Host Pathogen Interaction Flashcards
(108 cards)
1
Q
Pathogenicity
A
Ability of virus to cause disease in hose (harm it)
2
Q
Pathogen
A
virus which causes disease
3
Q
Pathogenesis
A
manner/mechanism of development of a disease
4
Q
Virulence
A
quantitative or relative measure of the degree of pathogenicity of the infective virus
Not an absolute property of a virus- depends on many variables
5
Q
Avirulent
A
not virulent (not harmful to host)
6
Q
Lethal dose 50
A
LD50
Dose of virus required to cause death in 50% of animals
Lower is more virulent
7
Q
Infectious dose 50
A
ID50
Dose of virus that will infect 50% of an experimental group of hosts/animals
Lower is more virulent
8
Q
Routes of entry into host
A
Skin
Mucous membranes
GI tract
Respiratory tract
9
Q
Skin defenses
A
Dense outer layer of keratin Low pH Presence of fatty acids Bacterial Flora Dryness Components of innate and Adaptive immunity (migratory dendritic cells: Langerhans cells)
10
Q
Transcutaneous injection
A
Bite of arthropods
Bite of infected animal
Contaminated objects
11
Q
Mucous membranes defenses
A
IgA
virucidal proteins
12
Q
GI tract defenses
A
Mucous membrane of oral cavity and esophagus
Acidity of the stomach
Alkalinity of intestine
Layer of mucus covering the gut
Lipolytic activity of bile
Proteolytic activity of pancreatic enzymes
Defensins (host defense peptides) with antiviral activity
IgA
Scavenging Macrophages
13
Q
Respiratory tract defenses
A
Mucociliary blanket Alveolar macrophages NALT BALT Temperature gradient (33-37) (nasal passages- alveoli)
14
Q
Disseminated infection
A
Infection spreads beyond the primary site of infection
15
Q
Systemic infection
A
If a number of organs or tissues are infected
16
Q
Virus spread in host
A
Directional shedding of viruses from the infected epithelium is critical to subepithelial spread
Apical release facilitates virus dispersal, whilst basolateral release provides access to underlying tissues, facilitating systemic spread
17
Q
Viremia
A
Presence of a virus in the blood
Virus may be free in blood or in a cell, such as lymphocytes
18
Q
Primary viremia
A
Initial entry of virus into blood after infection
19
Q
Secondary viremia
A
Virus has replicated in major organs and once more entered circulation
20
Q
Passive viremia
A
Direct inoculation of virus in blood.
Bite of arthropods or contaminated syringe
No initial replication elsewhere in host before
21
Q
Active viremia
A
Viremia following initial virus replication in host.
Release of virions from the initial site of replication, such as lymphatics or epithelium of intestine, to blood stream
22
Q
Neurotropic virus
A
Virus that can infect neural cells
Infection may occur by neural or hematogenous spread
23
Q
Neuroinvasive virus
A
Virus that can enter the CNS (spinal cord and brain) after infection of a peripheral site
24
Q
Neurovirulent virus
A
Virus that causes disease of nervous tissue, manifested by neurological symptoms and often death
25
Herpes
Low neuroinvasiveness bc it always enters PNS but rarely enters CNS
high neurovirulence bc severe when in CNS
26
Retrograde spread
Travel opposite direction of nerve impulse flow
| Invades axon terminals and then spread to Dendrite or cell body, and then cross synapse to reach next axon terminal
27
Anterograde spread
Travel in direction of nerve impulse flow
Virus invades dendrites or cell bodies and then spread to axon terminals, then cross synaptic contacts to invade dendrite of next neuron
28
Neural spread of virus through:
Olfactory route
| Blood Brain Barrier
29
Acute infection
Usually intensive shedding over short period of time
30
Persistent infection
Can be shed at low titers for months to years
31
Tropism
Specificity/affinity of a virus for a particular host tissue
32
Pantropic viruses
Can replicate in more than one host organ/tissue
33
Vesicles
Fluid filled sacs/elevations of skin
34
Ulcers
Opening in the skin causes by sloughing of necrotic tissue, extending past the epidermis
35
Nodule/tumor
Palpable, solid, elevated mass
Nodules with distinct borders
Tumors extending deep into dermis
36
Warts
Benign skin growths that appear when virus infects top layer of skin
37
Papule
Solid elevations without fluid with sharp borders
38
Erythema
Reddening of skin, consequence of systemic viral infections (endothelial injury in blood vessels throughout body, including those of the subcutaneous tissues)
39
Injury to GI tract
Ingestion
Hematogenous spread, systemic infection
Destruction of enterocytes due to viral replication, hypersecretion
Gastrointestinal disease, malabsorption, diarrhea
Pronounced dehydration, acidosis, hemoconcentration
40
Injury to Respiratory tract
```
Loss of ciliary activity
Loss of integrity of lining mucus layer
Multifocal destruction of epithelium
Inflammation
Exudation
Influx of inflammatory cells
Obstruction of air passages
Hypoxia and respiratory distress
Secondary bacterial infection
```
41
Injury to CNS
Encephalitis or encephalomyelitis
Characterized by neuronal necrosis, phagocytosis of neurons (neuronophagia) and perivascular infiltrations of inflammatory cells (perivascular cuffing)
Progressive demyelination- canine distemper
Neuronal vacuolation- prion disease
42
Damage to endothelium
Hemorrhages
Petechiae
Ecchymoses
43
Disseminated intravascular coagulation
Clots form in small blood vessels throughout body
organs do not get blood
organ failure
Later stages, raw material for clot exhausted due to over use
no clot formation in later stages
hemorrhages throughout body
44
Teratogenesis
Abnormal development or arrests in development of embryo or fetus
May result in death or malformations during the antenatal period
45
Virus induced immunopathology
Tissue injury mediated by host immune response to virus infection
Price paid by host to clear a viral infection
Depends on the delicate balance between the protective and destructive effects of the host immune response to viruses
46
Immunopathology
Tissue damage mediated by hypersensitivity reactions
Autoimmune diseases (moon blindness in horse)
Inflammation- mediated tissue damage (fibrosis)
Immunodeficiency disorders
47
Roll of T cells
Cytotoxic cell mediated lysis/killing of infected host cells
Release of cytokines from T cells (CD4+ and CD8+) and other cells that cause inflammation and tissue damage that becomes chronic against persistent virus infections
48
Toll like receptors TLRs
Persistent activation of these receptors of innate host cells by viruses causes production of pro-inflammatory cytokines and interferons, as well as signals that recruit and activate cells involved in inflammationIn
49
Injury
Can also be mediated by free radicals
Like Nitric oxide
Superoxide
50
Toxicity from antibody responses
Antibody responses to viruses may also contribute to tissue damage
51
Immunosuppression
Infectious bursal disease: Virus replication causes atrophy of the bursa and a severe deficiency of B lymphocytes, resulting in immuno suppression
As a result, infected birds become susceptible to other pathogens
52
Inapparent infections
Clinical signs and symptoms are not evident
Too few cells may be infected
Stimulate host immune response
Possible source of virus spread
53
Acute infection
Short term infection
Short clinical course
Rapid clearance from host immune response
54
Latent infection
Persistent infection
Infectious virus not demonstrable except when reactivation occurs
Reactivation is often stimulated by immunosuppression and or by the action of a cytokine or hormone
55
Chronic infection
Persistent infection
Acute infection followed by chronic infection in which the virus is continuously shed from or is present in infected tissue
56
Slow infection
Persistent infection
Prolonged incubation period, lasting months or years
Slow progressive lethal disease
57
Effects of viruses on host cells
Cytocidal (cell death- lysis, apoptosis)
Non-cytocidal (persistent infection)
Cell transformation (tumor cells)
58
Cytopathic effect
Damage or morphological changes to host cells during virus invasion
Cytopathogenic effect
59
Cell fusion
Syncytium or polykaryon formation
Involved fusion of the plasma membranes of four or more cells to produce an enlarged cell with four or more nuclei.
Prone to premature cell death
Result from the fusion of an infected cell with neighboring infected or uninfected cells
60
Inclusion bodies in host cell during viral infection
Abnormal structure in a cell nucleus or cytoplasm or both
Like aggregates of proteins, having characteristic staining properties and associated with certain viral infections
Help to identify certain viral infection
61
Inclusion bodies can be:
Accumulation of viral components
Resultant from degenerative changes in cell
Crystalline aggregates of virions
```
Intracytoplasmic or intranuclear or both
single or multiple
large or small
round or irregular in shape
Eosinophilic/acidophilic or basophilic
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62
Acidophilic staining
Affinity for acid dyes- stains pink
63
Basophilic staining
affinity for basic dyes- stains blue
64
General mechanisms of virus induced cell injury and death
Inhibition of host-cell nucleic acid synthesis
Inhibition of host cell RNA transcription (mRNA production and processing)
Inhibition of host cell protein synthesis
Some viruses cause lysosomes to release their hydrolytic enzymes, which then destroy the host cell
Interference with cellular membrane function
65
Apoptosis
Process of programmed cell death
Mechanism of cell suicide that host activates as last resort to eliminate viral factories before progeny virus production complete
Different from lysis
66
Lysis
Viral replication complete
| Host cell destroyed and new virions released (burst out)
67
Apoptotic pathways
Activation of host cell ccaspase enzymes mediate death of the cell
Once activated, caspases are responsible for degradation of the cell's own DNA and proteins
Mitochondrial pathway
Death receptor pathway
68
Intrinsic (mitochondrial) pathway
Mitochondrial pathway is activated as a result of increased permeability of mitochondrial membranes subsequent to cell injury, such as that associated with a viral infection
69
Extrinsic (death receptor) pathway
Activated by engagement of specific cell membrane receptors which are members of the TNF receptor family
Thus binding of the cytokine TNF to its cellular receptor can trigger apoptosis
70
T cells- apoptosis
Cytotoxic T lymphocytes and NK cells can also initiate apoptosis of virus-infected target cell, utilizing preformed mediators such as perforin and granzyme that directly activate caspases in target cell
71
Antibody dependent cell mediated cytotoxicity resulting from surface membrane fusion of enveloped viruses
Viral glycoproteins are retained on cell surface and since these are antigenic the cell can become a target of the immune system of the host
Ab binds Ag on surface of target cell
Fc receptors on NK cell recognize bound antibody
Cross-linking of Fc receptors signals the NK cell to kill the target cell
Target cell dies by apoptosis
72
Cell transformation
Changing of normal cell into cancer cell
73
Neoplasia
descriptive term
abnormal tissue overgrowth that may be either localized or disseminated
Process that leads to the formation of neoplasms
74
Oncology
Study of neoplasia and neoplasms
75
Benign neoplasm
Growth produced by abnormal cell proliferation that remains localized and does not invade adjacent tissue
76
Malignant neoplasn
Locally invasive and may also be spread to other parts of body (metastasis)
77
Oncogenic viruses
Viruses that cause or give rise to tumors
78
Metastasis
Spread of cancer cells from the part of the body where it started (primary site) to other parts of the body
79
Proto-oncogenes
Encode proteins that function in normal cell growth and differentiation
80
Tumore suppressor genes
Plays a role in keeping cell division in check
Encodes proteins that regulates and inhibits uncontrolled growth
Rb and P53
81
Oncogenes
Mutated forms of proto-oncogenes or aberrantly expressed proto-oncogenes
82
Rb: Retinoblastoma protein
Important tumor suppressor gene/protein
Blocks E2F and keeps cell division in check
E2F facilitates cell division
83
P53
Tumor suppressor gene/protein
Prevents cells with damaged DNA from entering into cell division
Tries to mediate repairing of the damage host cell DNA
If damaged DNA cannot be repaired, p53 mediates apoptosis of cell with damaged DNA
84
Tumor/oncogenic viruses
Viruses that causes cancer
Oncogenic viruses generally have DNA genome or generate DNA provirus after infection (retrovirus)
In permissive cells: can replicate successfully- no cancer
In non-permissive- cannot replicate, integrates into host DNA and causes cancer
85
Oncogenic DNA viruses
DNA tumor viruses interact with cells in one of two ways:
1. productive infection in permissive cell, in which the virus completes its replication cycle, resulting in cell lysis (no cancer)
2. Non-productive infection in non-permissive cell, in which virus transforms cell without completing replication cycle (cancer)
During non-productive, viral genome or a truncated version os it is integrated into cell DNA; alternatively complete genome persists as an autonomously replicating plasmid
86
Oncogenic RNA viruses
Acutely transforming retroviruses
These steal the proto-oncogene from the infected host cell DNA,
Then virus converts proto-oncogene into oncogene (cancer causing gene)
87
Slow/chronic transforming retrovirus
Oncogenic RNA virus
Virus genome gets inserted into regulator (enhancer) gene of host cell DNA
As result of insertion, regulatory gene cannot function properly
No control on proto-oncogene of host DNA
Excessive cell division or cancer as result
88
Expression of tumor antigens
FOCMA: feline oncoronavirus membrane-associated antigen
89
Host immune response
Innate immunity
Adaptive immunity
Passive immunity
90
Innate Immunity
Innate immune defenses exhibit neither antigen specificity nor memory
Provide critical line of first defense against viral infections because:
-constantly present
-operational immediately after infection
-only immune defense available for first few days after infection
91
Natural killer cells
Mediate death of virus infected cells via apoptosis
92
Cellular pattern recognition receptors
Cells at portals of virus entry possess surface receptors (pattern recognition receptors (PRR)) that recognize specific pathogen-associated molecular patterns (PAMPs)
One class of PRRs are the toll-like receptors (TLRs)
-phagocytosis
-chemotaxis
-inflammatory mediators
-interferons
93
Interferons
Group of cytokines that are secreted by somatic cells in response to viral infections and to other stimuli
Possess potent antiviral, immunomodulating and anti-cancer properties
Show no virus specificity
RNA viruses are stronger inducers of interferon than DNA viruses
Being glycoproteins, they are orally inactive, and should be administered via injection
3 types:
94
Interferon-1
IFN a and B
Inhibit virus replication in host cells
Activate NK cells to kill infected cells
Increase expression of MHC-1 molecules and antigen presentation
Stimulate differentiation of monocytes into dendritic cells
Maturation of dendritic cells
Stimulated memory T cell proliferation
95
IFN-a
Leukocyte interferon
| Produced in large quantities by plasmacytoid dendritic cells
96
IFN-B
Fibroblast interferon.
| Secreted by virus infected fibroblast
97
Interferon Type II
IFN-y- most immunoregulatory
| Produced by antigen stimulated T cells and NK cells
98
Interferon Type III
At least 3: IFN-L1, L2, L3
Recently discovered
Expressed in response to viral infections and activation of TLR
Primarily functions as immunoregulator
99
Adaptive Immunity
Includes humoral and cellular components
Humoral- mediated by antibodies released from B lymphocytes
Cellular-medicated by T lymphocytes
Antigen specific, so that these responses take time (several days) to develop, and this type of immunity is mediated by lymphocytes that possess surface receptors that are specific to each pathogen
Stimulated long-term memory after infection
Internal viral antigens usually elicit protective cell mediated immune response
Surface antigens elicit protective humoral and CMI responses
100
Antibody mediated Immunity (Humoral)
Antibodies may be directed against viral proteins on free virions (capsid or envelope), or against viral proteins expressed on surface of infected cells
101
Antiviral effects of antibodies- Virus neutralization
Neutralizing antibodies prevent virus attachment and entry into host cell, bind to viral capsid or host envelope
102
Antiviral effects of antibodies- Opsonization
Coating of virions with antibodies
| Antibody coated virion is recognized and phagocytosed by macrophages, and sometimes by neutrophils
103
Antiviral effects of antibodies-
Clumping of viruses- immunocomplex formation
Activation of complement system
Antibody-dependent cell mediated cytotoxicity
104
Cell mediated immunity
CD4+ helper T cells + microbial antigen in phagocyte
- activation of macrophages
- inflammation
- stimulation of B lymphocytes
CD8+ cytotoxic T cells + infected cell containing microbial antigen
-Killing of infected cells
105
Evasion of immune system- antigenic plasticity
Rapid changed in the structure of viral antigens
May be result of mutation, reassortment, recombination
Due to change in Ag structure, virus may become resistant to immunity generated by previous infection
106
Evasion of immune system- antigenic multiplicity
Antigenic variants with little or no cross-reactivity
107
Evasion of immune system- Negative cytokine regulation
Virokines- some viruses synthesize proteins with are homologs of cytokines/interferons
Viroceptors- some viruses encode proteins that are homologous to the receptors for cytokines. Competitive antagonist
108
Evasion of immune system-
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Down regulation of MHC class 1 pathway
Inhibition of complement activation
Evasion of neutralizing antibodies
Latency
Cell-to-cell spread of viruses
Inhibition of apoptosis
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