Host Pathogen Interaction Flashcards
Pathogenicity
Ability of virus to cause disease in hose (harm it)
Pathogen
virus which causes disease
Pathogenesis
manner/mechanism of development of a disease
Virulence
quantitative or relative measure of the degree of pathogenicity of the infective virus
Not an absolute property of a virus- depends on many variables
Avirulent
not virulent (not harmful to host)
Lethal dose 50
LD50
Dose of virus required to cause death in 50% of animals
Lower is more virulent
Infectious dose 50
ID50
Dose of virus that will infect 50% of an experimental group of hosts/animals
Lower is more virulent
Routes of entry into host
Skin
Mucous membranes
GI tract
Respiratory tract
Skin defenses
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)
Transcutaneous injection
Bite of arthropods
Bite of infected animal
Contaminated objects
Mucous membranes defenses
IgA
virucidal proteins
GI tract defenses
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
Respiratory tract defenses
Mucociliary blanket Alveolar macrophages NALT BALT Temperature gradient (33-37) (nasal passages- alveoli)
Disseminated infection
Infection spreads beyond the primary site of infection
Systemic infection
If a number of organs or tissues are infected
Virus spread in host
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
Viremia
Presence of a virus in the blood
Virus may be free in blood or in a cell, such as lymphocytes
Primary viremia
Initial entry of virus into blood after infection
Secondary viremia
Virus has replicated in major organs and once more entered circulation
Passive viremia
Direct inoculation of virus in blood.
Bite of arthropods or contaminated syringe
No initial replication elsewhere in host before
Active viremia
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
Neurotropic virus
Virus that can infect neural cells
Infection may occur by neural or hematogenous spread
Neuroinvasive virus
Virus that can enter the CNS (spinal cord and brain) after infection of a peripheral site
Neurovirulent virus
Virus that causes disease of nervous tissue, manifested by neurological symptoms and often death
Herpes
Low neuroinvasiveness bc it always enters PNS but rarely enters CNS
high neurovirulence bc severe when in CNS
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
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
Neural spread of virus through:
Olfactory route
Blood Brain Barrier
Acute infection
Usually intensive shedding over short period of time
Persistent infection
Can be shed at low titers for months to years
Tropism
Specificity/affinity of a virus for a particular host tissue
Pantropic viruses
Can replicate in more than one host organ/tissue
Vesicles
Fluid filled sacs/elevations of skin
Ulcers
Opening in the skin causes by sloughing of necrotic tissue, extending past the epidermis
Nodule/tumor
Palpable, solid, elevated mass
Nodules with distinct borders
Tumors extending deep into dermis
Warts
Benign skin growths that appear when virus infects top layer of skin
Papule
Solid elevations without fluid with sharp borders
Erythema
Reddening of skin, consequence of systemic viral infections (endothelial injury in blood vessels throughout body, including those of the subcutaneous tissues)
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
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
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
Damage to endothelium
Hemorrhages
Petechiae
Ecchymoses
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
Teratogenesis
Abnormal development or arrests in development of embryo or fetus
May result in death or malformations during the antenatal period
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
Immunopathology
Tissue damage mediated by hypersensitivity reactions
Autoimmune diseases (moon blindness in horse)
Inflammation- mediated tissue damage (fibrosis)
Immunodeficiency disorders
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
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
Injury
Can also be mediated by free radicals
Like Nitric oxide
Superoxide
Toxicity from antibody responses
Antibody responses to viruses may also contribute to tissue damage
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
Inapparent infections
Clinical signs and symptoms are not evident
Too few cells may be infected
Stimulate host immune response
Possible source of virus spread
Acute infection
Short term infection
Short clinical course
Rapid clearance from host immune response
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
Chronic infection
Persistent infection
Acute infection followed by chronic infection in which the virus is continuously shed from or is present in infected tissue
Slow infection
Persistent infection
Prolonged incubation period, lasting months or years
Slow progressive lethal disease
Effects of viruses on host cells
Cytocidal (cell death- lysis, apoptosis)
Non-cytocidal (persistent infection)
Cell transformation (tumor cells)
Cytopathic effect
Damage or morphological changes to host cells during virus invasion
Cytopathogenic effect
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
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
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
Acidophilic staining
Affinity for acid dyes- stains pink
Basophilic staining
affinity for basic dyes- stains blue
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
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
Lysis
Viral replication complete
Host cell destroyed and new virions released (burst out)
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
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
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
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
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
Cell transformation
Changing of normal cell into cancer cell
Neoplasia
descriptive term
abnormal tissue overgrowth that may be either localized or disseminated
Process that leads to the formation of neoplasms
Oncology
Study of neoplasia and neoplasms
Benign neoplasm
Growth produced by abnormal cell proliferation that remains localized and does not invade adjacent tissue
Malignant neoplasn
Locally invasive and may also be spread to other parts of body (metastasis)
Oncogenic viruses
Viruses that cause or give rise to tumors
Metastasis
Spread of cancer cells from the part of the body where it started (primary site) to other parts of the body
Proto-oncogenes
Encode proteins that function in normal cell growth and differentiation
Tumore suppressor genes
Plays a role in keeping cell division in check
Encodes proteins that regulates and inhibits uncontrolled growth
Rb and P53
Oncogenes
Mutated forms of proto-oncogenes or aberrantly expressed proto-oncogenes
Rb: Retinoblastoma protein
Important tumor suppressor gene/protein
Blocks E2F and keeps cell division in check
E2F facilitates cell division
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
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
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
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)
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
Expression of tumor antigens
FOCMA: feline oncoronavirus membrane-associated antigen
Host immune response
Innate immunity
Adaptive immunity
Passive immunity
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
Natural killer cells
Mediate death of virus infected cells via apoptosis
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
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:
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
IFN-a
Leukocyte interferon
Produced in large quantities by plasmacytoid dendritic cells
IFN-B
Fibroblast interferon.
Secreted by virus infected fibroblast
Interferon Type II
IFN-y- most immunoregulatory
Produced by antigen stimulated T cells and NK cells
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
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
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
Antiviral effects of antibodies- Virus neutralization
Neutralizing antibodies prevent virus attachment and entry into host cell, bind to viral capsid or host envelope
Antiviral effects of antibodies- Opsonization
Coating of virions with antibodies
Antibody coated virion is recognized and phagocytosed by macrophages, and sometimes by neutrophils
Antiviral effects of antibodies-
Clumping of viruses- immunocomplex formation
Activation of complement system
Antibody-dependent cell mediated cytotoxicity
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
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
Evasion of immune system- antigenic multiplicity
Antigenic variants with little or no cross-reactivity
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
Evasion of immune system-
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
