P44 Lecture Notes: Intro to Infectious Disease 1+2

General Terminology
1. Infection vs Disease
A. Infection= transmissible illness caused by a biologic agent such as microorganism/toxic product often due to invasion of host
tissue via pathogenic agent and its multiplication that causes a host response which causes disease
B. Disease refers to the secondary response of the host (cell death, inflammation, etc)
2. Normal vs Abnormal host
A. Abnormal host: includes defects (acquired or inherited) that affects the host ability to fend off infection such as CGD, HIV, etc
3. Communicable vs Contagious
A. Communicable= Transmissible to another person (STDs for example)
B. Contagious= something that is highly communicable/easily transmissible
4. HIV vs Influenza

Dividing the Effects of Infectious Disease and Naming of Infectious Disease Syndromes (either via infection or organism)

General Considerations: Factors increasing risk of ID

1. Susceptibility to ID weakened host defense (skin breaks, proton pump inhibitors which decrease GI acidity that could make it easier for bacteria
to survive, HIV, altered Microbiome, foreign bodies)
2. Exposure to a highly virulent organism

Dividing Causes of ID and Their General Effects

General Aspects of Pathogenesis
1. Reservoir
2. Transmission factors portal of entry and
virulence factors
3. Target Tissue= Tropism
4. Dissemination ability

Lump then Split: Identifying organism (patterns)

1. Bacterial infections more local usually
2. Viral infection usually more spread out through
body
3. Fungal may also cause focal infection like
bacterial (EX focal infiltrate in lung can happen in
bacterial and fungal)

Pathogenesis Mechanisms
1. Bacteria cell adhesion (facultative bacteria
invade epithelial cells, macrophages, or both),
Toxins (quorum sense), Biofilm, Dissemination
2. Virus enter host cell; can impair function or kill
cell, undergo transformation and potentially
cause cancer (HPV for example)
3. Fungi similar to bacteria mechanisms
4. Parasites invasion, obstruction, cell lysis
Modes of Transmission
1. Aerosol/Droplet: droplet usually limited in ability to extend throughout environment; aerosol is capable of spreading more
2. Direct contact
3. Vector-Borne and Zoonotic lick, bites scratches
4. Oral
5. Fecal/Oral
6. Sexual Contact
7. Vertical= spread through the placenta (Referred to as TORCH= toxoplasma, rubella, CMV, HIV infections)  then this spread occurs can
determine how infection impacts baby
8. Endogenous flora (may infect when person becomes immunocompromised)
9. Iatrogenic medical procedures/tools colonoscopy, blood transfusions, etc
10. Formites (inanimate object that can harbor/transmit infectious organism clothes, bedding, utensils, etc)

General at Risk Populations to Keep in Mind

1. Extreme age= neonates and geriatric patients
2. Pregnant women
3. Hospitalized Patients risk of nosocomial infections and foreign
bodies (central lines, valves, prostheses); NOTE: nosocomial generally
happens in patients that are in hospital for at least 48 hours and are
generally bacterial (MRSA, enterococcal infections, gram neg bacteria
like pseudomonas)
4. Chronic illness diabetes, cirrhosis, cancer
5. Malnourished
6. Immune Deficiency
7. Post-splenectomy more prone to infection via encapsulated
organisms

Tropism= preferred cell-tissue type

1. Syphilis small arterioles/endothelium leads to ulcerations and often the spirochete spreads throughout the body
2. Herpes virus epithelial cells
3. HPV squamous epithelium
4. HBV hepatocytes
5. TB/Histoplasma Monocytes/Macrophages
6. Candida epithelial cells (more in squamous cells)

Dissemination
1. When organism is able to proliferate and spread to sites beyond the local site
2. Route of spread= blood, lymph nerves
3. Potential consequences= sepsis, tissue seeding (endocarditis, meningitis, osteomyelitis, pyelonephritis)

Tissue Responses to Infections

General Methods of Diagnosis: Specimens and Special Studies
1. Specimens scraps, swabs, blood, urine, stool, fluid
aspiration, tissue/needle biopsy, etc
2. Special Studies H/E stains and Special Stains,
immunohistochemical stains, Molecular methods (ISH and
RT-PCR)
3. Special Stains
Gram Stain
AFBmycobacteria and
nocardia
Silver spirochetes, fungi,
bacteria
PAS fungi
Mucicarmine
cryptococcus
Chronic inflammation associated with organisms with
mechanisms to evade immune (hiding in host cell facultative
intracellular cells for example)
Mononuclear inflammation lots of lymphocytes are seen
Viral Inclusion Bodies= sites of viral production in the cell that can be used to help
diagnose
1. Nuclear Herpesvirus, Adenovirus, Measles
2. Cytoplasmic Rabies
3. Nuclear AND cytoplasmic CMV
4. NOTE: most viral infections are not associated with viral inclusions

Fever
Overview
1. Presence indicates a “re-set” of hypothalamic thermostat that is related to
cytokines (TNF, IL-1) endogenous pyrogens
2. Doesn’t always mean infection  may be in autoimmune conditions, due to
drugs being taken, etc
3. Consider timing, localizing clues, history, constitutional symptoms (rigors
shaking chills)
4. Generally defined as being temperature over 100.4 degrees F

Fevers of Unknown Origin

1. Defined as fever over 3 days in hospitalized immunocompromised patient or
over 1 weeks in an immune competent patient
2. Common diagnostic considerations= Infection, systemic inflammatory disorder
(vasculitis/autoimmune), malignancy especially non-Hodgkin lymphoma
3. Super prolonged fever is
less likely to be infectious (should look into alternative causes

Special Situations
Neutropenia risk for bacterial/fungal infection
Complement deficiency encapusalted (early complement), Niesseria (MAC
complex)
Spleen encapsulated
Fever and Operations

Post-Op Patients
Early worries= respiratory b/c breathing may not be as effective to get rid of pathogens
Catheters UTI risk

Overall: Potential Outcomes of infectious Disease

1. Resolution
2. Chronic active infection
3. Carrier State
4. Latency
5. Host death
Actinomyces infection
1. Often commensal
2. Necrosis, trauma, diabetes could lead to
dissemination to tissue
3. Elicits acute inflammatory reaction that
develops over period of time forms
abscess and may see organisms in pus
leaking out

Gas Gangrene in Skeletal Muscle: C. perferingens

1. Clostridial infection (gram positive rod)
2. No nuclei in skeletal muscle dead
3. Bacteria causes gas gas gangrene
4. Inflammation is not here
 5. Toxin A: detrimental to white cells, platelets, etc leading to potentially devastating outcomes

Diagnostic Methods

1. Specimens generally from areas of body that are normally sterile

2. Special stains help identify but need culture to determine antibody
susceptibility
3. Silver stain good at impregnating outer portion of cell (stronger than gram
stain so may be able to stain healing bacterial infection that may not be
abundant enough for gram staining)
4. India ink: for encapsulated organisms (will not penetrate and lead to white in a
black background)
Cutaneous Manifestations of Infectious Disease

Skin Impetigo
1. common, superficial contagious bacterial (usually Staph and strep skin normal flora) infection of skin that mainly
affects infants/children around nose/mouth; vesicular “honey-colored” crusted lesions
2. Histology epidermal (subcorneal) blister filled with inflammatory exudate
3. Often highly infectious
4. Serous exudate is what is forming the crust
5. Associated with skin flora
6. Very superficial lesion; doesn’t effect deep layer of epidermis generally
Blister= terms for vesicle/bulla
Vesicle= fluid filled raised lesion less than 5mm across
Bulla=fluid filled raised lesion over 5mm across rupture leads to risk of more infection

Primary Bacterial Skin Infections: Erysipelas, Cellulitis, Necrotizing Fasciitis

Erysipelas: pretty superficial, usually at face and generally from S. pyogenes

can spread rapidly

Cellulitis: deeper layers of skin; can

be from S. pyogenes or strep and
generally use antibiotic to treat
(usually assume strep/staph and treat
as if); red appearance that may look
like burn; may be confused for DVT

Necrotizing Fasciitis: very deep and

can be devastating and can include
muscle; need prompt antibiotics and
may need emergency surgery to
remove dead tissue; can be caused by
one or multiple pathogens (S. pyogenes, gram neg, clostridium) and patients are
systemically toxic

Bacterial: Hair Follicles Folliculitis, Furuncles,

Carbuncles
1. Usually from S. aureus
2. Most cases, lesions can be treated with incision and
drainage alone (larger lesion like carbuncle may need
antibiotics)
3. Inflammatory reaction of hair follicle areas furuncle is
deeper in hair shaft
4. Folliculitis more superficial area of hair shaft
 5. Carbuncle: extensive coalescence of multiple lesions; usually in nape of neck area
6. Folliculitis furuncles carbuncles in order from least to worst

Virus: Herpes Simplex Infection

1. May be secondary involvement of skin or primary infections of the
skin (varicella is systemic with tropism for epithelial cells while
herpes is direct primary skin lesion)
2. HSV Cowdry A inclusions, differentiate from varicella because more
localized by varicella is more diffuse

Virus: Molluscum Contagiosum

1. Contagious skin disease caused by poxvirus and mostly affects young children or immunocompromised adults
2. Transmission= direct skin contact or sexual contact
3. Usually self limited and goes away
4. Appearance= small, skin colored papules that often show central umbilication (indentation) and are often clustered
together
5. Histology: hyperplasia with necrosis of centrally affected cells that also have large eosinophilic inclusions

Fungal: Tinea type of fungus with tropism for keratinocytes, usually superficial and just need topical therapy; more issues if nail/hair follicle
involved
1. Named based on where they are found
2. Tinea= “worm” and is a superficial fungal mold infection of skin and appendages generally
acquired via contact
3. Tinea corporis=ringworm due to dermatophyte fungus (Trychophyton) with lesions that
can become large and are erythematous with scale and have ring like border that is more
prominent at the outer edge of rash from hyperkarytosis
4. Tines pedia= athlete’s foot= most common dermatophyte infection; tends to be
asymmetrical and may be unilateral; general presentations are itchy erosion and/or scales
between toes (often 4th-5th toes), Scale covering sole and sides of feet, or small-medium
blisters affecting inner aspect of foot
Fungal: Intertrigo (not always infectious)
1. Intertrigo=superficial dermatitis (inflammation) of skin in areas where skin rubs against each other (axillary, inguinal,
intergluteal, skin folds interiginous regions)  affected sites can be involved in isolation or conbo with other body
sites
2. Can manifest from skin-skin friction injury (non-infectious) or from candidial (main) or bacterial infection
3. Presentation= itching, burning erythema, pain
4. May see erythematous mirror image patch along skin fold
5. Commonly associated with Diabetes and obesity, diaper rashes
6. Diagnosis: often made clinically, can do KOH prep of skin scraping and see under microscope if you see yeast from
candida, may need to treat

Other causes of skin lesions may be indicative of systemic infectious disease

 1. Common issues: Chicken pox, Rocky mountain spotted fever (distal to central) (direct invasion of vasculature)
2. May be early sign of life threatening infection Petechiae in disseminated N. mengitidis
3. Pathogenesis: DIC/coagulopathies, direct vascular invasion by microbe, immune complex vasculitis, embolic, toxins

Chicken Pox : Recrudescence infections (zoster rupture can increase risk of other bacterial infection)

Recrudescence=recurrent
infections  zoster is recurrence of
VZV that recurs without re-
infection; seen in other herpes
infections

Typhoid Fever (Enteric Fever)

1. Systemic bacterial infection caused by invasive organism (Salmonella typhi) resulting primarily in small intestinal ulcers
and associated GI bleeding
2. Infection usually acquired via ingestion of contaminated water or food or from acutely infected individuals or chronic
carriers
3. Organism invades intestinal epithelium near Peyer’s patches usually where It is engulfed by macrophages in lymph
tissue can carried throughout body tropism for macrophages and other mononuclear cells
4. Rose spots= 1-5mm reddish skin macules related to hematogenous spread of bacterial emboli in skin could culture
salmonella from these

Blastomycosis: secondary manifestation of fungal infection

1. Silver stain= Broad based budding
2. Chronic granulomatous and suppurative infection caused by inhalation of conidia
(spores) of thermally dimorphic fungus Blastomyces dermatidis
3. Pulm infection is most common and may be limited to lungs or may also involve skin and
bones (can technically affect any organ)
4. Endemic to parts of N. America esp in US/Canadian areas around Great lakes,
southeast/south central US

Lung Infections: usually bacterial or viral

1. Pneumonia vs Pneumonitis: pneumonia is a type of pneumonitis (inflammation
of lung) caused by infection
2. Bacterial pneumonia (top): “alveolar filling process”
3. Rust colored sputum is associated with strep infections
4. General Patterns: Lobar, bronchopneumonia, atypical
(walking)
5. Viral pneumonia (bottom): interstitial inflammatory
process can can have secondary involvement of the air
space due to fact that virus is obligate intracellular so
causes an interstitial process
6. Aspiration: organism already present in flora that gets into
lung while inhalation exposure where you inhale from environment
7. NOTE: pneumonia refers to PRIMARY infection of lungs (not hematogenous
spread)
8. The more yellow/green the sputum, the more likely you have a bacterial
infection
Fungal Involvement of Lung

1. Less common than bacterial/viral but pose

diagnosis/treatment related problems
2. Endemic fungal lung infections usually due to dimorphic fungi
that are inhaled by people who live in certain geographic areas
in US
3. Invasive fungal lung infection due to ubiquitous fungi
(Aspergillis or Candida) usually in people with immune
deficiency
4. Aspergilloma: Patients with pre-existing cavities in lung may
develop colonization of cavity by Aspergillus “fungus ball”

Robbins Readings: p. 341-359: Ch. 9 General Pathology of Infectious Disease

General Principles of Microbial Pathologies

Categories of Infectious Agents
1. Prions= abnormal forms of host proteins (PrP= Prion Protein)
A. Associated Diseases: Kuru, Spongiform Encephalopathies (genera), CJD, bovine spongiform encephalopathy (mad cow)
B. Prp is normally found in neurons disease when resistant to protease; disease PrP form is also trigger for more disease forms
which leads to the transmissible nature of the disease
2. Viruses= obligate intracellular parasite that needs host metabolic machinery for replication
A. Composition= nucleic acid genome (DNA or RNA) surrounded by capsid (helical or icosahedral) protein coat
B. Other classifying features: replication mode and cell type for replication (Tropism), presence/absence of lipid envelope, pathology
C. Tropism= preferred cell type for replication
 D. Inclusion Bodies= aggregates of viral components/particles in infected cells that may be used from diag in light microscope (seen
in herpesvirus, smallpox, rabies, CMV)
E. Can cause transient infection or remain dormant (chickenpox shingles)
3. Bacteria= prokaryotes that make own DNA, RNA, Proteins; most have cell wall with peptidoglycan
A. Groupings: gram, shape, oxygen requirements, movement
B. Motility: flagella (long, helical filament that rotate to move bacteria)
C. Pili: surface projection to attach host cell or ECM
4. Fungi: eukaryotes with thick wall made of complex carbs (beta-glucans, chitin, mannosylated glycoproteins); endemic (invasive to particular
region) or opportunistic (found everywhere but usually don’t cause infection in healthy people)
A. Calcoflour white= fluorescent stain that binds chitin and helps to identify fungi
B. B-glucan assay: used to diagnose disseminated fungal infections
C. Shapes: rounded yeast cells, slender filamentous hyphae
D. Distinguishing characteristic: septate (cell wall separates individual cells) or aseptate
E. Thermal dimorphism: in some pathogenic fungi can grow as hyphal form in room temp and yeast form at body temp
F. Conidia= asexual spores (made more often than sexual spores) made on structures/fruiting bodies along hyphal filament
G. Dermatophytes= fungi that cause superficial infection
H. Infections caused:
Superficial tinea (on skin) tenia pedis is athlete’s foot; mycetomas= chronic infection (usually in feet)
Deep can spread systemically and destroy organs
I. Immunocompromised susceptibility Pneumocystis jiroveci is opportunistic fungus often affecting AIDS patients
5. Protozoa: single celled eukaryotes
A. Can replicate intracellularly in variety of cells
B. Common transmission via insect vectors where they replicate and pass onto human host
6. Helminths= parasitic worms that are highly differentiated multicellular organisms; complex life cycle
A. Many alternate between sexual reproduction in definitive host and asexual multiplication in intermediate host/vector
B. Adult worms usually don’t multiply once inside humans but may produce eggs/larvae that get passed in stool
C. Groupings= Roundworms (nematodes), Tapeworms (cestodes), Flukes (trematodes)
D. Roundworm= circular and nonsegmented; intestinal or tissue kinds
E. Tapeworms: head (scolex) and ribbon of multiple flat segments (proglottids); absorb nutrition via tegument and don’t have GI;
larvae can develop after egg ingestion and cause cystic disease
F. Flukes= leaf shaped flatworm with sucker to attach to host; liver and lung types
7. Ectoparasites: insects (lice, flea, bedbugs, arachnids) that cause disease by bite or by attaching/living on or in skin
A. Usually cause itching/excoriations
B. Pediculosis= caused by lice on hair
C. Scabies= caused by mites in stratum corneum
D. May serve as vectors for other pathogens

The Microbiome: diverse microbial pop of bacteria, fungi, virus in/on human body (most don’t cause harm)
1. Potential disease causing members: S. aureus, S pyogenes, Propionbacterium acnes (acne), S. mitis (tooth decay)
2. Aid in digestion/absorption, immune system, nutritional status (found to be less diverse in obese)
3. Greatest diversity in oral cavity and stool, intermediate in skin, least in vagina
4. Dysbiosis= change in composition of microbiome associated with disease  from
antibiotics (C. diff overgrowth risk), IBD found to also be affected by changes in viral
population in stool

Techniques for Identifying Infectious Agents

1. Culture: important for diagnosis (more for bacterial/fungal than viral); also use for
antibiotic sensitivity testing
2. Histology: H&E, special stains for specific agents Gram, acid fast, silver, mucicarmine,
Giemsa, antibodies
3. Serology: identify pathogen specific antibodies (IgM for acute, titers 4x rise in 4-6
weeks considered diagnostic usually); antibody assays, cross reacting antibodies
4. Molecular Diagnosis: PCR (imp for chlamydia, TB, Herpes encephalitis); high sensitivity,
qPCR used to measure viral loads in transplant recipients , NextGEN methods newer
5. Proteomics: mass spec to identify via protein content; rapid identification but not useful
for antibiotic sensitivity
Overview of Bacterial Diseases and Pathogens

Newly Emerging and Reemerging Infectious Diseases

Reasons for New Infectious Agents
1. New technology for detection (sequencing methods)
2. Pathogens from animals gaining ability to move to humans: Mid east respiratory coronavirus, SARs, HIV, B. burgdorferi
3. Gene acquisition over time to enhance virulence/overcome host defense mechanisms  E. coli acquisition of shiga-toxin via bacteriophage
4. Immunosuppression via AIDS, methods of preventing transplant rejection
5. Human behavior: traveling, burial practices
6. Environmental Changes: changes animal environment, temperature change
7. Antibiotic resistance rise
Zika:
1. Contract via Aedes mosquito or sexual transmission (maybe blood transfusion)
2. Often little symptoms; associated with causing GBS in some, can cause birth defects

Agents of Bioterrorism (See chart)

1. Ranked into A, B, C categories
2. Category A is highest risk category b/c readily disseminated from person to person and high mortality rate
3. Category B: lower risk, many spread via food/water
4. Category C: emerging pathogens that could be engineered for mass destruction

Transmission and Dissemination of Microbes

Modes of Entry
1. Resp, GI, GU usually occur via virulent microorganisms that can penetrate epithelial barriers
2. Skin infections usually via less virulent microorganisms that enter via breaks of skin
3. Skin
A. Keratinized layer is natural barrier, low pH (under 5.5), fatty acids inhibit microorganism growth outside normal flora
B. Catheters may lead to infection, needle sticks, animal/insect bites
C. Some organisms can cross skin barrier directly: Schistosoma larvae, some dermatophytes fungi
4. GI
A. Transmit via food/water often contaminated with fecal material
B. Acid is common defense, some agents (shigella, giardia cysts) have developed resistance to acid (require lower load for infection)
C. Other GI defenses: mucus, lytic pancreatic enzymes, flora, AMPs defensins, IgA in MALT (antibiotics may alter these defenses)
D. Some viruses (Hep A, rotavirus) can enter GI b/c they lack envelopes which bile acid/digestive enzymes normally inactivate
E. Enteropathogenic bacteria Infection mechanisms= Toxin production in food, adhesion and local proliferation, invasion (associated
with bloody stool, dissemination)
F. Fungal infection: more in immunocompromised
G. Intestinal Parasites: usually enter via ingestion of cysts, eggs, larvae and have multiple mechanisms of causing damage (G.
lambliaattach to epithelial brush border, Cryptosporidia are taken up by enterocytes, E. histolytica kills host cells via pore
forming proteins, helminths can accumulate to cause damage)
5. Respiratory Tract: inhalation in dust or aerosol particles
 A. Particle size is inversely prop to how for they can travel through resp tract initially (large usually stays in upper resp tract while
small may travel directluy to alveoli to be taken up by macrophages or neutrophils)
B. Mucus traps organisms and move via cilia to back of throat where they can be swallowed and enter GI or coughed out
C. Viral mechanisms of avoiding alveolar macrophages: attaching and enter epithelial cells of lower resp and pharynx (Influenza
usuaes hemagglutinin protein that bind sialic acid on epithelial cells to induce engulfment of virus)
D. Bacterial mechanisms of entering rep: toxins to paralyze cilia (H. influenzae, M. pneumoniae, B. pertussis)
E. NOTE: viral infections may damage cilia and lead to bacterial infections (S. pneumo, S. aureus)
6. Urogenital Tract
A. Invaded from exterior via urethra urine usually serves as defense to flush out the pathogens
B. Microorganisms (N. gonorrhoeae, E. coli) can adhere to urinary epithelium and cause UTI
C. Women more prone to UTI b/c shorter distance between urinary bladder and skin
D. UTI could spread to kidney and cause acute/chronic pyelonephritis
E. Lactobacilli: commensal bacteria that protects vagina from pathogen by maintaining low pH (can be killed by antibiotics)

Spread and Dissemination of Microbes Within Body

Mechanisms of spread
1. Lysis and invasion: secretion of lytic enzymes from extracellular bacteria/fungi/helminth EX: S. aureus secretes hyaluronidase to degrade ECM
2. Via blood and lymph: via extracellular fluid or within host cells, transport via plasma (all helminths, most bacteria/fungi), via RBC (Plasmodium
and Babesia), and leukocytes (herpesvirus, HIV, mycobacteria)
3. Cell to cell transmission: mech of most viruses, some propagate between cells
Consequences of Dissemination
1. Varies depending on seeding pattern and host factors/defense mechanisms
2. Can cause symptoms far away from point of microbe entry

Transmission Mechanisms of Microbes

1. Skin
2. Oral
3. Respiratory secretions M. tuberculosis and VZV can travel very long distances in air
4. Stool pathogens that replicate in liver or gallbladder
5. Blood
6. Urine main mode of exodus of S. haematobium (not many microbes use this route)
7. Genital tract STIs
8. Vertical transmission: transmission of infectious agent from mother to fetus or newborn
9. Zoonotic infections interaction with animal/animal products

How Microorganisms Cause Disease

Main Mechanisms
1. Enter/contact with host and directly cause death or infected cells
2. Toxin release to kill cells at distance, enzymes to degrade tissue or damage blood vessels
3. Trigger host immune responses

Mechanisms of Viral Injury

1. Replication in host cell at host expense
2. Tropism factors
A. Host receptors for viruses to allow viral entry to cell HIV binds CXCR4 and CCR5 on T cells and macrophages
B. Host protease: host protease is needed to activate influenza virus hemagglutinin
C. Specificity of transcription factors to allow viral replication JC virus promoter and enhancer are only active in glial cells
D. Physical characteristics of tissues:
3. Cell damage/killing mechanisms
A. Direct cytopathic effect preventing synthesis of critical macromolecules, produce destructive enzymes/toxins, trigger apoptosis
B. Anti-viral immune response: recognition via CTLs CTL kills hepatocytes in Hepatitis B
C. Transformation of Infected cells: certain oncogenic viruses can stim cell growth/survival and lead to cancers

Mechanisms of Bacterial Injury

1. Bacterial Virulence: adhere invade/deliver toxin damage to host
A. Virulence genes are often encoded in pathogenicity islands
B. Plasmids (small, independently replicating circ. DNA) and
Bacteriophages (viruses) are genetic elements that can carry
virulence
C. Quorum sensing coordination of gene expression within large
population of bacteriaS. aureus secretes autoinducer peptides
that stim exotoxin production
D. Biofilms: communities of bacteria that can live within viscous layer
of extracellular polysaccharides that adhere to host tissue/artificial
devices; can help protect bacteria from anti-microbial drugs
2. Bacterial adherence to host cells
 A. Bind adhesins on host cells/ECM
B. Utilize a variety of surface structures
C. Example: S. pyogenes has F protein and teichoic acid on cell wall to bind fibronectin on host cell/ECM
D. Pili: filamentous protein to help bind host  E. coli have pili specific to uroepithelial cell to cause UTI; N gonorrhoeae has pili with
antigenic variation to help escape immune response
3. Bacterial Toxins= any bacterial substance that contributes to illness; endotoxin (components of
bacterial cell) and exotoxins (secreted by bacteria)
A. LPS: endotoxin; long chain fatty acid anchor (lipid A) connected to core sugar chain
with variable carb chain Lipid A binds CD14 in surface of host leukocytes which
binds TLR-4 which stimulates immune response (can become excessive and cause
damage)
B. Enzymes: exotoxin; has huge variety of actions
C. A-B Toxins: exotoxin; alters intracellular signaling/regulatory pathways the A
component Is active with enzymatic activity and B component is binding for cell
surface receptors and delivers the A component to cytoplasm: In B. anthracis, EF
and LF are alternate A components
D. Superantigens
E. Neurotoxins C. botulinum and C. tetani; effect on neurotransmitter release;
muscle paralysis can lead to death if diaphragm muscles paralyze
F. Enterotoxins: affect GI with varied effects

Injurious Effects of Stimulating Host Immune Responses

1. Granulomatous inflammation: seen in TB
2. T cell mediated inflammation: HBV and HCV on hepatocytes
3. Innate immune inflammation: PAMPs bind DAMPS to stim inflammation
4. Humoral Immunity: example is poststrep glomerulonephritis in GAS
5. Chronic Inflammatory Diseases: cycle of inflammation/ epithelial injury with commensal bacteria IBD
6. Cancer: associated with HBV and HCV viruses and H. pylori bacteria via oncogene activation
Immune Evasion by Microbes
1. Antigenic variation: escape recognition by neutralizing antibodies of host
A. Utilize low fidelity viral RNA polymerases and reassortment of viral genomes
B. Borrelia, Trypanosoma, VSG
C. Can vary capsule, surface proteins, etc
2. Modification of surface proteins: cationic pore forming AMPs (defensins, cathelicidins, thrombocidins) resistance
A. Avoid killing by making surface molecules that resist or inactivate AMPs
3. Overcoming Antibodies and Complement:
A. Facultative intracellular pathogens activate alternative complement pathway to activate uptake but don’t undergo lysosome
destruction
4. Resist Phagocytosis and Bacterial Killing in phagosomes
A. Surface proteins that inhibit phagocytosis (Protein A in S. aureus and Protein M in GAS)
B. Blocking fusion to produce phagolysosome
C. Degradation of phagosome membrane listeriolysin O in Legionella
D. Killing of phagocyte, prevent oxidative burst
5. Escape the inflammasome: normally activated by IL-1 and 8 (pyroptosis)
A. Yersinia and Salmonella express virulence proteins that inhibit
inflammasome maturation, suppress caspase activation and
inflammation pathways
6. Disruption of Interferon Pathways
A. Production of homologs of IFN receptor to bind and block action of
IFNs
B. Produce protein to inhibit JAK/STAT path of IFN receptors
C. RIG-1 blocks downstream IFN pathway
D. Encode cytokine/chemokine or their receptor homologs to
block/compete with host defenses
7. Decreased T-cell recognition
A. DNA viruses can bind/alter localization of MHC-I and downregulate
B. May target the T-cells directly HIV infects CD4 T-cells
Spectrum of Inflammatory Responses to Infection
1. Mononuclear and Granulomatous Inflammation: seen more in intracellular bacteria,
viruses, spirochetes and some helminths
 Cytopathic-Cytoproliferative Reaction
1. Usually associated with viruses
2. Lesion characteristics= cell necrosis or
proliferation with sparse inflammatory
cells
3. Some viruses make aggregates that
are visible as inclusion bodies or
induce cells to fuse and form
Polykaryons which are multinucleated
cells
4. Blisters may form if epithelial cells
become detached
5. Viruses can trigger cell proliferation
that can contribute to development of
malignancy
6. Virus can cause widespread necrosis associated with inflammation HSV destruction of brain temporal lobes, Liver damage by HBV
Tissue Necrosis
1. Via production of power toxins that cause rapid/severe necrosis C. perfringens
2. Associated with E. histolytica
3. On histo: due to speed of necrosis, resemble infarct due to low amounts of inflammatory
cells

Chronic Inflammation and Scarring

1. Scarring can cause major
dysfunction schistosome eggs
can cause “pipestem fibrosis” of
liver or bladder wall, TB can
cause fibrous pericarditis
2. Schistosome eggs can cause
mononuclear and
granulomatous inflammation
3. Often hard to differentiate many
potential causes of inflammation
4. Immunocompromised
individuals may lack
characteristic inflammation
characteristics

Infections in Individuals with Immunodeficiencies

1. Antibody deficiency prone to bacterial infection via extracellular bacteria and
some viral infections
2. T-cell defects prone to intracellular pathogen infection, esp viruses and some
parasites
3. Early complement deficiency susceptible to encapsulated bacteria
4. Late complement deficiency susceptible to Neisseria infection
5. Neutrophil function deficiency susceptible to S. aureus, some gram neg and
fungi
6. Deficiency in TLR downstream molecules prone to pyogenic bacterial disease,
esp. S. pneumo
7. Impaired TLR3 associated with childhood HSV encephalitis
8. IL-17 impairment chronic mucocutaneous candidiasis
9. HIV: decrease in CD4 T cells leads to profound immunosuppression
10. Cystic fibrosis main infection is Pseudomonas aeruginosa
11. Asplenia and sickle cell susceptible to encapsulated bacteria like S. pneumo
Disease Specific Readings: p. 277, 519-537, 614-620, 862-865, 704-712, 713, 716, 717, 721, 726
Pulmonary Infections: p. 519-537
Pneumonia= any infection in lung (broad definition)
General Lung State
1. Lung parenchyma is normally sterile b/c lots of immune mechanisms from nasopharynx to alveolar air spaces
2. Reasons for infection many airborne microbes, nasopharyngeal flora can become aspirated during sleep, lung disease lower local immune
3. Immunodeficiency often is associated to increased risk of infection with pyogenic bacteria
A. MYD88 Mutation Protein required by TLR so mutation increase risk of severe necrotizing pneumococcal infections
B. Deficient IgA increase pneumonia risk by encapsulated organisms
C. TH1 deficiency increased risk of infection from intracellular microbes (atypical mycobacteria)
4. Bacterial pneumonia classification: based on etiologic agent or clinical setting of acquisition

Community Acquired Bacterial Pneumonias: often occur AFTEr a viral upper-respiratory tract infection
General Symptoms= abrupt fever, shaking/chills, mucopurulent sputum, pluritis, radiopaque areas
General TX: antibiotics often works quickly if correct organism identified/treated
Streptococcus pneumoniae= MOST COMMON community acquired acute pneumonia
1. Common settings: Chronic disease (CHF, COPD, Diabetes), congenital/acquired Ig production defect, asplenia/sickle cell
2. Spleen has largest collection of phagocytes response for pneumococcal clearance from blood; also important for Ab production against
polysaccharides found in encapsulated bacteria
3. Symptoms= lots of neutrophils in sputum; lancet gram pos diplococci
4. Diag: S. pneumo is part of endogenous flora in 20% adults which can lead to false positive; isolate in blood culture is more positive test
5. Vaccine= capsular polysaccharide from common serotypes
Haemophilus Influenzae=most common bacterial cause of COPD exacerbation
1. Both encapsulated and unencapsulated forms can cause pneumonia (encapsulated more serious though esp in children)
2. Adults at risk if they already have a chronic pulm disease (COPD, CF, bronchiectasis)
3. Most common bacterial cause of COPD acute exacerbation
4. Vaccine for H. influenzae type b which was formerly common cause of epiglottitis and suppurative meningitis in children
Moraxella catarrhalis=second most common bacterial cause of COPD exacerbation
1. Pneumonia more in older adults
2. Common cause of otitis media in children
Staphloccus aureus=MOST important cause of secondary pneumonia after viral respiratory illness
1. High incidence of complications lung abscess, empyema
2. Right side staph endocarditis is complication associated with IV drug abuse
3. Also associated with nosocomial pneumonia
Klebsiella pneumoniae=MOST COMMON cause of gram-NEG bacterial pneumonia
1. Risk group: debilitated and malnourished individuals esp chronic alcoholics
2. Current jelly sputum caused by bacterial production of viscid capsular polysaccharide
Pseudomonas aeruginosa
1. Commonly seen in nosocomial situations esp with cystic fibrosis
2. Risk: Also common in neutropenic patients, secondary to chemo or extensive burn patients; patients requiring mechanical ventilation
3. Can invade blood vessels and cause extrapulmonary spread bacteremia, vasculitis, secondary coagulative necrosis
Legionella pneumophila
1. Pontiac fever: related self-limited upper resp tract infection that can be caused and doesn’t display pneumonic symptoms
2. Associated with artificial aquatic environemnts cooling towards, water supplies
3. Mode of transmission=inhalation of aerosolized organisms or aspiration via contaminated drinking water
4. Risk groups= predisposed condition of cardiac, renal, immune system, hematologic disease, organ transplant recipients especially
5. Diagnosis= Legionella antigens in urine, positive fluorescent antibody test of sputum samples, Culture is standard, PCR sometimes
Mycoplasma pneumoniae
1. More in children/young adults school, military, other areas of close quarters
2. Diagnosis= PCR for mycoplasma DNA

Bacterial Pneumonia Morphology

1. Consolidation of lung= solidification due to replacement of air by exudate in alveoli
2. Bronchopneumonia= patchy consolidation at foci of acute suppurative inflammation; may
evolve over time; can be multilobar and often bilateral because secretions can gravitate to
lower lobes; LESIONS= elevated, dry, granular with grey-red to yellow color with poor
margins; exudate is neutrophil rich in bronchi/bronchioles/adjacent alveolar space
3. Lobar pneumonia= consolidation of large portion/entire lobe; 4 stages of inflammatory
response= congestion (heavy, red lung, vascular engorgement, lots of bacteria but low
neutrophils)  red hepatization (huge confluent exudation w/ neutrophil, RBC, fibrin in
alveolar space)  Gray hepatization (firm, airless lobe that looks like liver,
fibrinsuppurative exudate that’s grey/brown) Resolution (enzymes break down exudate
in alveolar space, leaving granular semifluid debris that macrophage/etc
reabsorb/reorganize)
4. Pleuritis= if consolidation extends to surface
5. General Complications: Abscess formation, Empyema (intrapleural fibrinosuppurative
reaction if spread to pleural cavity), Bacteremic dissemination.
Community Acquired Viral Pneumonias
1. Most Common= Influenza type A and B, respiratory syncytial viruses, Human metapneumovirus, Adenovirus, Rhinovirus, Rubeola, Varicella
2. General symptoms= upper-respiratory tract infections (common cold)
3. Mechanism: target resp epithelium and cause inflammatory response; can cause interstitial inflammation if extend to alveoli
4. Imaging: may not be able to distinguish from bacterial because can also cause alveolar space fluid buildup
5. Susceptibility to bacterial infection due to necrosis of resp epithelium which then decreases mucuciliary clearance of bacteria
6. Risk group= infants, malnourished, alcoholics, immunocompromised
7. Clinical Features
A. Varied
B. Initial presentation usually acute, nonspecific febrile illness with headache, malaise, later cough with little sputum
C. VQ mismatch from inflammatory exudate blocking oxygenation of blood
8. Influenza: Type A influenza virus is major cause of pandemic (antigenic shift) and epidemic (antigenic shift) influenza

Viral Pneumonia Morphology

1. Can be patchy or lobar; unilateral or
bilateral
2. Histo inflammation is largely
confined to walled of alveoli,
widened septi and edematous,
red/blue congestion, mononuclear
infultrates
3. Alveolar space classically free of
cellular exudate unless in severe
cases (can develop hyaline
membranes)
4. In mild cases, subsidence of disease is
followed by reconstitution of normal
architecture
5. Superimposed bacterial infection will
appear as mixed histology

Hospital Acquired Pneumonias

*common organisms: S. aureus, gram negative rods (Enterobacteriaceae and pseudomonas)

Aspiration Pneumonia
1. Aspiration of gastric contents while unconscious or when vomiting
2. Irritation from bacteria and gastric contents; often multiple organisms involved
3. More often caused by aerobes
4. Clinical Features: necrotizing, sudden onset (fulminant), abscess formation is
common complication
5. Microaspiration: more common, may exacerbate other lung diseases but doesn’t
lead to pneumonia
Lung Abscess
1. Definition= localized area of suppurative necrosis in pulm parenchyma and causes
cavity/cavities
2. Causative agents: aspiration of oral/gastric contents, complication of necrotizing
bacterial pneumonias (S. aureus, S. pyogenes, K. pneumoniae, Pseudomonas),
bronchial obstruction (may be tumor/cancer), aspiration of tumor fragments, septic
embolism from infective endocarditis of right heart, hematogenous spread of
bacteria in disseminated pyogenic infection (mainly staph bacteria)
3. Anaerobic bacteria are presents in almost all lung abscesses mainly organisms
found in oral cavity Prevotella, Fusobacterium, Bacteroides, Peptostreptococcuc,
microaerophilic streptococci
4. Morphology: aspiration origin usually causes abscess on right side b/c more vertical
airway in posterior segment of upper lobe/apical segment of lower lobe; abscess
from pneumonia or bronchiectasis usually are multiple, basal, and diffusely
scattered, septic emboli or hematogenous seeding can affect any part of lung
5. Infection spread: often ruptures airways eventually; may rupture into pleural cavity
and produce bronchopleural fistula which can lead to pneumothorax or empyema
(pus in pleural cavity)
6. Histology: suppurative focus surrounded by various fibrous scarring and
mononuclear infiltration
7. Clinical Features prominent cough with foul-smelling purulent sputum, may get
hemoptysis, fever/malaise, may lead to secondary amyloidosis
Chronic Pneumonias
 1. Generally localized lesion in immune-COMPETENT individual that may involve lymph nodes
2. Often granulomatous inflammation
3. May disseminate in immune-COMPROMISED
4. Most important chronic pneumonia= TUBERCULOSIS
Tuberculosis (Mycobacterium tuberculosis hominis=main, mycobacterium bovis=from milk, mycobacterium avium complex=less virulent)
1. Infection vs disease infection implies seeding of focus with organisms that may be causing clinical damage, disease involves damage occurring
2. Generally very little symptoms may appear as small fibrocalcific nodule at infection site
3. Can only transmit during ACTIVE disease
4. PPD test: positive if causes a palpable induration due to delayed hypersensitivity reaction that usually happens in people with TB may get false
neg in people with sarcoidosis, malnutrition, Hodgkin lymphoma, immunosuppressed or false pos in people with atypical mycobacteria infection
5. Pathogenic Process:
A. Entry to macrophage and replication within macrophage bacteria inhibits phagolysosome formation (major prolif
normally within first 3 weeks) in pulm alveolar macrophages and air spaces Generally ASYMPTOMATIC still
B. Development of cell mediated immunity (3 weeks after exposure) mycobacterial antigens reach lymph nodes and
present to CD4 T cells Th1 secreted from macrophages, IFN-y secretion
C. T-cell mediated macrophage activation and killing of bacteria (IFN-y from TH1 cells crucial)  Leads to increased TNF to
recruit monocytes which become epithelioid histocytes found in granulomatous response, iNOS to raise NO and make
nitrogen intermediates important in killing mycobacteria, and anti-microbial peptides (defensins)
D. Granulomatous inflammation and tissue damage TH1 response also leads to granuloma and caseous necrosis dev
b/c IFN-y stimulates macrophages to become epithelioid histiocytes that can aggregate to form granulomas
E. NOTE: TNF-a important for macrophage recruitment TNF antagonists increase risk of TB reactivation
6. NOTE: deficiencies in any part of TH1 response increases susceptibility for disseminated TB infection
7. Hypersensitivity: needed to counter and prevent spread of disease (immunocompromised don’t mount as strong as response)
8. Primary vs Secondary TB
A. Cavitation occurs more in the secondary form more likely to disseminate
B. Regional lymph node involvement less prominent in secondary TB
9. Potential Pathways of disease progression
A. Bronchus: forms ragged, irregular cavity lined by caseous material
B. Blood vessel erosion leads to hemoptysis
C. Miliary Pulmonary Disease: when organism reaches bloodstream then recirculate to lungs leading to scattered lesions
common areas of spread are liver, bone marrow, spleen, adrenal glands, meninges, kidneys, fallopian tubes, epididymis
D. Pott Disease: spread to vertebral body
E. Lymphadenitis: most frequent form of extrapulm TB; usually in cervical region and unifocal if immunocompetent
F. Intestinal TB: from drinking contaminated milk; less common in developed countries
Primary-Ghon complex (Left) vs Secondary (Right TB)
Ghon focus: inflammatory consolidation that often has caseous necrosis
in center
Ghon complex: combo of parenchymal and nodal lesions; usually
undergoes fibrosis when person develops cell-mediated immunity
Ranke complex: gohn complex that has undergone fibrosis/calcification
Nontuberculous Mycobacterial Disease
1. Mainly cause localized pulm disease in immunocompetent upper lobe cavitary disease common
2. Risk groups: alcoholics, smokers, COPD, Cystic fibrosis
3. M. Avium complex can cause disseminated disease in immunocompromised and may appear as foamy macrophage “stuffed” with atypical
mycobacteria, not necessarily granulomas

Dimorphic Fungi: Histoplasmosis, Coccidiodomycosis, and Blastomycosis

1. Usually isolated pulm involvement unless
immunocompromised which can disseminate
2. T-cell mediated immune response critical to
infection containment
3. H. capsulatum (upper left): Midwest/southeast
US mainly in moist soil with bat/bird droppings
4. C immitis (upper right): southwest US; “valley
fever”
5. B dermatitidis (lower left+right):
Midwest/southeast US

General Clinical Features/Possibilities

1. Acute pulmonary infection
2. Chronic granulomatous disease
3. Disseminated miliary disease

Primary Pulmonary Nodules

1. Have aggregates of macrophages filled with
organism that can become granulomas that
develop central necrosis and calcification
2. General cause flu-like symptoms and usually self-
limited

Disseminated disease
1. No well formed granulomas get focal collections of phagocytes with yeast forms
2. Febrile illness marked by hepatosplenomegaly, anemia, leukopenia, thrombocytopenia
3. Blastomyces can cause cutaneous epithelial hyperplasia in disseminated disease that
gets mistaken for squamous cell carcinoma

Pneumonia In the Immunocompromised Host

Common opportunistic pulmonary pathogens
1. Bacteria: P. aeruginosa, Mycobacterium, L. pneumophilia, Listeria, L pneumophilia
2. Virus: CMV, HSV
3. Fungi: P. jiroveci, Candida spp, Aspergillus, Cryptococcus neoformans

CMV: cytomegalovirus
1. Member of herpesvirus family
2. Infected cells exhibit gigantism of cytoplasm and nucleus (“owl’s eye”)
3. CMV pneumotitis can cause serious problems (CMV can affect any organ though)
4. In neonates cytomegalic inclusion disease
5. Transmission: transplacentally, during birth, via saliva, resp secretion/fecal-oral
 6. CMV Mononucleosis: asymptomatic in most people, could cause Mono but most people generally recover
7. CMV in Immunosuppressed: associated with transplant recipients usually or HIV/AIDS; generally affects lungs (pneumotitis), GI (colitis and
possible pseudomembrane), and retina (retinitis most common opportunistic CMV disease), usually no effect on CNS
8. Diagnosis: presence of CMV in tissue sections, viral culture, antibody titer, qPCR

Pneumocystitis: P. jiroveci (fungus)

1. Most people are carriers but don’t get infection
2. Largely confined to lung causes interstitial pneumonitis
3. Morphology: intraalveolar foamy pink staining exudate
(“cotton candy exudate”), thick septa, minimal mononuclear
infiltrate
4. Staining: use silver stain to view round cysts within alveolar
exudate
5. Diagnosis: identify organism in induced sputum or
bronchoalveolar lavage via immunofluorescence

Opportunistic Fungal Infections

1. Candidiasis
A. Common; normally in oral cavity, GI, vagina without issues
B. Morphology: yeastlike forms and true hyphae; pseudohyphae are diagnostic clue (budding
yeast cells joining at ends)
C. Stains: HE, Gomori metheamine-silver, PAS
D. Clinical features mainly mucous membranes, skin, deep organs involved
Most common oral cavity (thrush)
Other areas: vaginitis, Esophagitis, Skin infection, chronic mucocutaneous candidiasis
if patient has underlying T-cell defects (Job syndrome TH17 defect), invasive if blood borne
dissemination can cause organ abscess (leukemia patients are prone)

2. Cryptococcosis (C. neoformas)

A. Almost exclusively in immunocompromised
B. Morphology: thick, gelatinous capsule, Do NOT have true hyphal forms , capsule is key to
identification appear as halo in H/E, India ink or PAS can highlight fungus
C. Reproduces via budding
D. Cryptococcal latex agglutination assay: detects the capsular polysaccharide antigen
E. Clinical features can be pulm, CNS, or disseminate
F. Acquisition: inhalation of aerosolized soil/bird droppings
G. Can form “soap bubble lesions” in meninges

Opportunistic Molds: Mucormycosis and Invasive Aspergillosis (both images)

1. Morphology: both cause nondistinctive suppurative, sometimes granulomatous
reaction that invade blood vessel walls
2. Rhinocerebral/pulm mucormycosisgeneral colonize nasal cavity/sinuses and
can spread to brain, orbit, and other head/neck structures
3. Aspergillosis generally localizes to lung
4. Allergic bronchopulm aspergillosis asthma patients; develop exacerbated type
1 hypersensitivity; IgE mediated
5. Aspergilloma fungs ball formation, mass forms that can occlude cavities

Pulmonary Disease in HIV

1. Leading contributor to mortality/morbidity
2. Not all are associated with infectious disease
3. Immunosuppressed considered when CD4 is under 200 cells/uL

Perinatal Infections p. 277

 1. Ascending infection: acquisition for disease trans-cervically in utero or during birth usually via inhaling amniotic fluid; fetal infection is associated
with inflammation of placental membranes (chorioamnionitis) and inflammation of umbilical cord
Bacteria (more common): a-hemolytic strep
Viral: Herpes simplex
2. Hematologic infection: transplacental acquisition; pass via chorionic villi; if passed early in pregnancy, associated with chronic issues such as
growth restriction, mental retardation, etc, later in pregnancy usually causes tissue injury and inflammation
Main infections= TORCH
T=toxoplasma
O=other treponema pallidum, Zika
R= rubella
C=CMV
H= herpesvirus
Infectious Enterocolitis: p. 614-620

Cholera
1. Transmission via drinking water mainly; only animal reservoirs= shellfish and plankton
2. Pathogenesis: from toxin, not organism  interferes with absorption function of enterocytes (need flagellar protein to latch)
A. Hemagglutinin activated via secreted metalloproteinase important for bacterial detachment and shedding in stool
B. Toxin: 5 B-subunits and one A-subunit is delivered to ER via retrograde transport to interact with ADP ribosylation factors to activate Gs
C. Mucosal biopsy doesn’t show much morphological alterations
3. Clinical Features: usually mild diarrhea but could be really severe (death within 24 hours if bad)

Campylobacter Enterocolitis (C. jejuni usually)

1. Most common bacterial enteric pathogen in developed countries most important
cause of “Traveler’s diarrhea”
2. 4 major virulence properties: motility (flagella), adherence, toxin, invasion
mechanisms
3. Toxin; cytotoxin that causes epithelial damage, cholera-like toxin
4. Clinical presentation enteric fever when bacteria reaches lamina propria and
mesenteric lymph, blood diarrhea, reactive arthritis (HLA-B27 susceptible), GBS
possible
5. Incubation: up to 8
days and may shed
bacteria for up to a
1 month after clinical resolution

Shigella
1. Common cause of bloody diarrhea with low infectious dose; children more
affected
 2. Pathogenesis: taken up in M cell and can escape to lamina propria and infect small-intestinal and colonic epithelial cells through basolateral
membranes that express bacterial receptors; can also directly modulate epithelial tight junctions to expose basolateral bacterial receptors
3. Most commonly affects left colon
4. Incubation: 1-7 days that begins as watery diarrhea that can progress to dysenteric phase
5. Treatment: anti-diarrheal meds contraindicated b/c may slow down bacterial clearance
6. HLA-B27 may cause uncommon complication of reactive arthritis; more in men
7. HUS is another potential complication

Escherichia coli
1. Forms: ETEC, EPEC, EHEC, EIEC, EAEC
2. EPEC proteins for lesions encoded on pathogenicity island LEE (locus of enterocyte effacement) encoding type 3 secretion system

Salmonella (S. enteritidis)

1. Virulence genes encode type 3 secretion system that transfer bacterial content to M cell and enterocytes which activate Rho GTPases and
trigger actin rearrangement to increase bacterial uptake can cause enlarged Peyer patches in terminal ileum and ulcers
2. Secrete chemoattractant (eicosanoid)
3. Typhoid fever/enteric fever by S. typhi (endemic) and paratyphi (travelers and developed areas)
4. Humans are sole reservoir
5. Clinical presentation: anorexia, abd pain, etc followed by short asymptomatic phase followed by fever and flu symptoms (febrile phase= more
likely to be able to detect disease)
6. S. typhi and paratyphi CAN disseminate via lymph and blood while S. enteritidis CAN’T
7. Typhoid nodules= foci of parenchymal necrosis with macrophage aggregates that may be in liver, bone marrow, lymph nodes
8. Diagnosis: Serologic tests not great; use blood culture

Pseudomembranous Colitis (usually C. diff)

1. C. diff toxins cause ribosylation of small GTPases like Rho that causes disruption of epithelial cytoskeleton,
tight junction barrier loss, cytokine release and apoptosis
2. Morphology: layer of inflammatory cells and debris at sites of colonic mucosal injury; damaged crypts are
distended by mucopurulent exudate that erupts to surface
3. Treatment= metronidazole, vancomycin

Mycobacterial Infection: M. tuberculosis, M. bovis, M. avium

1. M. avium more common tends to accumulate within cytoplasm and
distended lamina propria histiocytes and cause malabsorption
2. Can present with granulomatous disease with caseous necrosis (unlike
Crohn disease)

Novovirus: causes about ½ GI outbreaks worldwide

1. Common cause of sporadic gastroenteritis in developed countries via
contaminated food/water
2. See in cruise ships
3. Short incubation period and usually self limited disease

Rotavirus
1. Common cause of severe childhood diarrhea and diarrhea related deaths
worldwide
2. Protection at birth from mother’s IgG but decreases by 6 months where
risk of infection increases
3. Infects and destroys mature enterocytes in small intestine and absorptive
villus surface is repopulated by immature secretory cells leading to
osmotic diarrhea and decreased ability to absorb nutrients

Parasitic Disease
1. Ascaris lumbricoides: nematode; fecal-oral; eggs hatch in intestine and
larvae penetrate intestinal mucosa and migrate via splanchnic circ to liver
 2. Strongyloides: larvae live in soil and can penetrate unbroken skin; unique b/c don’t need larvae stage to occur outside human host leading to
autoinfection cycles that can persist for life
3. Nector americanus and Ancylostoma duodenale: hookworms; larval penetration through skin and initial dev in lungs then get swallowed, suck
blood in duodenum; leading cause of iron-deficiency anemia in developing world
4. Giardia lamblia: most common pathogenic parasite in humans spread via fecally contaminated water/food; cysts are chlorine resistant;
excystation happens in acid stomach environment and cause IgA and IL-6 response (immunocomp less effective in clearing) ; variable surface
antigen to evade immune response
5. Entamoeba histolytica: cause dysentery and liver abscess; target cecum and ascending colon mostly; induce apoptosis of colonic epithelium,
invade crypts and burrow to lamina propria to recruit neutrophils; cause flask shaped ulcer; generally liver is other major organ that is affected

Sexually Transmitted Diseases p. 704-712

Syphilis: Treponema pallidum (spirochete)

1. Source of infections= contact with cutaneous/mucosal lesion in sexual partner in
early stages of syphilis via minute breaks in skin/membrane
2. Congenital spread: transplacental (usually early in pregnancy)  usually during
early stage of disease where spirochete nunbers are higher
3. Dissemination via lymphatics
4. Stages
PRIMARY: chancre lesion at entry site, systemic
dissemination, host immune response; antibodies cross
react with host and treponemal antigens but fails to
erdicate
SECONDARY: resolution of primary within 4-6 weeks;
generalized lymphadenopathy and mucocutaneous
lesion that are highly infectious; if early-latent phase
lesions can resolve themselves, can form condylomata
lata lesions
TERTIARY: if still left untreated can become late latent
phase (usually after 1 year without treatment); develop
lesion in CV, CNS, less likely some other organs, gumma
are large areas of parenchymal damage and have
cnetral zone of coagulative necrosis surrounded by
dense fibrous tissue
Morphology: rich in plasma cells; endarteritis
Cancre indurated, hard, in males found in glans, corona, perineal region; in females in labia
or vagina; small and painless at first and enlarge to painless ulcer with well-defined margins
Skin lesions: palm, soles of feet
Staining: silver staining
Late Syphilis: Hutchinson triad= notched central incisors, interstitial keratitis with blindness,
deafness

TX: penicillin usually effective

Diagnosis: serology with anti or nontreponemal (cardiolipan) antibody test detected via
Veneral disease research Lab (VDRL) NOTE 15% are false-positive results due to
antiphospholipid antibody syndromes

Gonorrhea: (second most common to chlymadia)

1. Humans are only natural reservoir
2. Bacterial generally attaches to columnar or transitional epithelium via adhesion
molecules and pili
3. Exudates tend to be less obvious in females, but inflammation in Bartholin
glands is common
4. Disseminated infection is not common; more frequent in females and are
associated with strains resistant to lytic action of complement
5. Ophthalmia
neonatorum eye infection in newborn contracted in birth canal; not a
serious problem now b/c antibiobic ointment at birth

Nongonococcal Urethritis and Cervicitis

1. Most common forms of STD
2. Can be caused by many types of orgnaisms C. trachomatis, Mycoplasma
genitalium, Trichomonas vaginalis, Ureaplasma urealyticum
3. Most in US are caused by Chlymadia Trachomatis
4. C. Trachomatis: 2 forms= elementary body and reticulate body
A. Elementary body= infectious form; limited survival in extracellular
environemnt; taken up by host via receptor mediated endocytosis
B. Reticulate body: differentiation within host; uses host nutrients to form
more elementary bodies which target columnar epithelium
C. C. trachomatis is the most common cause of epididymitis in young men
D. Can cause lymphogranuloma venereum and reactive arthritis (Reiter
syndrome  more in HLA-B27 people)
E. Diagnosis: can’t culture use nucleic acid amplification test

Lymphogranuloma Venereum (LGV)

1. LGV= chronic ulcerative disease cuased by certain strains of C. trachomatis
2. Morphology= nonspecific urethritis or papular/ulcerative lesion in lower genitalia; proctocolitis (inflammation of recturm/colon), lesion with
mixed granulomatous and neutrophilic inflammatory response, regional lymphadenopathy and stellate abscess, can cause fibrosis that cause
lymph obstruction and lymphedema
3. Clinical Features= 1-2 weeks after exposure; primary lesions can heal on own but organisms can drain into lymph and cause necrotizing
lymphadenitis 2-6 weeks after exposure and cause abscess formation/rupture and dissemination
4. Diagnosis=serologic not specific, nucleic acid amp more commonly used
Chancroid (Soft Cancre) Haemophilus ducreyi
1. Acute ulcerative infection by Haemophilus ducreyi (gram-neg
coccobacillus)
2. One of the most common genital ulcers in Africa/Southeast asia and
is coafector in HIV transmission; may be underdiagnosed in US b/c
not widely tested for
3. Morphology= initially papule that breaks down to produce ulcer; on
microscopy is ulcer with superficial zone of neutrophilic debris and
fibrin over granulation tissue that has areas of necrosis and
thrombosed vessels; dense inflammatory infiltrate
4. Clinical Features: 4-7 days of inoculation; males on penis, female in
vagina or periurethral area; ulcers more painful in male; lymph nodes
may enlarge in 1-2 weeks; may become draining ulcer if untreated
5. Diagnosis: need rare culture; usually diagnose via clinical features

Granuloma Inguinale calymmatobacterium granulomatis (in Klepsiella

genus)
1. Chronic inflammatory disease uncommon in US
2. If untreated extensive scarring causing lymph obstruction
3. Diagnosis: PCR and culture not widely available
4. Morphology: abundant granulation tissue, can cause disfiguring
scars, typically spares lymph nodes (unlike chancroid), epithelial
hyperplasia at ulcer borders that may mimic carcinoma
(pseudoepitheliomatous hyperplasia), mix of neutrophils and
mononuclear inflammatory cells at base of ulcer
5. Stain= Giemsa and silver stains

Trichomoniasis (T. vaginalis)

1. Sexually transmitted protozoan that causes vaginitis
2. Trophozoite form adheres to mucosa and causes superficial lesions
3. Associated with loss of acid-producing lactobacilli
4. Usually asymptomatic in males
Genital Herpes Simplex
1. HSV-2 very common but rates of HSV-1 are increasing  genital (HSV-2) and oral (HSV-1) herpes
2. HSV-2 associated with genital herpes usually but recent rise in HSV-1 causing genital herpes too
3. Virus is readily inactivated at room temp esp in dry conditions
4. Morphology= painful, erythematous vesicle on mucose or skin (anorectal area is common); on hist can see intraepithelial vesicles with necrotic
cellular debris, neutrophils, and cells harboring viral inclusion
5. Cowdry type A inclusion: light purple homogeneous intranuclear structure surrounded by clear halo
6. Diagnosis: Stain inclusion with antibodies
7. HSV actively shed when person has fever, muscle ache, headache until mucosal lesions are completely healed (asymptomatic viral shedding can
occur up to 3 months after diagnosis though)
8. Recurrences are milder and shorter in duration than primary episode; generally non-life threatening in immunocompetent
9. Can cause neonatal herpes infection can be life-threatening; spread during birth process; can damage organs, CNS, 60% mortality
10. Diagnosis: viral culture or nuclei acid amplification
Human Papillomavirus Infection (HPV)
1. Causes squamous proliferations in genital tract condyloma acuminatum
and several precancerous lesions that can become carcinomas (especially in
cervix but can affect penis)
2. Condylomata acuminata= veneral warts that can occur on penis or female
genitalia (NOT the same as condylomata lata of secondary syphilis)
3. Can be transmitted to neonates during delivery and cause respiratory issues
4. Morphology: condylomata in males usually in coronal sulcus of inner surface of
prepuce, in females usually on vulva
Vulvitis
1. Contact irritant eczematous dermatitis: well defined erythematous weeping
and crusting papules and placts  can be caused as reaction to urine, soap,
antiseptic, etc
2. Common infection cuases HPV, vulvar intraepithelial neoplasia, HSV-1,2, N.
gonorrhoeae, Treponema pallidum, Candida (not sexually transmitted)
3. Vulvitis complication obstruction of excretory ducts of bartholin glands that
can cause painful dilation of glands (Bartholin cyst) and form abscess
Vaginitis
1. Common condition that is usually transient
2. Associated with leukorrhea (vaginal discharge) and many things can cause it
 3. Associated organisms: Candida albicans, Trichomonas vaginalis
4. Candidal vaginitis: curdy white discharge associated; associated with normal flora
5. At risk conditions: immunodeficiency, pregnancy, abortion, antibiotic, diabetes
6. T vaginalis: sexually transmitted, watery gray-green discharge
7. Trichomonas: can be identified in about 10% asymptomatic women
Cervicitis
1. Very common and may be associated with purulent vaginal discharge
2. Can be subclassified as infectious and noninfectious
3. Organisms: strep, staph, enterococci, e. coli, candida
4. Chlamydia trachomatis, Ureaplasma urealyticum, T. vaginalis, Neisseria gonorrhoeae, HSV-2, HPV
5. C. trachomatis = most common of the pathogens causing cervicitis
6. Treatment: empirically with antibiotics that are active against chlamydia and gonococcus
Endometritis
1. Acute or chronic: acute neutrophil predominates, chronic lymphoplasmacytic infiltrate predominates
2. Common component of PID (seen in gonorrhoeae, C. trachomatis)
3. Histology: neutrophil infiltrate in superficial endometrium coexisting with stromal lymphoplasmacytic infiltrate
4. Can see lymphoid follicles in chlamydia infection
5. TB can cause endometritis (more in immunocompromised)
6. Could also happen from retained products of conception after miscarriage or presence of foreign body (like intrauterine device)
7. Clinical presentation: fever, abdominal pain, menstrual abnormalities
Fallopian Tubes
1. Most common disorder of fallopian tubes is inflammation (salpingitis) often occurring in pelvic inflammatory disease
2. Almost always caused by infection (common organisms= gonorrheam nongonococcal chlamydia, mycoplasma hominis, coliforms, strep/staph
more in postpartum setting are major offenders)
3. Can disseminate
4. Tuberculosis salpingitis is less common and often occurs with endometritis
5. Adherence of inflamed tube to ovary/adjacent ligamentous tissue can cause tuboovarian abscess and cause adhesions

Infections of the CNS p. 862-865

General Routes to CNS
1. Hematogenous spread via arterial blood supply=most common means of entry (venous
possible)
2. Direct implantation of microorganism usually via penetrating trauma or iatrogenic (less
common)
3. Local extension from infection of skull/spine
4. Peripheral nerves as path of entry esp in viruses
Epidural/Subdural Infections
1. Usually from direct local spread (bacteria/fungus)
2. Epidural often from adjacent focus like sinusitis or osteomyelitis
3. Subdural infection from skull or air sinuses and spread here and cause subdural
empyema without affecting arachnoid/subarachnoid space
4. Empyema may be treated via surgical drainage and heal with resolution occurring from
dural side
Meningitis
1. Inflammatory process involving leptomeninges within subarachnoid space
2. Meningoencephalitis if spread to brain
3. Non-infectious forms= chemical meningitis, carcinomatous meningitis
4. Infectious general forms= acute pyogenic (usually bacterial) and aseptic (viral usually),
chronic (TB, spirochetal, or fungal)

Acute pyogenic high neutrophils, elevated protein, reduced glucose

Viral moderate protein elevation, lymphocytosis, normal glucose
Fungal: can be chronic or parenchymal cryptococcus neoformas (can be fulminant and fatal), CSF
shows few cells, elevated protein, and mucoid encapsulated yeast on India ink stain (soap bubble
appearance); Histoplasma capsulatum commonly involves CNS, causes basilar meningitis with
elevated CSF protein, mildly decreased glucose, mild lymphocytic pleocytosis
Coccidioides immitis usually in cases of disseminated infection; high fatality w/o tx
Chronic:
TB: moderate increase in CSF cellularity with mononuclear cells/mix, very high protein, glucose
reduced/normal; may form intraparenchymal mass (tuberculoma) and arachnoid
fibrosis that can cuase hydrocephalus from intereference with CSF absorption
Spirochetal: Neurosyphilis patterns include meningovascular in base of brain, paretic from
parenchymal involvement (mental and physical function loss and dementia), Tabes
doralis; Borrelia burgdorferi infecition is called neuroborreliosis in the brain
Brain Abscess usually from bacteria
1. Causes: direct implantation, local extension from adjacent foci, hematogenous spread
2. Predisposing conditions= acute bacterial endocarditis releasing septic emboli, cyanotic congenital heart disease (right/left shunt) that cuases loss
of pulm filtration of organisms, chronic pulm infection
3. Abscess= discrete destructive lesion with central liquefactive necrosis surrounded by rim of vascularized granulation and fibrous tissue
4. Outside capsule= zone of reactive gliosis
5. TX: antibiotics and/or surgery

Parasite Readings: p. 345-346, 349-351, 357-359, 452-453, 434-435, 619-620, 868, 650-651
Protozoa and Helminths p.345-346
1. Protozoa= single celled eukaryotes
A. Can replicate intracellularly or extracellulaly depending on the species
B. Most prevelant pathogenic intestinal protozoans= entamoeba histolytica and giardia lamblia ingested as nonmotile cysts that become
motile trophozoites that can attach to intestinal epithelium
C. Bloodborn protozoa transmitted via insect vector where they replicate first then are passed to human hosts
2. Helminths= parasitic worms that are highly differentiated multicellular organisms with complex life cycles
A. Life cycle patterns: many alternate between sexual replication in a definitive host and asexual multiplication in intermediate host or vector
B. Forms: immature, adult, asexual larval
C. Normally don’t multiply once in humans, but can produce eggs or larvae that are often passed via stool
D. Groups of Helminths= Roundworms, Tapeworms, Flukes
Roundworms (nematodes)= circular in cross section and nonsegmented; intestinal or tissue types
Tapeworms (cestodes)= have head (scolex) and ribbon of multiple flat segments (proglottids); absorb nutrient via tegument
and don’t have digestive tract; generally reside in human intestine and can cause cystic disease
Flukes (trematodes)= leaf shaped flatworm with prominent sucker to attach to host
3. Ectoparasites= insects (lice, bedbug, flea, arachnid) that cause disease via biting or attaching to or living on skin
A. Mouth parts might be found on bite sites and cause inflammatory response
B. May serve as vector for other pathogens (Ex: Lyme disease and Ixodes tick)
Specific Parasite and Helminth Infections: 452-453, 434-435, 619-620, 868, 650-651
Malaria
1. Can be caused by 5 types of protozoa most important is Plasmodium falciparum: causes tertian
malaria which has a high mortality rate
2. Other plasmodium species: P. malariae, P. vivax, P. knowlesi, P. ovale cause more benign disease
than P. falciparum
3. Pathogenesis:
A. Mostquito bite saliva introduces sporozoites which infect liver cells
B. In liver cell, multiply to form schizont containing merozoites
C. After days-weeks depending on plasmodium species, infected hepatocytes release merozoites
D. Merozoites infect RBCs
E. Intraerythrocytic paracytes can either reproduce asexually to make more merozoites or from
gametocytes that can infect more mosquitoes
F. Asexual reproduction in RBCs forms trophozoites, and the asexual phase is completed when
trophozoites form new merozoites that escape via RBC lysis
4. Fatal falciparum malaria: usuall involves vessels of brain cerebral malaria
5. Malaria effect on RBC: RBCs normall express neg charge to prevent adherence to endothelium; P.
falciparum induces positive charges surface knobs to express on RBC increasing binding to
 endothelium (adhesion molecule binding ICAM mainly) which trap RBC in postcapillary venules that can cuase vessel to become engorged and
occuded

Clinical Features
1. Groups of new merozoites are released from RBC at intervals of 24 hr for P. knowlesi and
48hrs for P. vivax, ovale, and falciparum, and 72 hours for P. malariae
2. Symptoms= episodic shaking, chill, fever at each release interval
3. Cerebral malaria (not commom) associated with P. falciparum and progresses rapidly;
death in days/weeks
P. falciparum more often causes chronic course that can cause blackwater fever (red blood cells burst
in the bloodstream (hemolysis), releasing hemoglobin directly into the blood vessels and into the
urine, frequently leading to kidney failure)
4. Rise in drug resistant strains of P. falciparum
Myocarditis
1. Diverse group of clinical entities where infectious agents/inlammatory processes target myocaridum
2. Most common causes in US= coxsakieviruses A an B and other enteroviruses
3. Other potential causes: CMV, HIV
4. Infection mechanism: may kill cells directly, most cause injury via immune response against virally
infected cells; some cause cross reacting response against mysin heavy chain
5. Protozoa causes: Trypanosoma cruzi Chagas Disease (mainly in S. America), Toxoplasma gondii
effect more on immunocompromised
6. Helminth cuases: Trichinosis= most common helminthic to involve cardiac
7. Lyme disease: involves heart in 5% cases, usually self-limited conduction system disease that often
requires temporary pacemake
8. Noninfectious causes: SLE, polymyositis, drug hypersensitivity
Clinical Features
1. Broad asymptomatic to heart failure/arrhythmias
2. General signs= fatigue, dyspnea, palpitations, pain, fever

GI Parasitic Disease
1. Ascaris lumbricoides: nematode that infects via fecal-oral where eggs are ingested and hatch in intestine; larvae penetrate intestinal mucosa and
can migrate to splanchnic circ to liver and cause heptic abscess; can also reach lung (Ascaris pneumonitis) and aspirate and recirculate through
body diagnose via eggs in stool detection
2. Strongyloides: larvae in soil can penetrate unbroken skin and migrate to lungs to get swallowed and mature to adult worm in intestines unique
b/c don’t need to reach ovum or larval stage outside of human and instead, the eggs are capable of hatching in intestine to release larvae that
penetrate mucosa AUTOINFECTION risk and often persists for life; can be serious in immunocompromised
3. Necator americanus and Ancylostoma duodenale: hookworms that enter via larval penetration through skin that migrate to lung to get
swallowed; in duodenum, mature to adult and can attach to mucosa and suck blood and reproduce LEADING CAUSE of iron deficiency anemia
in developing world; diagnose via detection of eggs in stool
4. Giardia lamblia: protozoa; MOST COMMON pathogenic parasite in humans; spread in fecally contaminated food/water; can cause acute or
chronic malabsorptive diarrhea; acidic environemnt of stomach causes excystation and trophozoite release; normally secretory IgA and IL-6 is
used to clear infection; giardia can modify surface antigens to persist for long time and reduce expression of brush border enzymes and stim
apoptosis of small intestinal epithelial cells; NONinvasive; diagnose via stool antigen assay
5. Entamoeba histolytica: causes amebiasis, spread via fecal-oral, cause dysentery and liver abscess; Targets cecum and ascending colon most;
cause dysentery when amebae attach to colonic epithelium and induce apoptosis and invade crypts to burrow into lamina propria to cause an
inflammatory response; liver abscess has low inflammatory reaction at margins and have shaggy fibrin lining abscess can persist after acute
intestinal illness and could reach heart/other organs can present with abd pain, bloody diarrhea, weight loss

Cysticercosis: Tenia solium tapeworm

1. Consequence of end-stage infection of Tenia solium
2. Larvae leave GI lumen and spread to brain and subarachnoid space
3. Manifest usually as mass lesion and can cause seizure; symptoms get worse at first with therapy when encysted organisms die and stim an
inflammatory reaction in surrounding brain
4. Organism’s body wall and hooklets on mouth parts are commonly recognized

Amebic Meningoencephalitis
1. Associated organisms=Naegleria fowleri, Acanthamoeba
2. N. fowleri causes rapidly fatal necrotizing encephalitis
3. Acanthamoeba chronic granulomatous meningoencephalitis

Cerebral Toxoplasmosis
1. Risk groups=immunocompromised and newborns (esp via transplacental transmission)
2. Triad of consequences= chorioretinitis, hydrocephalus, intracranial calcification
3. Clinical symptoms subacute in most adults and can evolve over weeks
4. Inflammation can cuase breakdown of BBB and cuase edema
Hepatic Bacterial/Parasitic/Helminthic Infections
1. Often cause abscess, hepatomegaly, upper quadrant pain
2. May need surgery for larger lesions
General Mechanisms:
1. Ascending infection from gut/biliary tract; usually via gut flora during biliary tract occlusions
2. Vascular seeding usually via portal system via GI
3. Direct invasion from adjacent sources (bacterial cholecystitis)
4. Penetrating injury
Bacteria: S. aureus in toxic shock, S. typhi in Typhoid fever, Treponema pallidum

Schistosomiasis: common cause of noncirrhotic portal hypertension adult worms in gut produce eggs that can reach portal circ and lodge to induce
granulomatous reaction and fibrosis

Entamoeba Histolytica: cause dysentery and can ascend to liver via portal circ and cause secondary foci that can progress to large necrotic area to form
amebic liver abscess (more common in right lobe of liver) abscess cavity contains necrotic liver cell but no neutrophils

Liver Fluke: more in SE Asia, associated with cholangiocarcinoma organisms= Fasciola hepatica, Opisthorcis, Clonorchis sinensis

Echinococcal Infection: can cause formation of intrahepatic hydatid cysts that produce symptoms via pressure on surrounding structures or after rupture