Exam 4 Flashcards
(150 cards)
1
Q
Type 1 Interferons
A
IFN alpha, beta
2
Q
Describe the fx of IFN a/b in response to viral infection
A
- Internal cytoplasmic sensors of viral RNA (TLR 3, 7/8, 9) stimulate release of IFN a/b
- Block the spread of virus to uninfected cells via the destruction of mRNA and protein synthesis
- IFN’s stimulate chemokine production CXCL 9, 10, 11 that recruit lymphocytes and stim. MHC-1 expression
3
Q
What stimulates NK (Natural Killer) cells?
A
IFN a, b, and IFN-y (via ILC-1)
4
Q
What is unique about the function of NK cells?
A
The ability to kill virus-infected cells without any prior exposure (no need for TCR or BCR).
5
Q
How do NK cells recognize the cells it must kill?
A
Viruses often down-regulate MHC-1 on the surface of the cell to inhibit CD8 response. MHC-1 inhibits activation/ degranulation of NK cells.
6
Q
Two ways to activate CD8 T cells
A
- Intracellular/ endogenous pathogen processing and presentation on MHC-1 – TCR
- Cross-Presentation: extracellular pathogen presented via activated DC
7
Q
T/F: CD8 primarily defend against extracellular pathogens
A
F: they are primarily intracellular
8
Q
Mechanisms of attack for CD8 T Cells
A
- Cytokine secretion: IFN-y, TNF-a, Lymphotoxin-a
2. Trigger apoptosis: 2 mech. (LFA-1/ICAM-1)(Death Receptor)
9
Q
Describe LFA-1 and ICAM-1 mech. of apoptosis (CD8 T cells)
A
LFA-1 and ICAM-1 are non-specific adhesion molecules that form an immunological synapse between the CD8 and target cell. This allows perforins, granzymes, and granulolysin to be directed specifically towards the target cell.
10
Q
Function of Perforins (CD8TC)
A
Perforins are glycoproteins that are used to penetrate the cell wall and form complement-like structures that allow injection of granzymes to trigger the apoptosis pathway
11
Q
Fas-Fas Ligand pathway
A
Secondary way to kill virus infected cells; the main way is the LFA1 ICAM1 pathway thought; mainly used during negative selection in the thymus
12
Q
B Cell activation
A
- BCR recognizes whole antigen
2. B Cell processes antigen and presents it to T Helper 2 Cell w/ CD40/40L
13
Q
Antibodies (and fx)
A
- IgA: barrier fx, neutralizes and prevents infections
- IgG: neutralizes, opsonizes, ADCC w/ NK cells
- Compliment activation w/ IgM and IgG
14
Q
T/F: any level of virus load will trigger the adaptive immune response. it will just take longer to respond if there is less load
A
F: there is a specific cut-off level that the adaptive immune system won’t respond to if load is below that level
15
Q
2 possible end results of B cell activation
A
- antibody secreting plasma cells
2. non-secretory memory B cells
16
Q
Advantage of Activated Memory B cells
A
- have more CD80 and MHC2 than naive
- higher affinity of surface Ig and increased levels of co-stimulatory molecules allow them to initiate rxns w/ Tfh cells at lower antigen levels = faster response
17
Q
Understand the idea of Affinity Maturation
A
yeah
18
Q
How to use Ab to determine chronicity of dz
A
- IgM (acute) vs IgG (chronic) levels
19
Q
Do memory T cells undergo somatic hypermutation?
A
No, only B cells do that
20
Q
How long do the core vaccines confer immunity for?
A
roughly 7 years
21
Q
What is the rationale for increased interval between vax?
A
potential for adverse effects since we are activating the immune system every time. risk of overstimulation
22
Q
Methods to determine Ab titer (Distemper, Adenovirus-1, Parvovirus, Leptospira)?
A
Distemper - Virus Neutralization
Adenovirus-1 - Virus Neutralization
Parvovirus - HAI
Leptospira - MAT
23
Q
What are the 4 key components of every major immune response/ module?
A
- T helper subset (Th1, Th2, Th17)
- Innate Lymphoid Cells (assist the T cells)
- Phagocytes (do the dirty work)
- Antibody Isotypes (connect phag-pathogen)
24
Q
Components of Type 1 Immune Response/ Modules
A
Th1, ILC-1, macrophages, IgG
25
Components of Type 2 Immune Response/ Modules
Th2, ILC-2, mast cells/ basophils/ eosinophils, IgM
26
Components of Type 3 Immune Response/ Modules
Th17, ILC-3, neutrophils, IgG
27
How do T cells determine their differentiation pathway?
Signal 3 --> activation of T cell in presentation of specific cytokines. Cytokines can come from APC (in the case of Th1) or from the ILCs
28
Describe counter regulation of opposing Th subsets
- Th1 and Th2 subsets will antagonize each other
- IFN-y produced by Th1 will completely inhibit the Th2 pathway
- IL-4, -13 from Th2 will counter Th1
- Treg produce TGF-b that counters Th1 and Th2
29
T cells make a fate decision. What does this mean?
Fate Decision refers to the concept that once a T cell differentiates into Th1 or Th2, they will stay that way
30
Describe the process involved in the T cell fate decision.
expression of master transcription factors that direct expression of certain cytokines that positive feedback upon themselves and prevent transition into a different subset
31
Which T cell subsets are considered 'plastic'
Th17 and Treg
32
T/F: Autoimmune T cells can sometimes arise from exTh17 cells that turn into Th1.
True
33
How do we mount a variable T cell response in different locations in the body?
T cell differentiation is determined by the sentinel lymph node. Can mount a Th2 response to helminths in the GI tract while the rest of the body dose Th17 for extracellular bacteria from the invasion
34
Active vs Passive Immunity
Passive -- immunity not generated in the patient, giving the patient preformed Ab, protection is immediate but not long lasting
Active -- induces an immune response that will not be immediate, but will be long-lasting
35
Characteristics of Ideal Vaccine
- confers long-lasting immunity
- free of side effects
- stable, long shelf life
- adaptable to mass vaccination
- able to stim. immune response distinguishable from that induced via active infection (DIVA vax)
36
3 Types of Adjuvents
1. Depot
2. Particulate
3. Immunostimulatory
37
Depot Adjuvents
- slows removal of antigen providing longer exposure to the host
- triggers granuloma formation that can last for extended periods of time
- mineral oil, aluminum salts/ alum
38
Particulate Adjuvents
- mimic microorganisms to enhance delivery to antigne presenting cells
- emulsions, microparticles, immunostimulating complexes, and liposomes
39
Immunostimulatory Adjuvents
- Promote cytokine production by host
| - can be selective for Th1 (saponins) or Th2 (Bordatella pertussis)
40
Recombinant Vax USDA categories
1. vax that contains inactivated recombinant organisms or purified antigens derived from recombinant organisms
2. vax containing live organisms that contain gene deletions or heterologous marker genes
3. vax that contain live expression vectors expressing heterologous genes for immunizing antigens or other stimulants
41
DNA Vaccines
plasmid is used as vector; it contains genes for immunization; taken into cell where antigenic protein is made and produces good cell mediated immunity
42
DIVA vaccines
- removal of genes that code for unnecessary antigens
| - immune response to those removed regions = true infection and not vaccination
43
Advantages of Live Vaccines
Fewer doses, no adjuvents needed
decreased chance of hypersensitivity
relatively cheap
44
Advantages of Dead Vaccines
Stable on storage
Unlikely to cause disease
Unlikely to be contaminated
45
Vaccination of the young animal
- almost guaranteed lack of maternal Ab by 16 weeks of age so vaccination should work well then
- can lose maternal protection prior to 16 weeks so vaccination protocols begin long before then
46
Reasons for Vaccine Failure
1. Correct Administration, animal responds
2. Correct Administration, animal does not respond
3 Incorrect Administration
47
Role of genetics in vaccine variability
inbreeding can reduce the variability of MHC alleles and cause reduced ability to respond to some antigenic peptides
48
3 Types of Adverse Vaccine Responses
Errors, "Normal" Toxicity, and Inappropriate Response
49
Adverse Vaccine Response Error (end-results)
immunosuppression, clinical disease, fetal death
50
Adverse Vaccine Response N Toxicity (end-results)
fever, malaise, inflammation, pain
51
Adverse Vaccine Response not-N Response (end-results)
Type 1 - against adjuvant
Type 3 -
Type 4 - granuloma or sterile abscess
Fibrosarcoma in Cats
52
Antimicrobial Resistance Mechanisms
- reduced permeability to antimicrobial agents
- antimicrobial agent modification
- active efflux
- target modification
- alternate metabolic pathways
53
Disk Diffusion (pros and cons)
pros: easy, inexpensive, no special equipment
cons: no MIC, no slow-growing or fastidious microbes
54
Broth Dilution (What is it and pros and cons)
- serial dilution of drug that help determine MIC for a pathogen
pros: gives MIC, trends in resistance, good for fastidious or slow growing organisms
cons: specialized equipment needed, expensive
55
MIC vs Breakpoint
MIC - minimum inhibitory concentration
| Breakpoint - the [drug] at which the pathogen is considered susceptible to an antimicrobial
56
T/F: MIC is specific for each species and isolate
T
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T/F: MIC helps determine dosing [ ] while breakpoint determines frequency
F; MIC is for both dosing and frequency
58
Methicillin resistant Staph (general facts)
- Altered penicillin-binding protein so no B-lactams or carbapenems will work at all
- check for resistance w/ oxacillin
59
Subcutaneous Mycoses
- typically associated with injuries
- infections are chronic and insidious; establish in skin and produce a localized infection of surrounding tissue and lymph nodes
60
T/F: Subcutaneous Mycoses consist of all fungi and yeast
False: SM consist of dematiaceous or hyaline molds and dimorphic fungi
61
Oomycosis
- not from the fungal family, but clinically and morphologically look the same
- Pythium and Lagendium --> pyogranulomatous dz in animals
62
Phaeohyphomycosis
- caused by dematiaceous fungi
- hyphae are present
- CNS involvement is common (often goes systemic)
63
Cryptococcus neoformans
Pathology: ulcerative lesions involving the URT, CNS (meningitis), Eye
Species: mainly cats
Pathogenesis: stim. Treg to suppress inflammatory response in order to gain time to reproduce
Reservoir: dust, dirt, pigeon poop, amoeba
64
Systemic Mycoses (general characteristics)
- most agents are saprophytic fungi
- dimorphic (mostly)
- infection via inhalation
- pyogranulomatous lesions
- generally, non-contagious
65
Coccidiosis (systemic mycoses) (general facts)
- dimorphic fungi
- mainly dogs (some horses) gets pulmonary dz and osteomyelitis
- C. immitis, and C. posadasii
66
Coccidiosis (reservoir and transmission)
Reservoir: arthroconidias (very environmentally resistant form of spore, part. to dry, heat, acid)
Transmission: inhalation of arthroconidia
67
Histoplasma capsulatum var. capsulatum (reservoir and affected species)
Reservoir: birds as passive carriers, bats have intestinal infection
Affected species: all species, mainly dogs tho
68
Histoplasma capsulatum var. capsulatum (transmission and pathogenesis)
Transmission: inhalation
Pathogenesis: intracellular yeast; LN, lungs, and parenchymateous organs contain white, nodular lesions; macs filled with yeast
69
Blastomyces dermatitidis (general facts)
- dimorphic fungi
- humans, dogs (cats and horses rare)
- can survive w/in phagocytes
70
Aspergillus spp. (general facts)
Asp. fumigatas is the most frequent in animals and humans
Path:
- Avian: respiratory dz => elevated death rates
- Ruminants: abortions and mastitis
71
Defenses of respiratory tract
- Physical barriers (nasal passages, epiglottis and larynx, resp. mucocilliary apparatus)
- Immune Defense
72
Bovine Respiratory Disease Complex (define)
- a complex of pathogens, host factors, and environmental conditions that leads to resp. dz
- "shipping fever"
73
BRDC (4 causative viruses)
1. Bovine resp. syncytial virus
2. Infectious Bovine Rhinotraceitis
3. Parainfluenza
4. Bovine Viral Diarrhea
74
BRDC (pathology and prevention)
- death of epithelial cells, disruption of mucocilliary apparatus, and immunosuppression
- Vaccination, anhelmenthic, slow feed changes
75
BRDC (4 causative bacteria)
1. Mannhemia hemolytica
2. Pasteurella multocida
3. Histophilus somni
4. Mycoplasma
76
BRDC (Mannhemia hemolytica)
- secretes RTX toxin known as leukotoxin (pore forming toxin that affects PMNs and platelets)
- fibrinonecrotic pneumonia
77
BRDC (Pasteurella multocida)
- causes bronchopneumonia
| - can also causes hemorrhagic septicemia
78
BRDC (Histophilus somni)
- vascular damage -> fibrinonecrotic pneumonia
| - other dz: septicemia w/ thromboembolic vasculitis; abortion
79
BRDC (Mycoplasma)
- v host specific, lack cell wall
- Look like friend egg on culture growth
- variety of dz: pneumonia, septicemia, and contagious mastitis in cattle
(conjunctivitis in sheep and goats)
80
Enzootic Pneumonia of Sheep
effectively the same dz process and pathogenesis of BRDC
81
Porcine Atrophic Rhinitis (2 bacteria)
1. Pasteurella multocida (PMT toxin -- osteolysis and stimulates fibroplasia)
2. Bordetella bronchiseptica (paralysis of respiratory cilia)
82
Porcine Pneumonia (3 bacteria)
1. Pasteurella multocida
2. Actinobacillus pleuropneumoniae
- porcine necrotizing pleuropneumonia caused by RTX toxin called Apx -- [low] = resp. burst leading to tissue damage; [high] = destruction of phagocytes
3. Haemophilus parasuis (bronchopneumonia in pigs -- Glasser's Disease)
83
Frank vs Opportunistic pathogens
Frank - not normal flora
| Opportunistic - part of the normal flora that invades as a secondary infection normally
84
Strep equi equi (pathology, pathogenesis)
- Strangles
- Frank pathogen
- Pathology: URT infection w/ lymphadenopathy, but can disseminate systemically to lung, spleen, brain, mesenteric LN
- Pathogenesis: extracellular infection transmitted via aerosol or direct contact; capsule and M-proteins are antiphagocytic and prevent compliment deposition
85
Rhodococcus equi
- almost exclusively foals
- facultative intracellular pathogen so requires Th1 response of resolution
- pyogranulomatous inflammation
86
Coreynebacterium pseudotuberculosis
- transmitted by biting fleas
- facultative intracellular pathogen
- ventral abscesses and occasionally disseminates to abd. or thoracic cavity
- (sheep get caseous lymphadenitis)
87
List the 3 Frank pathogens ass. w/ resp. tract dz in horses
1. Strep equi equi (Strangles)
2. Rhodococcus equi
3. Corenybacterium pseudotuberculosis
88
List the 4 Opportunistic pathogens ass. w/ resp. tract dz in horses
1. Strep equi zooepidemicus
2. Actinobacillus equuli hemolyticus
3. Actinobacillus equuli equuli
4. Bardetella bronchiseptica
89
Strep equi zooepidemicus
- part of n flora
| - pneumonia, abscesses, neonatal infection/ septicemia
90
Actinobacillus equuli hemolyticus
- much more pathogenic than ...equuli
| - RTX toxin Aqx ( [low] = resp. boost; [high] = membrane damage to phagocytes) leads to necrotizing pneumonia
91
Actinobacillus equuli equuli
- septicemia in foals and can disseminate to cause microabscesses in kidneys
92
Bordetella bronchiseptica (equine)
- generally younger horses
| - path: binds to the cilia and secrete toxins that paralyze them --> pneumonia
93
Bordetella bronchiseptica - SA
- aerobic gram neg. cocci
- shared among dogs and cats, poss. zoonotic
- growing number of MDR strains
- path: binds to the resp. cilia and secrete toxins that paralyze them
94
Mycoplasma spp (particularly M. cynos) - SA
- can causes URT and LRT dz
| - commensal dz
95
Canine Parainfluenza Virus
- paramyxovirus
| - enveloped, single-stranded RNA virus
96
Canine Influenza Virus (general facts, 2 strains, pathology, trans, dx)
- orthomyxovirus
- enveloped RNA virus w/ high mutation rate
- low prevalence, primarily shelter outbreaks
- H3N8 (horses) and H3N2 (more important)
- path: no symptoms (20%); mild to sever URT dz w/ H3N2 being more pathogenic
- trans: not well understood
- Diagnosis: PCR gold, Ab detection bronze d/t vax
97
Canine Herpesvirus
- enveloped DNA virus
| - latency in trigeminal ganglia
98
Canine Coronavirus (resp.)
- lawnmower pathogen because it destroys all cilia
99
Canine Adneovirus-2
- (adenovirus-1 causes hepatitis)
| - encapsidated virus = v resistant
100
Canine Distemper Virus
- immunosuppression from the SLAM protein predisposes to secondary infection
- also respiratory, GI, and neuro signs
101
Canine Pneumovirus
- mild resp. dz
102
Canine Inf. Resp. Dz Complex (Epidemiology and Diagnosis)
Epid: aerosol transmission, variable shedding
Diagnosis: Airway lavage w/ PCR
103
Canine Resp. Vax
- Intranasal or oral (preferred for shelters)
| - Recommendations: two doses of parenteral 3-4 wks apart or 1 dose intranasal/oral
104
Feline calicivirus (FCV) (path, carrier status)
- encapsidated RNA virus
- Pathology: Lingual ulcerations, lethargy, fever, pneumonia, conjunctavitis, sneezing, nasal discharge, hepatic splenic pancreatic necrosis
- Carrier status: can shed constantly w/out symptoms
105
Feline Herpesvirus (FHV) (path, carrier status)
- large, enveloped DNA Virus
- infects epithelial cells and sensory neurons w/ latency in the trigeminal ganglia
- Path: repro dz (abortions, resorption, or birth defects); often severe dz w/ oculonasal discharge (oral ulcers can occur but smaller than FCV)
- Carrier Status: stress induced shedding (intermittent)
106
Chlamydia felis
- important ocular pathogen
| - does not cause resp. signs in the absence of conjunctivitis
107
Mycoplasma and Bordetella bronchiseptica
- uncommon in cats so look for other causes first
- myco -> URT w/ conjunctivitis
- bord -> URT, LRT
- PCR both; culter for bord
108
T/F: the order of environmental susceptibility for feline resp. pathogens is FHV > FCV > Chlamydia
F: FCV > FHV > Chlamydia
| FCV is encapsidated while FHV is enveloped making FCV much more resistant
109
Diagnosis of FCV, FHV, C. felis
PCR
110
Vaccination of cats regarding resp dz
does not 'cure' or prevent, but reduces the shedding rate of those infected
111
Principles of antifungal therapy
- most antifungals are fungistatic, fungi grow slowly, and so treatment must be of sufficient duration to allow n processs to take place
112
Amphotericin B (moa, toxicity, gen facts)
- severe systemic fungal infections, broad spectrum
MOA: fungistatic, -cidal at [high]; binds ergosterol to increase permeability of cell membrane (selectively toxic)
Toxicity: Nephrotoxicity, Phlebitis, fever and vomiting (can reduce nephrotoxicity by using lipid-complex formulation)
113
Azoles (two types)
1. Imidazole
| 2. Triazole
114
Triazoles (moa and toxicity)
MOA: inhibition of CYP450 to decrease ergosterol synthesis causing a change in fungal membrane fluidity
toxicity: hepatotoxicity concerns an drug-drug interaction problems
115
Ketoconazole (imidazole)
- extensive hepatic metabolism
- Toxicity common: nauseau, anorexia, vomiting, hepatic dz and failure (cats), inhibition of mammalian P450s, cortisol, and testosterone synth
116
Itraconazole (trazole)
- all fungi
| - well tolerated w/ minor concern for hepatotoxicity and cutaneous vasculitis
117
Flucytosine (synthetic)
- give w/ Amphotericin B to treat condida and cryptococcus
- Tox: bone marrow suppression
- Resist: permease/ deaminase enzyme changes
- MOA: entry into cell w/ permease and deaminase and causes inh. of protein and DNA synth
118
MOA of Amphotericin B and Azoles
Amphotericin B - binds directly to ergosterol
| Azoles - CYP450 inh. to decrease ergosterol synth
119
Acyclovir/ Valacyclovir (Use, MOA, tox.)
- Herpesvirus
- MOA: inhibitor of DNA polymerase
- tox: val is toxic in cats
120
Famciclovir/ penciclovir (MOA)
MOA: inhibitor of DNA ploymerase; subs. for guanosine
| non-linear PK in cats
121
Idoxuridine (IDU)/ Trifluiridine (TFT)
FHV-1
| MOA: subs. thymidine -> interupts transcription
122
Zidovudine (Target, MOA)
Retroviruses
| MOA: thymidine analog, inhib of reverse transcriptase (higher affinity for viral RT than mammalian DNA polymerase)
123
West Nile Virus (general facts)
enveloped single-stranded positive-sense RNA virus
124
West Nile Virus (Transmission/ Host cycle)
- primary host is birds (part. crows) that can generate high enough viremia to allow mosquitoes to finish the cycle
- mosquitoes can transmit virus to humans or horses
125
West Nile Virus (Equine Pathology)
- 80% asymptomatic
- 20% WN viremia (febrile, depression)
- <1% CNA disease (40-60% of those who become recumbant will die)
126
West Nile Virus (diagnosis)
- IgM capture ELISA
| - also PCR from blood
127
West Nile Virus (Treatment)
- supportive therapy, antiinflammatories, heavy bedding, sling, hyperimmune plasma
128
West Nile Virus (Prevention)
- Vaccination w/ annual booster in spring
129
Influenza A Virus (General facts)
- enveloped RNa virus w/ HA and NA surface proteins
| - segmented genome (8 segments)
130
Influenza (infection, replication)
- HA binds to sialic acid receptors upon the epithelial cells
- NA allows for release of the influenza virus post-replication
131
Influenza (Antigenic shift vs drift)
Drift - normal mutations causing change in genome but not a change in subtypes
Shift - multiple influenza viruses infecting the same cell allowing for recombination of subtypes
132
Influenza (Transmission and Pathogenesis)
Avian - alpha2,3 in gut
Mammals - alpha2,6 receptor in lung
Pigs - alpha2,3 and 2,6 allows for infection via both
133
Zoonotic influenza, pandemic influenza, vs seasonal flu
Zoonotic Influenza - viruses transmitted from animals to humans w/ limited human--human
Pandemic Influenza - new virus infects humans, causes dz, and spreads from humans--humans
Seasonal Flu - recurrent influenza viruses; variants of previous pandemic viruses
134
Influenza (OG source)
- wild aquatic birds
135
Influenza (Avian Influenza, Equine Influenza, Canine)
Avian -- extremely important w/ high and low path variants; H5N1
Equine -- H3N8; high morbidity, low mortality; jumped form horses to greyhounds
Canine -- H3N2
136
Influenza (Prevention and Treatment)
Prevention -- non-core vaccine
| Treatment -- antivirals (Tamiflu) blocks NA
137
Coronavirus (general facts, surface proteins)
- enveloped single-stranded RNA virus w/ club-shaped spikes
| - S (determines tropism) and N surface proteins
138
Coronavirus (replication)
- normal replication w/ nested set protein production
139
Coronavirus (Transmission)
- aerosol (resp symptoms)
| - fecal-oral (GI symtoms -- blunting, malabsorption, maldigestion)
140
Coronavirus (Diagnosis)
PCR (gold) and Immunostaining
141
Transmissible Gastroenteritis (TGEV) of Swine
- severe gi signs, dehydration, death in neonates
| - precursor to Porcine resp. coronavirus (mild resp. dz in piglets)
142
Porcine Hemagglutinating Encephalomyelitis Virus
- neural dz leading vomiting and wasting
143
Canine Enteric Coronavirus
- mild gi upset
144
Canine Respiratory Coronavirus
- lawnmower
| - shelter and boarding facilities
145
Bovine Coronavirus
- diarrhea in calves < 3mnths of age
- sporadic hemorrhagic diarrhea in older
- resp. signs in all ages
146
Equine Coronavirus
- Enteric, febrile, neuro (d/t hyperammonemia)
147
FIP (Feline Infectious Peritonitis) (2 viruses)
1. Feline Enteric Coronavirus - not bad at all and basically they all got it; infectious
2. FIP Virus - mutation in FECV causing severe clinical signs to manifest; non-infectious
148
FIP (Feline Infectious Peritonitis) (facts)
clinical signs = death
149
FIP (Feline Infectious Peritonitis) (pathogenesis)
- pyogranulomatous vasculitis
- immunosuppressed
- antibody dependent disease enhancement
150
FIP (Feline Infectious Peritonitis) (clinical signs)
Wet FIP - effusive
| Dry FIP - pyogranulomatous lesions
