Infectious diseases Flashcards

(158 cards)

1
Q

Selective Toxicity

A

An Ideal antibiotic agent targets a biological mechanism specific top the pathogen.
Easier to achieve with prokaryotes and viruses.

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2
Q

Minimum inhibitory concentration (MIC)

A

The lowest concentration of a compound that inhibits growth of the microorganism in vitro.

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3
Q

Minimum Bactericidal Concentration (MBC)

A

The lowest concentration of a compound needed to kill 99.99% of microorganisms in a colony count in vitro.

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4
Q

Other important pharmacokinetic factors with antibiotics

A

Ability to reach site of infection

Difficult areas to reach include bone, CNS, adipose.

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5
Q

Toxicities of Antibiotics

A

Allergic reactions
Idiosyncratic reactions
Pharmacogenomic reaction
Normal flora changes —> can lead to C. Diff

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6
Q

Bactericidal

A

Kills the microorganisms

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7
Q

Bacteriostatic

A

halts growth of an infection, innate immune system can then remove the pathogens

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8
Q

Broad Spectrum

A

Effective against a wide range of organisms

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9
Q

Extended spectrum

A

Agents with an intermediate range of effectiveness

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10
Q

Narrow spectrum

A

Effective against only a few organisms

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11
Q

Antibiotics that interfere with Cell Wall synthesis

A

Beta Lactams
Vancomycin
Bacitracin
Polymyxins

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12
Q

Antibiotics that interfere with Nucleic acid synthesis

A

Sulfonamides
Trimethoprim
Quinolones
Rifampin

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13
Q

Antibiotics that interfere with Protein synthesis

A
Macrolides (-mycins)
Linezolid
Chloramphenicol
Streptogramins
Tetracyclines
Aminoglycosides
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14
Q

Cell Wall synthesis inhibitors are ____

A

Bactericidal

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15
Q

Protein and Nucleic acid synthesis inhibitors are _____

A

Bacteriostatic

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16
Q

Cell wall synthesis inhibitors prevent ________

A

Peptidoglycan crosslinking. This requres transpeptidase to link together D-alanine residues on murein monomers

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17
Q

Beta-Lactam drugs work by ____

A

Targeting transpeptidase. The beta-lactam ring binds transpeptidase.

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18
Q

Examples of Beta-lactams

A

Penicillins- Natural effective against Gram+ Syphillis, Extended good for Gram +/-
Cephalosporins- 5 gens, each different
Carbapenems- potent, broad spectrum
Monobactams- narrow spec, Gram - only, safe for those with allergy to Beta-lactam ring.

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19
Q

Beta-lactamases are a ______ that work by _____

A

Bacterial resistance

Opening the Beta-lactam ring

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20
Q

Beta-lactamase can be over come with ___

A

Combination therapy of strong and weak Beta-lactam.
Ex. Amoxicillin/Clavulanate
Or
Modification of antibiotic so access to ring is restricted.
Ex. Methicillin.

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21
Q

Glycopeptides

A

Cell wall inhibitors that bind to D-alanine residues on monomers.
Ex. Vancomycin
Last line treatment for MRSA

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22
Q

Lipopeptides

A

Ex. Daptomycin

Cell wall inhibitors, insert into the plasma membrane to disrupt the cell wall.

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23
Q

Bacitracin

A

Cell wall inhibitor that prevents peptidoglycan subunits from being transferred to cell surface.
Only approved for external use.

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24
Q

Polymyxins

A

Cell membrane inhibitor.
Small, positively charged peptides that disrupt structure.
Gram - only
Cannot be absorbed in GI tract due to charge.

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25
DNA/RNA inhibitors
Broad spectrum Direct inhibitors are Bactericidal Indirect inhibitors are Bacteriostatic
26
RNA polymerase inhibitor
Rifampin
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Topoisomerase inhibitor
Quinolones
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DNA structure stability inhibitor
Metronidazole
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Inhibitors of folic acid synthesis
Sulfonamides Trimethoprim Used synergistically
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Protein synthesis inhibitors
Generally bacteriostatic | Either inhibit 50S or 30S ribosome
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50S inhibitors
Chloramphenicol Macrolides: Erythromycin, Clindamycin, Lincomycin Lenzolide
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30S inhibitors
Tetracyclines | Aminoglycans
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Additive Combination therapy
Drugs add to each other’s efficacy in a summative manner | Ex. Beta-lactamase inhibitor + beta-lactam
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Synergistic combination therapy
Drugs enhance each others efficacy greater than summative effect Ex. Sulfonamides and trimethoprim
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Antagonistic COmbination therapy
One drug impairs the efficacy of the other | Ex. Tetracyclines + Penicillins
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Categories of infectious agents
``` Bacteria Viruses Parasites Fungi Prions ```
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Transmission routes of infectious disease
``` Direct contact Fluid exchange Contamination Airborne Vector ```
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Portals of entry
Mucosal membranes Skin Parenteral route (puncture)
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Localized infection
Localized replication and spread of pathogen
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Systemic infection
Replication and spread to blood and neurons potentially
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Normal Host defenses
``` Skin Mucous membranes Resp tract GI tract UG tract Eyes ```
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Host factors
``` Influence the course of infection: Non-specific immune response Immune status Genetics Age Nutritional status Hormones Personal Habits Fever Microbiome ```
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Anti-viral effect of IFN
Virus infects cell and produces viral DNA, induces interferon synthesis, interferon is secreted. Antiviral state is induced by binding of interferon to receptor on cell surface.
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INTERFERON INDUCTION
EIF-2alpha Protein Kinase: inhibits initiation of mRNA translation Oligo-adenylate synthase: activates RNSase L, leading to degradation of mRNA and tRNA.
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Common types of vaccines
Inactivated pathogen Live, attenuated Subunit, purified antigen Toxoid
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What test delineates Staph and Strep?
Catalase test
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Characteristics of a Gram-positive infection
``` Bullous impetigo Draining sinus tracts Erythema Fever Murmur if endocarditis Petechiae is TSS present Superficial abscesses Warmth ```
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Streptococci
Gram positive cocci Forms chains of cocci Catalase negative Ex. S. Pneumoniae, pyogenes, agalactaie, viridans
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Staphylococci
Gram positive cocci Catalase positive S. Aureus and others S. Aureus is Coagulase positive
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Staph. Aureus diseases
``` Wound infection food poisoning Scalded skin syndrome TSS Endocarditis, osteomyelitis, pneumonia, brain abscesses, meningitis, and bacteremia ```
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MRSA
Methicillin resistant staph aureus
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Staph aureus virulence factors
``` Adhesins exotoxins- enterotoxins, TSS toxin, Exfoliative toxins Superantigens Biofilms Beta-lactamase ```
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Conjugation
One bacteria uses a sex pili to inject part of a resistance plasmid into another
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Transformation
DNA from one bacteria is lysed and incorporated into the genome of another bacteria that picks it up
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Transduction
Bacteria forms bacteriophage, which injects resistance genes into new bacteria cells.
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Biofilms
Aggregates of bacteria Extremely resistance to antibiotics Resistant to phagocytosis
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Gram positive bacilli
``` Clostridia Bacillus Listeria Erysipelothrix Corynebacterium Mycobacteria ``` Can be differentiated by catalase, fermentation, urease/gelatinase, and hemolysis
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Spore forming Gram + Baccilli
Clostridia | Bacillus
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Anaerobic Gram + baccilli
Clostridia Can cause abscesses and life threatening infections Ex. C. Diff, C. Perfringens (gas gangrene)
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Gram negative cocci
Neisseria | Moraxella
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Appropriate culture medium for GNC
Blood agar Chocolate agar Thayer-Martin agar(selective for neisseria)
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Neisseria
Oxidase positive Catalase positive (except, elongata) N. Gonorrhea N. Meningitidis
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Gram negative bacilli
``` Haemophillus Aggregatibacter Actinobacillus Pasturella Enterobacteriaceae Pseudomonas Burkholderia Stenotrophomonas Acinetobacter ```
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Enterobacteriaceae
``` Escherichia Salmonella Shigella Yersinia Klebsiella Proteus Citrobacter Enterobacter Serratia ```
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Type of Haemophillus
Inflenzae Aegyptius Ducreyi
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Most common Gram negative infections
``` E. Coli Pseudomonas aeruginosa Klebsiella Acinetobacter baumannii Enterobacteriaceae ```
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Risk factors for Gram - infection
``` Hospitalization Recent surgery Urinary catheter War wounds Dialysis Mechanical ventilator Weak immune system ```
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Gram - Spiral shaped bacteria
Campylobacteraceae | Helicobacteraceae
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Other Gram - bacilli
``` Bordetella pertusis Brucella Francisella tularensis Legionella pneumophila Bartonella Vibrio ```
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Moraxella catarrhalis
3rd leading cause of bacterial ear infections in children URI in adults Cause of COPD exacerbation
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Serratia marcescens
Hospital settings/ medical exposure Immunosuppresion, previous antibiotics, catherterization Infecctive endocarditis in drug users Enterobacteria family
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Haemophilus influenzae
Hib is primary causative agent of acute epiglottis
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Characteristics of bacteria
``` Prokaryotes Cell wall Nucleoids and plasmids Flagella, pili Capsules Virulence factors ```
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Bacterial cell wall is composed of
peptidoglycan branched together by Amino acids
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Cell wall in Gram Positive bacteria
Thick peptidoglycan layer outside plasma membrane
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Cell wall of Gram negative bacteria
Thin peptidoglycan layer between two lipid bilayers, outside layer contains imbedded endotoxins
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Objects of Antibiotic activity
``` Nucleic acid synthesis RNA polymerase Ribosome protein synthesis Folate synthesis Cell membrane Cell Wall LPS and/or TLR4 ```
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Differential media
Allows closely related bacteria to grow, in a unique way that allows their differentiation when compared to each other Ex. Blood agar
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Selective media
Used to isolate a particular kind of bacteria, allowing only the selected type of bacteria to grow.
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Blood Agar
Differential media, can be used to distinguish between bacterial species that are alpha hemolytic, beta hemolytic, and non-hemolytic
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Chocolate Medium
Non-Selective growth medium | Thayer-Martin Medium is has been treated with antibiotics so that it IS SELECTIVE ONLY to Neisseria.
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MacConkey Agar
Selective and differential medium It is SELECTIVE for Gram (-) and Enteric bacilli because of its crystal violet and bile salts, and DIFFERENTIATES based on amount of lactose fermentation by turning pink in the presence of fermentation.
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Bacterial virulence factors
Capsule Cell surface structures Secreted toxins and enzymes
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Indirect virulence factors
Siderophores Secretion machinery Catalase Regulatory factors
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Mycoplasma
Simplest bacteria, no cell wall, very small genome Complex nutritional requirements Triple later cell membrane Generally infects upper respiratory tract Attached to sialoglycoproteins Can secrete oxidants— damage tissues Mycoplasma pneumoniae Ureaplasma urealyticum Spread through droplets IgM, IgG and IgA in that order respond Immunity is not long lasting, can relapse.
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Mycoplasma pneumoniae clinical manifestations
``` Dry cough Wet cough after 3-4 days Tracheobronchitis Scattered rhonchi and expiratory wheeze Atypical pneumonia may develop Can exacerbate asthma ```
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Mycoplasma pneumoniae Diagnosis
Mild leukocytosis WBC up to 15,000 microliter Non-viscous sputum non-specific radiological images
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Mycobacteria
Aerobic, immobile, bacilli, gram positive Slow growing. Mycolic acid in cell wall—> only stain with Acid Fast Some species may be pigmented yellow or orange Lipid rich cell wall tuberculosis, NTM, leprae
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Mycobacterium tuberculosis
Can be caused by many species of Mycobacterium One of the world’s deadliest diseases Leading killer of HIV infected patients Lowenstein-Jensen culture media Infectious pulmonary TB, easy to transmit
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Nontuberculosis mycobacteria (NTM)
Over 150 found in nature M. Avium is most pathogenic Difficult to diagnose
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Mycobacterium lepra
Causes Leprosy Slow proliferation, incubation for months to years Only 5% of people can actually develop leprosy Close contact transmission Can be tuberculoid or lepromatous
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Legionella
Found in freshwater and human made building water systems Spread through droplets Elderly/immunocompromised most at risk Grows in Buffered charcoal yeast Extract agar
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Chlamydia
Biphasic developmental cycle Environmentally stable infectious particle (EB) EB stain purple with Giemsa, non-infectious RBs stain blue Elementary bodies enter host cell, form reticulate bodies which multiply and differentiate into elementary bodies. Forms inclusion in cell. Cell lysis spreads EBs. Obligate parasites Can only be cultured in Eukaryotic cell lines.
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Ricketsiaceae
``` Obligate intracellular parasite Transmitted via arthropod Fever, rashes, vasculitis Coccobacilli Multiply in endothelial cells of small blood vessels Infected cells swell, necrose ```
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E. Coli
Food poisoning, UTI, gastroenteritis, newborn meningitis
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Pseudomonas aeruginosa
Lung and UTI
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Klebsiella
Meningitis, lung, UTI and blood stream infections
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Acinetobacter baumannii
Several infections in war wounds
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Enterobacteriaseae
UTI, lung and bloodstream infections, food poisoning
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What is a virus?
A virus is a pathogen that is not alive. The basic structure of a virus is a genome composed of RNA or DNA, a capsid, and an optional envelope.
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Viral Genomes
Can be ssDNA or dsDNA, linear or circular Can be ssRNA, plus or minus sense, or dsRNA Genome can be complete or fragmented.
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Plus sense RNA
the genome is ready to be translated into proteins
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Minus sense RNA
The genome must first be transcribed to a plus sense RNA in order to be translated into protein
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Naked virus
Lacks an envelope
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Basic steps of viral life cycle
1. Attachment to host 2. Entry to host cell- Endocytosis or membrane fusion (doesn’t need step 3) 3. Uncoating 4. Viral gene expression 5. Viral genome replication 6. Assembly of capsids 7. Maturation 8. Egress- budding or cytolysis
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Cytopathic effects of viral replication
Lytic infection Syncytium formation Hyperplasia Transformation
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Lytic infection
Virus can only replicate via cell lysis, so it produces characteristic lysed cells, visible on stain by the lack of cytoplasm and shriveled nucleus remaining.
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Syncytia formation
Enveloped viruses can cause fusion between cell membranes of infected cells, forming giant cells. HIV does this.
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Hyperplasia
Cells multiply in order to absorb stimulus. Ex. Epstein Barr Virus, Papilloma virus
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Transformation
Changing of normal cell function to abnormal, usually cancerous growth. Ex. HTLV (leukemia), HPV (cervical cancer)
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Common viral causes of latent infection
Measles Herpes simplex Herpes zoster
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Immunopathological reaction example
Dengue virus causing plasma leakage in eye
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Example of viral cause of altered development
Zika virus— microcephaly | Rubella virus, cytomegalovirus can also cause birth defects
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Acute viral infections
Acute followed by clearing | Ex. Rhinovirus, rotavirus, Influenza virus
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Chronic infection
Virus does not clear after acute infection | Ex. Hepatitis B, C
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Latent infection
Reactivates at certain periods of time. | Ex. Herpes simplex and zoster
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Slow virus infection
Acute infection followed by persistent infection and virus overproduction. Ex. Measles virus SSPE, HIV
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Viral factors influencing outcome of infection
Virus host range Viral virulence $ of viral particles present in inoculum
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RNA viruses encode their own ____
RNA polymerase
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Picornavirus features
Rhinoviruses and Enteroviruses Naked Plus-sense ssRNA, linear Cytolytic
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Enteroviruses
PH range 3-10 Small intestine major site Prefer 37 degrees C
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Rhinoviruses
pH 6-8 Primary at nasal mucosa Prefer 33 degrees C
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Picornavirus syndromes
``` Aseptic meningitis Encephalitis Common cold Febrile rash illnesses (HFM disease) Conjunctivitis Herpangina Myositis and myocarditis Hepatitis ```
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Paramyxovirus Features
Negative sense ssRNA, linear Enveloped, fusion proteins, HNs Mumps, measles, respiratory tract infections (resp syncytial virus, parainfluenza virus, metapneumoviruses) Budding to spread
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Orthomyxovirus Features
``` Influenza viruses Negative sense, ssRNA, segmented Enveloped, Surface glycoproteins Hemagglutinin and Neuraminidase (HN) Very antigenically variant Transfer via budding ```
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Orthomyxovirus antivirals
Target unique replication features, attachment and polymerase
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Orthomyxovirus syndromes
Respiratory tract infections, mild to severe | Vaccination can decrease severity
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Reovirus Features
8-11 segments of dsRNA Naked Rotavirus Cytolytic
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Rotavirus
Leading cause of severe, dehydrating gastroenteritis in children under 5. Infects enterocytes, destroying them, decreasing GI absorption, causing diarrhea
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Retrovirus features
Plus sense, ssRNA with reverse transcriptase RNA is transcribed into DNA and inserted into cellular genome Enveloped. Transfers via budding HIV, feline leukemia virus
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Parvoviridae Features
Very small Naked linear, ssDNA with hairpins Only replicates in actively dividing cells
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Human Parvovirus B19
Replicates in immature erythroid cells Aplastic crisis Fifth disease Fetal death
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Polyomaviridae
Small Naked heat-stable, solute resistant Circular dsDNA Slow replication cycle, in cell nucleus, uses cellular enzymes JC virus, BK virus, Merkel cell virus Usually only in immunocompromised patients
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JC virus
Causes progressive multifocal leukoencephalopathy
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BK virus
Associated with nephropathy in transplant recipients
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Merkel cell virus
Associated with the majority of Merkel cell skin carcinomas
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Papillomaviridae
Small Circular, dsDNA Naked Causes warty lesions, many types, can cause genital cancers
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Adenoviridae
Medium sized, naked Capsisd contains spike-like attachment protein Linear, dsDNA with repeats Cytolytic “pan-handle” replication Causes acute respiratory disease, conjunctivitis, gastroenteritis
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Hepadnaviridae
Small, enveloped Circular, partially dsDNA Envelope contains lipid and viral surface antigens Hepatitis B, persistent infection associated with liver cancer
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Herpesviridae
Large, enveloped with glycoprotein spikes (peplomers) Linear, dsDNA Can establish latent infections Encodes its own DNA polymerase HSV, Zoster, Epstein-Barr, HHV 6, 7, 8, Cytomegalovirus
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Causes of mononucleosis
Epstein-Barr virus | Cytomegalovirus
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Poxviridae
``` Very large virus Lipid contraining envelope. Linear, covalently closed, dsDNA genome Replicate in cell cytoplasm Small pox, vaccinina, molluscum contagiosum, monkey pox ```
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Fungi
Yeast Molds Dimorphic Opportunistic
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Fungal branching
Hyphae
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True pathogenic fungi
Asperillus Candida Histoplasma
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Opportunistic fungi
Cryptococcus | Pneumocystis
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Mycotoxicoses
amanitin and phalloidin- Magic mushrooms Aflatoxin- grows on peanuts ergotism- grows on grains
148
Fungal cell wall
Composed of chitin Contains ergosterol Ergosterol is the main target of most antifungals
149
Pathogenesis of Fungal infections
Granuloma formation | Acute suppuration
150
Medium for culturing fungal infection
Sabouraud’s agar
151
Types of parasites
Protozoa: amoebas, sprozoans, flagellates, cilliates | Metazoa/Helminths: Roundworms, flatworms (flukes and tapeworms)
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Protozoan parasites
``` Entamoeba Giardia, Leishmania Trichomonads, trypanosoma Plasmodium (Malaria), Cryptosporidium Toxoplasma ```
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Helminths
Multicellular organisms Large parasitic worms Flukes, Tapeworms, and round worms (nematodes)
154
Pathogenesis of helminths
Toxic byproducts Mechanical tissue damage Immunopathology
155
Helminth evasion of immune system
Molecule mimicry Antigenic variation Intracellular location Immunosuppression
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Antiparasitic drugs
Heavy metals Quinolone derivatives Folic acid antagonists
157
Prions
Infectious, misfolded proteins Scrapies protein Fatal neurodegenerative diseases
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Prion diseases
``` CJD Variant CJD Gerstmann-Straussler-Scheinker Syndrom Fatal Familial insomnia Kuru Mad Cow disease (bovine) Chronic wasting disase (deer) ```