LOs: 28-32 Flashcards
28 Microbial strategies to evade phagocyte function:
Prior to phagocytosis
After phagocytosis
- Extracellular pathogens
- Production of exotoxins to kill/incapacitate phagocytes
- Production of slippery capsules or antiphagocytic surface proteins
- Intracellular pathogens
- Production of moleucles to inhibit phagosome:lysosome fusion
- Escape phagosomes
- Resist killing inside phagocytes
28 Antiphagocytic strategies used by extracellular pathogens:
Proteases
- Purpose
- Most common target
- Producers (4)
- Other (2)
Toxins
- Purpose
- Examples (2)
- Other (1)
- Degrade immunoglobulins to block opsonization
- IgA
- N. gonorrheae, N. meningitidis, H. influenzae, S. penumoniae
- Fabulation: coats Fab fragments, molecular mimicry, no opsoinzation
- Protein A (staph) or G (S. pyogenes): binds Fc region, molecular mimicry, no opsonization
- Affect phagocyte function to inhibit phagocytosis
- Streptolysin O & leucocidins
- Don’t need to kill
28 Capsules:
Composition (2)
How capsules interfere w/ phagocytosis (5)
- Polysaccharides (repeating glucose or glucuronic acid)
- Polypeptide (Bacillus anthracis, Yersinia pestis)
(1) Physically slipper, difficult for phagocytes to grab onto
(2) Bind inhibitory factors that block complement
(3) Don’t bind factors for complement
(4) Contain enzymes that block or inactivate complement
(5) Produce capsules that act as decoys & mop up antibodies
29 Streptococcus pneumoniae:
Biologic Characteristics
- Type
- Hemolysis
- Catalase
- Aerobe/Anaerobe
- Shape
- Classified by…
Reservoir/Colonization (3)
Transmission (2)
Pathogenesis (2)
Virulence Factors (5)
Importance of Capsule
- Microbiology
- Pathogenesis
- Immunity
Clinical Disease (2)
Therapy & Resistance
Prevention
BC
- Gram+ cocci
- Alpha hemolytic
- Catalase negative
- Facultatively anaerobic
- lancet shaped coccus
- Capsule
R/C
- Humans
- Upper respiratory tract
- Young, crowding, ethnic groups (African Americans, Native Americans)
T
- Respiratory droplets
- Close contacts
P
- Colonize: transmitted by droplets, prevent colonization
- Infect: aspirate to lower airway, enter bloodstream, infect locally or systemically
VF
- Adherence: neuraminidase
- Immune evasion: IgA protease
- Inflammation: LTA
- Immune evasion: capsule
- Defense damage: pneumolysin
IoC
- Capsular serotypes define pneumococcal strains (acapsular = avirulent)
- Prevents phagocytosis, inhibits complement
- Infection results in specific immunity to the capsular strain, immune deficiency compromises IgG production
CD
- Respiratory Disease: upper (otitis media, sinusitis, conjunctivitis) & lower (CA-pneumonia, death)
- Disseminated: bacteremia, meningitis, bacterial peritonitis, septic arthritis, osteomyelitis
T&R
- Beta-lactams for gram+ thick cell wall
- Resistance from PBP changes, overcome w/ more drug
P
- Immunization for children >2
- Conjugation vaccine (attached polysaccharide to protein carrier) for children
29 Streptococcus pneumoniae Pathogenesis:
Upper respiratory tract
- Protect
- Attack
Trachea and bronchi
- Protect
- Attack
Small airways & alveoli
- Protect
- Avoid phagocytes
How symptoms reflect pathogenesis
- Fever
- Dyspnea
- Chest pain
- Cough
- Protect: specific IgA & innate immunity
- Attack: IgA protease & capsule
- Protect: cough & innate immunity
- Attack: hijack viral coinfection (destroys ciliated cells & compromised mucociliary elevator)
- Protect: neutrophils & specific Ig opsonize & phagocytose bacteria
- Avoid phagocytes: capsule & pneumolysin
- Inflammatory cytokine release from LTA & pneumolysin
- Inflammation & cellular debris ina lveoli
- Lung parenchyma inflames pleural lining
- Fluid in alveoli, debris in bronchi
29 Staphylococcus aureus:
Biologic Characteristics
- Type
- Growth
- Catalase
- Coagulase
Reservoir/Colonizes
Transmission (2)
Pathogenesis (3)
Exotoxins (4)
Adherence (2)
Cell wall components (4)
Clinical Disease (5)
Therapy
Prevention
BC
- Gram+ cocci in clusters
- Beta-hemolytic on blood agar, golden colonies on chocolate agar
- Catalase+ (breaks HOOH into H2O & O2)
- Coagulase+ (clumps in presence of serum)
R/C
- Humans (carriers common)
- Warm, moist sites (nares, axilla, groin, perirectal area)
T
- Person to person
- Durable on fomites
P
- Attack w/ multiple adhesion molecules
- Lots of exotoxins
- Cell wall components (LTA, peptidoglycan)
E
- Hemolysins (cytotoxins)
- Enterotoxins (superantigens)
- Exfoliative epidemolytic (scalded skin syndromes)
- Toxic shock syndrome toxin
A
- Multiple, overlapping (MSCRAMMs)
- Protein A prevents opsonization
CWC
- Polysaccharide capsule: inhibits phagocytosis
- Peptidoglycan: triggers cytokine release
- Lipoteichoic acid: inflammatory
- Resistance molecules: altered PBP & beta-lactamases
CD
- Skin & soft tissue disease (*abscess, cellulitis, osteomyelitis, myositis, septic arthritis, impetigo, folliculitis, furuncles, fasciitis)
- Disseminated disease (*toxic shock syndrome (intoxication), septicemia, endocarditis)
- Device infections (*central venous catheters, implanted devices, post-surgical infections)
- CA-MRSA (presence of Panton-Valentine Leukocidin (PVL) gene)
- Superantigens (food poisoning)
T
- Altered PBP & beta-lactamases: resistance in penicillins, cephalosporins, macrolides, & quinolones
- Use: vancomycin, linezolid, daptomycin
P
- No Vaccine
30 Antigenic Variation:
Definition
Why it exists (2)
Phase variation definition & examples (5)
Antigenic drift definition, mechanism, & examples (3)
Antigenic shift definition, mechanism, & examples (3)
systematic changes or variations in proteins or other structures on the surface of pathogens to avoid elimination by the adaptive immune system of the host
- avoidance of antibodies
- for extracellular pathogens
- evolution in response to the immune response
- selective pressure by antibodies to change extracellular protein to avoid being killed
switching on or off genes that produce a phenotype
- Salmonella flagella
- E. coli fimbriae
- E. coli pap pilus operon
- molecular switch (inversion), mutations, methylation
- slipped strand mispairing
accumulation of mutations that alter antigenic composition
- error prone replication
- influenza virus, rhinovirus, HIV
abrupt change in surface antigen
- gene conversion, rearrangement, reassortment
- influenza virus, Neisseria gonorrhoeae, Trypanasoma brucei
30 Influenza Virus
Biology
- Family
- DNA/RNA
- Types
Principal determinant of an outbreak
Pathogenesis
- Infects…
- Important proteins (2)
- Protease
- Envelope
- Segments
Clinical Disease
- Infection
- Transmission
- Most susceptible
- Symptoms
- Complications
Diagnosis
Treatment
Vaccines
B
- Orthomyxoviridae
- (-)ssRNA w/ segmented genome
- Types A, B, & C (A most important)
PD
degree of match in specificities between surface antigens and antibodies against them that exist in the population
P
- respiratory epithelium
- (1) Hemagglutinin (HA) protein: binds carbohydrates, causes fusion for entry into cell, releases viral RNA inside cell
- (2) Neurominidase: releases new viral particles to infect new cells, prevents viral aggregation
- Cleaves HA to HA1 & HA2, allows viral gene segments to enter cell for viral replication
- host cell derived
- 8 RNA segments make up genome for reassortment & antigenic shift
CD
- respiratory
- respiratory droplet inhalation
- children & elderly
- *fever, cough, chills, headache, myalgia, malaise, anorexia
- primary influenza viral pneumonia, secondary bacterial pneumonia (return of symptoms, most often S. pneumoniae or H. influenzae), croup, exacerbation of chronic disease\
D
- nasal or throat swabs
T
- amantadine & rimantadine (for influenza A, interacts w/ M2 protein)
- oseltamivir & zanamivir (neuraminidase inhibitors)
V
- inactivated virus & live attenuated: stimulate antibodies against HA & NA
- trivalent vaccine: 2 A, 1 B
- live attenuated: intranasally
- effective if there is good antigenic match between vaccine virus and epidemic virus
- grown in chicken eggs, so can’t be given to ppl w/ severe egg allergies
30 Antigenic Variation & Influenza:
Antigenic Drift (4)
Antigenic Shift (2)
“Bird Flu”
AD
- minor changes in antigens due to accumulations of point mutations during replication in the human host
- involves HA & NA
- poor fidelity of RNA transcription
- antibody mediated selection: antibody generated by “parent” virus doesn’t neutralize “drifted” virus as effectively, new virus predominates
AS
- major changes in viral genome as a result of “reassortment” of HA or NA
- two influenza viruses present within the same host
exchange segments
BF
- H5N1 in many avian species
- very virulent
- high reassortment
- usually doesn’t infect humans
- pigs bind same sialic acid form as humans, so adaptation of avian virus may occur in pigs
- no vaccine b/c of antigen drift
- outbreak of avian flu: antigenic shift (HA not seen in humans) & drift (virulent/pathogenic for humans)
30 Neisseria gonorrhoeae:
Biology
- Type
- Oxidase
- Growth
- reservoir
Symptoms
- Male
- Female
- Neonatal
Diagnosis/Treatment
Virulence Factors (3)
Pathogenesis
- Attachment/penetration
- Pili
- Antigenic variation
- Phase variation
Other
- Immunity
- Protection
- Vaccine
B
- gram(-) diplococci (STI)
- oxidase +
- Thayer-martin media
- human pathogen
S
- M: acute urethritis, urethral dischare, dysuria, most resolve
- F: asymptomatic or cervicitis, urethritis, PID (bilateral abdominal pain, tenderness fever)
- N: conjunctivitis
D/T
- D: culture
- T: cephalosporins (ceftriaxone)
VF: phase & antigenic variation
- Pili: attachment
- Opa proteins: adherence
- LOS
P
- attaches to epithelial cells, penetrates to submucosal tissues
- PilS (recombined subunits) contain variable regions, transferred to PilE (expression site) for gene conversion
- antigenic variation: each PilS is different
- phase variation: pilus turns off if non-functional PilE/S combination occurs
O
- no immunity to reinfection
- antibodies aren’t protective
- no vaccine
30 Trypanosoma brucei:
Disease Specifics
- Causes…
- Type
- Transmission
- Inhabits…
- Course
Pathogenesis
- Survival
- Antigenic variation requirement
Antigenic variation occurs by… (5)
Diagnosis (3)
DS
- African trypanosomiasis (Sleeping sickness)
- flagellated protozoan parasite
- tsetse fly in Africa
- lives within the blood of mammalian host
- (stage I) chancre –> systemic spread –> fever, anemia, edema, rash –> (stage II) CNS
P
- survive in bloodstream
- requires antigenic variation of variable surface glycoprotein (VSG) which surrounds parasite (major protein on surface); as antibodies are raised against one type of VSG, new parasite with antigenically distinct VSG emerges
AV
- gene conversion
- homologous recombination
- telomeric exchange
- turning on a new expression site
- escape from antibodies
D
- demonstration of parasite
- blood smear (stage I)
- CSF examination (stage II)
30 Trypanosoma cruzi:
Causes…
Stages (2)
Antigenic variation
Pathogenesis
Chagas disease in South America
Blood stage (trypomastigote) and intracellular stage (amastigote)
Does NOT undergo classical antigenic variation
Evades complement to avoid killing in the blood
31 Intracellular environment for microbial pathogens:
Entry (2)
Phagosome & phago-lysosome fusion (5)
Evasion of phagolysosome fusion (5)
How macrophage activation happens (2)
Consequences of macrophage activation (4)
E
- Invasins: entry into non-phagocytic cells, bacterial proteins that bind to or induce uptake of the organism by a host cell
- Phagocytosis macrophages: complement receptor, mannose receptor, glucan receptor, phagocytosis
P
- acidification
- defensins
- iron-poor
- antibacterial enzymes
- reactive oxygen & nitrogen intermediates
E
- prevent fusion
- modify vacuole
- escape vacuole
- tolerate environment in vacuole
- reduce acidification
H
- T-cell mediated cytokines (IFN-gamma & TNF)
- signaling through pattern recognition proteins (like TLR)
C
- reactive oxygen intermediates (ROIs)
- reactive nitrogen intermediates (RNIs)
- increased phagosome-lysosome fusion
- increased MHC class II
31 Intracellular Pathogen Detection by T Cells:
How T cells eliminate intracellular pathogens
Strategies for avoiding detection by CD4 T cells (2)
Strategies for avoiding detection by CD8 T cells (5)
CD4 or CD8 T cells recognize pathogens
CD4
- downregulate MHC class II expression (M. tuberculosis)
- degrade MHC class II alpha chains (HCMV)
CD8
- downregulate MHC class I expression (most viruses)
- prevent MHC class I transport (adenovirus)
- prevent peptides from being loaded into MHC class I (herpes virus)
- sequester proteins in the trans-golgi network (HIV)
- direct MHC class I for degradation (CMV)
31 Listeria monocytogenes:
Causes… (2)
Biologic Characteristics
- Type
- Aerobe/Anaerobe
- Intracellular/Extracellular
- Catalase
- Oxidase
- Growth
Reservoir/Transmission
- Type or pathogen
- Found in…
- Reservoir
- Transmission
Virulence Factors
- Taken up into…
- Produces…
- Replicates & forms…
Other
- Diagnosis
- Prevention
- Treatment
C
- meningitis in babies
- bacteremia or meningitis in immunocompromised
BC
- gram+ rod
- facultative anaerobe
- intracellular
- catalase +
- oxidase (-)
- incomplete beta-hemolysis
R/T
- food borne (processed foods not reheated, soft cheeses)
- soil
- zoonotic
- also mother to fetus (crossing placenta)
VF
- phagosome
- a toxin (listeriolysin O; gene: hlyA) which breaks open the phagosome and allows the bacterium to enter the cytoplasm
- an actin tail by actA which propels the microbe around the cell, and sometimes into a neighboring cell, allowing cell to cell spread without leaving the cell (eliminates exposure to antibodies)
O
- D: clinical specimen of CSF/blood, gram stain
- P: don’t ingest processed foods that aren’t reheated, including soft cheeses
- T: ampicillin or TMP/SMX
31 Legionella pneumophila:
Clinical Relevance
- Conditions (2)
- At risk
- Symptoms
Biologic Characteristics
- Type
- Aerobe/Anaerobe
- Intracellular/Extracellular
- Growth
- Other
Reservoir/Transmission
- Natural habitat
- Growth
- Transmission
- Lives…
Virulence Factors
- Survival
- Virulence Genes (2)
- Other
- Other
Other
- Diagnosis
- Prevention
- Treatment
CR
- Legionnaires’ disease & Pontiac fever
- in elderly, smokers, & immunocompromised
- cough, fever, diarrhea
BC
- gram(-) rod or coccobacillus
- aerobe
- intracellular
- fastidious, requires special medium
- single flagellum, muliple fimbriae/pili
R/T
- water (chlorine-tolerant)
- as a biofilm
- aerosolized from contamianted water systems, air conditioners, humidifiers, etc. (not human to human)
VF
- intracellular
- (1) replication phase (abundant nutrients) & (2) transmission (limiting nutrients)
- Inhibition of phago-lysosome fusion by remodeling phagosome to look like the
RER by recruiting host secretory vesicles from the ER
- Type IV secretion system may allow rapid secretion of effector molecules to modulate phagosome and prevent fusion with lysosomes
O
- D: culture of sputum or bronchoalveolar lavage fluid, chest radiograph, & urinary antigen test
- P: survey hospital water sources, disinfect cooling towers
- T: macrolides, quinolones
31 Plasmodium falciparum:
Clinical Features
- Causes…
- Hallmark
- Most severe
Biologic Characteristics
- Type
- P. falciparum
- P. vivax & P. ovale
- P. malariae
Life Cycle
- Infection
- Traveling
- Differentiation
- Dormancy
- Invasion
- Other differentiation
- Symptoms
Reservoir/Transmission
- Reservoir
- Transmission
- Resistance
- Reinfection
- Immunity
- At risk
Virulence Factors
- Binding
- Protein
- Causes…
- Results in…
- Sequestration
- Circumsporozoite
Other
- Diagnosis
- Prevention
- Treatment
CF
- malaria
- cyclic fevers as RBCs lyse to release merozoites: fever paroxysm (cold/chilling stage), hot stage (high fever), sweating stage (sweating, fatigue, resolution of fever)
- due to P. falciparum: microvascular disease, hypoglycemia, cerebral malaria, renal failure, pulmonary edema, anemia, multiorgan failure, coma
BC
- protozoan
- most deadly, tropical regions, mosquitoes year round, infect RBCs, no dormant liver stage (hypnozoites, no relapse
- less severe, more temperate zones, mosquitoes during warmer months, hypnozoites (latent liver form), late relapse, only infects reticulocytes
- few serious cases
LC
- sporozoites from mosquito infects humans (through skin)
- travels to liver & invades hepatocytes
- differentiates into tissue shizonts & multiplies
- P. vivax & P. ovale remain dormant
- merozoites invade RBCs which are lysed so merozoites can infect more RBCs
- some differentiate into gametocytes & are taken up by mosquitoes to complete the sexual stage
- Occur during blood stage, not liver stage
R/T
- vector borne (anopheles female mosquito)
- mosquito-human-mosquito
- sickle cell anemia confers some resistance (abnormal RBC shape)
- humans can be reinfected multiple times
- partial immunity builds up over time & reduces chance of severe malaria
- unexposed persons, travelers, children, & pregnant women
VF
- parasitized RBCs bind to endothelial cells in capillaries & cause microvascular disease
- PfEMP (protein prodcued by P. falciparum) causes binding of RBC to many different host proteins
- causes “knobs”on P. falciparum parasitized RBC, allows binding & sequestration of RBC
- obstructions to tissue perfusion & multiorgan failure
- sequestration avoids clearance & benefits parasite growth
- circumsporozoite protein allows sporozoites to bind to & invade hepatocytes (site of parasite replication)
O
- D: blood smear (ring only seen in P. falciparum)
- P: bed nets, sprays, antimalarial drugs
- T: drugs, supportive care
32 Biochemical actions of the following bacterial toxins:
a. Tetanus toxins
b. Botulinum toxins
c. Cholera toxin and E coli heat-labile enterotoxins; E. coli heat-stable enterotoxin
d. Shiga toxin
e. Streptolysin O and listerolysin O
f. Diphtheria toxin and Pseudomonas exotoxin A
g. Staphylococcal superantigens
h. C. difficile toxins A and B
i. Pertussis toxin (later)
j. Staph. aureus alpha toxin
a. Travels up motor neurons into CNS, blocks release of inhibitory NTs (glycine), constant stimulation of motor neuron & muscle, spastic paralysis (neurotoxin)
b. Acts at NMJ, blocks release of excitatory NTs (ACh), muslces don’t contract, flaccid paralysis (neurotoxin)
c. Altering intestinal cyclic nucleotide levels (enterotoxin)
d. BLocks protein synthesis by inactivating ribosomes (enterotoxin)
e. Gram+ pathogens produce cholesterol-dependent cytolysin (hemolysin)
f. Toxins catalyze an ADP-ribosylation of Elongation Factor 2, shut down protein synthesis)
g. Superantigen induces an inflammatory response (enterotoxin)
h. Affecting tight junction permeability: monoglucosyltransferase (target rho proteins), also proinflammatory
i.
j. Disrupting membrane function by forming pores (hemolysin)
32 Enterotoxins:
Effects
Importance for human disease
- Diseases
- At risk
- Transmission
- Treatment
GI (diarrhea, abdominal cramps, vomiting)
- Diarrheal (morbidity, death)
- Children
- Fecal-oral
- Restoration of fluid/electrolyte balances
32 Neurotoxins:
Potency/Lethality
Two most important bacteria producing neurotoxins
Molecular action of botulinum & tetanus toxins (4)
Clinical use of botulinum toxins (2)
Very potent & lethal
Clostridium botulinum and Clostridium tetani
- proteolytic activity
- cleaves neuronal proteins
- prevents synaptic vesicle docking
- inhibits NT release
- inappropriate muscle contractions
- cosmetic purposes
32 Clostridium botulinum:
Biologic Characteristics
- Type
- Aerobe/Anaerobe
- Types
Reservoirs/Transmission (2)
Virulence Factors (2)
Types (5)
Disease
- Symptoms
- Symptoms due to…
Treatment (2)
Prevention (4)
BC
- gram+ spore-forming rod
- anaerobic
- 9 types based on serotypes (A-H)
R/T
- soil
- home-prepared foods (esp in Alaska)
VF
- Botulinum toxin (type A most serious, persists the longest in the neuron)
- Spores: heat-resistant (toxin is heat-sensitive)
T
- classical foodborne botulism: contaminated foods, intoxication
- infant botulism: most common form of botulism in US, GI tract colonized, infection
- adult infant botulism: GI tract colonized, disrupt normal flroa, toxin production
- wound botulism: toxin grows in wound
- class A select agent: bioterrorism, biowarfare
D
- double vision, swallowing difficulties, flaccid paralysis, breathing problems, constipation (infants)
- botulinum toxin
T
- botulinum antitoxin
- supportive therapy
P
- prepare foods carefully
- don’t feed infants honey
- heating inactivates heat-labile neurotoxin
- vaccine (special use)
32 Hemolysins (membrane active toxins):
Affect…
Disrupt…
Bacteria that produce hemolysins
WBCs & RBCs
Membrane function by forming pores (S. aureus alpha toxin) or by enzymatic action (C. perfringens alpha toxin)
- gram+ pathogens
- Staphylococcus aureus
- Uropathogenic E. coli
- C. perfringens
32 Pseudomonas aeruginosa:
Biologic Characteristics
- Type
- Aerobe/Anaerobe
- Oxidase
- motility
- Other (3)
Virulence Factors (7)
Transmission/Reservoir
- Causes…
- Penetration
- Other
Disease
- General
- In healthy ppl…
- Septicemic infections…
- Infections this is important for
Prevention (3)
Treatment
BC
- gram(-) rod
- aerobic
- oxidase +
- motile
- hardy, antibiotic resistant
- makes blue-green pigments
- extracellular
VF
- exotoxin A: necrosis
- endotoxin: shock
- pili: adhesion
- enzymes (proteases, elastase): tissue damage
- leucocidin: inhibits/kills WBCs
- phospholipase C: hemolysin, affects WBCs
- capsule (slime layer/biofilms): antiphagocytic, contributes to cystic fibrosis, inferferes w/ antibiotic action
T/R
- causes diseases through wounds, surgical incisions, burns, etc.
- can’t penetrate the epithelium
- ubiquitous, nosocomial
D
- opportunistic
- WBCs can resist disease
- often involve shock
- cystic fibrosis, burn infections, catheters (UTIs), & IV lines
P
- sanitation/hygiene: keep wound & room clean, keep IV lines & catheters to a minimum
- topical agents on wounds
- no vaccine
T
- supportive therapy for shock
- antibiotic resistant
32 Superantigens:
Examples (3)
Provides…
Leads to…
- toxic shock syndrome toxin
- staphylococcal enterotoxin
- streptococcal erythrogenic toxins (scarlet fever)
a way for gram+s to induce shock, fever, etc.
production of cytokines (ex. TNF & IL-1) that cause systemic effects such as shock
