Micro/Immuno Flashcards
1
Q
host-parasite relationship in humans
A
dynamic; based on the immune system of the host and the virulence factors of the parasite
2
Q
most common parasitic diseases in the US
A
- Trichomoniasis: (Tricomonas vaginalis) sexually transmitted
- Giardiasis: (Giardia lamblia) loss of appetite and diarrhea
- Cryptosporidiosis: (Cryptosporidium) from bad water and causes diarrhea
- Toxoplasmosis: (Toxoplasma gondii) raw meats and congenital transmission in cats
3
Q
parasite lifecycles
A
immature parasite partially develops in an intermediate host then grows to maturity in a principal/definitive host
4
Q
the 2 classifications of parasites
A
- Parasitic Protozoa (Unicellular)
2. Parasitic Helminths (Multicellular) –> “-todes”
5
Q
5 ways host animals can be infected by parasites
A
- ingestion of larvae, eggs or cysts
- eating the intermediate host
- penetration of parasite into host (foot–>vessels–>heart–>lungs–>ingested–>SI)
- maternal transmission (congenital)
- vector transmission
6
Q
parasitic diseases
A
can be gastrointestinal, blood borne or in tissues, chronic but may remain dormant until host is immunosuppressed and may not show symptoms or could be life threatening
7
Q
innate immune system
A
prevents colonization through release of specific immune cells and cytokines
8
Q
adaptive immune system
A
antibody formation to damage, neutralize and prevent spread of infection
9
Q
eosinophilia
A
high WBC count; eosinophils can destroy parasites
10
Q
IgE
A
increases with parasitic infections and binds to mast cells and basophils; binds to antigen and its Fc portion binds to cells inducing degranulation
11
Q
the 6 defense mechanisms of parasites from protective host responses
A
antigenic:
- concealment (antigens in host’s cells)
- variation (novel antigens by mutation)
- shedding
- mimicry (incorporation of host antigens on parasite’s surface)
- immunological subversion
- immunologic diversion (polyclonal B-cell activation)
12
Q
bacteria vs. parasites
A
bacteria have simple lifecycles and are unicellular whereas parasites have complex lifecycles and can be either unicellular (protozoa) or multicellular (helminthes)
13
Q
obligatory parasite
A
dependent on host
14
Q
facultative parasite
A
free-living in the environment or parasitic
15
Q
accidental parasite
A
affects unusual host
16
Q
temporary parasite
A
visits host for feeding
17
Q
permanent parasite
A
lives in (endoparasite) or on host (ectoparasite)
18
Q
opportunistic parasite
A
produces disease in an immunodeficient host
19
Q
Creutzfeldt-Jacob disease
A
most frequent of the human prion diseases
three different types: (Sporatic-sCJD, Familial- fCJD and Iatrogenic- iCJD)
20
Q
sCJD symptoms
A
spongiform encephalopathy, rapid loss of brain function (concentration, memory and judgment difficulties), mood changes, sleep disturbances, myoclonus provoked by startle and death within one year (1/1,000,000 have it)
21
Q
cause of prion diseases
A
proteins (protein-only hypothesis); differences in prions lead to incubation differences
22
Q
how to sterilize prions
A
autoclaving since they are resistant to conventional physical decontamination methods
23
Q
vCJD symptoms
A
loss of brain function (slower than sCJD), peripheral pathogenesis involving lymphoreticular tissues, death
24
Q
Variant Creutzfeldt-Jacob disease
A
type 4 prion (detected by ring of spongiform vacuoles after staining), bovine-to-human transmission of BSE (not in muscle or milk), 1/2,000 carry it and incubation period is 20-30 years
25
sCJD diagnosis
brain biopsy, detection of 14-3-3 protein in CSF, EEG pattern or abnormal T2-weighted MRI signal
26
PrP^c
35 kDa glycoprotein encoded by Prnp gene in host
27
PrP^sc
Scrapie/misfolded form of PrP^c that leads to prion disease and comes from a mutation of exogenous source
*there are 4 types distinguished by bands produced from protease digestion by proteinase K
28
prion self replication mechanism
native and prion conformers bind creating the "seed" which increases in size to an amyloid fibre (aggregates of insoluble fibers) which disseminates by fragmentation to spread the infection
29
populations infected with sCJD vs. vCJD
- sCJD- mean is 65 years old with a higher prevalence slightly in females and significantly in whites
- vCJD- mean is 29 years old
30
BSE and vCJD patterns
BSE peaked in 1992 whereas vCJD peaked 8 years later in 2000 due to BSE's predicted incubation period os 10-20 years
31
viruses are referred to as:
"filterable agents" since they are so small that they pass through a filter (pores= 220nm)
32
virus replication
they only replicate in cells thus are obligate intracellular parasites (do not form colonies on agar plates such as bacteria)
33
virus diversity
very genetically variable and there are many virus species
34
caspid
protein shell that encapsulates the nucleic acid genome and can be helical or icosahedral (20-sided crystal) in symmetry
**capsid shape is independent of genome
35
virion
the particle encoded by a virus genome which can be enveloped (lipid bilayer coating obtained from host cell) or naked (lacking an envelope)
36
3 basic gene modules of viruses
1. capsid proteins
2. replicon (has what is necessary for replication)
3. proteins (interact with the host)
37
virus classification
1. Host Cell/Kingdom
- eukaryotic or prokaryotic
- plant, insect or animal
2. Genome Type
- RNA or DNA
- single or double stranded
3. Virion Structure
- enveloped or naked
- helical, icosahedral or complex
38
survival mechanisms of viruses
1. capsid for protection (is encoded by genome)
2. information in genome to help with infection, replication, intracellular survival and virion assembly
3. transmission to a new host ensures that the virus will not die off
39
nucleocapsid
at the center and similar to the caspid
40
tegument
gel that is in between capsid and envelope
41
matrix
gives structure that lies underneath the envelope
42
envelope
membrane surrounding the particles (lipid bilayer contributed by the host cell)
43
glycoproteins vs. spikes
spikes embedded in the membrane which require glycosylation whereas spikes or fibers do not require glycosylation
44
inside to outside structure of virus
genome-->nucleocapsid-->tegument-->matrix-->envelope-->glycoprotein-->spikes
45
cytopathic effects (CPE)
damage to host cells that can be brought on by virus infection that can be used to study virus replication and infectivity
46
what does a virus need for growth?
the right host (tropism), correct receptors (susceptible), appropriate intracellular environment (permissive), biosynthetic machinery (virus does not have genes for this so the healthy cell's machinery is used), building blocks (nucleotides, ATP, lipids, sugars and AA's)
47
steps of virus replication
1. recognition
2. attachment
3. entry (penetration of fusion)
4. uncoating
5. mRNA transcription
6. protein synthesis (translation)
7. replication of genome
8. virions assembly
9. egress (lysis, budding or exocytosis)
48
host range
the preferred species
49
tissue tropism
the preferred cell type/host
50
susceptible
cells that a virus can enter due to their receptors
51
permissive
an appropriate intracellular environment allowing for virus replication and virion synthesis
52
penetration
engulfment of entire virion into cell through receptor-mediated endocytosis, phagocytosis or pinocytosis
53
fusion
envelope of virion fuses with the plasma membrane leaving parts of the virion behind
54
eclipse phase
starts with the uncoating of the caspids to release the genome into the cytoplasm of the host cell
no virus is recovered during the replication and assembly phases
ends with the assembly of virions in which viral DNA is inserted into capsid proteins that have formed an empty shell
55
where can uncoating occur?
the plasma membrane, within endosomes and at the nuclear pore
56
what regulates mRNA synthesis?
viral and host transcription factors
57
what makes mRNA?
viral or host polymerases
58
what translates the viral mRNAs?
the host machinery translated them into protein
59
how is the genome replicated?
viral and host DNA and RNA polymerases make new genomes using host cell nucleotides
60
routes of transfer of cell associated virions
cell-to-cell spread and cell fusion (syncytium formation)
61
this produces virus plaques
cell lysis
62
RNA viruses
RNA is the genetic material and the template for protein synthesis
63
RDRP
RNA-Dependent RNA polymerase, located in the cytoplasm, efficiently transcribes RNA into mRNA and helps copy the genomes of RNA viruses on cell membranes
* used since cells do not have enzymes to do this
* low fidelity
64
sense strand
+ strand of mRNA
65
antisense strand
- strand the is the template for mRNA
66
Poliovirus (Picornaviridae)
+ ssRNA genome with linear mRNA molecule which recognizes CD155 receptor and infects epithelial cells only in humans but can spread to muscles and neurons
can be prevented with vaccination with a live or killed virus and its transmission is fecal-oral and persists in water supply
67
Poliovirus entry
conformational change is induced once bound to receptor
capsid proteins become hydrophobic and RNA genome enters at plasma or endosome membrane
68
Rotavirus disease
causes severe gastroenteritis especially in children leading to dehydration which can be treated by oral rehydration solutions and prevented by live-attenuated vaccines
has segmented genome and once virions are assembles, they bud into the RER
69
influenza virus disease
acute respiratory illness in two types: uncomplicated and complicated
- ssRNA with segmented genome which is trafficked to the nucleus for transcription and replication by RDRP
virions assemble and egress by budding
there is an accumulation of viral proteins and genome segments at the plasma membrane
70
HIV cell tropism
virus binds to CD4 and chemokine receptors on T cells and macrophages
71
stages of HIV disease
1. transmission
2. acute phase (primary HIV infection)
3. seroconversion (production of antibodies)
4. latent period
5. early symptomatic HIV infection
6. AIDS- CD4 below 200
7. advanced HIV infection- CD4 below 50
72
differences in replication in DNA viruses
host RNA polymerase- transcription of mRNA
| host or viral DNA polymerase- replication of the genome
73
viral TF's
virulence factors
74
DNA polymerases vs RDRP
higher fidelity and DNA viruses are generally more stable
75
adenovirus disease
pharyngoconjunctival fever, bad cold
transmission: aerosol, fecal-oral
stressed individuals and children are susceptible populations
host RNA pol II- mRNA
viral DNA pol- genome
treatment= cidofovir but can be prevented by vaccination
76
human papilloma virus diseases
most commonly diagnosed sexually transmitted infection
warts (treated by excision), or malignancies (treated by oncotherapy)
Gardasil and cervarix are vaccines
tropism- differentiated epithelial cells
77
HIV drugs
NRTI (nucleoside reverse transcriptase inhibitors)
NNRTI (non-nucleoside reverse transcriptase inhibitors)
PI (protease inhibitors)
INSTI (integrase strand transfer inhibitors)
CCr5 antagonists
78
ART
antiretroviral therapy which combines drugs to avoid resistance
79
HIV lifecycle
FILL THIS ONE IN - 179 in notes
80
Herpesvirus
8 varieties which cause infections only in humans
81
HV life cycle
each HV targets a specific cell type inserting DNA genome into nucleus for mRNA transcription and genome replication (by viral polymerase); egress by exocytosis
82
HV latency
genome is present but infectious virions are absent (barrier to vaccines)
83
primary vs. recurrent
primary infection can happen from exposure and transmission in children or after asymptomatic shedding during latency or recurrent disease in adults
84
asymptomatic shedding
production of virions without even knowing it
85
HSV-1
Primary- close contact producing lesions and gingivostomatitis; latency established in neurons
Recurrent- tingling with contagious lesions
86
KSHV (HHV8)
Kaposi Sarcoma Herpes Virus
high prevalence in Africa and Mediterranean causing infection of B cells and endothelial cells and malignancies on those immunosuppressed (lesions)
no treamtments
87
final thoughts about HV
infections last a lifetime but usually do not cause an issue
asymptomatic shedding is the norm
immunosuppression is a risk for HVs to reactivate
antiviral therapy is helpful
88
Roseola infantum
HHV6b and HHV7 infecting CD4+ T cells characterized by a 3 day high fever and faint rash transmitted in saliva
diagnosis- rule out allergy
no treatment but avoid antibiotics
no prevention but maintain normal hygiene
89
Primary VZV
varicella (chicken pox)
aerosol transmission which is highly contagious and produces a rash
latency in dorsal root ganglia neurons
could lead to complications
90
Recurrent VZV
Herpes Zoster (Shingles)
common in the elderly and immunocompromised
prodrome and contagious lesions
severe complications can occur
91
HSV-2
Primary- from close contact between mucous membranes and acquired in adulthood causing lesions below the waist
Recurrent- prodrome and contagious lesions but shedding and transmission can occur without symptoms
92
HSV in the brain
Primary could cause meningitis while recurrent could cause encephalitis
HSV targets temporal lobe
93
HSV diagnosis and treatment
serology or PCR to distinguish between HSV-1 and HSV-2 while Acyclovir is the parent drug
no vaccines but prevent with safe sex, avoiding cold sore contact and Valtrex or Famvir for daily use to prevent outbreaks
94
VZV diagnosis and treatment
can be prevented with vaccines (live attenuated viruses)
diagnosis- clinical signs, PCR and serology
treatment- Zoster for first 3 days
95
Epstein Barr Disease
infection of oral epithelial cells and B cells transmitted by saliva which can reoccur during immunosuppression from EBV in B cells
malignancy- lymphoma
diagnosis- clinical signs, serology and blood smear for elevated WBC
96
Cytomegalovirus
usually asymptomatic but mononucleosis symptoms could occur
congenital transmission is high and could lead to hearing loss but can be treated by antiviral drugs
affects AIDS patients and transplant recipients
97
characteristics of viral genomes
```
DNA or RNA
single or double stranded
linear or circular
one segment or multiple segments
single copy of each gene
2-200 genes (not enough for independent survival)
```
98
what 2 components make up a viral gene
1. enhancer/promoter region
2. ribosomal entry site
3. open reading frame
**eukaryotic without operons and expression is induced by binding cellular transcription factors to promoter regions
99
2 differences between bacteria and viruses
bacteria- have operons and expression is induced by the interaction of the operator and the repressor/inducer
viruses- no operons and expression is induced when cellular transcription factors bind to promoter regions
100
simple genome
genes are in a linear arrangement on one RNA strand and there is only one promoter
101
complex genome
genes are on both strands to DNA and can overlap with each having a promoter
102
proteases
cleave polyproteins and are essential for drug targets
103
how are viral genomes efficient?
1. no non-coding regions to save space
2. overlapping reading frames
3. translational frameshifts
4. splicing changes AA sequence
5. polyproteins
104
stability of DNA and RNA viruses
RNA- unstable causing one mutation per generation
| DNA- stable causing one mutation per several hundred or several thousand generations
105
gene therapy
the transfer of appropriate genes to a patient in order to correct or prevent disease
*delivery of gene therapy by viruses involves host-range mutants
106
problems associated with gene therapy
short duration of expression and low efficiency of gene transfer
107
problems with the use of viruses for gene therapy
severe inflammation and the insertion of viruses into a recipient's genome could lead to malignany disease
108
complementation
two defective viruses that cannot grow independently but can grow when combined since they make up for what each other lacks
109
phenotypic mixing
the exchange of capsid proteins between healthy viruses. this produces viruses with phenotypic mixtures which cannot replicate
110
recombination
similar genomes will cross over after they overlap at regions of homology thus causing the production of new/hybrid viruses
111
interference
infection by one viruses tends to prevent infection by another (blocking receptors and competing for resources)
112
pseudotype
the genetic material of one virus in the capsid or envelope of another
113
where do we encounter viruses?
people, animals, food, water, insects
114
mechanisms of viral transmission
1. respiratory
2. fecal-oral
3. contact
4. zoonoses
5. blood
6. sexual
7. maternal-neonatal
8. genetic
115
what does the susceptibility and severity of viral diseases depend on?
nature of exposure
viral dose
status of person
virus-host interactions
116
smallpox
acquired through respiratory tract
disseminates in the blood
sheds from pustules on the skin
117
virus entry into GI
M cells sample the gut contents which includes the virus and presents it to underlying immune cells
**viruses infect M cells and therefore can reach the blood stream
118
IgA
offers protection and is present in the gut lumen (immunity to infection)
119
route of pathogenesis of viruses
surface of body--> lymph nodes and blood stream--> primary viremia --> secondary viremia--> transmission
120
primary viremia
leads to replication in internal organs which may occur without symptoms (incubation stage)
121
secondary viremia
disseminates the virus to organs where it is shed
122
chicken pox
transmitted by respiratory route affecting epithelial cells and fibroblasts which is spread by viremia to the skin
* *latent infection = in neurons
* *reactivation by immune suppression
123
excretion of HIV-1
in blood plasma, lymphocytes, CSF (as measured by PCR)
124
severity of virus
may be unnoticed, cause illness, induce autoimmunity, be persistent, or be lethal
125
what does it mean to be a successful virus
avoids destruction by the immune system and avoids destroying the host before replication is finished so it can be transmitted to others and live even if the host dies
126
general patterns of infection
```
acute
persistent
latent
slow
transforming
```
127
why are symptoms caused
they are the response of the host to the infection by the virus
128
what causes cell injury
a combination of virus replication and the host response
129
Norwalk virus
+ssRNA that is transmitted fecal-orally from contaminated water and food
resistant to usual means of disinfection
treatment- hydration
symptoms- diarrhea, vomiting, cramps, fever, malaise
prevention- hand washing, sanitation
130
direct effects
cell lysis
| cell inactivation
131
indirect effects
immunopathology (host immune response to a virus may be the sole cause of disease)
132
HOST factors that contribute to a viral infection
```
immune status
route of exposure
age
habits
barriers to dissemination
contagiousness
```
133
VIRUS factors that contribute to a viral infection
```
antigenic diversity
infectious dose
cell killing/inactivation
pattern of infection
ability to disseminate
shedding
```
134
how are hepatitis viruses related?
they are NOT closely evolutionary related to each other
*symptoms are similar because they all infect hepatocytes
135
how are the hepatitis viruses transmitted?
A- fecal-oral
| B/C- sex/blood/birth
136
which of the hepatitis viruses can be vaccinated against?
A and B
137
diagnosis by serology for Hep A, B and C
A- IgM- acute; IgG- recovered/vaccinated
B- viral surface antigen- acute; IgG against viral surface antigen= recovered/vaccinated
C- EIA (real or false positive), RIBA= confirmation
138
when should alternative medicine be used?
in addition to prescribed treatments for chronic Hep B and C when there is uncertain prognosis and treatment is grueling
139
Hep B and C treatment
polymerase inhibitors +IFN (has many side effects and are often ineffective)
first-generation protease inhibitors are improving treatment of serotype 1 (but have their own side effects)
second generation antiviral released last winter are producing exciting early results
140
Acyclovir
for Herpesvirus
nucleoside analog of guanosine
derivatives= valtex (valaciclovir), denavir (penciclovir), famvir (famciclovir)
141
Ganciclovir
for CMV
toxic
nucleoside analog of guanosine
derivative= Valcyte
142
Broadspectrum antiviral drugs
Foscarnet
Cidofovir
Ribavirin
143
Foscarnet
inhibits viral DNA polymerase
IV
damage to kidneys
144
Cidofovir
nucleoside analog to cytosine
Herpesvirus, Adenovirus, Papillomavirus, Poxvirus
145
Ribavirin
nucleoside analog of guanoside
off-label use
Hep C
146
Drugs for Hep B
drugs for Hep C or HIV
Entecavir
Tenofovir
147
Drugs for Hep C
combination therapy- peg-interferon-alpha with Ribavirin
sofobuvir combined with peg-interferon-alpha and ribavirin
sofobuvir combined with NS5A inhibitors (Daclatasvir or Ledipasir)
148
NS5A inhibitors
Baclatasvir or Ledipasir
*combine with Sofobuvir to treat HepC
149
AZT
drug for AIDS
nucleoside analog of thymidine
NRTI
150
Sofosbuvir
nucleoside analog of uridine
inhibits RDRP
chain terminator
151
Drugs for influenza
Tamiflu (Oseltamivir)
Relenza (Zanamivir)
**sialic acid analogs that inhibit salidase
***virions remain attached to cell
152
unique things about fungi
no peptidoglycan
no 70S ribosomes
eukaryotic heterotrophs
grow in cold, dry, high pressure environments
153
yeast
single celled
reproduce by budding
closed fungal mitosis
154
mold
complex reproduction
grow in hyphae/mycelia
fungal mitosis
155
conida
asexual spores
1. Arthrospores- fragmentation at end of hyphae
2. Blastospores- from budding
3. Conidospores- chains at ends of hyphae
4. Chlmydospores- resistant, round, thick-walled
5. Sporangiospores- in sac
156
antifungal agents
1. Polyenes- toxic, effective, disrupt membranes where ergosterol binds; Amphotericin B
2. Azoles- less toxic, prevent ergosterol synthesis; Fluconazole and Diflucan treat candidiasis and cryptococcosis
3. Echinocandins- low toxicity, prevent beta-glucan synthesis; effective against candida and aspergillus
157
how to diagnose fungi
```
PPD
KOH-mount microscopy with fungal stains
culture on Sabouraud's agar
PCR- dangerous systemics
Serology- epidemiology
```
158
superficial mycoses
fungal growth on superficial skin layer
thermal dimorphism is NOT required
common but symptoms are minor
treat with topical azoles and oral griseofulvin
example: dermatophytosis
159
dermatophytosis
type of superficial mycoses
infects superficial keratinized structures
produces keratinases
symptoms- tinea (jock itch, ringworm, athletes foot)
transmission by fomites and autoinoculation
treat with topical azoles or oral griseofulvin
160
subcutaneous mycoses
introduced by trauma
slow spread to trunk by lymphatics
thermal dimorphism
history of ineffective antibiotic treatment
treatment--> oral azoles and Amphotericin B (polyene)
example- sporotrichosis
161
Sporotrichosis
type of subcutaneous mycoses
painless ulcer- spreads up lymphatics
diagnose by biopsy and culture (pus)
treatment- oral azoles and Amphotericin B
**complications:
pulmonary (if COPD present)
meningitis (if immunosuppressed)
162
systemic mycoses
```
environmental-spores in soil
inhaled into lungs
thermal dimorphism
range of severity (clearance--> death)
NOT transmitted person-to-person
mimics TB
```
example- coccidioides
163
coccidioides
systemic mycoses
US southwest
thermal dimorphism
mold in wet then arthrospore release in dry
risk factors- age, pregnancy, race, immunocompromised
diagnosis- exam, PPD, history, biopsy, culture, serology
treatment- oral azoles, Fluconazole, Amphotericin B
***mild (asymptomatic/flu), moderate (valley fever), and severe (pneumonia)
164
opportunistic mycoses
varied disease/severity based on host's pre-existing conditions
optimal treatment- treat infection and underlying problem
example: cryptococcosis
165
cryptococcosis
opportunistic mycoses
environmental
suppressed inflammatory response
meningitis, skin nodules, pulmonary issues
diagnosis- biopsy
treatment- oral azoles and Amphotericin B
166
Stribild
4 drug combination for HIV
* includes Cobicistat (prevents liver from breaking down drugs)
* AZT (Zidovudine) is also used for HIV
167
Cobicistat
one of the components of Stribild that prevents the liver from breaking down drugs (it is a liver enzyme)
