC + T cell secrete activating cytokines ●Activated cell proliferates, divides ●Produces clonal naïve helper T cells ●These differentiate into subtypes with different functions

bonds in DNA

●5ʹ-3ʹ phosphodiester bonds (covalent) form between nucleotides ●Constructs sugar-phosphate backbone ●Phosphates released are hydrolyzed to provide energy

primary immunodeficiency

●>250 inherited defects of innate or adaptive immunity ●Increased susceptibility to infection; seen shortly after birth or in early childhood ●Defect of single cellular or humoral component OR more than one component ○Chronic granulomatous disease ○X-linked agammaglobulinemia ○Selective IgA deficiency ○Severe combined immunodeficiency disease

Cross Presentation

●APCs have both MHC I & II ●When directly infected, present antigens on MHC II - activate helper T cells ●When not infected, obtain antigens from infected cells and present on MHC I - activate cytotoxic T cells ●This is called cross presentation

Tumor

●Abnormal mass of cells ●Can be benign (not cancerous) or malignant (cancerous)

microbial growth ph

●Acidity - concentration of [H+]; measured as pH ●pH < 7.0 are acidic, > 7.0 are basic ●Extreme pH affects structure of all macromolecules ●Hydrogen bonds between DNA break; lipids hydrolyze ●Proton motive force needs concentration gradient ●Proteins are most sensitive to pH - changes folding causing denaturation, destroying activity ●Optimum pH -most favorable ●Minimum & max pH -lowest & highest pH tolerated; ●Microbe survival in stomach depends on pH ●Most bacteria are neutrophiles- grow optimally at a pH within 1-2 pH units of of 7 ●Escherichia coli, Staphylococci, Salmonella spp. are neutrophiles; cannot survive in stomach ●Pathogenic E. coli, S. typhi - more resistant to acid ●Fungi like slightly acidic pH - 5-6 ●Helps preserve food

acidophile

●Acidophiles - optimal at pH 3 ●Sulfolobus spp. (hot springs @ Yellowstone) ●Lactobacillus spp, in vagina tolerates low pH ●How do aciophiles survive strong acidic environments? ○Proteins have increased negative surface charge to stabilize them ○Pumps actively eject H+ ions out ●Helicobacter pylori (peptic ulcers) is not an acidophile!

secondary immunodeficiency

●Acquired impairment of B cells, T cells, or both ●Caused by: ○Systemic disorders -diabetes mellitus, malnutrition, hepatitis, or HIV infection ○Immunosuppressive treatments -cytotoxic chemotherapy, bone marrow ablation before transplantation, or radiation therapy ○Prolonged critical illness- infection, surgery, or trauma in the very young, elderly, or hospitalized patients ●Reversible if underlying cause is resolved ●Increased susceptibility to opportunistic pathogens ●HIV & AIDS -profound CD4 T-cell lymphopenia (decrease in lymphocytes) ●Severe malnutrition- affects both innate and adaptive immunity- more research needed on severe malnutrition

Specific Adaptive Host Defenses

●Acquired through active infection / vaccination ●3rd line - pathogens that have evaded innate immunity ○Specificity- target specific pathogens ○Memory- quick response to previously exposed pathogens ●Primary response- programming due to 1st exposure ●Secondary response - faster & stronger due to memory of 1st exposure

Mechanical Defenses

●Actions that physically remove microbes & debris ●Shedding of skin cells ●Mucociliary sweeping ●Coughing ●Peristalsis- muscular contractions in digestive tract ●Eyelashes, eyelids -prevents dust, airborne microbes ●Blinking flushes them out, bathes eyes in tears ●Flushing of bodily fluids (e.g., urination, tears)

Activation & Differentiation of Helper T Cells

●Activated by APCs presenting processed foreign epitopes with MHC II ●1st step -T cell receptor (TCR) recognizes foreign epitope on MHC II ●2nd step- CD4 interacts with MHC II to anchors MHC II-TCR complex ●Helper T cell must recognize both foreign ("nonself") epitope and "self" antigen of the APC for activation ●3rd step - APC + T cell secrete activating cytokines ●Activated cell proliferates, divides ●Produces clonal naïve helper T cells ●These differentiate into subtypes with different functions

Apoptosis

●Activated cytotoxic T cells & NK cells induce apoptosis ●NK cells recognize nonspecific signals of cell abnormality ●Cytotoxic T cells recognize infected cells through antigen presentation ●Releases enzymes to destroy cell ●Controlled, efficient programmed cell death destroys, removes cells without releasing pathogens

classifications of adaptive immunity

●Active immunity- activation of own adaptive defenses ●Passive immunity- transfer from another person/ animal ●Natural active immunity - after natural exposure to pathogen - E.g. lifelong immunity after measles ●Length of time of protection varies depending upon pathogen, antigens ●E.g. protein spike structures can activate lifelong immunity; carbohydrate capsule may activate shorter-term immunity ●Natural passive immunity-passage of antibodies from mother to her child ○IgG crosses placental barrier ~ 6 months after birth ○Secretory IgA transferred through breast milk ●Artificial passive immunity -transfer of antibodies from a donor ○Prophylactic (prevents disease after exposure), e.g. against rabies & fast infections e.g. Ebola ○Active infections in immunocompromised patients ○Treatment of bacterial toxins e.g. tetanus anti-toxin

General Signs and Symptoms of Urogenital Infections

●Acute or chronic ●Cystitis -inflammation of bladder ●Urethritis- inflammation of urethra ○In men- burning, discharge, blood in semen or urine ○In women- painful, frequent urination, vaginal discharge, fever, chills, abdominal pain ○If urethritis is caused by a sexually transmitted pathogen- painful vesicles (blisters), warts, ulcers Pyelonephritis ●Serious infection of one/both kidneys ●Fever, chills, nausea, vomiting, lower back pain, frequent painful urination ●Chronic in individuals with malformations/ damage in kidneys Glomerulonephritis ●Inflammation of glomeruli of nephrons - acute or chronic ●Excessive protein, blood in urine, increased blood pressure, fluid retention (edema of face, hands, feet) ●Epididymitis- inflammation of epididymis (men) -pain in scrotum, testicles, groin, swelling, redness, warmth ●Orchitis- inflammation of testicle -complication of mumps ●Prostatitis -Inflammation of prostate gland ○Fever, chills, pain in bladder, testicles, penis, burning during urination, difficulty emptying bladder, painful ejaculation ●Vaginitis- inflammation of vagina ○Overgrowth in microbiota, or infections by transient pathogens (bacteria/yeast) ○No symptoms, or discharge, odor, itching, burning ●Pelvic inflammatory disease (PID)- infection of uterus, cervix, fallopian tubes, ovaries ○by Neisseria gonorrhoeae, Chlamydia trachomatis ●Salpingitis - Inflammation of fallopian tubes- serious PID ○Pain in lower abdomen, vaginal discharge, fever, chills, nausea, diarrhea, vomiting, painful urination

Variolation

●Deliberate inoculation of individuals with infectious material from scabs / pustules of smallpox ●Originated in 10th century China - risky

Class switching

●After initial secretion of IgM, plasma cells switch to produce IgG, IgA, or IgE = class switching or isotype switching ●Allows plasma cells cloned from same activated B cell to produce variety of antibodies with same epitope specificity ●Accomplished by genetic rearrangement of gene segments encoding constant region ●Variable region is not changed, so antibody retains original epitope specificity

akaliphile

●Alkaliphiles -optimal pH 8- 10.5 ●E.g. Vibrio cholerae (cholera) survives pH 8-11 ●How do alkaliphiles survive in high pH? ○Evolutionary modification of lipid & protein structure ○Proton motive force in an alkaline environment - uses Na+ ion gradient

Gene regulation

●All genetically identical cells don't express same genes ●Only some proteins are expressed at a given time ●Genomic DNA = structural genes +regulatory genes ●Gene expression is tightly regulated (gene regulation) ●Prokaryotes- point of transcription- conserves resources ●Eukaryotes - regulated post-transcriptionally; allows for cell differentiation PROKARYOTES ●Structural proteins with related functions encoded together in a block called "operon " ●Transcribed together under a single promoter ●Forms a polycistronic transcript ●All genes for particular pathway can be encoded this way ●In E. coli, all genes for enzymes to use lactose as an energy source lie next to each other ●Lactose (or lac) operon controlled by single promoter, the lac promoter ●Some products are required consistently, so they are unregulated ●Constitutively expressed- transcribed & translated continuously ●Enzyme products for cell maintenance -DNA replication, repair, expression, core metabolism ●Others produced on as-needed basis - regulated by transcription factors ●Regulatory region of an operon = promoter + region near it where transcription factors bind EUKARYOTES ●Repressors and activators used for regulation ●Also use enhancers for regulation - factors that bind to regions far away from the gene ●Epigenetic regulation by chemical modification of DNA or histones ●Influences packaging state of DNA affecting the availability of unwound DNA for transcription

RNAI tech gene silencing

●Antisense RNA (complementary to specific parts of mRNA) - seen in RNA interference (RNAi) ●Natural mechanism -prevents mRNA from guiding protein synthesis (used as protection against viruses)

Bisbiguanides

●Antiseptic -chlorhexidine, alexidine ●Broad-spectrum- yeasts, bacteria, enveloped viruses ●Pseudomonas aeruginosa, develops resistance up on repeated exposure ●Disrupts cell membranes; bacteriostatic at lower concentrations, bactericidal at higher concentrations ●Ineffective against Mycobacterium spp and spores ●Used as oral rinse, hand scrub for medical personnel

Legionnaires Disease

●Atypical pneumonia- Legionnaires disease legionellosis) aerobic Gram -ve bacillus, Legionella pneumophila TEST QUESTION: ●Bacterium infects free-living amoebae that inhabit moist environments ●Infections occur from human-made reservoirs- air-conditioning cooling towers, humidifiers ●Aerosols cause infections in susceptible individuals, people with chronic heart or lung disease or weakened immune system ●Bacteria enters alveoli, is phagocytized ●Inserts proteins in endosomal membrane of macrophage ●Prevents lysosomal fusion, allowing proliferation ●Mild to severe pneumonia, depending on host status ●Fever, nausea, vomiting, confusion ●Diagnosis is complicated- (fastidious) hard to culture ●Rapid diagnostic test works only for 1 serotype ●Treated with fluoroquinolone and macrolide antibiotics ●Sometimes fatal, no vaccine

Myasthenia Gravis - systemic Autoimmune

●Autoantibodies directed against acetylcholine receptors in synaptic cleft of neuromuscular junctions ●Affects neuromuscular transmission ●Symptoms - extreme muscle weakness, potential death through respiratory arrest in severe cases

multiple sclerosis -systemic Autoimmune

●Autoimmune central nervous system (CNS) disease- affects brain, spinal cord ●Lesions in multiple locations in CNS ●Immune cells infiltrate across blood-brain barrier ●T cells promote inflammation, demyelination, neuron degeneration -disrupt neuronal signaling ●Symptoms- visual disturbances; muscle weakness; difficulty with coordination, balance; numbness, prickling, or "pins and needles"; cognitive, memory problems

AW- water activity

●Available moisture- Aw = ratio of vapor pressure of medium to that of pure distilled water ●Aw of water is equal to 1.0, bacteria need high Aw (0.97-0.99); fungi tolerates dryness ●Used to preserve food ●Bacteria that need high atmospheric pressure- barophiles (live at the bottom of the ocean)- hard to grow in lab

B cell production and maturation

●B cells- from multipotent hematopoietic stem cells in bone marrow ●Lymphoid stem cells become lymphoblasts, continue to mature in bone marrow Maturation ●After assessment of antigen-binding receptors ○+ve selection - B cells with normal functional receptors ○-ve selection to eliminate self-reacting B cells to minimize autoimmunity ■by apoptosis ■editing/modification of receptors ■induction of anergy in the B cell ●Cells that pass, travel to spleen for final maturation - become naïve mature B cells awaiting activation

cloning using transformation

●Bacteria take up free DNA from surrounding ●Some bacteria (Bacillus spp.) are naturally competent ●Bacteria can be made artificially competent -by introducing pores using chemicals or electricity ●Antibiotic-containing medium used to inhibit untransformed host cells ●Blue-white screening used to locate plasmid vector

Cystitis

●Bacterial infection, or a reaction to radiation treatment, hygiene sprays, or spermicides ●Bladder pain, dysuria (burning, discomfort, or pain), pyuria (pus), hematuria (blood) ●Common in women, elderly- increased risk with catheterization, kidney stones or prostatitis ●Gram -ve: Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae ●Gram +ve: Staphylococcus saprophyticus, Enterococcus faecalis, Streptococcus agalactiae ●Screened with routine manual urinalysis ●Strips used to test for nitrites, leukocyte esterase, protein, or blood - can indicate active bacterial infection ●Rapid tests have low specificity & sensitivity ●Urine culture on blood agar, MacConkey agar to confirm bladder infection ●Treated with antibiotics, pain meds for dysuria ●Treatment more difficult in elderly patients

Biofilm Infections of Skin and Eyes

●Bacterial infections of skin, eyes usually caused by more than 1 pathogen - multiple pathogens in biofilm ●Biofilms interfere with healing process ●Biofilms vary in composition, difficult to replicate in lab

base pairing

●Base pairing between purine and pyrimidine (H bonds) ●A & T are complementary- 2 H bonds ●C & G are complementary- 3 H bonds ●Heat or chemicals can break H bonds causing DNA denaturation ●Reversible - Cooling or removing chemicals leads to renaturation (reannealing) ●Harder to break bonds between C & G (why?)

Anatomy of the Urinary Tract

●Basic structure common between males and females ●Urinary & genital structures overlap in males ●Kidneys made of filtration units called nephrons ●Nephron contact blood through capillary bed- glomerulus ●Urine collects in kidney, empties through ureter, drains to urinary bladder for storage ●Released from bladder to urethra, excreted through opening of urethra

Bacterial growth curve 1. Lag phase

●Beginning of growth curve (inoculum) ●Cells gear up for next phase , # does not change ●Cells grow larger; more metabolically active ●Synthesize required proteins, repairs damaged cells ●Duration determined by ○species, genome, medium, size of inoculum

Pertussis (Whooping Cough)

●Bordetella pertussis, Gram -ve coccobacillus ●Mucus accumulation in lungs leads to severe coughing ●Following coughing, a "whoop" sound is produced as air is inhaled through inflamed, restricted airway ●Adults also infected, symptoms worse in infants, children ●Highly communicable through droplet transmission ●Following inhalation, bacteria attaches to epithelial cells using an adhesin- filamentous hemagglutinin ●Bacteria grows at site of infection, produces exotoxins Infection has 3 stages ●Catarrhal stage- initial infection, mild, but most infectious -nasal congestion, runny nose, sneezing, low-grade fever ●Paroxysmal stage- mucus accumulation leads to uncontrollable coughing spasms that can induce vomiting; lasts several weeks ●Convalescence stage -chronic cough for several months; (100-day cough) ●In infants, coughing can be forceful enough to cause fractures in ribs; prolonged infections can lead to death ●Diagnosis by culturing directly on specialized medium with sample taken in first 2 weeks ●Specimens require quick transport, >24 hours ●Within first month, diagnosed using PCR techniques; later stages ELISA ●Generally self-limiting; erythromycin or tetracycline effective only during early stages ●Antibiotics given later reduce rate of transmission ●Active vaccination is best approach - DTaP & Tdap vaccines ("aP" component is a pertussis toxoid)

Severe Combined Immunodeficiency (SCID)

●Both B-cell + T-cell defects RARE ●Cannot develop memory; no protection by vaccination ●Live attenuated vaccines actually cause infection ●Most common form is X-linked SCID (50%) in males ●Diagnosed within first few months of life after developing severe, life-threatening, opportunistic infections by Candida spp. or pathogenic strains of E. coli ●Without treatment, babies do not survive infancy ●Bone marrow transplant may help but risky ●Famous case -David Vetter (1971-1984), "Bubble Boy" lived in plastic bubble to avoid opportunistic microbes ●Received bone marrow transplant from his sister ●Latent Epstein-Barr virus infection in her bone marrow, led to mononucleosis, he died of Burkitt lymphoma at age 12

supercritical fluid

●CO2 becomes supercritical pressurized ●Sterilizes -forms carbonic acid, lowers cell pH ●Nonreactive, nontoxic, nonflammable; effective at low temps, preserves integrity ●Foods (spices, juices), med devices (endoscopes) ●Disinfects tissues- skin, bones, tendons, ligaments prior to transplantation ●Also used for pest control; kills insect eggs, larvae

DNA supercoiling

●Can be underwound < 1 turn per 10 bp ●Overwound > 1 turn per 10 bp when relaxed ●Topoisomerases -enzymes that maintain supercoiled structure ●Prevents overwinding during replication

Fungal Infections of Reproductive System

●Candida - dimorphic, part of normal microbiota ●Adheres, invades host cells, forms biofilms, secretes hydrolases ●Can change phenotype to protect from immune system ●Imbalance in Lactobacilli due to antibiotic therapy, diabetes, pregnancy ●Severe immunosuppression in HIV infection allows Candida to thrive Vaginal candidiasis- yeast infection ●Inflammation with symptoms itching, discharge, odor ●Cutaneous candidiasis, oral thrush ●Can be sexually transmitted but not considered as STI ●Diagnosis- microscopic evaluation of vaginal secretions to determine excess of Candida ●Culturing not useful because it is part of microbiota ●Topical or oral antifungals ●Prevention is difficult - many ways can occur

Candidiasis of the Skin and Nails

●Candida albicans causes cutaneous candidiasis part of normal microbiota ●Intertrigo -rash that occurs in skin folds, or other localized rashes on the skin ●Also infects nails - yellow and hard ●Diagnosed by clinical observation, culture, wet mounts ●Susceptibility testing for anti-fungals is recommended ●Treated with topical or systemic antifungals ●Can be invasive, immunocompromised patients need preventive treatment ●Repeat infections occur ●Reduced by avoiding excessive moisture, maintaining good health, practicing good hygiene, using appropriate clothing and footwear

DNA function

●Carries genetic code ●Instructions to build, control cell ●But no structural role ●Transmitted from parent to offspring (VGT) ●DNA replicated first, cell then divides ●Can be enzymatically degraded to reuse nucleotides

mRNA

●Carries message from DNA ●When a certain protein is required, the gene for it is "turned on" ●mRNA synthesized through transcription ●mRNA interacts with ribosome ●Directs protein synthesis of protein through translation ●Relatively unstable, short-lived, esp in prokaryotes ●So, proteins only made when needed ●rRNA, tRNA -stable types of RNA

Signs and symptoms of Respiratory Infection

●Cause acute inflammatory response ●Rhinitis - inflammation of nasal cavities -cold, hay fever, allergies ●Sinusitis- inflammation of sinuses Pharyngitis- sore throat might need antibiotic ●Otitis- inflammation of ear; Otitis media (middle ear) ●Laryngitis- can cause voice loss ●Tonsillitis -inflammation of tonsils; chronic cases may be treated surgically with tonsillectomy

Viral Infections of Skin and Eye

●Cause rashes or lesions on skin; infections originate from various portals of entry Papillomas ●Warts- human papillomavirus (HPV) transmitted by direct contact ●Vaccination available for some strains ●Types- common warts, plantar warts, flat warts, filiform warts and genital warts ●Common warts -fingers, backs of hands, around nails ●Plantar warts (foot warts) - sole of foot, can grow inwards, causing pain, pressure during walking ●Flat warts- anywhere on body, numerous, smooth ●Filiform warts- long, threadlike warts that grow quickly ●Treatment is sometimes required -frozen off with liquid nitrogen, topical application of salicylic acid ●Electrosurgery (burning), curettage (cutting), excision, laser treatments, treatment with bleomycin, chemical peels, immunotherapy

Herpes keratitis

●Caused by HSV-1, spreads to eye leading to keratoconjunctivitis ●Affects conjunctiva & cornea, causing irritation, excess tears, light sensitivity ●Deep lesions form in cornea, leading to blindness ●Laboratory testing necessary to confirm diagnosis ●Once confirmed, antiviral medications may be prescribed

Tineas

●Caused by dermatophytes- require keratin ●Trichophyton, Epidermophyton, Microsporum cause cutaneous mycoses ●Tineas (ringworm) named based on location, symptoms ●Found in moist, dark, environment, in soils ●Spores spread on hair Diagnosis ●Wood's lamp (black lamp that emits UV) -causes spores, hyphae to fluoresce ●Microscopic evaluation from skin scrapings, hair, or nails ●Grown on Sabouraud dextrose agar- selective for dermatophytes, inhibits bacteria, saprophytic fungi ●Initial identification by macroscopic colony morphology; confirmed by microscopic morphology ●Topical & oral antifungals

frameshift mutation

●Change in codon triplet- change of 3 nucleotides (milder) ●Frameshift mutations insertions or deletions of a # of nucleotides -not a multiple of 3 ●Extremely problematic - shifts in the reading frame ●Every AA after point of mutation is changed ●New reading frame may have stop codon before end ●Almost always nonfunctional

double helix

●Chargaff Rules ○Amount of A = amount of T ○Amount of G = amount of C ●Rosalind Franklin & R.G. Gosling used X-ray diffraction to visualize DNA ●Watson & Crick - proposed double helix model + base pairing

Inflammation-Eliciting Mediators

●Chemical mediators of inflammation & fever ●Stimulated by cytokines 1.Acute-phase proteins (act as opsonins, activating complement through lectin pathway) 2.Mast cells & basophils -release histamine (proinflammatory compound) ●Histamine receptors are found on many cells ●Cause proinflammatory events -bronchoconstriction & smooth muscle contraction Leukotrienes ●Released by mast cells ●More potent & longer lasting than histamine ●Induce coughing, vomiting, diarrhea, to expel pathogens 4. Prostaglandins ●Helps set body temperature higher, leading to fever 5. Bradykinins ●Contributes to edema

Antimicrobial peptides ( AMP's)

●Chemical mediators with broad-spectrum antimicrobial properties ●Produced routinely or in response to pathogens ●Induces cell damage in microbes ●Defensins & bacteriocins

Chlamydia

●Chlamydia trachomatis - also causes nongonococcal urethritis (NGU), epididymitis, orchitis in men ●Many infections are asymptomatic ●In women, causes urethritis, salpingitis, PID ●Chlamydial infections may be associated with an increased risk of cervical cancer ●Routine screening is recommended for sexually active women <age 25, at high risk (i.e., not in a monogamous relationship), or beginning prenatal care ●Some serovars cause infection of lymphatic system in groin - lymphogranuloma venereum ●Common in tropicals, can also co-occur with HIV infection ●After microbes invade lymphatic system, buboes (large lymph nodes) form, burst, releasing pus ●Male genitals can become greatly enlarged; in women rectum may become narrow ●Azithromycin or doxycycline prescribed

Pneumocystis Pneumonia (PCP)

●Pneumocystis jirovecii- leading cause of pneumonia in AIDS patients, premature infants, immunocompromised ●Fever, cough, shortness of breath - fatal if untreated ●Diagnosis is difficult- microscopic examination of tissue, fluid samples from the lungs ●PCR-based test for asymptomatic patients with AIDS ●Sulfa drugs used for treatment (heavy side effects)

Gonorrhea

●Clap- common STD- prevalent in people aged 15-24 ●Neisseria gonorrhoeae (gonococcus/GC) have fimbriae to attach to epithelium ●Can also infect other tissues -skin, meninges, pharynx, conjunctiva ●Many infected individuals are asymptomatic carriers ●Symptoms are different between males & females ●Men -pain, burning during urination, discharge from penis -yellow, green, or white; testicles swollen or tender ○Over time, symptoms increase, spreads, causes chronic infection ○Can also develop in rectum, causing discharge, soreness, bleeding, itching, pain ●Women- pelvic pain, discharge, intermenstrual bleeding, pain or irritation with urination ○Chronic infection can increase menstrual flow ○Infections that spread to endometrium, fallopian tubes can cause PID ●PID can lead to infertility -scars, blocks fallopian tubes (salpingitis) ●Increases risk of life-threatening ectopic pregnancy ●If it spreads through blood (bacteremia) can affect other organs - heart (gonorrheal endocarditis), joints (gonorrheal arthritis), meninges around brain (meningitis) ●Urethritis by N. gonorrhoeae is difficult to treat due to antibiotic resistance -cephalosporins prescribed ●Treatment of sexual partners is recommended to avoid reinfection, spread

cleaning protocols

●Clinical items - Critical, semicritical, noncritical ●Critical - Must be sterile; used inside body ○Surgical instruments, catheters, IV fluids (will reach blood) ●Semicritical - May contact mucous membranes or nonintact skin; (does not penetrate tissues) ○Needs high level of disinfection ○Gastrointestinal endoscopes, nebulizers (breathing machine) ●Noncritical - May contact but not penetrate intact skin ○Needs to be clean, disinfection not required ○Bed linens, furniture, stethoscopes, & BP cuffs Degerming ●Gently scrubbing of living tissue with mild chemical ●Remove most (not all) microbes from skin's surface ●Handwashing, alcohol swabs at injection site Sanitization ●Cleansing fomites( inanimate objects) to levels safe for public health ●Commercial dishwashers (restaurants) , hospital sanitizers

genomic library

●Clone genomic fragments into plasmid or bacteriophage ●Enzymatically digested genomic DNA ●Ligate into plasmid OR a pre-digested bacteriophage (then packed into phage particles) ●Infect E. coli host cells ●Plaques can be screened for gene of interest ●Phages useful for larger fragments, e.g. ƛ phage for E.coli

Growth Curve

●Closed culture (batch culture) ●No nutrients added, waste is not removed ●Culture density - # of cells per unit volume ●In closed environment, culture density = # of cells in population ●Infections of body don't always follow growth curve

Aspergillosis

●Common filamentous fungus in soil -most people exposed but very few become sick ●In immunocompromised patients causes aspergillosis ●Inhalation of spores leads to asthma-like allergic reactions ●Shortness of breath, wheezing, coughing, runny nose, headaches ●Fungal balls, or aspergilloma, form when hyphal colonies collect in the lungs ●Fungal hyphae invade causing pulmonary hemorrhage, bloody cough ●In severe cases, death after pneumonia or brain hemorrhage ●Laboratory diagnosis requires chest radiographs microscopic examination of tissue and respiratory fluid ●Treated with iv antifungals ●Allergic symptoms managed with corticosteroids to suppress immune system, reduce inflammation

cDNA library

●Complementary DNA -libraries from mRNA ●mRNA cannot be cloned directly ●Used as template by reverse transcriptase ●Advantage -contains DNA from only expressed genes; introns, promoters etc are removed ●Disadvantage - cannot be used to study genome in its entirety

T Cell-Dependent Activation of B cells

●Complex, stronger immune response, develops memory ●BCRs interact with free protein antigen or antigens on intact pathogen ●Antigen is internalized, processed, presented by MHC II, recognized by helper T cells specific to antigen ●TCR recognizes Ag, CD4 molecule interacts with MHC II ●Coordination between B cells & helper T cells specific to the same antigen is called linked recognition ●After linked recognition, T helper cells produce cytokines to activate B cell ●B cells clone, differentiate into memory B cells & plasma cells ●Plasma cells secrete IgM antibodies

Phenolics (chemical)

●Compounds with a benzene ring & -OH group (phenol) ● Phenolics-Stable, persistent on surfaces, less toxic than phenol (ex. Antiseptic mouthwashes, throat lozenges, antibacterial soap) ●pHisoHex in hospitals (betadine) ●Prevent contamination of citrus crops (pesticide) ●Natural phenolics in plants- thymol, eucalyptol ●Denatures proteins, disrupts membranes ●E.g. active ingredient in Lysol, Triclosan

cloning using conjugation

●Conjugation- uses F plasmids ●Transduction - uses bacteriophages ●DNA fragments engineered into phagemid - plasmids with phage sequences packaged into bacteriophages ●Bacterial are infected with bacteriophages ●Depending on type of phage, it can integrate into host genome (lysogeny), or exist as a plasmid

Infections of the eye

●Conjunctiva -portal of entry for pathogens ●Conjunctivitis (pink eye) -Inflammation of conjunctiva ○Acute purulent conjunctivitis -pus formation ○Acute hemorrhagic conjunctivitis- bleeding ●Blepharitis- inflammation of eyelids ●Keratitis - inflammation of cornea ●Keratoconjunctivitis-inflammation cornea & conjunctiva ●Dacryocystitis- inflammation of lacrimal sac, nasolacrimal duct is blocked ●Infections caused by bacteria, viruses, allergens, pollutants etc ●Viral conjunctivitis -fever, watery discharge with upper respiratory infection, itchy eyes ●Infections of structures beneath cornea are less common

The complement system

●Connects innate and adaptive immunity ●Innate - found circulating in plasma to act quickly ●Precursor proteins (>30 proteins- C1 - C9) ●Adaptive - activated in cascading sequence in the presence of microbes - complement activation ●3 pathways of activation- Alternative pathway, Classical pathway, Lectin pathway

Antibody Classes

●Constant region determines class/ isotype ●IgG, IgM, IgA, IgD, and IgE IgG ●Monomer, most abundant & versatile ●Can cross placental barrier IgM ●Produced as monomer, secreted as a pentamer ●1st antibody to be produced - diagnostic marker for active /recent infections IgA ●Dimer, secretory- common in secretions -mucus, breast milk, tears, saliva IgD ●Not secreted- membrane-bound monomer on surface of B cells as antigen-binding receptor IgE ●Least abundant ●Restricted to anti-parasitic defenses ●Central to allergic reactions

Coronavirus SARS-CoV-2

●Coronavirus disease -19, zoonotic (bats) ●First seen in China in Dec 2019, declared pandemic in March 2020 ●Airborne and droplet transmission ●Fever, cough, headache, fatigue, breathing difficulties, loss of smell & taste ●1/3rd of the infected are asymptomatic ●Acute complications especially in elderly - pneumonia, sepsis, cytokine storm, shock, death ●Children have lesser risk of infection, less severe symptoms ●Long covid - long term complications still being studied ●Diagnosed by PCR methods ●Self isolation, quarantine, social distancing, masking ●mRNA vaccine available, passive antibodies, antivirals under EUA ●486 million infected (81 million in US), 6 million deaths (1 million in US) ●So much still unknown

Diphtheria

●Corynebacterium diphtheriae - Gram +ve rod ●Diphtheroids- common in nostril ●Pathogenic strains have bacteriophage-encoded protein— diphtheria toxin, makes it dangerous ●Also causes impetigo-like lesions on skin ●Affects all ages, most severe in < 5 years or >40 years ●Transmitted in droplets, aerosols from coughing ●After colonizing throat, bacterium remains in oral cavity; begins producing diphtheria toxin ●Toxin blocks host protein synthesis, causes cell death, inflammatory response ●Grayish exudate of dead host cells, pus, red blood cells, fibrin, infectious bacteria form a pseudomembrane across throat within hours ●Covers membranes of nasal cavity, tonsils, pharynx, larynx ●Obstructs pharynx, trachea, leads to suffocation and death ●Intubation (placement of a breathing tube in trachea) is required in advanced infections ●If toxin spreads, it can damage other tissues -myocarditis (heart damage), nerve damage that impairs breathing ●Presumptive diagnosis based on clinical symptoms (pseudomembrane) + vaccination history ●Confirmed with bacterial cultures of throat swabs ●Toxin can be directly detected using modern techniques ●Broad-spectrum antibiotics- penicillin, erythromycin are effective in early stages but ineffective against preformed toxins ●If toxin production has already occurred, antitoxins (preformed antibodies against the toxin) are administered, passive immunity ●Effective in neutralizing toxin, but may lead to serum sickness due to horse-origin ●Widespread vaccination has reduced diphtheria ●4 combination toxoid vaccines available ●DTaP, Tdap, DT, Td ("d," "t," "p" = diphtheria, tetanus, pertussis; "a" stands for acellular) ●Capitalized letters indicate a full-strength dose; lowercase letters indicate reduced dosages ●Current recommendations- children - 5 doses of DTaP vaccine in youth + Td booster every 10 years ●Children with adverse reactions to pertussis vaccine may be given the DT vaccine in place of the DTaP

Transcription in prokaryotes

●DNA info is transcribed into mRNA (RNA transcript with A, C, G, uracil U) ●Mobile molecular copy of original DNA ●Needs DNA helix to partially unwind (transcription bubble) ●1 strand used as template - antisense strand ●RNA product is complementary to template strand ●Almost identical to non-template strand (sense strand) ●RNA pol adds nucleotides to growing chain -does not require a primer INITIATION:●RNA polymerase binds at a sequence (promoter) ●Genes of proteins with related functions -transcribed under same promoter ●Forms polycistronic mRNA - codes multiple polypeptides ●Nucleotide pair to first 5' RNA nucleotide transcribed -initiation site ●Nucleotides before initiation site are "upstream"; those after it are downstream ●Promoters are upstream of genes they regulate ●Promoter sequences vary among bacteria ●Initiation site is designated +1 ●At -10 and -35 positions prior to the initiation site are 2 promoter sequences ●-10 consensus sequence-TATA box, is TATAAT ●-35 sequence is recognized, bound by σ ELONGATION:●In 5' to 3' direction- rate of ~ 40 nucleotides per sec ●DNA is continuously unwound ahead of enzyme and rewound behind it TERMINATION:●Polymerase dissociates, liberates new RNA ●DNA template has repeated nucleotide sequences that are termination signals ●Causes RNA pol. to stall & release RNA transcript

Nitrogen bases

●DNA named according to nitrogenous bases ●Purines - adenine (A), guanine (G) Pyrimidines -cytosine (C) and thymine (T)

extrachromosomal DNA

●DNA outside chromosomes - also part of genome ●In eukaryotes - chromosomes from organelles ●Genomes of some DNA viruses can be maintained independently during latent viral infection ●E.g. human papillomavirus (HPV) ●In Prokaryotes = plasmids

Chronic Granulomatous Disease

●Defect in phagocytic cells ●Prevent production of superoxide radicals in phagolysosomes ●Impairs antibacterial activity; infections persist longer ●Leads to chronic local inflammation called a granuloma

X-Linked Agammaglobulinemia

●Deficiency in B cells due to defective differentiation ●Lacks specific antibody production known as X-linked agammaglobulinemia ●Inherited on X chromosome; absence of Ab in serum ●Recurrent infections due to extracellular pathogens that cause pyogenic infections (produce puss) ●Cell-mediated immunity not impaired ●Patients protected from infections by viruses or intracellular pathogens

Haemophilus Pneumonia

●Encapsulated strains of Haemophilus influenzae cause meningitis; nonencapsulated strains cause pneumonia ●Small, Gram -ve coccobacillus; found in healthy children ●Haemophilus pneumonia mainly in the elderly ●Spread by droplets, aerosols from coughing ●H. influenzae (fastidious) grows only on specialized media ●Infects alveoli, causes inflammation, accumulating fluids ●Antibiotic resistance is developing

Cryptococcosis

●Encapsulated yeast Cryptococcus neoformans ●Ubiquitous in soil, isolated from bird feces ●Immunocompromised people infected by inhaling spores ●Fever, fatigue, dry cough; in immunocompromised patients, pulmonary infections disseminate to the brain ●Causes meningitis with headaches, sensitivity to light, confusion; left untreated, often fatal ●Diagnosis- microscopic examination of lung tissues, CSF ●Long term treatment with antifungals

Histoplasmosis

●Endemic to Mississippi Valley of US, Central & South America, Africa, Asia, Australia ●Histoplasma capsulatum, is a dimorphic fungus ●Grows as a filamentous mold in environment; as a budding yeast ininfections ●Primary reservoir- soil, locations rich in bat or bird feces ●Caused by inhaling microconidial spores; cannot be transmitted from human to human ●Symptoms only in young, elderly, immunocompromised ●Similar to Tuberculosis- following inhalation, spores enter lungs, are phagocytized, survives, multiplies within phagocytes ●Forms granulomatous lesions, resembling Ghon complexes, even in asymptomatic cases ●Can become chronic; reactivation can occur ●Pulmonary histoplasmosis -fever, headache, weakness with some chest discomfort ●Initial diagnosis by chest radiographs, cultures grown on Sabouraud's dextrose agar ●Complement fixation assay to confirm diagnosis ●Mostly self-limiting; antifungal therapy not required except in the immunocompromised

Fifth disease

●Erythema infectiosum- highly contagious distinct rash, common in children ●Parvovirus B19, transmitted by respiratory secretions ●Some asymptomatic; others have cold-like symptoms (headache, fever, and upset stomach) during early stages when illness is most infectious ●Several days later, distinct red facial rash appears called "slapped cheek" rash ●2nd rash on arms, legs, chest, back, or buttocks; may come and go for weeks ●Disappears in 7-21 days, gradually becoming lacy ●In children, resolves without medical treatment ●Adults have more serious symptoms ●No rash, joint pain, swelling for weeks or months ●Immunocompromised individuals develop severe anemia ●Serological testing can be conducted for confirmation

Generation Time

●Eukaryotic generation time- time between same points in life cycle in 2 successive generations ●Prokaryotic generation time = doubling time through 1 round of binary fission ●Escherichia coli doubles in 20 minutes ●Longer harsh environments ●Most pathogens grow rapidly, like E. coli ●Exceptions - Mycobacterium tuberculosis, 15- 20 hours & M. leprae (leprosy), doubling time is 14 days

genetic research

●Excellent models for study of genetics ●Easy to grow in high population densities ●In small amount of space & short time ●Structurally simple, easy to manipulate genetically

bacterial growth curve 2. Log phase

●Exponential growth ●Actively divides by binary fission ●Generation time under specific growth conditions is genetically determined= intrinsic growth rate ●Constant growth rate, uniform metabolic activity ●Used for industrial and research work ●Most susceptible to disinfectants, antibiotics that affect protein, DNA, cell-wall synthesis

effectiveness of disinfecting agent

●Exposure time - depends on microbial load (longer time for dirtier things) ●Susceptibility to disinfecting agent or protocol ●Concentration or intensity of exposure - depends on level of cleanliness desired

Viral Pneumonia

●Fewer cases than bacteria; in children and elderly ●Adenoviruses, influenza viruses, parainfluenza viruses, respiratory syncytial viruses (RSV) ●Symptoms depend on strain, strength of host defenses ●RSV common in infants- can be life-threatening ●No therapies or vaccines, but is self-limiting in adults ●Highly contagious droplets from coughing, sneezing ●Survives a long time on environmental surfaces

Codons

●First 2 positions important for determining AA ●3rd position (wobble position) is less critical- if changed, same AA can still be incorporated ●AUG (methionine) - start codon ●61 triplets code for amino acids ●3 codons code to terminate synthesis = stop/nonsense codons - UAG, UAA, UGA ●Reading frame set by start codon near 5' end Each set of 3 nucleotides after start is read as 1 codon

Mucormycosis

●Fungi in order Mucorales - bread molds- Rhizopus and Mucor; Rhizopus arrhizus ●Colonize different tissues in immunocompromised patients, but often infect skin, sinuses, or lungs ●Infections in rare in healthy individuals ●Exposure through inhalation, ingestion or absorption of spore through wounds ●Respiratory mucormycosis affects cancer or transplant patients ●Pulmonary mucormycosis- infection of lungs with fever, cough, chest pain, shortness of breath ●Severe cases- coma, death ●Diagnosing is challenging; no serological or PCR-based tests ; tissue biopsy specimens are examined ●Treated with antifungals; surgical debridement ●Immunocompromised patients develop viral, bacterial secondary infections; mortality rate 54%

Syphilis (worst bacterial Sexual transmitted disease)

●G -ve spirochete Treponema pallidum ●T. pallidum lacks LPS endotoxin found in G -ves ●After entering body, T. pallidum moves rapidly into bloodstream, other tissues ●If not treated, goes through 3 stages: primary, secondary, tertiary Primary Stage ●Single lesion on cervix, penis, or anus within 10-90 days of transmission ●Lesions contain T. pallidum cells- highly infectious ●Called a hard chancre, is initially hard, painless, develops into an ulcerated sore ●Localized lymph node swelling can also occur ●In some cases, symptoms are mild, lesion may heal on its own within 2-6 weeks ●Lesions are painless, occur in hidden locations, infected individuals sometimes do not notice them Secondary Stage ●After primary chancre has healed or begun to heal ●Rash affects skin, mucous membranes of mouth, vagina, or anus ●Begins on palms or soles of feet, spreads to trunk, limbs ●On mucous membranes, manifests as patches or wart-like lesions called condylomata lata ●Accompanied by malaise, fever, swelling of lymph nodes ●Highly contagious in secondary stage, lasts 2-6 weeks, is recurrent in about 25% of cases Latent Phase ●After secondary phase, enters latent phase, with no symptoms but high microbial levels- can persist for years ●Blood tests still detect disease during latency Tertiary Stage ●10-20 years after infection, produces most severe symptoms, can be fatal ●Granulomatous lesions called gummas develop in many locations- mucous membranes, bones, internal organs ●Gummas -large, destructive, causing massive tissue damage ●Most deadly lesions in cardiovascular system (cardiovascular syphilis) & CNS (neurosyphilis) ●Cardiovascular syphilis - fatal aortic aneurysm (rupture of aorta) or coronary stenosis (blockage of coronary artery) ●Damage to CNS- dementia, personality changes, seizures, general paralysis, speech impairment, loss of vision, hearing, loss of bowel, bladder control ●Early syphilis diagnosed with darkfield or brightfield (silver stain) microscopy of tissue or exudate ●Presumptive diagnosis with nontreponemal serologic tests ●Detects nonspecific Abs (for lipid antigens) ●Confirmatory testing, must be done with treponemal tests ●Neurosyphilis diagnosis requires multiple tests ●Treatment with parenteral penicillin G, tetracycline, doxycycline

Chancroid

●G-ve rod Haemophilus ducreyi (fastidious) ●Soft chancres on genitals, mouth, anus ●Unlike hard chancres in syphilis, soft chancres are painful, open sores with bleeding & highly contagious fluid ●Bacteria invade lymph nodes, pus discharge from lymph nodes in groin ●Soft chancres compromise protective barriers of skin or mucous membranes, increasing susceptibility to other STIs ●Diagnosis based on clinical observation of genital ulcers ●Tests to rule out other diseases, such as syphilis, genital herpes should be performed ●Azithromycin, ciprofloxacin, erythromycin, ceftriaxone prescribed

Genetic Engineering

●Genetic engineering -process of manipulating DNA in vitro for new combinations of genetic material ●Recombinant DNA is introduced into a host organism ●If DNA is from different species, host organism becomes transgenic

Gene therapy

●Genetic engineering to cure diseases -still experimental ●So far relatively ineffective -exceptions is cystic fibrosis RISKS: ●Adenovirus vector can trigger inflammatory response leading to organ failure ●Virus vector may infect cells not targeted for therapy, maybe cause cancer ●Modified virus could revert to being infectious ●Inserted gene could unintentionally inactivate other important normal gene - can cause tumors or cancers OVERSIGHT: ●Food and Drug Administration (FDA) ●Office of Human Research Protection (OHRP) ●Recombinant DNA Advisory Committee (RAC) at the National Institutes of Health (NIH) ●Gene therapies are under more extensive review by FDA ●Does it inhibit progress in gene therapy research? ●Currently used only in somatic cells- changes are not inherited ●Germ-line therapy in future is more concerning ●U.S. government does not currently fund research projects for germ-line gene therapies ETHICAL: ●Which genetic traits are worthy of being "corrected"? ●For cosmetic reasons or to enhance abilities? ●Used to impart desirable traits to unborn? ●What about social inequality? ●Who is responsible for regulating and policing?

DNA discovery

●Genetics- science of heredity ●Mid 1800s- Mendel showed heritability of specific traits ●Nucleus discovered, NA, then nucleotide bases within

Genotype

●Genome = all of organism's genetic material ●Genes = segments of DNA - instructions for synthesizing proteins, enzymes etc.,. ●Genotype = full collection of genes in a cell ●Cell does not express all genes simultaneously ●Turns on (expresses) or turns off genes as needed G VS P ●Streptococcus mutans produces sticky slime layer to adhere to teeth, forming dental plaque ●Genes for slime layer only expressed in sugar is present ●Genotype of S. mutans is constant (always has the genes to produce it) ●Phenotype (gene expression) changes depending on presence/absence of sugar in environment

Bacterial Pneumonia (know different types of pneumonia)

●Pneumonia- infection of lungs with inflammation, accumulation of fluids, wbcs in alveoli ●Caused by bacteria, viruses, fungi ●Alveoli fill with fluids + wbc (consolidation), air exchange is impaired causing respiratory distress ●Can lead to pleurisy- infection of pleural membrane surrounding lungs, making breathing painful ●3 most common bacteria- Streptococcus pneumoniae, H. influenzae, Mycoplasma pneumoniae

DNA Replication in eukaryotes

●Genomes are more complex, larger ●Multiple linear chromosomes, multiple origins of replication ●Humans -3 billion bps per haploid set of chromosomes ●30,000 to 50,000 origins of replication! ●Rate ~ 100 nucleotides per sec—10x slower DIFFERENCES:●Elongation by eukaryotic DNA pol. ●Leading strand by pol δ (delta) ●Lagging strand by pol ε (epsilon) ●Ribonuclease H (RNase H) removes RNA primer ●DNA ligase seals gaps ●At the end, no place to make primer for last fragment ●Telomerase comes to the rescue TELOMERASE: ●Non-coding repetitive sequences at ends of linear chromosomes ●Protects coding sequences from being lost ●Telomerase (has built-in RNA template) extends ends to prevent degradation ●In humans, telomerase is active only in germ cells, adult stem cells ●In somatic cells -ends of lagging strand remain unpaired, get shorter over time (aging)

Antibodies

●Glycoproteins in blood and tissue fluids ●4 protein chains held together by disulfide bonds ●2 large heavy chains, 2 smaller light chains ●Joined together to form Y-shaped structure

Defences of the respiratory system

●Goblet cells in epithelium secrete mucus (viscous, acidic) ●Mucociliary escalator effect- prevents inhaled microbes from migrating lower -Ciliated epithelial cells- dislodge, propel mucus, trap microbes, upward to epiglottis, to be swallowed ●Upper tract- mucosa-associated lymphoid tissue (MALT) responsible for Secreted antibodies (IgA), lysozyme, surfactant, defensins

Grafts

●Graft -transplantation of organ/ tissue to different location ●Allografts - From one genetically distinct individual to another within same species ●Isograft - From one twin into another (monozygotic twins, genetically identical) -never rejected ●Autograft - From one area on an individual to another area on same individual Xenograft - From an animal into a human

Bacterial infection of the skin

●Gram-positive Staphylococcus spp, Streptococcus spp. Staphylococcal Infections of the Skin ●S. aureus part of normal microbiota, but pathogenic strains cause infections ●Quite contagious & prevalent in community ●Many people are chronic nasal carriers -transfer to hands, fomites or others ●Problematic in hospitals- antibiotic-resistant strains, immunocompromised patients (MRSA) ●Antibiotic sensitivity test required is to identify suitable antibiotic ●Suspected S. aureus infections treated with drugs known to be effective against MRSA - e.g. clindamycin or a tetracycline Staphylococcal virulence factors ●Hemolysins, leukocidins, toxins ●Coagulase +ve; plasma-clotting protein Diagnosis - Samples from wound are cultured ●Microscopy - Gram +ve grapelike clusters ●Colonies on blood agar- opaque white to cream ●Catalase test distinguishes Staph (catalase +ve) from Strep (catalase -ve) Superficial Staphylococcal Infections ●S. aureus pyoderma- purulent skin infections with pus ●Starts as folliculitis, leads to furuncles or carbuncles Folliculitis - ●Bumps, pimples, itchy, red, pus-filled -usually self-limiting ●Due to sweat, skin injuries, ingrown hairs, tight clothing, irritation from shaving ●Identified by skin inspection ●Treatment with topical antibiotics started without culturing, identifying causative agent Furuncles (boils)- deeper infections of superficial staph infection ●Common in young adults, teens- contact sports, sharing athletic equipment, poor nutrition, live in close quarters, or weakened immune systems ●Good hygiene prevents it from becoming more infective, and helps resolve itself ●If furuncles spread/increase - systemic symptoms like fever, chills, then medical care is needed ●Need to be drained, treated with antibiotics Carbuncles - Multiple boils develop into a deeper lesions ●Larger, recurrent, or worsening carbuncles show systemic symptoms ●Need to be drained, treated with antibiotics ●Easy to identify visually but, culturing is recommended ●Antibiotic resistance is common Proper hygiene is important for prevention Staphylococcal scalded skin syndrome (SSSS) -superficial infection by S. aureus in infants ●Bacterial exotoxins cause erythema, severe peeling of skin (like scalding) ●Diagnosed by examination, blood tests for elevated WBC & culturing ●IV antibiotics, fluid therapy for treatment Impetigo ●Infection with vesicles, pustules, with or without bullae (fluid-filled blisters ), around nose, mouth ●S. aureus, Streptococcus pyogenes or coinfection ●Common in children; highly contagious ●Diagnosed through observation, treated with topical or oral antibiotic ●S. pyogenes can lead to serious sequelae -acute glomerulonephritis (AGN)- severe inflammation of kidneys Nosocomial S. epidermidis Infections ●Opportunistic pathogen, not as virulent as S. aureus ●Only in hospital settings - infections are difficult to treat when skin is breached ●Antibiotic resistant; localized infections become systemic if not treated quickly ●To reduce risk, health-care workers must follow strict procedures for handling, sterilizing medical devices before, during surgical procedures Streptococcal Infections of Skin ●Gram +ve cocci in chains- catalase-negative ●Categorized in serological Lancefield groups based on characteristics of surface carbohydrates ●Most clinically important- S. pyogenes - group A streptococcus (GAS) ●Produces extracellular enzymes- streptolysins O & S, hyaluronidase, streptokinase ●Causes many diseases in skin & other organ systems ●E.g. pharyngitis, scarlet fever Cellulitis -In dermis or hypodermis -red skin. warm, painful to touch -caused by S. pyogenes or staphylococci Erysipelas- Large, inflamed patch of dermis (legs, face) Erythema nodosum -Inflammation in subcutaneous fat cells of hypodermis; red nodules on skin, most frequently on shins ●Antibiotic susceptibility test required for treatment ●Penicillin for cellulitis & erysipelas ●Erythema nodosum is self-limiting -treat with NSAIDs, cool wet compresses, elevation, bed rest Necrotizing Fasciitis ●Rare, potentially life-threatening condition = flesh-eating bacterial syndrome ●Caused by S. pyogenes or Klebsiella, Clostridium, Escherichia coli, S. aureus, Aeromonas hydrophila ●Fascia (thin connective tissue between skin & muscle) becomes infected ●S. pyogenes produce proteases- infiltrate, destroy tissues, inactivate complement, prevent neutrophil migration ●Infection, tissue death spread very rapidly; large areas of skin become detached and die ●Treatment requires debridement (surgical removal of tissue) or amputation to stop spread ●Surgery supplemented with IV antibiotics ●Does not always originate from a skin infection; sometimes no known portal of entry ●Experiencing blunt force trauma may increase risk of NF Pseudomonas Infections of the Skin ●Pseudomonas aeruginosa- Gram -ve, oxidase +ve, aerobic bacillus found in water, soil, human skin ●Opportunistic pathogen of wounds, burns ●Hot tub folliculitis -users of pools, hot tubs ●Otitis externa (swimmer's ear) ear canal infection with itching, redness, discomfort, fever, pain, swelling ●Forms biofilms - wounds have distinctive odor of grape soda or fresh corn tortillas- caused by chemical virulence factor used in quorum sensing ●Produces blue-green pus due to pigments pyocyanin ●Resistant to most antibiotics- produces β-lactamases ●Otitis externa - ear drops swimmers ear with acetic acid, antibacterials, steroids to reduce inflammation + antifungals Wound infections treated with topical antibiofilm agents Acne ●80% of teens, young adults; hormonal changes overproduce sebum ●Hair follicles become clogged by shed skin cells, sebum, causing non-inflammatory lesions- called comedones ●Lead to infection by Propionibacterium acnes (Gram +ve, non-spore-forming, aerotolerant anaerobic bacillus on skin that consumes sebum) ●Treatment depends on severity- 3 levels based on number of comedones, inflammatory lesions, types of lesions ●Mild acne - topical agents with salicylic acid (to remove old skin cells) or retinoids ●Moderate acne- antibiotics (erythromycin, clindamycin), acne creams (e.g., benzoyl peroxide), hormones ●Severe acne -isotretinoin shrinks sebacous glands ●Phototherapy, laser therapy kill bacteria and possibly reduce oil production Anthrax ●Zoonotic disease - Bacillus anthracis, Gram +ve, endospore-forming, facultative anaerobe ●Affects sheep, goats, cattle, deer, humans ●Wool sorter's disease; transmitted to humans through contact with infected animals or animal products ●Exposure to endospores in soils ●Majority of cases (>95%) occur when endospores enter body through abrasions of skin -cutaneous anthrax ●Endospores on skin germinate, produce a capsule to prevent phagocytosis, 2 binary exotoxins that cause edema and tissue damage ●Forms nodule in which cells die, forming a black eschar ●Localized infection leads to bacteremia, septicemia ●If untreated, causes death in 20% of patients ●GI anthrax- through digestive tract, (pulmonary or inhalation anthrax) through respiratory tract- more difficult to treat ●Mortality rate for GI anthrax -40%, even with treatment ●Inhalation anthrax- causes influenza-like symptoms, mortality 45% with treatment, 85% without ●Injection anthrax in Europe in IV drug users when drugs are contaminated with B. anthracis ○Signs, symptoms of severe soft tissue infection different from cutaneous anthrax ○Delays diagnosis and treatment, high mortality rate ●can be treated with Broad spectrum antibiotics -penicillin, erythromycin, tetracycline ●Anthrax is a Bioweapon- on United Nations' list of potential agents of bioterrorism ●2001- letters to media, US Congress with anthrax spores ●11 developed cutaneous anthrax, 11 developed inhalation anthrax; 5 with pulmonary anthrax died ●Spores had been carefully prepared to be aerosolized,- perpetrator had a high level of expertise in microbiology ●Vaccine is available for anthrax- unique in formulation and protocols for receiving it ●Administered through 5 intramuscular injections over 18 months with annual boosters ●Approved prior to exposure for at-risk adults (lab workers, animal product handlers, veterinarians, military) ●Protects against cutaneous and inhalation anthrax ●Not approved for routine use after exposure to anthrax at this time

bacterial growth curve 3. Stationary phase

●Growth rate slows & finally stalls ○Waste products accumulate, nutrients used up ○Gradual depletion of oxygen limits ●# of live cells reaches a plateau ●# of new cells = # of cells dying (population relatively stagnant) ●Culture density is constant ●Switch to a survival mode ●Synthesis of peptidoglycans, proteins, NA slow down ●Less susceptible to antibiotics ●Endospores producing bacteria undergo sporulation ●In certain pathogenic bacteria, virulence factors, are expressed ●E.g. Staphylococcus aureus produces enzymes to break down human tissue and clear the way to new tissue

Oral Herpes

●HSV-1- oral contact, causes oral herpes ●HSV-2- sexually transmitted, causes genital herpes ●Both infect mucous membranes ●HSV-1- cold sores, fever blisters, on or around the lips ●Highly contagious, many patients are asymptomatic ●Virus can be latent, residing in trigeminal nerve ganglia between recurring bouts of symptoms Recurrence triggered by stress or environment ●Lesions may blister, break open, crust ●Lips, mouth, face common sites, can spread elsewhere ●Herpes gladiatorum- lesions on neck, shoulders, and trunk of wrestlers, other contact sports ●Herpetic whitlow- lesions on fingers ●Diagnosed from their appearance ●No cure, antivirals like acyclovir reduce symptoms & risk of transmission

Psychrotrophs

●Psychrotrophs - psychrotolerant ●Prefer cooler temps (25 -4 °C) ●Organisms that spoil refrigerated food ●Psychrophiles - found in arctic lakes (<0 °C) ●Optimum temp- 15 °C; cannot survive >20 °C ●Psychrophiles, psychrotrophs important decomposers in cold climates

Genital Herpes

●HSV-1- oral lesions like cold sores ●HSV-2-genital herpes ●Many infected individuals are asymptomatic, do not realize that they carry the virus ●Symptoms - fever, chills, malaise, swollen lymph nodes, pain before fluid-filled vesicles that are irritating, uncomfortable ●Vesicles burst, releasing infectious fluid ●Open lesions increases risk of HIV ●Condoms are ineffective at preventing genital herpes; lesions can occur on areas other than genitals ●In men, lesions on penis, with or without watery discharge ●In women, vesicles develop on vulva, vagina or cervix ●Can become latent, virus hides in neurons, recur on reactivation (when under stress) ●Reactivation causes formation of new vesicles ●Frequency of reactivation varies ●Even between outbreaks and no obvious vesicles, virus can still be transmitted ●Virologic, serologic techniques are used for diagnosis ●PCR is rapid and best for detecting systemic infections ●No cure or vaccine for HSV-2 infections ●Antiviral medications keep it latent, reducing signs, symptoms ●If medication is discontinued, condition returns to original severity ●Medications taken at start of an outbreak or as method of prophylaxis- acyclovir, famciclovir, valacyclovir

Granulocytes (the infantry)

●Have a lobed nucleus & granules in cytoplasm ●Neutrophils Eosinophils Basophils

physical methods of killing microorganisms

●Heat -Thermal death point (TDP)- lowest temp at which all microbes are killed in a 10-minute exposure -Thermal death time (TDT)- length of time to kill all microbes at a given temperature Boiling -Kills vegetative cells, some viruses -Not effective at killing endospores (can survive~ 20 hours) -Becomes less effective at higher altitudes -Not a useful sterilization technique ●Refrigeration. freezing ●Pressure ●Desiccation (drying) ●Radiation ●Sonication ●Filtration ●most ^Kills by disrupting membranes ●Changes permeability ●Damages proteins & NA by denaturation, degradation, or chemical modification

commercial sterilization (food)

●Heat at temperature low enough to preserve food quality ●High enough to destroy pathogens ●Low- & medium-acid foods - 121 °C for of 2.52 minutes ●Time to reduce population of 1012 endospores per can to 1 ●High margin of error-safety is more important than flavor ●Does not eliminate presence of all microbes IT DOES eliminate only pathogens + spoilage organisms concerned with food flavor and sterilizes- thats why it doesn't kill everything

microbial growth at high temperature

●Heat denatures proteins, NA & impairs metabolism ●In thermophiles - ○Lipids have more saturated FA ○DNA sequences > G+ C bases (3H bonds) instead of A-T (2 H bonds) ○Amino acids are replaced to stabilize folding, resist denaturation ●Thermoenzymes from thermophiles have important practical applications

indicators of quality control in autoclaves

●Heat sensitive tape - inexpensive; used every run ●Biological indicator spore strip- endospores of thermophile: Geobacillus stearothermophilus (hardest to kill highest temp) ●Diack tube- glass ampule with temp-sensitive pellet, melts at sterilization temp

Classes of T cells

●Helper T cells, Regulatory T cells, Cytotoxic T cells ●Helper T cells - activate, direct functions of humoral & cellular immunity ●Regulatory T cells - prevent undesirable, damaging immune responses ●Cytotoxic T cells- recognize, target infected cells for destruction ●T cells produce surface glycoproteins called CD -cluster of differentiation molecules ●Helper T cells & regulatory T cells express CD4 ○only activated by APCs presenting Ags with MHC II ●Cytotoxic T cells express CD8 ○recognize Ags presented with MHC I by any cell

Mutations

●Heritable change in DNA sequence ●Wild type- phenotype most commonly seen in nature ●Mutant - change in phenotype compared to wild type In DNA sequence ●Point mutation- Affects 1 base - substituted by another ●Insertions -Addition of 1 or more bases ●Deletions - Removal of 1 or more bases

Sonication (physical)

●High-frequency ultrasound ●Causes rapid changes in intracellular pressure ●Leads to cavitation - formation of bubbles in the cell ●Disrupts cell structures & lyses ●Surgical instruments, lenses etc (can't be heated)

DNA packaging

●Histones - wrap, attach DNA to scaffolding proteins ●Chromatin - histones + DNA ●In eukaryotes, packaging of DNA is influenced by environment (epigenetics) ●Mechanism for regulating gene expression without altering sequence of nucleotides ●Can be maintained through multiple divisions (inheritable)

General Causes and Modes of Transmission

●Hormonal changes increase susceptibility to infections ●Estrogen maintains elasticity, strength, thickness of vaginal wall; keeps it lubricated, reducing dryness ●Low levels of estrogen = thinning of vaginal wall = increasing risk of abrasions that breach protective barrier ●Fecal contamination- E. coli -most common cause of UTI in women; good hygiene can reduce infections Sexually transmitted disease/infection ●CDC prefers term STD, WHO prefers STI ●STI = infections that result in disease + subclinical or asymptomatic infections ●Often affect external genitalia, skin ●Lymph nodes in genital region may also become swollen ●Systemic effects can be mild (e.g., general malaise) to severe (e.g., liver damage or serious immunosuppression)

Fever

●Inflammatory response beyond site of infection- overall increase in body temperature ●Temperature is regulated, maintained by hypothalamus ●Some bacterial or viral infections cause pyrogen production, chemicals that alter the "thermostat setting" ●Pyrogens may be exogenous or endogenous - E.g. endotoxin LPS, produced by G -ve bacteria, is exogenous what happens During a fever ●Fever stimulates leukocytes to kill pathogens ●Rise in temp inhibits growth of pathogens ●Skin becomes pale due to vasoconstriction ●Hypothalamus diverts blood flow away from extremities, to minimize heat loss to raise temp ●Shivering is stimulated to generate heat ●Crisis phase occurs when fever breaks ●Hypothalamus stimulates vasodilation returning blood flow to skin, sweating cools skin ●Low-level fever may help but high fever is dangerous ●Bacterial superantigens cause life-threatening fever ●Superantigens- bacterial or viral proteins that excessively activate T cells and release of cytokines

Biofilm

●Humans have both beneficial & harmful biofilms ●In intestinal, respiratory mucosa - help ward off infections ●Plaque on teeth contributes to dental, periodontal disease ●Also form in wounds, causing serious infections that spread ●Forms on medical devices used in or on body -in-dwelling catheters, artificial joints, contact lenses INSIDE BIOFILMS ●Pathogens exhibit higher resistance to antibiotics ○Cells in deep layers are metabolically inactive ○EPS slows diffusion of antimicrobials ○Ideal environment HGT, including antibiotic resistance genes ○Phenotypic changes like increased production of efflux pumps

Extracellular polymeric substances (EPS)

●Hydrated gel of polysaccharides, proteins, nucleic acids, lipids ●Maints integrity & function ●Channels allow movement of nutrients, waste, gases ●Keeps cells hydrated, preventing desiccation ●Shelters from predation by other microbes or WBCs ●Properties vary according to residents & environment

Unregulated Activation of T Cells

●If T cell activation is controlled, regulated = effective protective response ●If T cell activation is unregulated, excessive = life-threatening response ●Occurs when there is excessive, uncontrolled release of cytokines = cytokine storm ●Some pathogens produce toxins known as superantigens that trigger unregulated response ●E.g. Toxic shock syndrome toxin (TSST)

ABO blood group incompatability

●Immunohematology- study of blood & blood-forming tissue in relation to the immune response ●Karl Landsteiner identified 4 blood types ●Presence or absence of surface carbohydrates "A" & "B" ●ABO blood types are inherited as alleles with patterns of dominant & codominant inheritance ●Alleles for A & B blood types are codominant, both are dominant over blood type O ●Isohemagglutinins -IgM that cross-react with antigens not present on individual's own RBCs ●Produced within weeks of birth

MIcrobiome

●Important first-line defense ●Occupy cellular binding sites, compete for nutrients ●Prevent critical early steps of pathogen attachment and proliferation required for establishing infection ●E.g. Candida spp in vagina ●Increased susceptibility to infections when microbiota is disrupted or eliminated

Anatomy of the reproductive system

●In males- urethra part of both urinary & reproductive system ●Testes- produces sperm, epididymis- collects sperm, passes to vas deferens for sperm maturation ●Seminal vesicles, prostate- accessory glands- produce fluid that supports sperm ●During ejaculation, vas deferens releases mixture of fluid & sperm (semen) into urethra to end of the penis ●Female reproductive system- external genitalia (vulva)- open to vagina, that connects to cervix ●Cervix- lower part of uterus -common site of infection ●Uterus leads to fallopian tubes, ovaries ●Ovaries ○site of ova, estrogen, progesterone production ○involved in maturation of gametes ○maintenance of reproductive organs ○preparation of uterus for pregnancy ○regulation of menstrual cycle

Graft-versus-Host Disease (GVHD)

●In recipients of bone marrow transplants & peripheral blood stem cells ●Unique -transplanted tissue produces immune cells ●APCs in donated bone marrow recognize host cells as non-self, activate donor cytotoxic T cells ●Once activated, donor's T cells attack recipient cells ●Develops within weeks after transplant, causing tissue damage to skin, GI tract, liver, eyes ●Acute GVHD may lead to cytokine storm ●Chronic GVHD develops months after transplant ●Donated bone marrow is processed to remove as many donor APCs & T cells as possible, leaving mostly hematopoietic stem cells

Obligate anaerobes

●In soil, bottom of ocean, intestinal tract ●E.g. Bacteroidetes- microbes in human gut ●Transient anaerobic conditions when do not have blood circulation ●Ideal breeding ground for obligate anaerobes ○C. tetani - deep puncture wounds ○C. perfringens- infection starts in necrotic tissue ●Facultative - Staphylococci & Enterobacteriaceae ●Enterobacteriaceae- gut, upper respiratory tract; can spread to urinary tract ●Mixed bacterial infections - when facultative anaerobes use up oxygen, allows obligate anaerobes to grow ●Aerotolerant anaerobes- lactobacilli, streptococci in oral microbiota ●Campylobacter jejuni - microaerophile

Refrigeration and Freezing (cold sterilization) (physical)

●Ineffective against psychrophiles ●Refrigerators 0-7C degree - inhibits metabolism, slows growth; e.g. foods, medical supplies, lab cultures ●Freezing < −2 °C -stops growth, kills susceptible microbes ●Thaw in fridge with cold water changed every 30 min or directly in microwave ●Treat thawed food like fresh perishables ●Bacterial cultures, medical specimens for long-term storage frozen at < −70 °CHe

immunodeficiency

●Inherited (primary) or acquired (secondary) disorders ●Immune defenses are absent/functionally defective ●In developed countries, most immunodeficiencies are inherited; seen as recurrent infections in infants ●Globally, malnutrition is most common cause of immunodeficiency -acquired immunodeficiency; develops later in life

function of DNA

●Responsible for inheritance ●Direct, regulate proteins synthesis ●Transcription - DNA is "read" ●Translation - mRNA is translated to protein ●Gene Expression (transcription +translation)-synthesis of a specific protein

Acute Otitis Media (AOM)

●Infection of middle ear- common between 3 mo- 3 yrs ●Formation, accumulation of pus ●Unable to drain, pus builds up, leads to severe bulging of tympanic membrane & otalgia (ear pain) ●Inflammation leads to swelling of eustachian tubes, fever, nausea, vomiting, diarrhea (in infants) ●Infants and toddlers exhibit nonverbal signs -holding, tugging, or rubbing ear, uncharacteristic crying or distress ●Caused by many bacteria- S. pneumoniae, E. coli, Enterococcus spp., Streptococcus ●In older infants, children < 14 years old, S. pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis ●In S. pneumoniae infections, encapsulated strains cause more frequent AOM ●Strains of H. influenzae, M. cattarhalis do not have a capsule ●Otitis media with effusion (OME)- blockage of eustachian tubes, with or without infection, fluid becomes trapped, accumulates in middle ear ●Accumulated fluid -reservoir for microbial growth; leads to secondary bacterial infections ●Recurring & chronic earaches, especially in children ○eustachian tubes are shorter, drain at a shallower angle ○spend more time lying down, causing draining into middle ear bottle feeding while lying down enhances this risk ●Diagnosis made on clinical signs, symptoms ●High-dose amoxicillin is prescribed ●Pneumococcal conjugate vaccine (PCV13),prevents meningitis, flu vaccine can decrease infection

Basophils

●Inflammation and allergy ●Granules contain histamine, which is chemotactic Opens gaps between cells in blood vessels

Nongonococcal Urethritis (NGU)

●Inflammation of urethra unrelated to N. gonorrhoeae ●Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis ●Women are often asymptomatic ●Men have mild disease, with purulent discharge, dysuria ●Most individuals unaware that they are infected, but are carriers ●Untreated NGU can spread to reproductive organs, causing PID, salpingitis in women & epididymitis, prostatitis in men ●C. trachomatis causes chlamydia STD ●Mycoplasma genitalium, Ureaplasma urealyticum, and Mycoplasma hominis -common normal microbiota ●Sometimes cause urethritis (in males & females) or vaginitis, cervicitis (in females) ●M. genitalium -more common than N. gonorrhoeae but less common than C. trachomatis ●Attaches to epithelial cells, uses antigenic variation to help it evade host defenses ●Treated with tetracyclines, azithromycin or erythromycin ●Tetracyclines, fluoroquinolones for M. hominis, U. urealyticum ●Doxycycline, azithromycin, moxifloxacin for M. genitalium

chemical food preservatives

●Inhibits microbial growth, minimizes spoilage ●Sorbic acid, benzoic acid, propionic acid, potassium sorbate, sodium benzoate, calcium propionate- controls molds in acidic foods ●Nontoxic, flavorless, readily metabolized by humans ●Decreases pH, inhibits enzymatic function ●Other chemical preservatives - sulfur dioxide, nitrites ●Sulfites- cause allergies, asthma Nitrites- can be carcinogenic

protein synthesis

●Initiation complex forms at ribosomal binding site ●Shine-Dalgarno sequence -upstream of 1st AUG codon ●Initiator tRNA interacts with start codon AUG ●50S ribosomal subunit binds to complex, forming intact ribosome ●In eukaryotes - no Shine-Dalgarno sequence, binds instead to 5' cap of the mRNA ELONGATION: ●3 functionally important ribosome sites ○A (aminoacyl) site binds incoming charged aminoacyl tRNAs ○P (peptidyl) site binds charged tRNAs carrying AA ○E (exit) site releases dissociated tRNAs ●Elongation proceeds with single-codon movements of ribosome -translocation event ●Charged tRNAs enter at A site, shift to P site, removed at E site ●E. coli translates 200 amino-acid protein in 10 seconds! TERMINATION:●When nonsense codon (UAA, UAG, or UGA) is encountered ●On aligning with A site, nonsense codons recognized by release factors ●P-site AA detaches from tRNA, releasing polypeptide ●Ribosomal subunits dissociate - immediately recruited into another initiation complex

Steps in Replication

●Initiation, elongation, termination ●Initiation -at origin of replication (Eg. E. coli - oriC) ●~ 245 base pairs long; rich in AT sequences (why?) INITIATION:●Topoisomerase (DNA gyrase) relaxes supercoiled DNA ●Helicase separates strands by breaking H bonds ●Y-shaped replication forks form making replication bubble ●DNA near fork coated with single-stranded binding proteins to prevent rewinding ●DNA pol III can add nucleotides only in 5' to 3' direction primer:●DNA pol. needs free 3'-OH group to start - RNA pol doesn't (no free 3'-OH group in ss of DNA) ●RNA primase (RNA pol.) synthesizes a primer ●5-10 nucleotides long; complementary to template ●DNA pol. III can now extend primer ELONGATION:●Leading strand synthesized continuously ●Lagging strand - synthesized in short fragments ●Okazaki fragments -each requires own primer ●RNA primers replaced with DNA nucleotides by DNA pol I. ●DNA ligase seals gaps between fragments TERMINATION:●Completed circular genomes need to be concatenated ●Topoisomerase IV cuts and reseals them ●Bacterial DNA gyrase, topoisomerase IV unique to prokaryotes - target for antimicrobial quinolone

Quorum sensing

●Inside, different species establish metabolic collaborations ●E.g. aerobes consume oxygen, help anaerobes grow ●Quorum sensing - coordinates cell activities in response to environment ●Occurs between cells of different species ●Cell density is detected through autoinducers ●When population reaches critical threshold (a quorum), autoinducers bind to receptors ●Initiates a cascade of signaling events ●Activates genes for functions beneficial to a critical cells density ●Responses to QS ○Increase in production of signaling molecules (autoinducer) ○E.g. synthesis of certain virulence factors when enough cells are present to overwhelm immune defenses

cloning using transfection

●Introduction of recombinant DNA molecules into eukaryotes ●Transgenic plants, livestock - e.g. delayed ripening tomatoes, animals that secrete pharmaceutical products ●Eukaryotic cells more challenging - not naturally competent ●Electroporation, microinjection or viral vectors (gene therapy) ●Transfection in plants- more difficult because of thick cell walls ●Needs gene guns or shuttle vectors (plasmids that move between prokaryotes and eukaryotes

Halogens (chemical)

●Iodine, Chlorine, Fluorine ●Oxidizes, destabilizes macromolecules ●Iodine - Topical antiseptic, hand scrub for medical personnel (betadine- iodophor) ●Chlorine - water disinfectant, water treatment plants, household bleach, food processing, swimming pools Fluorine - prevention of dental caries

mutagen Radiation

●Ionizing or nonionizing radiation induces mutations ●Strong ionizing radiation (X-rays, gamma rays) cause breaks in DNA backbone and/or modify bases ●Used to kill microbes to sterilize medical devices, foods ●Non Ionizing radiation (UV) light, induces dimer formation ○2 adjacent pyrimidines become covalently linked ○If unrepaired, both replication & transcription will stall ○DNA pol may replicate dimer incorrectly

Normal Microbiota of the Urogenital System

●Kidneys are sterile; urine has antibacterial components but not sterile ●In males, skin bacteria present in distal urethra ●In females - distal 1/3rd of urethra and vagina ○Established shortly after birth; complex, dynamic population, fluctuates to environmental changes ○Nonspecific defense -occupies cellular binding sites, competes for nutrients ●Microbiota produces lactic acid, hydrogen peroxide, bacteriocins ●Lactic-acid-producing bacteria is dominated by Lactobacillus spp -use glycogen from vaginal epithelium for metabolism, produce lactic acid ●Regulated by hormone estrogen; increased estrogen levels = increased vaginal glycogen & lactic acid = lower vaginal pH ●Decreases in estrogen during menstrual cycle & menopause = decreased vaginal glycogen & lactic acid, =higher pH more venerable to pathogens

Radiation (physical)

●Kills or inhibits growth ●Ionizing - X-rays, Ɣ rays, high-energy electron beams ○Causes double-strand breaks in DNA ○Can penetrate paper ○Heat-sensitive medical equipment, some foods (in Europe) (america doesn't use as much) ●Nonionizing (UV light) - for disinfection ○Causes thymine dimers in DNA Water purification, biological safety cabinets

Pasteurization

●Kills pathogens, reduces spoilage microbes while maintaining food quality (consistency, sensory qualities) ●Not sterile, will eventually spoil ●High-temp short-time (HTST)- 72 °C for 15 second for Refrigerated milk ●Ultra-high-temperature (UHT) - 138 °C for 2-3 seconds for shelf stable milk ○Shelf stable, won't spoil until opened ○Alters taste slightly changes protein molecules Lewis Pasteur

Agranulocytes

●Lack visible granules in cytoplasm ●Lymphocytes & monocytes ○Lymphocytes- B cells & T cells ○Monocytes-Become macrophages & dendritic cells ●Part of specific adaptive immunity (natural killer cells is an exception)

Ribosomes

●Large & small subunits associated only during synthesis ●Small subunit -binds mRNA, large binds tRNAs ●mRNA is simultaneously translated by many ribosomes ●Direction of synthesis - from 5' to 3' ●Polyribosome - structure containing mRNA with multiple ribosomes

microbial growth at low temperatures

●Membranes lose fluidity, damaged by ice crystals ●Reactions, diffusion slow ●Proteins too rigid to catalyze reactions; may denature ●In psychrophiles ○Proteins rich in hydrophobic residues (greater flexibility) ○Antifreeze proteins, solutes that lower freezing temperature found in cytoplasm ○Lipids tend to be unsaturated to increase fluidity

Monocytes

●Largest WBCs - no lobes in nucleus or granules in cytoplasm ●Phagocytes that engulf pathogens & apoptotic cells ●When monocytes leave blood, enter a specific body tissue they differentiate into tissue-specific phagocytes ○Macrophages & dendritic cells ●Highly phagocytic, produce & release cytokines ●Bridge between innate & adaptive immunity

Neurocysticercosis

●Larval form of pork tapeworm, Taenia solium ●Larvae invade brain, cause adult onset epilepsy ●Diagnosed by MRI, CT scans to detect cysts ●Treatment depends on location, #, size, stage of parasite ●Antihelminthic chemotherapy kills viable cysts ●Surgical intervention may be required to remove intraventricular cysts

Leptospirosis

●Leptospira - found in many animals, excreted in urine; humans infected from contaminated soil or water ●Fever, headache, chills, vomiting, diarrhea, rash with severe muscular pain ●If disease progresses, infection of kidney, meninges, or liver may occur; leading to organ failure or meningitis ●Weil's disease - kidney, liver become seriously infected ●Pulmonary hemorrhagic syndrome can develop in lungs, with jaundice ●Mechanism of pathogenicity not well understood ●Extremely rare in US, endemic in Hawaii ●Working with animals or animal products increases risk ●Bacteria is cultivated in specialized media but diagnosis is faster with immunologic testing ●Treatment is broad-spectrum antibiotics -penicillin, doxycycline ●For serious cases -antibiotics may be given by IV

Anatomy and microbiota of the eye

●Like skin- open to external environment ●Nasolacrimal drainage system- tears secreted by lacrimal gland keeps eyes moist, flow from eye into nasal cavity ●Antimicrobials in tears - defensins, lactoferrin, lysozyme ●Conjunctiva- mucous membrane of surfaces of eyeball, inner eyelid pink eye ●normal Microbiota exist in conjunctiva ●Contact lenses can change normal microbiota in conjunctiva ●Vitreous humor - watery material inside of eyeball ●Protected from contact with environment; sterile, no normal microbiota

Mucous membranes (the front-line forces)

●Lines nose, mouth, lungs, urinary & digestive tracts ●Epithelial cells with tight junctions ●Secretes sticky mucus (the land mines & trip wires) - protects tissue, traps matter, antimicrobial peptides ●Mucus flushed out with trapped microbes ●E.g. Ciliated epithelial cells part of mucociliary escalator ○Keeps lungs nearly sterile ○Damaged by smoking, cystic fibrosis etc ●Intestinal tract - epithelial cells, interspersed with mucus-secreting goblet cells ○Mucus mixes with material from stomach, traps microbes, debris ○Peristalsis moves it through GI tract excreting material in feces

Endothelia

●Lines urogenital tract, blood vessels, lymphatic vessels & some other tissues ●E.g. Endothelium of blood-brain barrier protects CNS ●Cell junctions in blood vessels traveling through CNS are tightest and toughest in the body

Natural killer cells (SWAT)

●Lymphocytes -use non-specific mechanisms to destroy abnormal cells (cancer cells, cells with viruses) ●Recognize molecular markers (major histocompatibility complex-MHC) & activating receptors on normal cells ●MHC -expressed only by healthy cells; indicates "self" ●Abnormal cells diminish or eliminate MHC markers ●NK cell sees this as abnormality or as a cell in distress and acts ●Express proteins & cytokines to activate apoptosis - controlled cell suicide ●Release toxins from granules - perforin & granyzymes ●Binds & releases destructive payload, and detaches

Major Histocompatibility Complex (MHC)

●MHC molecules-expressed on surface of cells ●2 types of MHC molecules - I and II ●MHC I ○Found on all nucleated cells ○Identify cell as normal/ self ○Present antigens from cytoplasm ○Both normal self-antigens + abnormal/nonself pathogens ●MHC II ○Found only on professional antigen presenting cells (APCs)= macrophages, dendritic cells, B cells ○Present only abnormal/nonself pathogen antigens that have been engulfed & degraded

Pathogen degredation

●Macrophages, dendritic cells process remains ●Present antigens to stimulate adaptive immunity

rRna

●Made of protein + rRNA ●Synthesized from DNA as long RNA molecules ●Cut to release individual rRNA ●Eukaryotes- in nucleolus, prokaryotes - in cytoplasm ●Provides location for mRNA binding ●Aligns mRNA & ribosomes during protein synthesis ●Also acts as enzyme catalyst

Thymic Selection

●Maturation of T Cells -3 critical steps ●1st step - in cortex of thymus ○development of functional T-cell receptor (TCR) required for activation ○negative selection of thymocytes with defective TCRs ●2nd step - in cortex of thymus ○positive selection of thymocytes that will interact appropriately with MHC ●3rd step - in cortex & medulla of thymus ○Central tolerance - negative selection to remove self-reactive thymocytes ●Peripheral tolerance- for those that escape central tolerance ○Induction of anergy - non responsiveness due to lack of co-stimulatory signal ○Rest are inhibited by anti-inflammatory cytokines ●Thymic selection eliminates 98% of thymocytes ●Remaining 2% exit thymus, migrate to sites of secondary lymphoid tissues (lymph nodes, spleen, tonsils) mature naïve T cells ●Mature naïve T cells await activation through antigen presentation by APCs Activation of T cells is a complex process

Viral Respiratory Diseases Causing Skin Rashes

●Measles, rubella (German measles), chickenpox ●Systemic symptoms but portal of entry is respiratory tract Measles (Rubeola) ●Caused by measles virus (MeV); very contagious ●Major cause of childhood mortality worldwide ●Spread by direct contact with secretions or inhalation of droplets spread by breathing, coughing, or sneezing ●High fever, conjunctivitis to eyes, sore throat ●Causes characteristic rash initially on face, later spreads to extremities ●Red, raised macular rash become confluent, lasts for several days with extremely high fever ●diagnosed by Koplik's spots- white spots on inner lining of inflamed cheek tissues ●Usually self-limiting, can lead to pneumonia, encephalitis, death (15% fatality rate in highly virulent strains) ●Predisposes patients to secondary infections ●Preliminary diagnosis based on rash and Koplik's spots ●Hemagglutination inhibition tests to confirm ●No effective treatments; Vaccination is widespread Rubella (German Measles) ●Mild viral disease- rash similar measles ●Transmitted in aerosols from coughing or sneezing ●Half of all infected remain asymptomatic, but contagious ●Begins with facial rash, spreads to extremities, less intense, shorter lived (2-3d), lower fever than measles ●Congenital rubella syndrome is most severe clinical complication cause miscarriages and birth defects -occurs in pregnant women ●Virus is teratogenic; can cause developmental defects if it crosses placenta during pregnancy ●High incidence of stillbirth, spontaneous abortion, or congenital birth defects ●Postnatal infections- self-limiting, no complications ●Preliminary diagnosis on patient's history, vaccination records, rash - confirmed by Hemagglutination test ●No antiviral therapies, effective vaccine (MMR) available Chickenpox & Shingles ●Chickenpox (varicella) -varicella-zoster virus - herpesvirus family ●In children, disease is mild, self-limiting, easily transmitted by direct contact or inhalation of material from skin lesions ●In adults, more severe, can lead to pneumonia, birth defects ●Reye syndrome -serious complication in children (if pt takes aspirin) ●Once infected, patients acquire lifetime immunity to future chickenpox outbreaks ●After initial viral exposure, incubation period is 2 weeks ●Infection of respiratory tract - viremia, fever, chills ●Pustular rash develops on face, progresses to trunk, extremities; lesions burst, form crusty scab ●Infectious from 2 days before outbreak of rash until all lesions have scabbed over ●Like other herpesviruses, varicella-zoster virus becomes dormant in nerve cells ●Can remain latent for decades ●Dormant viruses may be reactivated later due to stress, aging, immunosuppression ●Once reactivated, moves along sensory nerves to skin of face or trunk -causes painful lesions as shingles ●Symptoms last for 2-6 weeks, can recur ●Postherpetic neuralgia- pain signals from damaged nerves long after other symptoms have subsided ●Can spread to other organs in immunocompromised ●Person with shingles lesions can transmit virus to a nonimmune contact, causing chickenpox ●Shingles cannot be transmitted between persons ●Primary diagnosis based on pustular rash on the trunk, PCR-based tests can confirm ●Treatment in children is usually not required ●In patients with shingles, acyclovir treatment reduces severity, length of symptoms, postherpetic neuralgia ●Effective vaccine for chickenpox ●Shingles vaccine available for adults > 60 years ●Reduces likelihood of a shingles by boosting immune defenses

Mechanisms of horizontal gene transfer

●Method for genetic diversity in asexual prokaryotes ●More common among evolutionarily related organisms & ●Any 2 species living together in a community ○Transformation: naked DNA taken up from environment. ●Frederick Griffith's "transforming principle," experiment ●Prokaryotes take up naked DNA from environment ●Ability to do so - competency ●Many bacteria are naturally competent -actively bind & transport to environmental DNA, make it ss ●Ds foreign DNA is destroyed by nucleases to defend against viral infection ●DNA that contains fragments of DNA from different organisms is called recombinant DNA ●DNA recombination can give new phenotypic properties ●E.g. uptake of toxin gene ●Taking up plasmid DNA is also transformation ●Method of acquiring virulence factors & antibiotic resistance ●Transformation is relatively inefficient ○Transduction: genes transferred between cells in a virus ●Viruses infect bacteria, move short pieces of chromosomal DNA around ●Generalized transduction -any piece of chromosomal DNA transferred by accidental packaging ●Specialized transduction -chromosomal DNA adjacent to integration site of a lysogenic phage ●Change in host phenotype is lysogenic/phage conversion ●Seen in many toxin-producing bacteria ○Conjugation: hollow tube called conjugation pilus transfers genes ●Conjugation pilus brings organisms into direct contact ●In E. coli, genes for conjugating located on F plasmid ●Conjugation pilus is called F pilus ●Cells capable of forming F pilus are F+ cells or donor cells ●Cells lacking F plasmid are F− cells or recipient cells ●F pilus from F+ cell contacts F- cell; retracts ●Pulls cell envelopes to form cytoplasmic bridge ●F− cell becomes an F+ cell ●In a mixed bacterial population all cells will eventually become F+ ●Conjugation can also transfer chromosomal DNA by integrating the plasmid into chromosome - forms Hfr cell (high frequency of recombination) ●Integrated F plasmid may be imprecisely cut & maintained as plasmid or recombined into new cell's chromosome R plasmid:●Genes encoding antibiotic resistance ●Contain genes that control conjugation & transfer of plasmid ●Able to transfer between cells of same species and between cells of different species ●Single R plasmids commonly contain multiple genes conferring resistance to multiple antibiotics Transposons:●"Jumping genes" = DNA with inverted repeat sequences at ends + presence of gene for transposase ●Entire sequence can be "cut and pasted" (transposition) ●Found in both prokaryotes and eukaryotes ●Most transposons are nonreplicative ●Some may be replicating -retain location in DNA while making a copy to insert elsewhere; "copy and pasted"

Neutrophils - PMNs (polymorphonuclear neutrophils)

●Migrate through walls of blood vessels to fight bacteria ●First to arrive at site of infection ●Granules contain defensins, hydrolytic enzymes ●Arrive, degranulate to release toxic molecules, form neutrophil extracellular traps (NETs) ● Toxic proteins in NETs cause collateral damage ●Causes purulent or suppurative discharge - buildup of leukocytes, cellular debris, bacteria at infection site ●Indicates immune defenses have been activated

The common cold VIRAL

●Mild infections of nasal cavity; caused by > 200 different viruses - rhinoviruses, coronaviruses, adenoviruses ●Direct contact, droplet transmission from coughing and sneezing- rhinoviruses live on surfaces for 1 week ●Viral contact of nasal mucosa or eyes lead to infection ●Runny nose, congestion, sore throat, coughing, sneezing, headaches, body aches TEST QUESTION ... (no fever!!!!!) ●Can progress to otitis media middle ear infection, pharyngitis, or laryngitis ●Self-limiting within 1-2 weeks

Mutagens

●Mistakes in replication cause spontaneous mutations ●DNA polymerase error rate= 1 wrong base per million bp ●Exposure to mutagens cause induced mutations ●Increases rate of mutation more than 1000-fold ●Mutagens often carcinogens ●Nearly all carcinogens are mutagenic, but all mutagens are not necessarily carcinogens CHEMICAL: ●Nucleoside analogs - structurally similar to nucleotides ○Interact with DNA or modify bases -induce mutations by changing base pairing ●Intercalating agents- slide between stacked N bases ○Distort molecule creating atypical spacing ○DNA pol. may either skip nucleotides (deletion) or insert extras (insertion) ○Both may lead to a frameshift mutation

Classical Pathway

●More efficient mechanism ●Depends on production of antibodies by specific adaptive immune system ●To initiate classical pathway -specific antibody must first bind to pathogen to form an antibody-antigen complex ●This activates 1st protein in cascade- C1 complex ●Remaining classical pathway complement proteins are then recruited and activated in a cascading sequence

Viral Conjunctivitis

●More watery discharge than thick discharge of bacterial conjunctivitis ●Associated with colds, caused by adenoviruses ●Contagious, spreads from eye to eye and others ●Antibiotic treatment ineffective ●Resolves without treatment within a week or two both **know difference between viral and bacterial

Physical defenses of innate immune system

●Most basic form of nonspecific defense ○Physical barriers- skin, mucous membranes ○Mechanical defenses - physically remove microbes, debris ○Microbiome - compete with pathogens for nutrients & cellular binding sites

Cell-Mediated Response to Tumors

●Most cancer cells, do not have self-proteins -present tumor antigens ●Stimulates naïve helper T cells that activate NK cells ●NK cells and cytotoxic T cells recognize cancer cells, induce apoptosis ●Malignant tumors actively suppress immune response ●In some cancers, immune cells themselves are cancerous ●In leukemia, lymphocytes become abnormal ●Cancerous cells can become resistant to apoptosis

Rheumatoid Arthritis -systemic Autoimmune

●Most common chronic inflammatory joint disease ●Type III hypersensitivity reaction ●Activated CD4 T cells release cytokines, tumor necrosis factor-α (TNF-α), produce rheumatoid factor (RF) antibodies forming immune complexes ●Increased levels of acute-phase proteins -C-reactive protein (CRP) produced by liver participate in complement fixation with antibodies on immune complexes ●Immune complexes cause inflammation in joints, hands, feet, legs ●Diagnosis by elevated levels of RF, inflammation biomarkers ●Radiographs, ultrasound, or MRI can identify joint damage ●Poorly understood environmental, genetic causes tends to run in family -easier to diagnose

Selective IgA Deficiency

●Most common inherited immunoglobulin deficiency ●Patients produce normal levels of IgG, IgM, but not secretory IgA- predisposes them to lung and GI infections

Hypersensitivity Pneumonitis

●Occupational or environmental disease ●Lungs inflammation- allergic reaction to inhaled dust, endospores, bird feathers, bird droppings, molds, chemicals ●Both type III & type IV reactions ●Coughing, dyspnea, chills, fever, sweating, myalgia, headache, nausea ●Poultry worker's lung, cheese handler's disease, farmer's lung

Process of Binary fission

●Most common mechanism ●1st cell grows, increases cellular components ●Replication starts at origin of replication - chromosome is attached to inner cell membrane ●Replication in opposite directions until terminus is reached ●Center of enlarged cell constricts- 2 daughter cells are formed ●Each offspring receives a complete copy of parental genome ●Cytokinesis & cell division- directed by protein FtsZ ●FtsZ assembles into a Z ring on membrane ●Z ring anchored by FtsZ-binding proteins - defines division plane ●Additional proteins added to form a divisome ●Divisome activates to produce a peptidoglycan cell wall ●Septum forms, divides daughter cells ●Cells' outer layers are remodeled

osmotic and barometric pressure

●Most environments have lower solute concentrations ●Rigid cell walls protect in low osmotic pressure ●In high pressure, water flows out- plasmolysis (protoplasm shrinks) cell dies ●Used to preserve food ●Halophiles need high salt concentrations ●Marine environments, salt ~ 3.5% ●Extreme halophiles grow in hypersaline lakes - Great Salt Lake, Dead Sea

Sterilization

●Most extreme control protocol ●Complete removal/killing of all vegetative cells, endospores & viruses ALL THREE ●very important in Labs, medical, manufacturing, & food industry ●Physical method- high heat, pressure, or filtration ●Chemical - sterilants ●Medical procedures - aseptic technique, sterile field

Black Death

●Most fatal pandemic in history ●In Europe, Asia in mid-1300s ●75-200 million dead in 4 years ●People still believed in "miasma" theory of disease ●Waned, recurred in repeated epidemics ●Start of social distancing & quarantining (40 day isolation)

Viral Infections of Reproductive System

●Most of viral infections of reproductive system are incurable ●Have high risk of persistent sexual transmission ●Herpes simplex virus (HSV) Human papillomavirus (HPV)

Normal Microbiota of the Respiratory system

●Nasal passages & sinuses - Actinobacteria, Proteobacteria, Staphylococcus, Corynebacterium spp. (diphtheroids), Propionibacterium spp., Haemophilus spp ●Oropharynx - some bacteria, fungus Candida ●Many healthy humans asymptomatically carry potential pathogens in upper tract- Staphylococcus aureus in nostrils, Haemophilus, and Neisseria in pharynx ●Lower tract -not many microbes (Pseudomonas, Streptococcus, Fusobacterium) ●Can be opportunistic pathogens ●Mucosal pathogens produce virulence factors- adhesins, capsules, exotoxins, endotoxins ●Once infection is established, it impairs mucociliary escalator, limiting ability to expel microbes ●Bacterial infections are mostly localized -respond to antibiotics ●Viral infections- frequent, but mild and self-limiting

Loiasis

●Nematode Loa loa (African eye worm)- endemic to West, Central Africa ●Does not occur elsewhere unless carried by travelers ●Individual genetic differences affects susceptibility- travelers more susceptible than native population ●Spread by deerflies- ingest larvae from infected human via blood meal ●On biting, deposits larvae into blood ●After 5 months, develop into adults, live for years ●Adult worms live in subcutaneous tissues, travel at about 1 cm per hour ●Diagnosis- observing migration through eye, or under skin ●Maybe asymptomatic, or fever, areas of allergic inflammation called Calabar swelling ●Worms migrating through conjunctiva cause eye pain, itching, but no lasting damage ●Some patients have itching, hives, joint, muscle pain ●Worms can be surgically removed from eye or skin to relieve discomfort; does not cure infection ●Treatment is diethylcarbamazine- produces severe side effects in some individuals- brain inflammation, death in patients with heavy infections ●If untreated, can damage kidneys, heart, lungs, though these symptoms are rare

Secondary response

●Occurs more quickly & forcefully ●Lag period decreased to only a few days ; IgG is significantly higher ●Antibodies are more effective, bind with higher affinity ●Plasma cells in secondary responses live longer ●Levels of antibodies remain elevated for a longer period

recombinant DNA pharmaceuticals

●New antibiotics ●Subunit vaccines - safer; only single antigenic molecule, lack any part of genome of pathogen ○E.g. New mRNA vaccine for COVID-19 ●Hormones - insulin, growth hormone

Future of Transplantation

●New organs grown in vitro from own harvested cells - no risk for rejection ●Alternative approach- genetic modification of donor animals, such as pigs ●Involves excising genes in pig (in embryo) that are most responsible for rejection reaction ●Challenge - Finding these genes, effectively removing, identifying, neutralizing risks from viral sequences embedded in pig genome

Infections of the skin

●Normal microbiota can become opportunistic when introduced to different location ○E.g. MRSA getting into surgical site OR upon injury ●Infections usually localized, but if it reaches blood becomes systemic ●Rashes, inflammation on skin

Nucleic acid

●Nucleotides- monomers of NA ●Base sequence- order of nucleotides in each strand ●Base sequence of DNA- carries, retains hereditary information ●Nucleotides in DNA are deoxyribonucleotides ●5C sugar deoxyribose + phosphate + nitrogenous base ●Nucleoside = 5C sugar + nitrogenous base ●C atoms are numbered 1ʹ, 2ʹ, 3ʹ, 4ʹ, and 5ʹ

oxygen requirements

●Obligate aerobes - respire aerobically, cannot grow without it ●Obligate anaerobes cannot grow in O2 - only fermentation, anaerobic respiration ●Facultative anaerobes- better growth in presence of O2 but can grow without it ●Aerotolerant anaerobes cannot do aerobic respiration, but can grow in O2 ●Microaerophiles need oxygen to grow, but at low concentration (<10%) ●Enzymes that detoxify ROS - Peroxidase, superoxide dismutase, catalase ●Obligate anaerobes- lack all three enzymes ●Aerotolerant anaerobes do have SOD but no catalase ●Capnophile- requires higher than atmospheric concentration of CO2 to grow

Tuberculosis

●One of deadliest infectious diseases in history ●1/3rd of world's population is infected ●M. tuberculosis- acid-fast, high G + C, nonspore-forming ●Cell wall- rich in waxy mycolic acids (acid fast stain will only show) ●Causes chronic granulomatous disease that can infect any area of body, but mostly lungs ●Spread by inhalation of respiratory droplets or aerosols from an infected person Very small infectious dose - M. tuberculosis -10 cells! CHRONIC ●Bacteria enter alveoli, are phagocytized ●Survive, multiply within because of waxy mycolic acid ●If not eliminated, causes inflammation, accumulation of neutrophils, macrophages ●Weeks to months before response by T cells + B cells ●Lesions in alveoli are walled off, forming tubercles (Because can't get rid of) ●Inside tubercles the Bacteria continue to be released into center of tubercles ●Chronic immune response results in tissue damage, induction of apoptosis in a process called liquefaction ●Creates a caseous center (air pocket) where aerobic M. tuberculosis grows and multiplies ●Tubercles rupture, bacteria invade pulmonary capillaries, spread through bloods to organs- miliary tuberculosis ●Rupture facilitates, increases, transmission to other individuals via droplet aerosols from coughs ●Droplets are very small and stay aloft in air for a long time ●Those caring for patients with TB, have to use of face masks, negative-pressure ventilation, filtering systems ●Most lesions heal to form calcified Ghon complexes ●Diagnosed by Ghon complexes on chest radiographs ●Even after disease has ended, viable bacteria remain sequestered in these locations ●Release of these at a later time can produce reactivation tuberculosis (or secondary TB) ●Seen in people with alcoholism, elderly, or immunocompromised ●Chronic disease, chemotherapeutic treatments continue for months or years ●Multidrug resistant (MDR-TB), extensively drug-resistant (XDR-TB) strains seen due to misuse of antibiotics ●Common antibiotics prescribed -isoniazid, rifampin, ethambutol, pyrazinamide ●TB vaccine- uses bacillus Calmette-Guérin (BCG) strain of M. bovis found in cattle ●In US, BCG only given to health-care workers & military ●Individuals born in other countries are vaccinated to prevent childhood tuberculous, meningitis, miliary disease ●Mantoux tuberculin skin test is used in US to screen for potential TB exposure but prior vaccinations with BCG vaccine causes false +ve results ●Chest radiographs to detect Ghon complex formation required to confirm exposure

Antigen Presentation with MHC II Molecules

●Only done by professional APCs ●Pathogen internalized into phagosome, fuses with lysozyme to create phagolysosome ●Pathogen degraded, protein antigens are processed and presented ●Only most antigenic or immunodominant epitopes are presented This activates helper T cells

Health Care-Associated Pneumonia

●Opportunistic bacteria -Klebsiella pneumoniae, Staphylococcus aureus, proteobacteria -Escherichia, Proteus, Serratia ●Patients at risk are elderly, those with preexisting lung conditions, immunocompromised, those receiving supportive therapies-intubation, antibiotics, immunomodulatory ●Invasive med. devices can introduce pathogen into body ●Disrupts mucociliary escalator and other defenses

Optimum oxygen concentration

●Optimum oxygen concentration -ideal concentration fastest growth rate ●Minimum permissive oxygen concentration- lowest concentration that allows growth ●Maximum permissive oxygen concentration - highest tolerated concentration Organisms will not grow outside this range

microbial growth temperature

●Optimum temperature - Highest growth rates ●Minimum & max temp- lowest & highest at which organism can survive + replicate ●Mesophiles -moderate, optimal is room temp (20 -45 °C) ●Human body core temp is 37 °C (98.6 °F) ●Normal microbiota & many pathogens are mesophiles

Influenza

●Orthomyxovirus, affects upper respiratory tract, can extend into lower tract ●Transmitted by direct contact, inhalation of aerosols ●Fever, chills, body aches + symptoms similar to cold ●Self-limiting; serious cases lead to pneumonia in very young & elderly) ●Some strains (1918-1919 variant) more lethal to young adults because of cytokine storm ●Very young, elderly - less susceptible to cytokine storm ●Reye syndrome- complication of influenza in children and teenagers - associated with use of aspirin ○swelling in liver, brain; may progress to neurological damage, coma, or death ●Seen with other viral infections, like chickenpox ●CDC recommends aspirin and products with aspirin never be used to treat viral illnesses in children < 19 years ●Uses hemagglutinin to bind to host respiratory epithelium ●Gets endocytosed, takes over host genetic machinery to replicate . ●3 genetically related influenza viruses -A, B, and C ●Influenza A viruses -subtypes based on structure of hemagglutinin and neuraminidase proteins ●Serologically characterized by type of H & N proteins ●>200 different combinations, only a few (like H1N1 strain) cause human disease ●Influenza A viruses - most virulent causes seasonal epidemics, can infect some animals ●Influenza B virus- less virulent, Influenza C virus is mildest ●Most lethal flu pandemic in 1918- 1919 ●Antigenic shift with avian & human viruses produced a new H1N1 virus ●Strain rapidly spread worldwide; killed 40-50 million ●Called Spanish flu, but originated in US- made worse by WW1 ●Diagnosis by Rapid Influenza Diagnostic Tests (RIDTs) ●Results in 15-20 minutes but common false-negatives ●Hemagglutination of erythrocytes or complement fixation tests can be used, but too time-consuming, expensive ●3 drugs inhibit influenza neuraminidase activity -inhaled zanamivir, oral oseltamivir, and intravenous peramivir ●If taken at onset of symptoms can shorten disease; vaccination is more effective

Eusinophils

●Parasitic infections & allergy ●Granules contain histamine, degradative enzymes

Pressure (physical)

●Pascalization - kills microbes while maintaining quality, extending shelf life (pressure canning) ●100-800 MPa (SL = 0.1 MPa) to kill vegetative cells ○E.g. Hyperbaric oxygen therapy for infection- gas gangrene from Clostridium perfringens ○pure oxygen at higher than normal pressure ○Increases oxygen saturation, controls microbes with ROS, boosts immune system, reduces toxin production

Congenital Syphilis

●Passed from mother to fetus when untreated primary or secondary syphilis is present ●In many cases, infection leads to miscarriage or stillbirth ●Children show secondary syphilis symptoms -mucus patches that deform the nose ●In infants, gummas cause damage to organs, teeth ●Complications -osteochondritis, anemia, blindness, bone deformations, neurosyphilis, cardiovascular lesions ●Screened with TORCH panel

Antigens

●Pathogen-specific molecular structures that trigger adaptive defenses -similar to PAMPs ●PAMPs on many pathogens; antigens are unique to specific pathogen ●Antigens - antibody generator ●Antigens also stimulate cellular immunity; now called immunogens ●Antigens- carbohydrates, lipids, NA, proteins, or combinations ●More structurally complex = more effective ●Proteins more effective than carbs (only T cells) ●Lipids, NA- only when combined with protein or carb ●Epitopes - exposed regions on antigen surface that T cells interact with ●Large antigenic structures have multiple epitopes ●Haptens - free epitopes not part of complex 3D structure ●Antigens too small to be antigenic, need to attach to larger carrier molecule (a protein) to produce conjugate antigen ●Seen mostly in allergens

phagocyte migration

●Phagocytes - seek, recognize, destroy by engulfing ●Rolling adhesion- cells stick slightly to adhesion molecules, slow down, roll along blood vessel walls ●Extravasation (diapedesis)- leukocytes pass through walls of capillaries within tissues ●Transendothelial migration- At cellular junction, bind to adhesion molecules, flatten out, squeeze through ○Occurs only in capillaries, takes many days

microbial growth light

●Photoautotrophs need sufficient light intensity ●Light energy captured by pigments, converted into chemical energy ●Archaea -Halobacteria, use light energy to drive for proton, sodium pumps ●Pigment protein complex in bacteria is bacteriorhodopsin

Filtration (physical)

●Physical separation ●HEPA - high-efficiency particulate air filter ●Pore sizes 0.3 µm, captures bacteria, spores, viruses ●Nearly sterilizes air -cars, airplanes, home Membrane Filters ●Removes microbes from liquids ●Pore size 0.2 µm, < average size of bacteria (1 µm)

Plasma Protein Mediators

●Plasma -fluid portion of blood ●Contains clotting factors, electrolytes, sugars, lipids, proteins ●Acute-phase proteins- produced in liver, secreted into blood in response to inflammatory molecues ■E.g. C-reactive protein, serum amyloid A, ferritin, transferrin, fibrinogen, mannose-binding lectin ●Complement proteins ●Cytokines

mutations in protein structure and function

●Point mutations- wide range of effects ●Redundancy -reduces chance of AA change ●Silent mutation - no effect on protein's structure ●Missense mutation -different AA ○Chemistry & location (e.g. active site) of AA change is important ○Mostly result in proteins still functional, to some degree ●Conditional mutations - missense mutations- effects seen only under some environmental condition ●Rarely, missense mutation can be beneficial -provide a selective advantage ●Nonsense mutation- converts a sense codon into stop codon (nonsense codon) ○Protein will be shorter and usually not functional

Cancer Vaccines

●Preventative cancer vaccines ○Target viral infections that are known to lead to cancer ○Human papillomavirus (HPV) for cervical cancer, hepatitis B for liver cancer ●Therapeutic cancer vaccines -mostly experimental ●Genetically engineered vaccines - uses recombinant plasmid with genes for tumor antigens ●FDA Approved cancer vaccines -few ○1st one for prostate cancer -custom designed using patient's own cells ○APCs are removed and cultured with a tumor-specific molecule and returned ●Therapeutic cancer vaccine - for skin cancer ○Contains a virus injected into tumors, where it infects and lyses tumor cells

Cutaneous Aspergillosis

●Primary cutaneous aspergillosis starting in skin is rare ○Aspergillus fumigatus or Aspergillus flavus ○Patients injured working in outdoor environment ●Secondary cutaneous aspergillosis- starts in respiratory system, spreads into skin, disseminates systemically- causes distinctive eschars ●Opportunistic in health-care settings- site of iv catheters, venipuncture wounds, burns, surgical wounds, or occlusive dressing (second most common nosocomial fungus) ●Diagnosed using patient history, culturing, histopathology using a skin biopsy ●Treated with antifungals ●For immunosuppressed, burn patients - medication, surgery or immunotherapy treatments

The Respiratory system

●Primary function - exchange gases (O2 & CO2) for metabolism ●Main portal of entry for pathogens Upper respiratory tract- from nostrils until epiglottis ●Direct contact with external environment ●Nasal cavity- air-filled space behind nostrils lined with hairs to trap particles ●Lined with mucous membrane & Bowman's glands ●Nasopharynx- part of upper throat ●Middle ear- connects to nasopharynx via eustachian tube ●Lacrimal glands drain into nasal cavity ●Allows microbes to move from nasal cavity to sinuses, middle ears, lower respiratory tract ●Oral cavity- secondary opening for respiratory tract ●Oral & nasal cavities connect Lower respiratory tract - below epiglottis ●Trachea extends from larynx bifurcates into bronchi ●Bronchi branch into bronchioles that end in alveoli ●Surrounding capillaries = site of gas exchange ●Lungs protected with double-layered pleural membrane

natural chemical food preservatives

●Produced by microbes ●Nisin, antimicrobial peptide made by Lactococcus lactis -Disrupts cell wall production -Preserves cheeses, meats, beverages -Natamycin- antifungal antibiotic -Streptomyces natalensis -Prevents fungus in dairy products (USS), meat preservation (other countries)

Pseudomonas Pneumonia (within health care associated pneumonia)

●Pseudomonas aeruginosa -opportunistic pathogen -serious in Cystic Fibrosis patients hospitalized with ventilators ●Extremely antibiotic resistant; produces exotoxins ●P. aeruginosa infects more than half of all patients with CF ●Produces alginate, a viscous exopolysaccharide to inhibit mucociliary escalator ●Lung damage from chronic inflammatory response is leading cause of death in patients with CF END OF BACTERIAL PNEMONIA

Rh factors

●RBC antigens named after rhesus monkey ●Rh positive (Rh+) - Rho/D antigen present ●Rh negative (Rh−) - Rho/D antigen absent ●ABO antigens- carbohydrates, but Rh antigens- proteins ●Leads to T-dependent B cell activation, class switching ●Exposure of Rh− blood to Rh+ positive RBCs activates primary antibody response ●On subsequent exposure, response is strong and immediate

Autoclaves

●Raise temps above boiling point, sterilizes surgical equipment ●Kills vegetative cells, viruses, endospores without damage to items (plastic) ●Charles Chamberland designed modern autoclave in 1879 ●Retorts - industrial size autoclaves ●Air is removed; replaced with increasing amount of steam ●Trapped steam increases internal pressure and temp above boiling point ●Standard operating temps - 121 °C or, 132 °C, pressure of 15- 20 psi, 20 minutes or more ●Time depends on volume, nature of materials ●Steam must make direct contact, items are loosely packed ●Complete sterilization -Temps high enough to kill endospores ●Regular quality control very important!!!!! ●Recorders record pressure, temps from each run

Blastomycosis

●Rare- dimorphic fungus, Blastomyces dermatitidis ●Soil is reservoir, spores inhaled from disturbed soil ●Pulmonary form -mild flu-like symptoms, self-limiting ●In immunocompromised people, chronic cutaneous disease with subcutaneous lesions on face, hands ●Skin lesions -crusty, discolored, cause deforming scars ●Systemic blastomycosis is rare, if untreated, always fatal ●Preliminary diagnosis - microscopic examination of budding yeast in sputum samples ●Treated with antifungals

Transplant Regection

●Recipient's immune system recognizes donor tissue as foreign (non-self), triggers immune response ●Major histocompatibility markers MHC I & II from genetically different individual/species is recognized as non-self by host's dendritic cells ●Dendritic cells process, present foreign MHC antigens to host's helper T cells, cytotoxic T cells, & activate them ●Cytotoxic T cells target, kill grafted cells through same mechanism used to kill virus-infected cells ●Helper T cells release cytokines to activate macrophages to kill graft ●3 MHC I genes in humans (HLA-A, HLA-B, HLA-C) code for six-allele genotype ●Odds extremely low for random chosen donor match ●Parent or a sibling may be best donor -genetic match between MHC genes is more likely, organ less likely to be rejected ●Matching all MHC genes lowers risk for rejection ●All non-self grafted tissue will be rejected to some extent ●More similar MHC gene match, more likely graft will be tolerated for a longer time ●Transplant recipients, even with well matched MHC genes, require immunosuppressant drugs for life ●Makes them vulnerable to complications from infectious diseases ●Results in transplant-related malignancies -body's normal defenses against cancer cells is suppressed

Pathogen Recognition

●Recognize opsonins & PAMPs (pathogen-associated molecular patterns) ●Common pathogen structures PPG, flagellin, viral NA, LPS ●Pattern recognition receptors (PRRs) recognize PAMPs ●Interaction signals & activates phagocytes

Activation & Differentiation of Cytotoxic T Cells

●Recognizes antigen on MHC I & interacts with CD8 ●Both foreign + self-antigens need to be recognized ●APC then secretes cytokines to activate proliferation & differentiation ●Differentiate into - ○Effector cytotoxic T cells- target pathogens for destruction ○Memory cells ready to respond to subsequent exposures

alarmones

●Regulon -a group of operons all controlled simultaneously ●Alarmones - molecules made in response to environmental stresses; stimulate expression of specific stress-response genes ●When pathogens encounter host defenses, the operons for virulence genes are upregulated in response to alarmones OPERON The trp operon - repressible operon The lac operon - inducible opero

RNA splicing

●Removing introns & reconnecting exons ●Introns removed in nucleus ●Intron function = gene regulation & mRNA transport ●mRNA with spliced exons transported out of nucleus

types of regulation

●Repressor binds to operator to block transcription ●Operator -sequence between RNA pol. binding site and 1st structural gene ●Activator helps RNA pol. bind to promoter, to enhance transcription ●Inducer influences transcription by interacting with a repressor or activator ●E.g. The trp operon - repressible operon The lac operon - inducible opero

Roseola 6th disease

●Roseola infantum or exanthem subitum ●Sudden rash- mild viral infection by human herpesvirus-6 ●Spread via direct contact or droplet aerosols of saliva or respiratory secretions ●Common in children -runny nose, sore throat, cough, high fever ●After 3-5 days of fever, rash appears on chest, abdomen ●No discomfort- spreads to neck, arms, sometimes continues face, legs ●Diagnosis based upon observation, confirm with serological tests ●Treated for fever, disease usually resolves without treatment a week after fever develops ●Antivirals for the immunocompromised

transcriptomics

●Science of entire collection of mRNA ●Metagenomics & metatranscriptomics ●Pharmacogenomics, or toxicogenomics -evaluates drug effectiveness, safety using individual's genomic sequence ○Changes in gene expression early indicator of toxic effects ○Medications prescribed based on patient's genotype?

Bacterial Rhinosinusitis

●Secondary infection after a viral infection, by opportunistic pathogen ●Inflammation within paranasal sinuses and rhinitis ●Most common causes are similar to those for AOM, including S. pneumoniae, H. influenzae, and M. catarrhalis

phenotype

●Set of genes being expressed at given point in time ●Determines cell's activities & observable characteristics ●Constitutive genes = genes that are always expressed ●They are housekeeping genes -necessary for basic functions ●Genotype remains constant, phenotype can change in response to environmental

SARS and MERS

●Severe acute respiratory syndrome by coronaviruses ●Middle East respiratory syndrome by coronaviruses ●Zoonotic- Bats for SARS; camels for MERS ●SARS- southern China in 2002, spred to 37 countries; >8,000 people infected 800 dead ●High fever, headache, body aches, cough, pneumonia ●MERS- Saudi Arabia in 2013 -asymptomatic or mild cold-like symptoms, high fever, aches, cough, pneumonia ●>1,300 people in 27 countries, 500 dead

Lectin activation pathway

●Similar to classical pathway ●Triggered by binding of mannose-binding lectin to carbohydrates on microbial surface ●Lectin is an acute-phase protein produced by liver cells ●Upregulated in response to inflammatory signals All pathways lead to same protective outcomes -Opsonization ●Coating of a pathogen by chemical substance (opsonin) ●Allows phagocytic cells to recognize, engulf, destroy ●Opsonins from complement cascade -C1q, C3b, C4b ●Mannose-binding proteins, antibodies -Inflammation ●Triggered by cascade of chemical mediators & cellular responses ●Occurs when cells are damaged/ stressed/ when pathogens breach physical barriers ●Necessary to recruit cellular defenses ●Process involves phagocyte migration, pathogen recognition, pathogen degradation -Chemotaxis -Cytolysis

The skin barrier (boarder)

●Skin - 3 layers ○Epidermis - keratin + fatty acids ■mechanically tough ■resistant to bacterial enzyme degradation ■dry, salty, acidic environment ■frequently shed along with microbes ○Dermis - contains follicles, sweat glands, nerves, blood vessels ○Hypodermis - Fatty tissue with blood & lymph vessels

Psoriasis -systemic Autoimmune

●Skin disease- itchy/ sore patches of thick, red skin, silvery scales on elbows, knees, scalp, back, face, palms, feet ●Psoriatic arthritis with joint inflammation ●Keratinocytes attacked by dendritic cells, T cells, cytokines ●Normal cell turnover, skin cells rise to surface over 1mo ●In psoriasis cell turnover happens in just a few days ●Thick inflamed patches of skin develop because skin cells rise too fast

Plasmids

●Smaller loops - genes not essential for normal growth ●Bacteria exchange plasmids by HGT ●Can encode virulence factors or antibiotic resistance ●Used in genetic engineering, biotechnology to move genes from one cell to another

tRNA

●Smallest stable RNA -70-90 nucleotides long ●Carries AA to site of protein synthesis in ribosome ●Base pairing between tRNA and mRNA allows correct AA to be inserted ●Mutations in tRNA or rRNA= global problems for cell

Cytokines

●Soluble proteins- act as communication signals ●When released they stimulate - ○production of chemical mediators ○cell proliferation & differentiation ○inhibition of cell division ○apoptosis & chemotaxis ●Effect depends on type of cytokine & type of receptor ●Functions of cytokine can be autocrine, paracrine, or endocrine ●Autocrine- self-stimulation by a cell ●Paracrine -stimulates nearby cells ●Endocrine- stimulates cells much farther away

Autoimmune Disease

●Specific adaptive immune response attacks self sometimes ●Due to loss of immune tolerance ●They are responsible for type II, III, IV hypersensitivity reactions ●Difficult to diagnose - variety of mixed symptoms that flare up, then disappear ●Why? combination of genetic makeup + environmental influences CAUSES ●Antigen mimicry between pathogenic antigens and self antigens leads to cross-reactivity & autoimmunity ●Hidden self-antigens exposed due to trauma, drug interactions, disease states, trigger an autoimmune response ●Results in inappropriate inflammatory responses ●Treatment= immunosuppressive drugs, corticosteroids has many side effects more susceptible

Pneumococcal Pneumonia

●Streptococcus pneumoniae- part of normal microbiota ●Colonizes bronchioles, spreads to alveoli, escapes phagocytosis with capsule only presents when immune sysytem is down (usually secondary infection) ●Pneumolysin O, -pore-forming protein damages host cells, promotes bacterial adherence, enhances pro-inflammatory cytokine production ●Inflammatory response causes alveoli to fill with exudate rich in neutrophils and rbc Leads to a productive cough with bloody sputum ●Antibiotics- Penicillin or macrolides; fluoroquinolones if resistant to penicillin ●2 pneumococcal vaccines available Given to the vulnerable- children <2, adults >65 years

Alkylating Agents

●Strong disinfectants -inactivate enzymes, NA ●Formaldehyde- gaseous disinfectant, biocide ●Kills bacteria, viruses, fungi, & endospores, leading to sterilization at low temperatures ●Storage of tissue specimens (not good on living tissue) ●Not antiseptic -very irritating to tissues, carcinogenic ●Others - glutaraldehyde, o-Phthalaldehyde, ethylene oxide, β-Propionolactone

Peroxigens

●Strong oxidizing agents - disinfectants, antiseptics ●Hydrogen peroxide disinfects surfaces, contact lenses ●Works by producing ROS ●Broad-spectrum activity against bacteria, fungi, viruses, endospores ●Acne medication, toothpastes, topical medication ●Ozone gas used to clean air or water supplies ●Peroxygens are highly effective, commonly used, no environmental hazards (selectively toxic) doesn't hurt us

tRNA

●Structural RNA - many different types ●Each tRNA binds to specific codon on mRNA ●Adds corresponding AA to polypeptide chain ●"Translates" language of RNA = language of proteins ●tRNA "charging" - process of adding AA to tRNA ●tRNA linked to cognate AA - aminoacyl tRNA synthetases ●All tRNAs with specific anticodon carry same AA

RNA structure

●Structurally similar to DNA ●DNA- long, ds -long term storage of genes ●RNA- shorter, ss -short-term functions - protein synthesis ●Ribose instead of deoxyribose - Uracil (U) instead of thymine (T)

Chromosomes

●Structure in which organism's genome is organized ●May contain several thousand genes ●Eukaryotes - multiple, linear, diploid ●Length greatly exceeds length of cell ●Needs to be packaged into very small space to fit ●Length of human genome (3 billion bp) ~ 6' completely stretched out ●Some eukaryotic genomes are even larger ●Supercoiling - process of twisting DNA to fit inside cell ●Single circular haploid chromosome ●Arranged in supercoiled domains by topoisomerases ●DNA gyrase- type of topoisomerase, in bacteria, some archaea, helps prevent overwinding ●Some antibiotics kill bacteria by targeting DNA gyrase

proteomics

●Study entire complement of proteins (proteome) ●All cells of an organism have same genes, but produce different proteins ●Genome is constant, but proteome varies ●Used to study cancer, now infectious diseases ●Identifies biomarkers affected by disease process

Genomics

●Study, comparison of entire genomes ●Study of human genome and genomes of pathogens ●New antibiotics, diagnostic tools, vaccines, medical treatments, and environmental cleanup techniques

T Cell-Independent Activation of B cells

●T-independent antigens (non-protein) cross-link with multiple BCRs - 1st signal ●Interaction with PAMPs - 2nd signal ●B cells activate, clone, differentiate into plasma cells ●Plasma cells become antibody factories, secrete IgM ●Short-lived response, no memory B cells formed, no secondary response

Alternative Pathway

●Target pathogens in non-specific manner ●Initiated by spontaneous activation of complement protein C3 to produce C3a, C3b ●In absence of microbes C3b is degraded ●In the presence of microbes, C3b attaches to surface of microbes ●Recruits other complement proteins in a cascade

Cellular Immunity

●Targets & eliminates intracellular pathogens T Cell Production ●T cells form from multipotent hematopoietic stem cells (HSCs) in bone marrow ●1st differentiate into immature lymphocytes (lymphoblasts) ●Travel to thymus for final maturation into thymocytes

Thermophiles

●Thermophiles optimum temp- 50- 80 °C ●Cannot grow at room temperature ●Hot springs, geothermal soils, compost piles ○E.g. Thermus aquaticus, Geobacillus spp ●Hyperthermophile - 80-110 °C; can survive temp > 121 °C ●Hydrothermal vents -bottom of ocean ~ 340 °C ●Optimally growth in lab at >100 °C E.g. Archaea @ 105 °C

physical barriers of immune system

●Tight junctions between cells ●Made of proteins connecting extracellular matrix or complementary proteins between cells ●Types of cell junctions - tight junctions, desmosomes "shoe laces" , gap junctions only through special channels ●Microbes attempt to break these down enzymatically

bacterial growth curve 4. Death/Decline phase

●Toxic waste accumulates; nutrients are exhausted ●Cells die; exponential decrease ●# of dying cells > # of dividing cells ●Cells lyse, release nutrients ●Persister cells - cells with slower metabolic rate ○cause chronic infections that do not respond to antibiotics

HPV (human papilloma virus)

●Warts of all types ●Condylomata acuminata- genital or venereal warts ○Irregular, pink growths on external genitalia or anus ●Often asymptomatic, self-limiting, often co-occurs with other STIs ●Some (not genital) are associated with cervical cancers ●Oropharyngeal cancer, anal cancer, vaginal cancer, vulvar cancer, penile cancer ●HPV cannot be cultured, detected by molecular tests ●Routine screening with a Pap smear test, women aged 30 & every 5 years after that ●Pap smears show presence of cells called koilocytes ●Regular Pap testing can detect abnormal cells that might progress to cervical cancer ●Vaccines for some high risk HPV types are available ●Vaccination is most effective way to prevent infection with oncogenic HPV; but not all oncogenic types are covered ●Recommended for both boys and girls prior to sexual activity (ages 9-15)

Hemolytic transfusion reaction (HTR)

●Transfusion with incompatible blood ●Strong, potentially lethal type II cytotoxic response ●Activation of classical complement pathway -complement membrane attack complex causes massive hemolysis ●Destroyed RBCs occlude blood vessels in lungs, kidneys ●Within 1-24 hours -fever, chills, itching, hives, dyspnea, hemoglobin in urine, hypotension ●Severe cases - dangerously low blood pressure, shock, multi-organ failure, death Hemovigilance systems - procedures to track transfusion information from donor to recipient

Genetic Code

●Translation of mRNA requires the genetic code ●Protein sequence consists of 20 AA ●Each AA defined by triplet of nucleotides - codon ●Relationship between codon and corresponding AA is the genetic code ●3-nucleotide code = 64 possible combinations ●Some amino acids encoded by more than 1 codon- redundancy / degeneracy

B cell receptors

●Transmembrane protein similar to antibodies ●Use genetic rearrangement to provide diversity ●BCRs do not require antigen presentation with MHC ●Directly interacts with epitopes, antigens ●Unlike T cells, these can recognize non-protein antigens ●Protein antigens are dependent on T cells for B cell activation through antigen presentation - T dependent ●Others (T-independent antigens) activate B cells directly

Protozoan Infections of the Urogenital System

●Trichomoniasis, or "trich," is most common non viral STI ●Flagellated protozoan Trichomonas vaginalis ●T. vaginalis -amoeboid shape when attached to vaginal cells, oval shape in culture ●Normal microbiota- vaginitis when there is disruption ●Capable of phagocytosing other microbes of normal microbiota, contributing to imbalance for infection ●Men generally asymptomatic, women symptomatic ●In men- itching, irritation, discharge, burning after urination or ejaculation ●In women- dysuria; itching, burning, redness, soreness of genitalia, vaginal discharge; may spread to cervix ●Increases risk of HIV & preterm birth ●Microscopic evaluation of wet mounts or nucleic acid amplification testing (NAAT) or rapid test ●Maybe detected on Pap test, -not considered diagnostic ●Oral antifungals for patient and sexual partners

Chronic Inflammation

●When acute inflammation is unable to clear infection ●Ongoing (and often futile) lower-level battle ●Wounded area may heal superficially ●Pathogens remain in deeper tissues, stimulate ongoing inflammation ●Can form granulomas- pockets of infected tissue walled off, surrounded by WBCs, e.g. TB granulomas in lungs ●Seen in both bacterial and viral infections

Herd Immunity

●When population has very few susceptible individuals, they will be protected by herd immunity ●Occurs because disease is unable to spread ●Vaccination programs create herd immunity by reducing susceptible individuals ●As long as a certain percentage is immune, the few susceptible individuals will not be exposed to pathogen ●Continuing vaccination programs are necessary to maintain herd immunity

Hypersensitivity

●Type I -IgE against soluble antigen -triggers mast cell degranulation ●Allergy- adaptive immune response, to an allergen ●When presensitized individual is exposed to an allergen, a rapid immune response occurs almost immediately ●1st exposure activates a primary IgE antibody response ●Sensitizes individual to type I hypersensitivity upon subsequent exposure ●Mucus secretion in nasal passages (runny nose) ●Tear formation from lacrimal glands (water eyes) ●Histamine interacts with nerve endings (itching, sneezing) ●Vasodilation- hives, headaches, angioedema (swelling), hypotension (low blood pressure) ●Bronchoconstriction- wheezing, dyspnea (difficulty breathing), coughing ●In severe cases, cyanosis (bluish color) ●Simulation of vomiting center in cerebellum ●Relaxation of intestinal smooth muscles (diarrhea) ●Localized type I - hay fever rhinitis, hives, asthma ●Systemic type I - anaphylaxis or anaphylactic shock ●Anaphylaxis - severe and life-threatening ○Swelling of tongue, trachea, blockage of airways, dangerous drop in blood pressure, shock, death within minutes ●Type II - IgG, IgM against cellular antigens -cell damage by other effectors (Cytotoxic) Hypersensitivities ●IgG & IgM bind to antigens ●Activate complement or cause antibody-dependent cell-mediated cytotoxicity (ADCC) ●Ag may be self-antigen- autoimmune disease ●Ag may be exogenous, cell-surface molecules (Ags on RBCs) - opsonization, lysis of RBC, complement activation ●E.g. hemolytic transfusion reaction (HTR), hemolytic disease of the newborn (HDN) (on own definition) ●Type III -IgG, IgM, IgA interact with antigen to form immune complexes -tissue damage by other effectors ●Immune-complex reactions - Localized & Systemic Arthus reaction- localized reaction to non-self serum proteins ●Antigens bind with IgG- leads to accumulation of antigen-antibody aggregates called immune complexes ●Excess IgG + low conc of antigen = immune complexes ●Deposits on inner lumen of small blood vessels, tissues ●Leads to a cascade of inflammatory events ●Causes extracellular destruction damaging localized cells ●Activates coagulation causing thrombi (blood clots) Systemic type lll -serum sickness occurs when immune complexes deposit in various body sites ●Tissue destruction -chills, fever, rash, vasculitis, arthritis ●Autoimmune diseases -SLE (lupus), rheumatoid arthritis ●Type IV -T-cell-mediated reactions - tissue damage by activated macrophages & cytotoxic T cells ●Regulated by T cells ●Delayed-type hypersensitivities , e.g. Mantoux reaction for TB, contact dermatitis like latex allergy ●T cell mediated reactions causing chronic asthma or allergic rhinitis ●Cytotoxic T lymphocyte (CTL)-mediated reactions - tissue transplant rejection, contact dermatitis like poison ivy

Systemic Lupus Erythematosus (lupus) -systemic Autoimmune

●Type III hypersensitivity reactions ●Autoantibodies against nuclear & cytoplasmic proteins ●Anti-nuclear antibodies (ANAs), anti-double-stranded DNA (ds-DNA)- unique to SLE ●Cell death and components released afterwards leads to formation of immune complexes Symptoms occur in many body locations ●Fatigue, fever with no other cause, hair loss, sunlight-sensitive butterfly / wolf-mask (lupus) rash (in 50% patients), arthritis of fingers, hands, wrists, knees ●Headaches, numbness, tingling, seizures, vision problems, personality changes, abdominal pain, nausea, vomiting, arrhythmias, shortness of breath, blood in the sputum, edema, weight gain ●Raynaud phenomenon - color change in fingers when cold ●Diagnosis- identification of four of 11 of most common symptoms + confirmed production of unique autoantibodies ●Positive test for ANAs alone is not diagnostic

chemical methods of control

●Type of microbe targeted ●Level of cleanliness desired ●Effect on the item's integrity ●Safety to animals, humans, environment ●Cost, ease of use

DNA Repair

●Uncorrected mistakes lead to serious consequences ●Cells have many repair mechanisms ●Mistakes during replication are corrected by DNA pol. through proofreading ●Proofreading -DNA pol. reads bases, ensures it is complementary before adding next one ●If an incorrect base is added, it cuts it out and replaces ●Mismatch repair- errors corrected shortly after replication machinery has moved - enzymes recognize wrong nucleotide, excise & replace it ●Errors due to thymine dimers is common- many organisms cannot avoid UV light ○Excision (dark) repair- enzymes cut upstream and downstream of dimer and replace it ○Direct (light) repair - photoreactivation in presence of light by enzyme photolyase (found in all organisms except placental mammals)

Urogenital system

●Urinary tract + reproductive system ●Both systems open to external environment ●Infections from outside OR from microbiota imbalance ●Urinary system- filters blood, excretes wastes, maintains appropriate electrolyte, water balance ●Reproductive system- production of gametes, conception, & development of offspring (in females) ●Urinary Tract Infection & STI/STD

Protozoan & Helminthic Infections of the Skin and Eyes

●Use skin or eyes as a portal of entry ●May physically burrow into skin or mucosa of eye, breach skin barrier by insect bite, enter through a wound ●Macroscopic parasites such as lice, scabies, mites, ticks- not covered in microbiology

Classes of Vaccines

●Vaccine must expose an individual to pathogen-specific antigens that will stimulate adaptive immunity Live attenuated vaccines -weakened strain to establish subclinical infection ●Pathogens are weakened to decrease their virulence ●Activates cellular & humoral immunity, stimulates memory ●Disadvantages -long-term storage, transport, potential to develop disease (in immunocompromised patients), risk of reverting back to full virulence inactivated vaccines contain whole pathogens that have been killed or inactivated ●Inactivation must not affect structure of key antigens ●Does not produce an active infection ●Weaker response - only humoral immunity ●Requires higher doses, multiple boosters ●Advantages- long-term storage, stability, ease of transport, no risk of severe infections ●Can have mild side effects Subunit vaccines- expose patient to key antigens—not whole cells or viruses ●Pathogen chemically degraded to isolate key antigens ●Genetic engineering ●Low risk of side effects Toxoid vaccines- inactivated bacterial toxins, called toxoids ●Prevent diseases in which bacterial toxins play an important role in pathogenesis ●Activate humoral immunity to neutralizes toxins Conjugate vaccine- subunit vaccine with a protein conjugated to a capsule polysaccharide ●Causes T-independent activation of B cells to produce antibodies ●For children < 2 years

Bacterial Infections of Reproductive System

●Vaginitis -inflammation by bacterial infection ●Vaginosis (BV)- imbalance in normal microbiota without inflammation ●Asymptomatic or mild -thin, white-to-yellow, homogeneous discharge, burning, odor, itching ●Main cause- Gardnerella vaginalis; others Bacteroides, Fusobacterium, Ureaplasma, Mycoplasma ●Self-limiting, antibiotic treatment recommended if symptoms develop ●G. vaginalis- more virulent, flourishes when Lactobacillus spp. decreases, part of normal microbiota ●Attaches to vaginal epithelium, forms thick biofilm (difficult to get rid of) ●Produces a cytotoxin- vaginolysin- lyses vaginal epithelial cells, RBCs ●Diagnosis of BV- direct examination of vaginal secretions, not culture of G. vaginalis ●Slides of vaginal swabs, distinguish lactobacilli (long, G+ve rods) from G -ves ●A shift from G+ve bacilli to G-ve coccobacilli can indicate BV ●Slide may contain "clue cells" -epithelium with stippled appearance due to bacteria being attached to surface ●Presumptive diagnosis requires Amsel's diagnostic criteria - 3 out of 4 following characteristics: ○white- yellow discharge, fishy odor -most noticeable when KOH is added, pH > 4.5, presence of clue cells ●Self-limiting, sometimes, topical or oral antibiotics can be prescribed

Q fever

●Zoonotic- Coxiella burnetii- common in farmers ●In domesticated livestock; transmitted by ticks, exposure to fluids of infected animal ●In humans, inhalation of contaminated farmyard aerosols ●Humans very susceptible; organism very hardy ●High fever, headache, coughing, pneumonia, malaise ●Culturing is difficult, hazardous - PCR & ELISA are used ●Doxycycline for acute Q fever; hydroxycholoquine in chronic Q fever not commonly seen

measuring microbial control

●cide (or -cidal) - kills microbes (bacterial) ●-stat (or -static)- does not kill but stop growth (temporary stop) ○Less toxic ○Impregnated safely into plastics (toys, cutting boards) ○Used to treat an infection in healthy individual (static drug) Prevents pathogen from multiplying allowing healthy immune system to clear it

Arthropod-Borne Viral Diseases

Arboviruses - by infected mosquitoes; hemorrhagic fevers Yellow Fever ●Once common in the US, now only in areas of South America, Africa ●Flavivirus transmitted by mosquito vectors ●In mild disease- sudden dizziness, fever, chills, headache, myalgia ●Flushed face, nausea, vomiting, constipation, severe fatigue, restlessness, irritability, resolves in 1-3 days ●In moderate disease- fever falls, recurs, jaundice, petechial rash, mucosal hemorrhages, scant urine, epigastric tenderness, bloody vomit, confusion, apathy ●After a week, patients recover rapidly ●In most severe form- fever, delirium, bleeding, seizures, shock, coma, multiple organ failure, death ●Patients become severely immunocompromised, susceptible to bacterial superinfections and pneumonia ●Diagnosis on clinical signs, travel history, culture, PCR ●No effective treatments, prevention is best, vaccine available Dengue fever ●Breakbone fever, Flavivirus transmitted by mosquitoes ●Mostly self-limiting- abrupt high fever, intense headaches, rash, nose or gum bleeding, muscle, joint, bone pain ●Some patients develop drowsiness, irritability, severe abdominal pain, severe nose or gum bleeding, persistent vomiting with blood, black tarry stools, leads to dengue shock syndrome (DSS) ●Circulatory failure, blood pressure drop causes death ●Diagnosis by serologic testing; no specific treatments or vaccine Chikungunya fever ●Chikungunya virus (CHIKV), transmitted by mosquitoes ●High fever, joint pain, rash, blisters, with joint pain persisting for several months but self-limiting ●Tissue culture, serological tests for diagnosis ●No specific treatments; manage symptoms with fluids, analgesics, bed rest

Removing a tick

It should be grasped gently with blunt tweezers on the head, near its site of attachment, and pulled very carefully until it releases its grip.

Microbial Diseases of the Mouth & Oral Cavity

Dental Caries ●Cavities- microbial lesions that cause damage to teeth ●Lesions in outer enamel layer, infect underlying dentin or even innermost pulp ●If untreated, becomes an abscess, spreads to roots or bloodstream ●A layer of proteins and carbohydrates forms when clean teeth come into contact with saliva ●Microbes are attracted to this food source, form a biofilm called plaque ●Important cariogenic species- Streptococcus mutans ●Sucrose is broken down by bacteria into glucose, fructose ●Glucose is turned into dextran, to form extracellular matrix of biofilm ●Fructose is fermented, producing organic acids; dissolves minerals of tooth, including enamel ●Over time, plaque becomes thick, calcifies into tartar or dental calculus ●To prevent tooth decay- prophylactic treatment, good hygiene -brushing, flossing, regular dental cleanings ●Fluoride protects against acidity, is bacteriostatic ●If caries develop, prompt treatment prevents worsening Periodontal Disease ●Inflammation, tissue damage surrounding teeth- reversible, preventable with good oral hygiene ●Gingivitis - Inflammation of gums with irritation, bleeding ●When plaque accumulates, bacteria colonize gingival space and environment becomes anaerobic ●Allows Porphyromonas, Streptococcus, Actinomyces to flourish- products cause inflammation, damage ●Diagnosed by visual inspection, X-rays ●Good hygiene, professional dental cleaning, antibiotics ●Chronic gingivitis develops into serious periodontitis ●Gums recede, expose parts of tooth below crown ●Newly exposed area is unprotected, bacteria grow, spread underneath enamel, cause cavities ●Also erodes cementum, which helps to hold teeth in place leading to loss of teeth ●Bones of jaw can erode if infection spreads ●Results in bleeding and halitosis (bad breath) ●Treated with cleaning, hygiene, antibiotics if needed Trench Mouth - acute necrotizing ulcerative gingivitis/ Vincent's disease ●Prevotella intermedia, Fusobacterium, Treponema vicentii ●Severe periodontitis with gums erosion, ulcers, pain with chewing, halitosis ●Diagnosed by visual examination and X-rays More common in immunocompromised

Oral Infections

Herpetic Gingivostomatitis ●HSV-1 -ulcers of mucous membranes inside mouth ●Self-limiting except in immunocompromised patients ●Diagnosed through clinical examination ●Treatment- mouthwashes, antiviral medications Oral Thrush ●Candida infection in oral cavity- in infants, HIV patients ●White patches, pseudomembranes in mouth with bleeding ●Treated topically Mumps ●Viral infection of parotid glands (largest pair of salivary glands) by mumps virus (MuV) ●Transmitted through respiratory droplets or contact with contaminated saliva ●Fever, muscle pain, headache, pain with chewing, loss of appetite, fatigue, weakness, swelling, pain ●Virus can enter bloodstream, spread to organs, CNS ●Complications, -encephalitis, meningitis, deafness ●Inflammation of pancreas, testes, ovaries, breasts can cause permanent damage ●Diagnosis using culture, molecular or serologic tests ●No specific treatment, only supportive therapies ●Vaccination is most effective prevention

Babesiosis

zoonotic disease caused by protist parasite Infect red blood cells spread by certain ticks

Signs and Symptoms of Oral & GI Disease

●2 categories: infection (growth of a pathogen in GI tract) or intoxication (presence of microbial toxin in GI tract) ●In mouth, fermentation by anaerobic microbes produces acids that damage teeth and gums ●Leads to tooth decay, cavities, periodontal disease (chronic inflammation, erosion of gums) ●Infections of mucosa, glands, leads to inflammation, sores, cankers Ulcer - open sore in mouth or GI tract Infections & intoxications of lower GI tract ●Nausea, vomiting, diarrhea, aches, and fever ●Vomiting, diarrhea -cause severe dehydration ●Gastritis- inflammation of stomach lining with swelling ●Enteritis- inflammation of intestinal mucosa ●Hepatitis- inflammation of liver ●Colitis- inflammation of colon (due to food intoxication) ●Inflamed colon wont reabsorb water, leads to diarrhea ●Dysentery- damage to epithelial cells of colon causes bleeding, excess mucus in watery stools

Hanta Virus

●2 major (sometimes overlapping) syndromes: hantavirus pulmonary syndrome (HPS), hemorrhagic fever with renal syndrome (HFRS) ●Transmission through inhalation of aerosols of wild rodent urine, feces ●HPS -nonspecific flu-like illness, headache, fever, myalgia, nausea, vomiting, diarrhea, abdominal pain ●Rapid pulmonary edema, hypotension pneumonia, shock, death ●Mortality upto 50% ●HFRS- high fever, headache, chills, nausea, inflammation or redness of eyes, or a rash, hemorrhaging, hypotension, kidney failure, shock, death ●Serological and immunohistological staining ●No clinical treatments available

Granulomatous Amoebic Encephalitis (GAE)

●Acanthamoeba, Balamuthia- free-living amoebae in fresh water - human infections are rare ●In immunocompromised patients, causes GAE ●Microbe enters through nasal sinuses or breaks in skin, spreads to CNS by blood ●Causes inflammation, lesions, encephalitis; nearly always fatal; not diagnosed until late in the infection ●Lesions detected using CT or MRI; live amoebae in CSF ●Antiparasitic drugs for treatment, mortality rate is high

Transmissible Spongiform Encephalopathies (prions)

●Acellular infectious agents cause group of related diseases -transmissible spongiform encephalopathies (TSEs) in humans, animals ●Degenerative, fatal neurological disease occurs when brain tissue is infected by prions ●Slow onset; symptoms not apparent until after incubation period -years- decades ●Death occurs in months- years after 1st symptoms ●Scrapie in sheep, chronic wasting disease in deer and elk, mad cow disease ●Transmitted to humans through consumption of infected nerve tissues, tissue transplants, blood transfusions ●In humans- Creutzfeldt-Jakob disease & kuru (rare disease endemic to Papua New Guinea)(canabolism) ●Prions are proteins, have no nucleic acid ●Normally found in healthy brain tissue, if protein is misfolded it causes disease; also induces other proteins to misfold and spread ●As protein accumulates, aggregates, forms fibrils within nerve cells causing cells to die ●Brain tissues show amyloid plaques giving brain a spongy appearance (spongiform encephalopathy) ●Memory loss, personality changes, blurred vision, uncoordinated movements, insomnia ●Gradually worsens over time to coma, death ●Diagnosis - histological examination of brain biopsies ●Prion-infected materials are highly contagious ●Cannot be cured; medications may help slow progress Individuals with transmissible spongiform encephalopathies develop neurofibrillary tangles and amyloid plaques.

Infectious Arthritis

●Acute or a chronic inflammation of joint tissues by bacteria ●Secondary to bacteremia, with rapid onset of moderate to severe joint pain, swelling ●Pathogen introduced through wound or surgical site ●Acute infections occur after joint replacement surgery in immunocompromised patients ●S. aureus most common cause in general population, Neisseria gonorrhoeae in sexually active individuals ●Chronic type is less common; in patients with preexisting conditions ●HIV infection, bacteria or fungal oral infection, prosthetic joints, rheumatoid arthritis (RA), immunosuppressive chemotherapy ●Onset in single joint; mild or no pain, gradual swelling, mild warmth, minimal or no redness ●Diagnosis requires aspiration of synovial fluid from joint for microscopy, culture, antimicrobial susceptibility testing ●Prognosis poor even with treatment, permanent joint damage is common

Human African Trypanosomiasis

●African sleeping sickness -Trypanosoma brucei ●Transmitted by bite of tsetse fly; chancre forms at site; organisms spread, move into blood cause undulating fever -2-3 days, remissions of a week in between ●In final phase, pathogens move from lymphatics into CNS ●Daytime sleepiness, insomnia, mental deterioration ●Strong immune response not sufficient to eliminate it ●Initially causes high fevers -with immune response, organisms decrease, symptoms abate ●Pathogen alters surface coat antigens by antigenic variation, evades immune response ●Rapidly proliferates, causes another bout of disease; if untreated, it is usually fatal; early diagnosis is important ●Diagnosis by clinical symptoms- chancre at site of infection, Winterbottom's sign (enlargement of lymph nodes on back of neck— indicative of cerebral infections) ●Following successful treatment, follow-up examinations of CSF for 2 years to detect possible relapses ●Prevention by controlling insect vector populations

Chagas disease

●American trypanosomiasis- zoonosis caused by flagellated Trypanosoma cruzi ●Transmitted through feces of triatomine bugs ●Also contaminated blood transfusions, organ transplants, congenital transmission from mother to fetus ●Endemic through Mexico, Central America, and South America - neglected tropical disease (NTP) ●Kissing bugs active at night, take blood meals by biting faces, lips, often defecate near site of bite ●Infection occurs when host rubs feces into eyes, mouth, bite wound, or other break in skin ●Protozoan enters blood, invades tissues of heart, CNS, macrophages, monocytes ●3 phases of disease- acute, intermediate, chronic depending on immunocompetence of patient ●Acute phase disease- fever, headache, myalgia, rash, vomiting, diarrhea, enlarged spleen, liver, lymph nodes ●Localized nodule (chagoma) may form at portal of entry, swelling of eyelids or side of face = Romaña's sign ●Symptoms may resolve but if untreated, can persist in tissues, causing irreversible damage to heart or brain ●In rare cases, young children may die of myocarditis or meningoencephalitis ●Following acute phase- a prolonged intermediate phase- mostly asymptomatic, few or no parasites in blood ●Many remain asymptomatic for life; decades after exposure, about 25% will develop chronic disease that is debilitating, life threatening ●In chronic phase- painful swelling of colon, twisting, constipation, bowel obstruction; painful swelling of esophagus, dysphagia, malnutrition; flaccid cardiomegaly (enlargement of heart), heart failure, sudden death ●Direct microscopic observation of trypanosomes in blood ●Treated with anti-parasitic drugs but efficacy is much lower when disease is chronic ●Avoiding exposure through vector control is best

Viral Encephalitis

●Arboviral Encephalitis- by insect-borne viruses ●Endemic to specific regions ●4 types - eastern equine encephalitis (EEE):transmitted by Aedes, Coquillettidia, and Culex mosquitoes; birds are reservoirs western equine encephalitis (WEE): transmitted by Culex tarsalis mosquitoes; has caused relatively few cases in the United States. St. Louis encephalitis:carried by three species of Culex mosquitoes; a serious outbreak occurred in 1975 Japanese encephalitis (JEV):worldwide, causes the most cases of vaccine-preventable encephalitis; reservoirs include birds and pigs West Nile encephalitis (WNE):transmitted by Culex mosquitoes; birds are a reservoir; became a problem in the United States in 1999 ●Diagnosis- clinical symptoms, serologic testing of CSF ●No antiviral drugs; just supportive care ●Equine encephalitis in horses, humans ●All 4 - birds are reservoirs; transmission by mosquitoes ●Mostly asymptomatic or mild disease ● JEV -has a vaccine-recommended for travelers

Normal Microbiota

●Archaea, bacteria, fungi, protists, viruses ●Very important for normal functioning ●Microbiota of oral cavity - bacteria, archaea ●Teeth, cheeks - unique communities of aerobic and anaerobic microbes ●Chewing mixes microbes with saliva for easy removal ●Lysozyme in saliva damages microbes ●Fluids containing Antibodies & phagocytic cells are produced in gingival spaces

Gastroenteritis by Astroviruses

●Astroviridae- severe gastroenteritis, in infants, children ●Diarrhea, nausea, vomiting, fever, abdominal pain, headache, malaise ●Transmission: fecal-oral route (contaminated food, water) ●Diagnosis by testing stool samples using serological techniques ●Treatment- supportive rehydration and electrolyte replacement if needed

peripheral nervous system

●Nerves that connect organs, limbs, other anatomic structures to brain, spinal cord ●PNS is not protected by bone, meninges, or a blood barrier; more susceptible to injury/infection ●Microbial damage to peripheral nerves causes tingling or numbness -neuropathy ○can also be caused by trauma, noninfectious causes such as drugs or diabetes

Neonatal meningitis

●Babies up to 3 months of age ●S. agalactiae- encapsulated gram -ve cocci ●Found in urogenital, GI microbiota of 30% of humans ●Neonatal infection- early onset or late-onset ●Early onset disease - infants up to 7 days old ●Infected during childbirth; incidence reduced by iv antibiotics to mother during labor ●Late-onset - infants between 1 wk- 3 mo ●Premature infants have a greater risk ●Early onset- temperature instability, apnea, bradycardia, hypotension, difficulty feeding, irritability, limpness; when asleep, baby may be difficult to wake up ●Late-onset -seizures, bulging fontanel (soft spot), stiff neck, hemiparesis (weakness on one side of body), opisthotonos (rigid body, arched back, head thrown backward) ●Diagnosis by cultures of CSF or blood ●Treated with iv antibiotics

Giardiasis

●Backpacker's diarrhea / beaver fever ●Flagellated protist Giardia lamblia / Giardia intestinalis / Giardia duodenalis ●Uses a large adhesive disk (comprised of microtubules) to attach to intestinal mucosa ●Blocks absorption of nutrients ●Transmitted through contaminated food, water, directly from person to person ●Children in day-care centers at risk ●Large outbreaks if public water supply is contaminated ●Has a resistant cyst stage, able to survive cold temp, chlorination treatment, filtration to remove cysts ●Cysts are consumed, develop into active tropozoite ●Asymptomatic or GI symptoms, with weight loss ●1-3 weeks after exposure- diarrhea, nausea, stomach cramps, gas, greasy stool (because fat absorption is being blocked), possible dehydration ●Parasite remains in colon; does not spread ●Symptoms clear in 2-6 weeks ●Chronic infections resistant to treatment may develop ●Weight loss, episodic diarrhea, malabsorption syndrome ●Diagnosis by observation by microscope for ova and parasite (O & P) ●Treated with anti-parasitic drugs

Streptococcal Toxic Shock-Like Syndrome

●By Streptococcus pyogenes ●50% of patients develop bacteremia, necrotizing fasciitis ●Can cause acute respiratory distress syndrome (ARDS)-rapid disease with fluid accumulation in lungs, inhibits breathing, causes hypoxemia ●Higher mortality rate even with aggressive therapy ●In patients with streptococcal soft-tissue infection such as bacterial cellulitis, necrotizing fasciitis, pyomyositis, recent influenza A infection, or chickenpox

Zoonotic febrile disease

●By bacteria that require arthropod vectors ●Obligate intracellular species - Anaplasma, Bartonella, Ehrlichia, Orientia, Rickettsia, Borrelia ●Isolation, identification of these are performed in BSL-3 labs because of low infective dose ●Diagnosis by serological tests, PCR or microscopic examination ●Mostly treated with antibiotics ●Anaplasmosis & - ehrlichiosis- tickborne diseases ●Epidemic Typhus - Rickettsia prowazekii from body lice; can establish a chronic carrier state in humans ●Murine (Endemic) Typhus- Rickettsia typhi from bite of rat flea ●Rocky Mountain spotted fever (RMSF) -Rickettsia rickettsii by bite of hard-bodied ticks; can be fatal even in healthy patients ●Relapsing Fever- Borrelia spp -louseborne & tickborne relapsing fever ●Trench Fever -louseborne disease by Bartonella spp, from feces of infected body lice Lyme disease ●Borrelia burgdorferi transmitted by tick bite ●Most commonly reported vectorborne illness in US (Nationally Notifiable disease) ●Symptoms in 3 stages: early localized, early disseminated, late stage ●Bull's-eye rash, malaise, headache, fever, muscle stiffness in localized stage ●Severe headache, neck stiffness, facial paralysis, arthritis, carditis in early disseminated ●Late-stage occurs years after exposure- severe arthritis, meningitis, encephalitis, altered mental states ●Diagnosis - by bull's-eye rash & serological tests ●Treated with antibiotics

Nervous System

●CNS - brain, spinal cord ●PNS- nerves connecting CNS to muscles, sensory structures ●Brain - coordinates all sensations, mobility, emotions, intellect ●Meninges - 3 layers of membrane under skull ●Dura mater (tough)- topmost meningeal layer ●Arachnoid mater (spiderlike)-middle layer ●Pia mater (tender)- innermost meningeal layer

Blood brain barrier

●CNS is not exposed to blood or immune system for protection ●Blood vessels for brain lie on top of pia mater; their capillaries are less permeable ●Form tight junctions that control transfer of blood components ●Materials have very limited ability to interact with CNS- blood-brain barrier ●Blood-brain barrier protects CSF from contamination ●No normal microbiota in the CSF ●BBB inhibits many drugs into brain ●Treatment of CNS infections of CNS is difficult ●Inside bones of the vertebrae are meninges + a blood-spinal cord barrier ●To cause an infection in CNS, pathogens must breach blood-brain barrier or blood-spinal cord barrier ●4 virulence factors/mechanisms to do this ●Intercellular (paracellular)- toxins, or inflammation-mediated processes pass through ●Transcellular- factors that allow adherence, trigger uptake by vacuole- or receptor-mediated mechanisms ●Leukocyte facilitated - Trojan-horse mechanism- infects peripheral leukocytes to directly enter CNS ●Nonhematogenous -enter without encountering BBB -olfactory or trigeminal cranial nerves that lead to CNS

Tapeworms (Taeniasis)

●Caused by pork (Taenia solium), beef (Taenia saginata), Asian (Taenia asiatica) tapeworms in undercooked meat ●Consumption of raw or undercooked fish, contaminated sushi = fish tapeworm (Diphyllobothrium latum) infection ●Tapeworms attach to intestinal wall, produce eggs that are excreted in feces ●After ingestion, eggs hatch, larvae emerge, reside in intestine, or move to muscle or brain tissue ●Cysticercosis- T. solium larvae form cysts in tissues or muscles, eye (ophthalmic cysticercosis), or brain (neurocysticercosis) ●Infections are asymptomatic or have mild GI symptoms -epigastric discomfort, nausea, diarrhea, flatulence, or hunger pains ●Common to find tapeworm segments in stool ●Cysts in muscles may be asymptomatic, or painful ●Microscopic analysis of stool from 3 separate days ●Treated with anti-helminthics

Cryptococcal Meningitis

●Cryptococcus neoformans- fungal pathogen causes meningitis; yeast found in soils, pigeon droppings ●Thick capsule inhibits clearance by phagocytosis ●Subclinical respiratory infections; resolves spontaneously ●In immunocompromised patients -progress to meningitis, granuloma formation in brain tissues ●Easily cultured in lab from urine samples, identified by capsules ●Prolonged treatment with antifungal drugs is required

Cryptosporidiosis

●Cryptosporidium parvum or C. hominis ●In animals; spread in feces of mice, birds, farm animals ●Transmission by contaminated water, food or contact with infected animals or their feces resistant to chlorine!! ●In US, outbreaks through contamination of public water supply or water parks, swimming pools, day-care centers ●Watery diarrhea, nausea, vomiting, cramps, fever, dehydration, weight loss -self-limiting within a month ●Immunocompromised are at risk of severe illness or death ●Diagnosis -direct examination of stool for Ova and Parasite over multiple days ●Treatment -oral rehydration therapy + anti-diarrheals ●Broad-range anti-parasitic drugs

Cytomegalovirus Infections

●Cytomegalovirus (CMV)- HHV-5 ●Non-Epstein-Barr infectious mononucleosis ●In AIDS patients, neonates, transplant recipients ●Mostly asymptomatic; in adults, if symptoms occur - fever, fatigue, swollen glands, pharyngitis ●Transmitted through contact with body fluids, sexual contact, nursing, blood transfusions, organ transplants ●Pregnant women with active infections pass it fetus, causing congenital CMV infections ●Serious symptoms in newborns - growth retardation, jaundice, deafness, blindness, mental retardation ●Most infected infants never have symptoms ●Diagnosis by TORCH screening ●Many receiving blood transfusions & nearly all receiving kidney transplants ultimately become infected with CMV ●Approximately 60% of transplant recipients will have CMV, > 20% develop symptoms ●Diagnosis by microscopy of stained tissue specimens, EIA, PCR, antiviral drugs for serious infections

Rabies

●Deadly zoonotic disease caused by rabies virus (RV) ●Transmitted through bite of infected mammal ●Rhabdoviridae- bullet shaped enveloped RNA viruses ●Most common reservoirs in US - raccoons, bats, skunks, foxes responsible for 93% ; remaining 7.4% of cases- dogs, cats, horses, mules, sheep, goats, llamas ●Low incidence in US due to widespread vaccination ●Oral vaccine delivered in a package of bait that is dropped by airplane in endemic areas ●Most countries require a quarantine/ proof of vaccination for domestic pets brought in; especially strict in island nations where rabies is not yet present- Australia ●Incubation period -weeks, months to over a year ●Virus replicates, moves from site of bite into motor, sensory axons of peripheral nerves ●Spreads from nerve to nerve using a process called retrograde transport, reaching CNS through spinal ganglia ●In the brain, leads to encephalitis caused by disruption of normal neurotransmitter function ●Virions compete with neurotransmitters in synapses ●Continues to spread through nerves to tissues ●As disease progresses, virus is found in salivary glands, taste buds, nasal cavity, tears ●Early symptoms -discomfort at bite, fever, headache ●Virus reaches brain, later symptoms appear, always fatal ●Terminal rabies cases ends as furious rabies or paralytic rabies ●Furious rabies- patients become agitated & hyperactive; hydrophobia caused by muscular spasms in throat ●Excess salivation, desire to bite can lead to foaming of the mouth ●Behaviors enhance viral transmission; contact with infected secretions like saliva or tears is sufficient ●Ends after just a few days with terror, confusion, cardiovascular & respiratory arrest ●Paralytic rabies -longer course of disease ●Muscles at site of infection become paralyzed ●Paralysis spreads through body, culminates in coma, death ●No tests to detect virus in humans at time of bite or shortly thereafter ●Most suspected infections are treated as positive; better that patients undergo unnecessary therapy due to false-positive result, than die due to a false-negative result ●Treated with multiple doses of attenuated vaccine ●Vaccination of an already-infected individual can slow progress of disease, allowing time antibodies to develop Also treated with human rabies immune globulin to encourage passive immunity, neutralize free viral particles

Anatomy of Digestive system

●Digestive system/ gastrointestinal (GI) tract ●Begins with mouth, ends with anus ●Mouth - teeth, gums, tongue, oral cavity ●Pharynx, esophagus, stomach, small intestine, large intestine, rectum, anus ●Accessory organs -salivary glands, liver, gallbladder, spleen, pancreas

Hydatid Disease

●Echinococcus granulosus -found in dogs (definitive host), intermediate hosts (sheep, pigs, goats, cattle) ●Transmitted through eggs in feces from infected animals ●Occupational hazard for individuals in agriculture ●Eggs hatch in small intestine, release larvae ●Larvae invade intestinal wall, enter blood ●Form hydatid cysts in lungs or liver ●Cysts grow slowly; undetected until they become large ●Severe allergy (anaphylaxis) occurs when cysts burst ●Cysts in liver can cause enlargement of liver, nausea, vomiting, right epigastric pain, pain in the right upper quadrant, allergy symptoms ●Cysts in lungs lead to alveolar disease- abdominal pain, weight loss, pain, malaise ●Detected through imaging of cysts ●Surgery to remove cysts, other treatments also available

Hook worm

●Eggs develop into larvae in soil with dog or cat feces ●Larvae penetrate skin, travel through venous circulation, reach lungs ●Coughed up, swallowed, enter intestine mature into adults ●Adults attach to intestinal wall, feed on blood, can potentially cause anemia ●Cough, itchy rash, appetite loss, abdominal pain, diarrhea ●In children, affect physical + cognitive growth ●Some hookworm found in cats, dogs, can penetrate skin ●Larvae of hookworms migrate in skin, cause cutaneous larva migrans- skin disease ●As they move across subcutaneous tissue, pruritic tracks appear ●Diagnosed using microscopic examination of stool, for eggs, treated with anti-helminthics

Zika virus infection

●Emerging arboviral disease spread by mosquito vector ●Fever, skin rashes, conjunctivitis, muscle, joint pain, malaise, headache ●Can be transmitted sexually, or from mother to baby or through a blood transfusion ●Mostly mild except for developing fetus- brain damage, microcephaly- abnormally small head ●Diagnosis on clinical symptoms, serological tests ●No antiviral treatments or vaccines, only supportive care

Pneumococcal Meningitis

●Encapsulated gram +ve bacteria S. pneumoniae -in microbiota of pharynx of young children ●Crosses blood-brain barrier in susceptible individuals ●Identified in CSF samples using Gram's stain, PCR assays ●Virulence factors- pilin for adherence, cytoplasmic bacterial toxin pneumolysin ●Drug-resistant strains are a problem; treated with broad-spectrum antibiotics

Haemophilus influenzae Type b

●Encapsulated pleomorphic Gram -ve coccobacilli ●Now uncommon, because of Hib vaccine ●In throats of healthy individuals, infants, young children ●By 5 years of age, most children develop immunity ●Infants > 2 months of age do not produce a sufficient antibody response, susceptible to serious disease ●Intracranial pressure = 5% mortality rate, 20% incidence of deafness or brain damage ●Preliminary diagnosis by PCR or smear of CSF ●Confirmation with fastidious growth on chocolate agar ●Treated with antibiotics; preventable with Hib polysaccharide conjugate vaccine ●Recommend all children receive it at 2, 4, 6 months of age, final booster at 12 to 15 months

Amoebiasis (Amebic Dysentery)!!!

●Entamoeba histolytica through water or food with fecal contamination ●Widespread in developing world ●Low infective dose < 10 cysts ●Mild diarrhea to severe amoebic dysentery ●Severe infection causes fever, distended abdomen ●Parasite may live in colon without causing symptoms or invade mucosa to cause colitis ●Spreads to spleen, liver, brain, genitourinary tract, lungs ●Chronic infection with intermittent diarrhea, mucus, pain, flatulence, weight loss ●Examination of fecal specimens for Ova and Parasites obtained on multiple days for diagnosis ●Magnetic resonance imaging (MRI) can be used to detect liver abscesses Treated with anti-parasitics

Pinworms (Enterobiasis)

●Enterobius vermicularis- tiny pinworms, common in US ●Mild, abdominal pain, insomnia from itching of perianal region at night when worms leave anus to lay eggs ●Itching contributes to transmission, through fecal-oral route ●Larvae hatch in small intestine, move to colon, develop into adults ●From colon, female adult exits body at night to lay eggs ●Diagnosed in 3 ways ○Inspection of perianal region for worms while patient is asleep at night ○Removal of eggs from area around anus with tape, first thing in the morning for 3 days to yield eggs for microscopic examination ○Detection of eggs through examination of samples from under fingernails, where eggs lodge due to scratching ●Treated with anti helminthics

Anatomy and Normal Microbiota of the GI Tract

●Environment of GI tract - harsh to aid digestion, immunity ●Stomach- extremely acidic (pH <3.5) kills many microbes ●Environment in small intestine- able to support microbial communities- lactobacilli, diphtheroids, fungus Candida ●Large intestine (colon)- diverse, abundant microbiota important for normal function ○Bacteroidetes, Firmicutes, methanogenic archaea, fungi ●Gut microbiota aid in digestion, production of feces, flatus ●Produce valuable nutrients that humans cannot synthesize themselves ●E. coli breaks down food, helps produce vitamin K, for blood coagulation ●Defenses of GI tract ○Peyer's patches- lymphoid tissue that detects pathogens - site of antigen presentation, secretion of IgA ○Goblet cells secrete a gel-forming mucin- for mucus ●Constant movement helps move pathogens out ●Feces ~ 25% microbes, 25% sloughed epithelial cells, 25% mucus, and 25% digested or undigested food ●Normal microbiota is an additional barrier- outcompete pathogens for space, nutrients =competitive exclusion ●Secretes protein toxins -bacteriocins (bind to specific receptors on surface of susceptible bacteria)

Gastroenteritis by Rotaviruses

●Family Reoviridae spread by fecal-oral route; preventable through vaccination ●Widespread in day-care centers; adults resistant or asymptomatic, elderly vulnerable ●Fever, vomiting, diarrhea; can cause lactose intolerance ●Illness after incubation of 2 days,lasts for ~1 week ●Severe fluid loss, dehydration, death ●Diagnosis- serological tests, or RT-PCR ●Supportive treatment with oral rehydration therapy

Flukes

●Flatworms with leaf like appearance Liver Flukes ●Interfere with the bile duct ●Fasciola hepatica, Fasciola gigantica in contaminated raw or undercooked aquatic plants (e.g., watercress) ●Adults develop in bile duct, release eggs into feces ●Spend part of their life cycle in freshwater snails ●Humans infected when eating aquatic plants contaminated by larvae ●From intestine, migrate to bile duct to mature ●Acute infection- nausea, vomiting, abdominal pain, rash, fever, malaise, breathing difficulties ●Chronic- cirrhosis, pancreatitis, cholecystitis, gallstones ●Diagnosis -patient history, examination of samples ●Treated with anti-helminthics Intestinal Flukes ●Ingested from contaminated aquatic plants ●Cysts are consumed, larvae emerge in duodenum, develop into adults attached to intestinal epithelium; eggs released in stool ●Often asymptomatic, if not - mild diarrhea, abdominal pain ●Severe symptoms- vomiting, nausea, allergic reactions, anemia ●High parasite loads may lead to intestinal obstructions ●Diagnosis, treatment similar to liver flukes

Staphylococcal Food Poisoning

●Food intoxication- enterotoxins produced by Staph ●Nausea, diarrhea, cramping, vomiting within 1-6 hours ●Severe cases- headache, dehydration, changes in blood pressure, heart rate-resolves within 24 to 48 hours ●S. aureus in raw, undercooked, cooked foods including meat, dairy products ●Commonly found on hands; transmitted to prepared foods through poor hygiene ●Greatest risk is for food left < 60 °C (140 °F); cooked foods should be reheated to at least 60 °C (140 °F) ●Raw meats - cooked to higher internal temperatures ●Staphylococcal enterotoxins- resistant to low pH, heat stable, not destroyed by boiling at 100 °C ●Bacteria itself may be killed, enterotoxins alone can cause vomiting and diarrhea ●Enterotoxin is a superantigen, provokes strong immune response ●Rapid onset of signs, symptoms helps diagnosis ●Confirmed by identifying toxin in a food sample or in biological specimens using serological techniques ●Resolves quickly, within 24 hours, without treatment ●Sometimes supportive treatment in a hospital may be needed

Bacterial Infections of GI Tract

●Foodborne disease due to toxins ●Infection or intoxication depends on location ●Infection- microbe is ingested, colonizes gut, produces toxins, intoxication- toxins in food before ingestion ●Toxins damage cells lining GI tract- mainly colon ●Diarrhea, abdominal cramps, or severe dysentery ●Nausea, vomiting -mechanisms to expel toxins ●Most bacterial GI illness is short-lived, self-limiting ●Dehydration-greatest risk- oral rehydration with electrolyte essential

Fungal & Parasitic Diseases of Nervous System

●Fungal infections of circulatory system are very rare ●Fungal infections of nervous system, called neuromycoses, are rare in healthy individuals ●Devastating in immunocompromised or elderly patients ●Eukaryotic parasitic infections of nervous system are uncommon but life-threatening in immunocompromised individuals

Tularemia

●G -ve Francisella tularensis causes zoonotic rabbit fever ●Eating contaminated meat, handling of infected animal tissues (skinning rabbits) ●Also transmitted by bites of infected arthropod - dog tick, lone star tick, wood tick, deer flies ●Not directly communicable between humans ●Exposure to aerosols of F. tularensis cause life-threatening infections ●Highly contagious, infectious dose <10 cells ●Pulmonary infections- 30%-60% fatality rate if untreated ●Biosafety level-3 (BSL-3) organism, potential biological warfare agent ●Bacteria move to lymph nodes, phagocytosed, grows, multiplies intracellularly ●Spreads to other organs, produces granulomas ●After 3 day incubation, skin lesions at site of infection - fever, chills, headache, swollen painful lymph nodes ●Direct diagnosis challenging because it is so contagious ●After presumptive diagnosis special handling is required Specimens only handled by BSL-2 or BSL-3 labs with Federal Select Agent Program ●Rare in US, similar to many other infections ●Direct fluorescent-antibody (DFA) microscopic examination, serological test or PCR ●Acute- and convalescent-phase serum samples required to confirm an active infection ●Diagnosed on clinical findings, likely exposure ●Treated with antibiotics

Malaria

●Genus Plasmodium: P. falciparum, P. knowlesi, P. malariae, P. ovale, and P. vivax ●Infects red blood cells, transmitted through bite of Anopheles mosquitoes ●P. falciparum- common, lethal, causes falciparum malaria ●Cycles of extreme fever & chills; sudden, violent symptoms of malaria start with malaise, abrupt chills, fever, rapid faint pulse, polyuria, headache, myalgia, nausea, vomiting ●After 2-6 hours fever falls, profuse sweating for 2- 3 hours, followed by extreme fatigue ●Organ damage resulting from hemolysis causes patients to develop sludge blood (i.e., rbcs agglutinate into clumps) ●Can lead to lack of oxygen, necrosis of blood vessels, organ failure, death ●Tertian malaria - cycles of fever, chills occur every 2 days - caused by P. vivax & P. ovale ●Quartan malaria - cycles every 3 days- by P. malariae ●Parasite has a complex life cycle- developmental stages alternating in mosquitoes & humans ●Sporozoites in mosquito salivary gland are injected into humans ●Parasites circulate to liver, develop divide releasing many merozoites at once ●Merozoites move to bloodstream, infect rbcs, develop into trophozoites that produce more merozoites ●Synchronous release of merozoites from rbcs in the evening causes symptoms ●Parasite is transferred to mosquito, reproduces sexually in its gut, undergoes developmental stages before migrating to salivary glands to complete life cycle ●Diagnosis by microscopic observation of developmental forms of Plasmodium in blood smears ●Treatment - anti-malarial drugs; developing resistance ●Insecticides, insecticide-treated bed nets can limit spread ●Despite efforts to develop a vaccine, none available

Cells of the nervous system

●Glial cells & neurons ●Cell body (soma)- metabolic center -nucleus + organelles ●Finely branched extensions from soma are dendrites ●Elongated extension of soma is the axon ●Axons are surrounded, insulated by myelin sheath produced by Schwann cells ●End of an axon forms branches called synaptic terminals ●Neurons form junctions called synapses ●Synaptic terminals contain vesicles with neurotransmitters

Foodborne Illness Due to Bacillus cereus

●Gram +ve endospore-forming rod found in soil ●Endospores survive cooking, produce enterotoxins in food after it has been heated ●Illnesses occur after eating rice, prepared foods left at room temp for too long, nausea, pain, abdominal cramps ●Produces 2 toxins: one causing diarrhea, other vomiting ●Diagnosis by isolating bacteria from stool samples, vomitus, uneaten infected food ●Rehydration, antibiotics not needed, illness is usually mild

Clostridium difficile

●Gram +ve rod part of gut microbiota ●Due to long-term antibiotic use, C.difficile overgrows leading to diarrhea ●Risk factors- immunocompromisation, hospitalization for extended periods, age, recent antibiotic use, gastrointestinal procedures, or PPI use ●Forms endospores, survives for extended periods of time in harsh conditions, produces 2 toxins ●Highly concerning in health care settings ●Focal necrosis, ulceration with exudate, progressing to pseudomembranous colitis ●Watery diarrhea, dehydration, fever, loss of appetite, abdominal pain, perforation of colon, septicemia, death ●Diagnosis -patient history, presentation, imaging, endoscopy, lab tests, confirm with PCR/ELISA for toxin ●Treatment- stop antibiotic use, start electrolyte replacement ●Metronidazole or vancomycin ●Fecal transplant to restore microbiotica in recurrent cases The fibrin layer of dead epithelial cells and leukocytes that can develop during Clostridium difficile infection is called a pseudo membrane

Clostridium-Associated Diseases

●Gram +ve, endospore-forming obligate anaerobic rods ●Endospores, produces most protein exotoxins ●2 potent known biological toxins: botulinum neurotoxin (BoNT) tetanus neurotoxin (TeNT) ●Lethal dose is 0.2-10 ng per kg body weight ●Diagnosis involves bioassays to detect toxin in fecal specimens, blood, foods

Peptic Ulcers

●Gram -ve Helicobacter pylori tolerates acidic environment ●Colonizes cells using pili for adhesion, produces urease, creates ammonia to neutralize acid ●Damages stomach lining, leading to gastritis, ulcers ●Toxin induces vacuole formation in host cells ●Nausea, lack of appetite, bloating, burping, weight loss ●If not treated ulcers get deeper, stomach perforates; allows digestive enzymes and acid to leak into body causing serious condition ●Diagnosis - breath test with radiolabeled urea; H. pylori ●Blood testing for antibodies, bacteria with stool test or stomach wall biopsy ●Antibiotics used to treat infection- USDA recommends triple therapy with antibiotics, proton pump inhibitors ●There are risks to eradicating -it may protect against some cancers

Plague

●Gram -ve bacillus Yersinia pestis ●Acute febrile disease in rodents, small mammals, humans ●High mortality rate if left untreated ●3 forms- bubonic (most common form), septicemic, pneumonic plague, based mode of transmission & initial site of infection

Brucelosis

●Gram -ve coccobacilli -zoonotic infections in animals & humans, brucellosis (mediterranean fever or Malta fever) ●B. abortus-cattle, B. canis- dogs, B. suis- swine, B. melitensis- goats, sheep, and camels ●Rare in US, but common in Mediterranean, south, central Asia, central, South America, Caribbean ●Human infections -ingestion of meat or unpasteurized dairy products or through inhalation or contact with skin wounds ●In US, mostly found in slaughterhouse workers, vets ●Escapes phagosome, grows within cytoplasm, spreads forming granulomas ●Acute infections- undulant (relapsing) fever, untreated infections develop into chronic disease- recurring flu-like signs, symptoms ●Found in blood only during acute fever stage; difficult to diagnose by cultivation, BSL-3 pathogen ●Immune tests used for serodiagnosis ●Treated with antibiotics

Circulatory and Lymphatic Systems

●Networks of vessels + pump- transports blood & lymph ●Microbes can be spread rapidly leading to disease ●Normally circulatory & lymphatic systems have no microbiota ●Immune cells eliminate microbes before they establish infection CIRCULATORY ●Delivers nutrients, immune factors, O2, removes waste ●Thick-walled arteries -carry blood from heart ●Arteries → arterioles → capillaries ●Capillaries → venules → veins- blood back to heart ●Kidneys filter blood, removes wastes ●Liver filters blood, removes damaged/defective RBCs ●Spleen filters, stores blood, immune factors ●All filtering structures entrap microbes LYMPHATIC ●Runs through body but not a full circulating system; not pressurized by heart ●Fluid moves from extremities to drainage points in veins above heart ●Primary lymphoid tissues -bone marrow, thymus ●Secondary -spleen, lymph nodes, others underlying epithelium ●Spleen- filters blood, captures pathogens, antigens ●Lymph nodes- rich in B, T cells ●Both contain macrophages, dendritic cells ●Lymph enters nodes through afferent lymphatic vessels; exits through efferent lymphatic vessels

E.coli infection

●Gram -ve rod - part of normal microbiota of colon ●Mostly commensal, some pathogenic ones, cause dangerous diarrheal disease ●Pathogenic strains have special fimbriae or produce toxins Enterotoxigenic E. coli (ETEC) ●Traveler's diarrhea in less developed countries (Montezuma's Revenge) ●Watery diarrhea, abdominal cramps, malaise, low fever ●Produces heat-stable enterotoxin similar to cholera toxin ●Mild, self-limiting; diagnosis by culturing, PCR ●Antibiotics may shorten infection, but resistance is a problem Enteroinvasive E. coli (EIEC) ●Similar to shigellosis ●Large plasmid helps epithelial cell penetration ●Watery diarrhea, chills, cramps, malaise, fever, dysentery ●Self-limiting; diagnosis by culturing, PCR ●Antibiotics not recommended, only supportive therapy Enteropathogenic E. coli (EPEC) ●Potentially fatal diarrhea, especially in infants ●Fever, vomiting, diarrhea lead to severe dehydration ●Has a protein that attaches to intestinal epithelia ●Diagnosis by culturing, PCR; treatment similar ETEC Enterohemorrhagic E. coli (EHEC) ●Most dangerous strain- capable of causing epidemics-e.g. E.coli O157:H7 ●Produces a Shiga-like toxin called verotoxin from horizontal gene transferred from Shigella spp ●Disease ranges from mild to life-threatening ●Bloody diarrhea, severe cramping, no fever ●Self-limiting but can lead to hemorrhagic colitis and profuse bleeding; can lead to HUS ●Diagnosis by culture based on sorbitol fermentation ●Serological typing, PCR, genetic testing for Shiga toxin ●Antibiotics not recommended -may worsen HUS! ●Supportive therapies recommended

Foodborne Illness Due to Yersinia

●Gram -ve rod transmitted through fecal-oral route, ●Intoxication from endotoxin & exotoxins ●Mild, self-limiting ●Severe diarrhea, dysentery in infants ●In adults, infection can spread, cause reactive arthritis, thyroid disorders, endocarditis, glomerulonephritis, eye inflammation, and/or erythema nodosum ●Bacteremia in rare cases

Salmonellosis

●Gram -ve rods- S. enterica, S. bongori serotypes Enteritidis & typhi ●Part of microbiota of humans & poultry ●Disease severity depends on serotype, size of inoculum, health of host ●Ingestion of contaminated food, handling of eggshells, or exposure to certain animals -exposure to raw eggs, raw poultry increases risk ●Handwashing, cooking foods thoroughly reduce transmission ●Can survive freezing but not high temperatures ●Upon ingestion bacteria penetrate epithelium, trigger inflammatory processes, hypersecretion of fluids ●Can persist inside phagosomes, cross epithelium, enter bloodstream, lymphatic system ●Some strains also produce an enterotoxin ●Fever, nausea, abdominal cramps, vomiting, headache, diarrhea ~week- usually self-limiting ●Diagnosis by culture, serotyping, DNA fingerprinting ●Positive results should be reported to CDC ●Serotyping is important for determining treatment ●Oral rehydration therapy is common, antibiotics only for serious cases

Campylobacter jejuni Gastroenteritis

●Gram -ve, spiral or curved bacteria with flagella in contaminated poultry ●Fever, diarrhea, cramps, vomiting, sometimes dysentery ●Bacteremia, meningitis, pancreatitis, cholecystitis, hepatitis; usually self-limiting ●Associated with autoimmune Guillain-Barré syndrome, neurological disease with temporary paralysis ●Culture under special conditions- elevated temperature, low oxygen tension, media with antimicrobial agents ●Antibiotics not usually needed

Infectious Mononucleosis / Burkitt Lymphoma (VIRAL)

●HSV 4 = Epstein-Barr virus (EBV), most people exposed in childhood ●Virus resides in B cells, remains dormant for long time Infectious mononucleosis ●In uninfected young adults exposed to EBV ●Spread through body fluids (saliva, blood, semen) ●Pharyngitis, fever, fatigue, swollen lymph nodes ●Self-limiting after about a month ●Main symptom, extreme fatigue, can continue for months ●Complications in immunocompromised ●Diagnosis- clinical symptoms, antibody test Burkitt Lymphoma ●In patients with malaria or HIV, EBV can lead to fast-growing malignant cancer ●Non-Hodgkin lymphoma- solid tumors of aberrant B cells ●Common in Africa, frequent in children ●Virus repeatedly reactivates in immunocompromised (HIV) ●Diagnosis- biopsy specimen from lymph node ●Intensive chemotherapy can cure 90% of children & adults

Ebola Virus Disease

●Highly contagious - Ebolavirus, BSL-4 filovirus ●Direct contact with body fluids, indirect contact by contaminated fomites ●Initial symptoms- fever, severe headache, myalgia, cough, chest pain, pharyngitis, abdominal pain, diarrhea, vomiting ●Hemorrhaging starts after 3 days, in GI tract, skin ●Leads to delirium, stupor, coma, shock, multiple organ failure, death, mortality -50% to 90% ●Diagnosis difficult - similar to many diseases ●No effective, approved treatment

human immunodeficiency virus (HIV)

●Human T-lymphotropic viruses (HTLV)= HIV, retrovirus ●Causes acquired immune deficiency syndrome (AIDS) ●2 main variants of human immunodeficiency virus (HIV). HIV-1 worldwide, HIV-2 in West Africa ●Spread through direct contact with body fluids ●Casual contact, insect vectors are not sufficient ●Sexual contact, sharing of needles by IV drug users ●Many years before effects of HIV are detected ●HIV not dormant, virions continually produced ●Immune system continually attempts to clear infection ●Virus persistently infects CD4 T cells until CD4 T-cell population is devastated, leading to AIDS ●3 stages based on CD4 T-cell counts ●Stage 1: Acute HIV -2-4 weeks after infection, flu-like illness for a few weeks ●> 500 cells/μL CD4 T cells; large amount of virus in blood ●Very contagious during this stage ●To confirm acute infection, nucleic acid test ●Stage 2: Clinical latency- HIV enters dormancy ●200-499 cells/μL CD4 T cells; HIV still active, reproduces at low levels, patients may not experience symptoms ●In untreated patients, this period can last decade or longer ●For patients receiving AVT, lasts for several decades ●Viral load increases, CD4 T-cell count decreases, leading to symptoms, susceptibility to opportunistic infections ●Stage 3: Acquired immunodeficiency syndrome (AIDS) ●Diagnosed with AIDS when CD4 T-cell count <200 cells/μL or patient develops certain opportunistic illnesses ●Immune system becomes severely damaged by HIV ●Chills, fever, sweats, swollen lymph glands, weakness, and weight loss ●Rare cancers (Kaposi's sarcoma), opportunistic infections- pneumocystis pneumonia, TB, cryptosporidiosis, toxoplasmosis ●Fatal progression in terminal stages- wasting syndrome, dementia complex ●Patients with AIDS have a high viral load & highly infectious; survive about 3 years without treatment ●Initial diagnosis by serological test for antibodies ●Confirmed by Western blot or PCR ●Can take weeks or months for body to produce antibodies ●Due to provirus formation, it is currently not possible to eliminate HIV from infected patient's body ●Elimination by antibodies is ineffective due to rapid mutation ●ART extends life expectancy

osteomyelitis

●Inflammation of bone tissues due to infection ●Acute or chronic- by S. aureus, M. tuberculosis, P. aeruginosa, S. pyogenes, S. agalactiae, Enterobacteriaceae ●In adults, bacteria gain direct access to bone through trauma or surgery ●In children, bacteria introduced from bloodstream, spreading from focal infections ●Long bones (femur) commonly affected in children ●Fever, localized pain, edema, ulcers in soft tissues near site of infection ●Can lead to tissue damage, bone loss ●If infection spreads to joints -infectious arthritis, or sepsis, thrombosis (formation of blood clots) ●Diagnosed using x-rays, imaging, blood or bone cultures ●Broad spectrum antibiotics given parenterally ●In serious cases, surgery to remove site of infection ●Other treatment - hyperbaric oxygen therapy, implantation of antibiotic beads or pumps

Hepatitis

●Inflammation of liver has many causes ●Viral cause - 5 hepatitis viruses; other viruses- Epstein-Barr virus (EBV), yellow fever, cytomegalovirus (CMV) can also cause hepatitis ●5 hepatitis viruses differ, but have affinity for hepatocytes ●Virus enters blood, spreads to spleen, kidneys, liver ●Malaise, anorexia, loss of appetite, dark urine, pain in the upper right quadrant of abdomen, vomiting, nausea, diarrhea, joint pain, gray stool ●When liver is diseased, it is unable to break down hemoglobin, bilirubin builds up causing jaundice ●Severe cases, death from liver necrosis HAV ●Transmitted by fecal-oral route, close personal contact, or exposure to contaminated water or food ●Develops after incubation of 15- 50 days ●Normally mild or asymptomatic, self-limiting ●Rare severe form, fulminant hepatitis, high fatality rate ●Vaccination available, recommended especially for children HBV ●Incubation period of 120 days ●Transmitted through infectious blood or body fluids through skin puncture, across placenta, or mucosal contact, not by casual contact ●Risk of infection is greatest for IV drug users,sexual contact with an infected individual, health care workers ●Infection becomes chronic, progresses to cirrhosis or liver failure; also associated with liver cancer ●Chronic infections have highest mortality rates, more common in infants ●Vaccination available and is recommended for children and adults at greater risk ●Health-care agencies should offer vaccine to all workers who have occupational exposure HCV ●Often undiagnosed; incubation period of 45 days, transmitted through contact with infected blood ●Some cases asymptomatic and/or resolve spontaneously, 75%-85% of infected individuals become chronic carriers ●Highest risk for drug users and those who had sexual contact with infected individuals ●Spread through contaminated blood products, and personal products -toothbrushes, razors HDV ●Uncommon in US: only occurs in individuals who are already infected with HBV by contact with infected blood ●Vaccination against HBV, also protective against HDV HEV ●Rare in US but many have antibodies ●Fecal-oral route through food and/or water contamination, or person-to-person contact ●Consumption of undercooked meat, especially deer or pork, and shellfish can lead to infection ●Pregnant women at particular risk ●Self-limiting within two weeks ●Blood tests for liver function ●Serological test panels used to detect antibodies ●Supportive therapy, rest, fluids ●Immunoglobulins used prophylactically following possible exposure; interferon therapy ●In severe cases, liver transplants may be necessary

Bacterial Endocarditis and Pericarditis

●Inflammation of tissue lining muscles, valves of heart ●Staphylococcus aureus, viridans streptococci, Enterococcus faecalis, HACEK bacilli: Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae ●Enters blood due to breaches (dental procedures, body piercings, catheterization, wounds) ●Preexisting heart damage, prosthetic valves, cardiac devices, history of rheumatic fever have higher risk ●Rapidly destroys heart valves, leads to death if untreated ●Subacute endocarditis- heart valve damage over months ●Blood clots form, protect bacteria from phagocytes forming tissue-associated bacteria called vegetations ●Fibrosis of heart valves, require replacement ●Fever is outward sign of subacute endocarditis ●Diagnosis -combination of blood cultures, echocardiogram, clinical symptoms ●High doses IV antibiotics after antimicrobial susceptibility testing ●Staphylcoccus, Streptococcus spp. infect, tissues surrounding heart, leads to acute pericarditis ●Chest pain, difficulty breathing, dry cough, usually self-limiting ●Diagnosis by chest x-ray, electrocardiogram, echocardiogram, aspirate or biopsy of pericardium ●Can also be caused by viruses, fungi or eukaryotic parasites

Ascariasis

●Large nematode roundworm Ascaris lumbricoides- soil-transmitted helminth ●Infections common in warmer climates, warmer times ●Eggs transmitted through contaminated food, water ●Embryonated eggs (with a developing embryo), travel to intestine for larvae to hatch ●Produce proteases that allow for penetration, degradation of host tissue ●Juvenile worms enter circulatory system, migrate to lungs, enter the alveoli ●Crawl to pharynx, follow gut lumen to return to small intestine, mature into adult roundworms ●Females release eggs that leave host via feces ●Worms can cause blockage in intestines, ducts of pancreas or gallbladder ●Infection is commonly asymptomatic; shortness of breath, cough, nausea, diarrhea, blood in stool, abdominal pain, weight loss, fatigue ●Roundworms may be visible in stool or coughed up ●In severe cases, children experience intestinal blockage ●Eggs identified by microscopic examination, X-rays, ultrasounds, MRIs ●Self-limiting, can last 1-2 years because worms inhibit inflammatory response ●Treated with anti-parasitics -in severe cases, surgery

Viral Meningitis

●Less severe than bacterial meningitis ●Occurs as sequelae of primary infection like herpes, influenza, measles, mumps; resolves spontaneously

Hansen's Disease (Leprosy)

●Long, thin, filamentous rod Mycobacterium leprae- obligate intracellular pathogen, acid -fast bacteria ●Affects Peripheral Nervous System, leading to permanent damage, loss of appendages or other parts ●Communicable but not highly contagious; approximately 95% of humans have natural immunity ●Person-to-person transmission by inhalation, prolonged, repeated contact with infected skin ●Armadillos, 1 of 5 susceptible mammals can also transmit ●In human body, grows best at cooler temperatures found in peripheral tissues like nose, toes, fingers, and ears ●Capsule enable it to bind, invade Schwann cells ●Causes progressive demyelination gradually destroying neurons of PNS ●Loss of neuronal function leads to hypoesthesia (numbness) in infected lesions ●Able to survive, move within macrophages like Listeria ●Extent of disease is related to immune response of patient ●Initial symptoms may not appear for 2 to 5 years after infection; begins with small, blanched, numb areas of skin ●In most individuals, resolves spontaneously ●Tuberculoid (paucibacillary) Hansen's disease- flat, blanched skin lesions with small nodules at edges ●Lesions persist for years- decades ●Individuals unable to contain infection later develop lepromatous (multibacillary) Hansen's disease ●Progressive form -nodules filled with bacilli, macrophages ●Impaired function of infected Schwann cells causes PNS damage- sensory loss, ulcers, deformities, and fractures ●Damage to ulnar nerve (wrist) causes of crippling of hand ●Chronic tissue damage lead to loss of fingers or toes ●Disfiguring lesions on nose, face can also occur ●Diagnosed based on symptoms; confirmed by presence of acid-fast bacilli on skin smears or in skin biopsy ●Does not grow in vitro on any known laboratory media; cultured in vivo in footpads of lab mice or armadillos ●PCR, genotyping of DNA used for diagnosis ●Responds well to antibiotics, if diagnosed, treated early, does not cause disability ●Since 1995, WHO made free multidrug therapy available to all patients worldwide, so prevalence has declined ●No universally accepted vaccince

Clostridium perfringens Gastroenteritis

●Mild foodborne disease from undercooked meats ●Gram +ve, rod-shaped, endospore-forming anaerobic tolerant of high and low temperatures ●At high temperatures forms endospores that germinate rapidly in foods, intestine ●Food poisoning by enterotoxin- cramps, diarrhea ●Severe form- pig-bel or enteritis necroticans- hemorrhaging, pain, vomiting, bloating May result in gangrene of intestines ●Diagnosis by detecting toxin in stool by PCR or ELISA ●Bacteria itself may be detected in foods, feces ●Rehydration therapy, electrolyte replacement, IV fluids ●Antibiotics are not recommended- imbalances gut microbiota ●Proper handling, cooking of foods at high temps, prompt refrigeration

Bacterial Meningitis

●Most serious form of meningitis ●Enters CNS through blood- trauma or toxins ●Can spread from structures in upper respiratory tract - normal microbiota ●Non-neonatal bacterial meningitis caused by -Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae ●Spread from person to person by respiratory secretions ●Colonizes, crosses through mucous membranes of the oropharynx, nasopharynx ●In blood, pathogens disseminate, establish infection, trigger inflammation ●Without treatment, fatality rate ~70% ●20% of survivors - irreversible nerve or tissue damage or hearing loss, neurologic disability, or loss of limb ●Other bacteria (Listeria monocytogenes, Escherichia coli) also capable of causing meningitis ●Infects arachnoid mater, Cerebral Spinal Fluid after spreading through blood or sinuses infection ●Streptococcus agalactiae- commonly found in vagina, GI, causes bacterial meningitis in newborns ●Initially -severe headache, fever, confusion, nausea, vomiting, photophobia, stiff neck ●Systemic inflammatory responses- hemorrhaging, purpuric lesions on skin ●Then shock, convulsions, coma, death—within hours ●Diagnosis -analysis of CSF obtained by lumbar puncture ●Abnormal levels of polymorphonuclear neutrophils (PMNs), glucose, protein suggest bacterial meningitis

Leishmaniasis

●NTD ~20 spp of Leishmania, transmitted by sand fly ●Dogs, cats, sheep, horses, cattle rodents, humans ●Parasite is phagocytosed by macrophages, uses virulence factors to avoid destruction ●Reproduces within macrophage, lyses it, progeny infect new macrophages ●3 forms of disease - cutaneous, visceral, mucosal ●Formation of sores at site of insect bite start as papules or nodules before becoming large ulcers ●Visceral leishmaniasis -months to years; enlargement of lymph nodes, liver, spleen, bone marrow ●Triggers fever, weight loss, swelling of spleen, liver ●Causes anemia, leukopenia, thrombocytopenia ●Patient becomes immunocompromised, susceptible to fatal infections of lungs and GI tract ●Mucosal (least common; lesions similar to cutaneous in mucous membranes of mouth, nares, or pharynx ●Can be destructive, disfiguring ●Diagnosis by smears, cultures, or PCR

Infections of the Circulatory System

●No easy portals of entry ●Circulating immune defenses (antibodies, complement proteins, phagocytes, other immune cells) ●Microbes access through breach in skin or from other body sites ●Bacteremia- bacteria in blood; septicemia -bacteria reproducing in blood ●Viremia - viruses in blood; toxemia - toxins in blood ●Systemic inflammatory response syndrome (SIRS) severe counterproductive immune response ●Causes more damage than infection, leads to sepsis ●Sepsis -production of excess cytokines, leads to inflammation- fever, vasodilation, edema ●Inflammatory response is dysregulated, disproportionate to threat of infection ●Critical organs become dysfunctional, increased heart, respiratory rates, disorientation Without prompt treatment, patient goes into shock, dies ●Endocarditis - inflammation of inner lining of heart - can damage heart valves to require surgery ●Pericarditis - inflammation of sac surrounding heart ●Myocarditis -inflammation of heart's muscle tissue, edema, congestive heart failure ●Vasculitis - inflammation of blood vessels- become damaged/ruptured; spots called petechiae appear on skin ●Ischemia - damage causes reduced blood flow ●Affected tissues die, become necrotic; require debridement or amputation

Tetenus

●Non Communicable disease -uncontrollable muscle spasms (contractions) caused by action of TeNT ●Clostridium tetani infects wound, produces TeNT ●Toxin rapidly binds to neural tissue, causing intoxication (poisoning) of neurons ●Depending on site, extent of infection -localized, cephalic, or generalized Localized tetanus ●Affects muscle groups close to injury site; no CNS involvement; mild symptoms ●Localized muscle spasms caused by dysfunction of surrounding neurons ●Individuals with partial immunity—previously vaccinated individuals who did not get recommended boosters—most likely to develop localized tetanus from puncture wound Cephalic tetanus ●Rare, localized form of tetanus associated with wounds on head or face ●Patients see double images, because of spasms affecting muscles that control eye movement ●Both localized, cephalic tetanus may progress to generalized tetanus if TeNT spreads further Generalized tetanus ●TeNT enters neurons of PNS from wound, retrogrades (backs up) to inhibitory neurons in CNS ●Prevents release of gamma aminobutyric acid (GABA)- neurotransmitter responsible for muscle relaxation ●Muscle spasms first occur in jaw muscles, leading to lockjaw ●As toxin progressively blocks neurotransmitter release, other muscles become involved ●Uncontrollable, sudden muscle spasms powerful enough rupture tendons, fracture bones ●Muscle spasms in neck, back, legs cause body to form a rigid, stiff arch- opistotonos ●Spasms in larynx, diaphragm, muscles of chest restrict ability to swallow, breathe, leading to death by asphyxiation (insufficient supply of oxygen) Neonatal tetanus ●Generalized tetanus in a newborn- when stump of umbilical cord is contaminated with C. tetani spores ●Common in countries that lack maternal immunization ●Week old infected infants become irritable, feed poorly, develop rigidity with spasms ●Very poor prognosis with- mortality rate of 70%-100% ●Treatment -assisted breathing through ventilator, wound debridement, fluid balance, antibiotic therapy ●TeNT antitoxin to neutralize non fixed toxin ●Tetanus toxoid (TT) vaccine- for protection + prevention part of DTaP, Tdap, Td ●CDC recommends children receive doses at 2, 4, 6, 15-18 months of age and at 4-6 years of age ●1 dose of Td for adolescents, TT booster every 10 years for adults

Lesteriosis

●Nonencapsulated, non sporulating, gram +ve rod, foodborne pathogen ●At-risk groups -pregnant women, neonates, elderly, immunocompromised ●Leads to meningitis in about 20% of cases ●In pregnant women, can cause spontaneous abortion ●Listeria monocytogenes -in fresh fruits, vegetables, frozen vegetables, processed meats, soft cheeses, raw milk ●Psychrophile - able to grow at refrigerated temperatures Ingestion leads initially to infection of GI tract ●Produces listeriolysin that allows it to spread across cells ●Identified by cultivation of samples from a normally sterile site (blood or CSF) ●Antibiotics for treatment; no vaccine available

Gastroenteritis by Noroviruses

●Noroviruses or Norwalk viruses ●Highly contagious, transmitted by direct contact, touching contaminated surfaces, contaminated food ●Widespread infections in confined spaces ●Virus not killed by disinfectants at standard concentrations ●Watery diarrhea, mild cramps, fever, projectile vomiting, dehydration-no medications, mild, self-limiting ●PCR or enzyme immunoassay for diagnosis ●Rehydration therapy, electrolyte replacement ●Good hygiene, careful food preparation reduce risk

Infections of the Lymphatic system

●Only microbes with strong virulence factors can establish infection ●When localized infection spreads, microbes are detected in lymphatic system ●Lymphangitis- inflammation of lymphatic vessels, produces visible red streaks under skin ●Lymphadenitis- inflammation of lymph nodes causing a bubo (swollen lymph node)

poliomyelitis

●Poliovirus, primarily intestinal disease ●Sometimes, proceeds to CNS, causing paralysis, death ●Highly contagious, transmission by fecal-oral route or aerosols or droplets ●Mostly asymptomatic; 25% result in mild intestinal disease, nausea, fever, headache ●1 in every 200, poliovirus affects cells in CNS ●Enters through mouth, replicating in pharynx, GI tract ●Invades local lymphoid tissue, enters blood, may infect CNS ●Replicates in motor neurons in spinal cord, brain stem, leads to flaccid paralysis ●In severe cases, respiration becomes arrested causing death ●Direct detection of virus from throat or feces done using PCR or sequencing ●Serological tests used to determine vaccination No therapeutic measures; only supportive ●Pain relievers, rest, heat therapy to ease spasms, physical therapy, braces for walking, mechanical ventilation for breathing ●2 different vaccines introduced in 1950s ●Salk vaccine -inactivated poliovirus delivered by intramuscular injection, given in US ●Sabin vaccine-oral polio vaccine, attenuated virus, not given in US ●4 doses: 2, 4, 6-18 months of age, 4-6 years of age ●In 1988, WHO launched Global Polio Eradication Initiative - now endemic only Afghanistan, Pakistan, Nigeria

Cholera & Other Vibrios

●Poor sanitation, esp. following natural disasters; spreads through contaminated water, food that has not been heated to high temperatures Vibrio cholerae serotype O1 Gram -ve, curved rod ●Killed by acid, large doses needed to reach intestines ●Motile cells travel through mucous layer of intestines, attach to epithelium, release cholera enterotoxin ●Profuse diarrhea ("rice water stool"), rapid dehydration, electrolyte imbalance ●Diagnosed by culturing Vibrio from stool sample ●May be self-limiting, rehydration with electrolytes ●Antibiotics only for severe disease ●Good sanitation—appropriate sewage treatment, clean cooking supplies, purified drinking water—important to prevent infection V. parahemolyticus -consumption of contaminated seafood causes GI illness with watery diarrhea, nausea, fever, chills, abdominal cramps ●Produces a heat-stable hemolysin, leading to dysentery ●Sometimes causes wound infections ●Diagnosed using cultures from blood, stool, or a wound Vibrio vulnificus- found in warm seawater; not associated with poor sanitary conditions ●In raw seafood, or through open skin wounds ●Can spread to bloodstream causing septicemia ●Skin infection- edema, ecchymosis (discoloration of skin due to bleeding), abscesses ●Diagnosed by culturing from stool samples, blood samples, or skin abscesses; treated with antibiotics ●2 other vibrios, Aeromonas hydrophila, Plesiomonas shigelloides -found in marine environments, raw seafood ●Cause gastroenteritis, wound infections and septicemia ●Diagnosed by culture, antibiotics not needed

Amoebic Meningitis

●Primary amoebic meningoencephalitis (PAM) by Naegleria fowleri in free-living in soil, water ●Rare disease in young and otherwise healthy individuals ●Infected while swimming in warm bodies of freshwater such as rivers, lakes, hot springs ●Trophozoite infects brain by initially entering through nasal passages to sinuses; travels to subarachnoid space ●Inflammation and destruction of gray matter leads to severe headaches and fever ●Within days, confusion, convulsions, seizures, coma, death- nearly always fatal ●Progression very rapid; not diagnosed until autopsy ●Diagnosis by direct observation of CSF

Puerperal Sepsis

●Puerperal sepsis/infection/fever, or childbed fever- nosocomial infection during puerperium—time following childbirth ●May originate in genital tract, breast, urinary tract, or surgical wound ●Initially localized to uterus, quickly spreads, results in peritonitis, septicemia, death ●S. pyogenes, Staphylococcus, Enterococcus, Chlamydia, E. coli, Klebsiella, Proteus, some anaerobes ●Diagnosis on timing, extent of fever; isolation and identification of microbe ●Antimicrobial susceptibility testing must be used ●Before 19th century, major cause of mortality among new mothers following childbirth ●Reduced through antiseptics, handwashing protocols

Botulism

●Rare, frequently fatal due to intoxication by BoNT ●Clostridium botulinum; BoNT produced in vivo, or direct introduction of BoNT into tissues Botulism Infections ●Wound botulism -C. botulinum introduced directly into wound after a traumatic injury, deep puncture wound, or at injection site ●Infant botulism- in infants < 1 year of age ●Adult intestinal toxemia- in immunocompromised adults, from ingesting C. botulinum endospores in food ●Botulism Intoxications - BoNT is produced outside body, introduced directly through food, air or clinical procedure ●Foodborne botulism- most common- BoNT produced in contaminated food, ingested with food ●Inhalation botulism- rare; BoNT is unstable as an aerosol and does not occur in nature ●Iatrogenic botulism - also rare; associated with injections of BoNT used for cosmetic purposes ●BoNT enters blood from GI tract, wound, or lungs, transferred to neuromuscular junctions of motor neurons ●Binds irreversibly to presynaptic membranes, prevents release of neurotransmitter acetylcholine ●Loss of muscle activity, leading to muscle relaxation, eventual paralysis ●Food botulism - blurred vision, drooping eyelids, difficulty swallowing, abdominal cramps, nausea, vomiting, constipation, or possibly diarrhea ●Followed by progressive flaccid paralysis, gradual weakening, loss of control over muscles ●Hearing is normal, consciousness is not lost, patient is fully aware ●In infants- weak cry, decreased ability to suckle, hypotonia (limpness of head or body) ●Death from respiratory failure due to progressive paralysis of upper airway muscles, diaphragm, chest ●Treated with an antitoxin specific for BoNT ●If administered in time, stops progression but cannot reverse paralysis ●Can regain neurological function, over several weeks or months, depending on severity ●Must remain hospitalized, breathe through a ventilator

Shigellosis (Bacillary Dysentery)

●Rod-shaped, gram -ve; S. dysenteriae, S. flexneri, S. boydii, and/or S. sonnei colonize GI tract ●Spread from hand to mouth or through contaminated food, water- fecal-oral route ●Bacteria invade intestinal epithelium, are phagocytosed ●Escapes, lives within cytoplasm or moves to adjacent cells ●Epithelium become ulcerated, cause loss of fluid ●Stomach cramps, fever, watery diarrhea with pus, mucus, and/or blood often develop ●Severe cases- ulceration of mucosa, dehydration, rectal bleeding- develops into hemolytic uremic syndrome (HUS) ●Serious condition- damaged blood cells build up in kidneys, cause kidney failure, or reactive arthritis ●Can also develop chronic post-infection irritable bowel syndrome (IBS) ●S. dysenteriae type 1 produces Shiga toxin -affects protein synthesis in epithelial cells ●Leads to hemorrhaging, lesions in colon ●Toxin also targets glomerulus resulting in HUS ●Stool samples analyzed with serological or molecular techniques ●Severe cases require antibiotics

Schistosomiasis

●Schistosomiasis (bilharzia) -NTD caused by blood flukes ●Schistosoma mansoni, S. haematobium, or S. japonicum ●Only trematodes that invade through skin; all others infect by ingestion ●Human hosts shed eggs in urine, feces, contaminating freshwater habitats of snails (intermediate hosts) ●Eggs hatch in water, infect snails, mature, multiply ●Leave snail, enter water, penetrate skin of swimmers ●In humans enter bloodstream, mature, mate releasing fertilized eggs ●Eggs travel through blood, excreted in urine/ stool to start life cycle again ●Few days after infection, itchy rash appears at site ●Within 1-2 months fever, chills, cough, myalgia ●Eggs that are not excreted circulate through body, become lodged in tissues ●Trigger inflammation, scarring that can damage liver, CNS, intestine, spleen, lungs, bladder ●Abdominal pain, enlargement of liver, blood in urine or stool, problems passing urine ●Increased risk for bladder cancer; repeated infection in children cause malnutrition, anemia, learning difficulties ●Diagnosis by microscopic observation of eggs in feces ●Anti-parasitic drug is effective treatment ●Improving wastewater management, educating at-risk populations can help ●Eggs of some species can transform into adult worms, complete life cycle only in animal hosts ●Still capable of penetrating human skin, but unable to establish productive infection ●Instead triggers immune response, resulting in itchy raised bumps = cercarial dermatitis (swimmer's itch or clam digger's itch) ●Self-limiting, rarely serious; treated with antihistamines

Bacterial Sepsis

●Sepsis, septic shock - mostly seen with bacteria ●Bacterial pneumonia, intra-abdominal infections, UTI ●Infections with superficial wounds, animal bites, catheters ●Initially minor, localized infections caused by Staphylococcus, Streptococcus, Pseudomonas, Pasteurella, Acinetobacter, Enterobacteriaceae

Rheumatic Fever

●Sequelae from S. pyogenes infection ●Puerperal fever, acute rheumatic fever (ARF) leading to rheumatic heart disease ●In children, 2-3 weeks after untreated/inadequately treated pharyngitis - not so common these days ●Due to cross-reaction between antibodies to bacterial surface proteins & similar proteins in the body ●Damages nervous tissue or joints, leads to joint pain and swelling, is reversible ●Damage to heart valves is irreversible, leads to scarring, stiffness of valve - produces heart murmur ●Antibiotic treatment regimen every 3-4 weeks, depending on patient's risk for reinfection ●Additional prophylactic antibiotic treatment recommended depending on age, risk for reinfection

Meningococcal Meningitis

●Serious infection by gram -ve coccus N. meningitidis ●Death within a few hours of onset ●Nonfatal cases can have irreversible nerve damage- hearing loss, brain damage, amputation of extremities due to tissue necrosis ●Infects people of any age, highest among infants, adolescents, young adults ●Incidence reduced due to vaccines ●Transmitted by contact with respiratory secretions ●Unique sign of meningococcal meningitis -petechial rash on skin or mucous membranes, with tiny, red, flat, hemorrhagic lesions ●Appears soon after onset, as response to endotoxin, adherence virulence factors ●Triggers formation of tiny blood clots- blood leaks into tissue ●As infection progresses, hemorrhagic lesions increase in size; lesions >1.0 cm in patients developing shock ●Sepsis = rapid multiple organ failure, shock, disseminated intravascular coagulation, death ●The disease progresses very rapidly ●Variety of clinical specimens are required -blood, CSF, naso- oropharyngeal swabs, urethral, endocervical swabs, petechial aspirates, biopsies ●Safety is important for handling, transport of specimens ●Presumptive diagnosis - Grams stain of CSF showing gram -ve diplococci ●Treated with antibiotics but preventive vaccination is best ●CDC recommends- children between 11-12 years of age be vaccinated with a booster at age 16

Typhoid Fever

●Severe type of salmonellosis (untreated mortality rate of 10%) caused by some serotypes ●High fever, body aches, headache, nausea, lethargy, a possible rash ●Some individuals are asymptomatic carriers, continually shed in feces - "Typhoid Mary" ●Penetrates intestinal mucosa, grows in macrophages, transported to liver, gallbladder ●When macrophages lyse, they release S. typhi into bloodstream & lymph ●Mortality from ulceration, perforation of intestine ●Complications - pneumonia, jaundice ●Clinical examination, culture for diagnosis; treatment with antibiotics ●Individuals must be extremely careful to avoid infecting others during treatment ●Can be prevented through vaccination for individuals traveling to parts of the world where it is common

Meningitis and Encephalitis

●Skull can be problematic during infections ●Swelling of brain or meninges from inflammation causes intracranial pressure, leading to severe damage ●Meningitis -inflammation of meninges ○severe headache, fever, photophobia (increased sensitivity to light), stiff neck, convulsions, confusion ●Encephalitis - inflammation of brain tissue ○similar to meningitis, lethargy, seizures, personality changes ●Inflammation of meniges or brain- serious, can lead to blindness, deafness, coma, death ●Caused by pathogens or noninfectious causes (head trauma, cancers, drugs that trigger inflammation) ●Lumbar puncture is performed to obtain sample of CSF to determine infection ●If CSF contains increased levels of wbcs + abnormal glucose, protein levels, it indicates that inflammation is a response to an infection want cerebral spinal fluid to be sterile and clear

Strongyloidiasis

●Strongyloides stercoralis, soil-transmitted helminth - free-living & parasitic ●In parasitic form, larvae penetrate body through skin or transmitted through organ transplantation ●When excreted, larvae can become free-living adults ●Free-living worms reproduce, laying eggs that hatch into larvae that can develop into parasitic form ●Parasitic life cycle is very similar to the hookworms ●But in intestine female produce eggs that develop asexually, larvae are excreted ●Only free-living forms reproduce sexually ●Generally asymptomatic, severe symptoms develop after treatment with corticosteroids due to immunosuppression ●When immune system is suppressed, rate of autoinfection increases, huge amounts of larvae migrate to organs throughout body causing hyperinfection ●Cause rash at site of entry, cough, fever, nausea, difficulty breathing, bloating, pain, heartburn, arthritis, or cardiac or kidney complications ●Direct examination of stool for over 7 days for diagnosis ●Treated with ivermectin

Anatomy of Oral cavity

●Tongue, teeth, salivary glands, parotid, sublingual, submandibular glands ●Salivary glands produce saliva- lubricates food, contains digestive enzymes ●Teeth - crown, enamel, dentin, pulp cavity, root, gums (gingiva) ●Food enters through mouth, mechanical digestion (by chewing), chemical digestion (by enzymes in saliva) begins

Toxic Shock Syndrome

●Toxemia by Staphylococcus aureus = staphylococcal toxic shock syndrome (TSS) ●Due to superantigen -TSS toxin-1 ●Complication of pneumonia, osteomyelitis, sinusitis, skin wounds ●Highest risk- women with preexisting S. aureus in of vagina- if tampons, contraceptive sponges, diaphragms are left longer than recommended ●Sudden onset of vomiting, diarrhea, myalgia, fever ●Rapid-onset hypotension with a systolic blood pressure < 90 mm Hg for adults ●Diffuse erythematous rash, peeling, shedding skin 1-2 weeks after onset ●Additional involvement of 3 or more organ systems ●Diagnosis- clinical signs, serologic tests to confirm species, detection of toxin ●Treatment -decontamination, debridement, vasopressors to elevate blood pressure, antibiotic therapy pending susceptibility results

Toxoplasmosis

●Toxoplasma gondii -in birds, mammals ●Domestic cats- definitive hosts, main reservoirs ●Infected cats shed oocysts in feces, spread to humans through contact with fecal matter ●Parasite has complex life cycle that involves multiple hosts from cats, birds, rodents ●Cats can be reinfected after consuming birds, rodents ●Immunocompetent individuals are asymptomatic -don't require treatment ●Infection appears to be able to modify host's behavior ●Infected mice lose fear of cat pheromones, become easier prey for cats, facilitating transmission ●Parasite may be able to influence personality, psychomotor performance of infected humans ●Symptoms if they occur -mild, similar to mononucleosis ●Asymptomatic toxoplasmosis reactivates in immunocompromised - transplantation, chemo or AIDS ●Cause encephalitis, retinitis, pneumonitis, cognitive disorders, seizures, death ●Parasite can cross placenta, serious infections in fetus ●Extent of damage depends on severity of maternal disease, damage to placenta, gestational age of fetus when infected, virulence of organism ●Congenital toxoplasmosis leads to fetal loss or premature birth, damage to CNS, manifesting as mental retardation, deafness, or blindness ●Diagnosis during pregnancy by TORCH testing ●Congenital infections by detecting parasitic DNA in amniotic fluid, using PCR ●In adults, diagnosis is by observation of tissue cysts ●Prevention -wash hands after handling raw meat, soil, or cat litter, avoiding consumption of poorly cooked meat ●Neonates, pregnant women, immunocompromised treated with anti-parasitic drugs

Neurotoxoplasmosis

●Toxoplasma gondii enters through circulatory system ●In immunocompromised patients, crosses BBB ●Enters brain through capillary epithelium ●Brain lesions detected using MRI or CAT scans; confirmed by direct observation in CSF ●Treatment with anti-parasitic drugs with long-term maintenance doses to prevent recurrence

Gas Gangrene

●Trauma, medical conditions (diabetes) cause damage to blood vessels interrupting blood flow ●Tissues die, create anaerobic environment, leads to ischemia ●Clostridium perfringens endospores readily germinate ●Gas gangrene with rapidly spreading myonecrosis ●Sudden onset of excruciating pain at infection site, rapid development of foul-smelling wound with gas bubbles, thin, yellowish discharge with a small amount of blood ●Edema, cutaneous blisters with bluish-purple fluid form; tissue liquefies, sloughs off ●Margin between necrotic & healthy tissue advances several inches per hour even with antibiotics ●Septic shock, organ failure mortality rate > 50% ●Diagnosed on clinical signs; confirmed through Gram stain and anaerobic cultures ●Treatment- surgical debridement of necrotic tissue; advanced cases may require amputation ●Antibiotic treatments, hyperbaric oxygen therapy

Trichinosis

●Trichinella spiralis transmitted in undercooked pork ●Larvae emerge from cysts when exposed to acid, pepsin in stomach ●Develop into mature adults within large intestine, migrate into muscles forming cysts ●Mostly asymptomatic, symptoms begin in 1-2 days after consuming nematodes ●Diarrhea, constipation, abdominal pain, headache, light sensitivity, muscle pain, fever, cough, chills, conjunctivitis ●More severe symptoms affecting motor coordination, breathing, heart sometimes occur ●Takes months to resolve, occasionally fatal ●Mild cases may be mistaken for influenza ●Diagnosed using clinical history, muscle biopsy for larvae ●Difficult to treat larvae that have formed cysts in muscle ●Most azoles kill only adult worms in intestine Steroids to reduce inflammation if larvae are in muscles

Acellular Disease of the Nervous System

●Viruses and subviral particles ●Viral diseases more common than bacterial in nervous system - also milder, resolve spontaneously ●Viral meningitis ●Zika virus infection ●Rabies ●Polio ●Transmissible spongiform encephalopathies (TSEs)

Trichuriasis

●Whipworm Trichuris trichiura through ingestion from soil-contaminated hands or food ●Common in warm environments with poor sanitation, fecal contamination of soil, or food is grown using manure ●Symptoms may be minimal or nonexistent ●When a substantial infection develops- frequent diarrhea occurs with mucus, blood ●Can cause rectal prolapse- portion of rectum becomes detached from body, protrudes from the anus ●Severely infected children may experience reduced growth and cognitive defects ●Fertilized eggs are ingested, travel to intestine ●Larvae emerge, attached to mucosa of colon, cecum ●After maturation (60- 70 days), females lay 3-20k eggs per day ●Diagnosis- examination of feces for presence of eggs on multiple days ●Treated with common anti-helminthic drugs

Helminthic Infections of the GI Tract

●Widespread intestinal parasites ●Round-bodied worms - nematodes (roundworms, pinworms, hookworms, whipworms) ●Segmented flat-bodied worms - cestodes (beef, pork,, fish tapeworms) ●Non-segmented flat-bodied worms trematodes (flukes) ●Although infection can have serious consequences, these parasites are so well adapted that infection is not obvious (subclinical infection)

pnemonic plague

●Y. pestis causes an infection of lungs ●Through inhalation of droplets from infected individual or spread to lungs from elsewhere ●Incubation 1- 3 days; fever, headache, weakness, rapid pneumonia, shortness of breath, chest pain, cough with bloody or watery mucus, rapid respiratory failure, shock ●Only form that can be spread from person to person ●If untreated, mortality is near 100%; with antibiotics 50% ●High mortality rate is due to virulence factors ●Capsule help avoid phagocytosis ●Culturing, direct microscopic exam, bacteriophage lysis ●Prompt antibiotics resolve bubonic plague, other types are difficult to treat because shorter incubation ●Survival depends on early, accurate diagnosis, appropriate antibiotics

Septicemic Plague

●Y. pestis directly introduced into blood through cut/ wound ●Incubation 1- 3 days, fever, chills, extreme weakness, abdominal pain, shock ●Disseminated intravascular coagulation (DIC) -blood clots, ischemia, necrosis in surrounding tissues ●Necrosis in extremities- fingers, toes, become blackened ●Quickly leads to death, mortality rate near 100% if untreated ●Even with antibiotic treatment, mortality rate is about 50%

Bubonic Plague -most common

●Y. pestis transferred by bite of infected fleas ●After a 2-6-day incubation period, abrupt onset fever, headache, hypotension, chills ●Pathogen localizes in lymph nodes, causing inflammation, swelling, hemorrhaging & purple buboes ●Buboes form in lymph nodes of groin first, then everywhere ●Average mortality rate for bubonic plague is 55% if untreated, 10% with antibiotic treatment

Rat Bite fever

●Zoonosis- Streptobacillus moniliformis, or Spirillum minor ●Contact with fomites (inanimate objects), food, or water contaminated by rat feces or body fluids ●Fever, vomiting, myalgia, arthralgia, maculopapular rash on hands, feet ●Ulcer may also form at site of bite, swelling of nearby lymph nodes; mostly self-limiting ●Culture, PCR, ELISA, direct microscopic observation ●Treated with antibiotics

Cat scratch disease

●Zoonosis- cat-scratch disease or cat-scratch fever ●Bacterial infection introduced to lymph nodes when bitten/ scratched by a cat ●Gram -ve Bartonella henselae, infects RBCs ●Cats infected from flea feces - ingest while grooming ●Small nodule with pus forms in location of scratch 1-3 weeks after initial injury ●Bacteria migrate to nearest lymph nodes, cause swelling, pain, fever, chills, fatigue ●Mostly self-limiting, but immunocompromised patients may develop complications ●Prevented by keeping cats free of fleas, promptly cleaning scratches with soap, warm water ●Diagnosis is difficult; bacteria hard to cultivate ●Serology, PCR, gene sequencing to identify species ●Antibiotics not normally prescribed except for immunocompromised