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
