PID Exam 2 Flashcards
What are the 3 main complement pathways?
Classical, Alternative, Lectin.
Do all 3 complement pathways have the same terminal pathway?
Yes.
What are the 4 end effects of the Complement Pathways?
- Cell Lysis
- Inflammation
- Opsonization
- Clearance of Immune Complexes
When a complement is cleaved which segment is labeled ‘B’ and which is labeled ‘A’?
The larger segment is named ‘B’ and the smaller is named ‘A’.
Older literature may not be clear on this distinction. This is fairly recent.
What 2 things activate the Classical Complement Pathway? Which is innate and which is adaptive?
The binding of C1q to an antibody (IgM or IgG) complexed with antigens (ADAPTIVE - binding of Ab to Ag) or when C1q binds directly to the surface of a pathogen (INNATE - C1 reactive protein binding)
What is the Initial Complement Component in the Classical Pathway?
C1-Complex is composed of 1 molecule of C1q, 2 molecules of C1r and 2 molecules of C1s.
C4 and C2 are also present.
For the Classical Complement Pathway what is C3-convertase and C5-convertase composed of?
C3-Convertase: C4bC2b
C5-Convertase: C4bC2bC3b
What is the function of C3-Convertase and C5-Convertase in any of the 3 complement pathways?
C3-Convertase acts to cleave C3 into a and b
C5-Convertase acts to cleave C5 into a and b
What activates the Lectin Complement Pathway?
The binding of Mannose-Binding Lectin (MBL) to mannose residues on the pathogen surface. This binding activates the MBL-Associated Serine Proteases: MASP-1 and MASP-2.
What is the Initial Complement Component of the Lectin Complement Pathway?
C4 and C2
What is C3-Convertase and C5-Convertase composed of in the Lectin Complement Pathway?
C3-Convertase: C4bC2b
C5-Convertase: C4bC2bC3b
What activates the Alternative Complement Pathway?
The contact of microbial cell wall with C3.
Does not rely on pathogen-binding antibodies like the other pathways.
The internal thioester bond of C3 undergoes spontaneous hydrolysis and this reacts with hydroxyl or amino group of a molecule on the surface of a cell or pathogen. Constantly activated at a low level (think car idling)
What is the Initial Complement Component of the Alternative Complement Pathway?
C3, Factor B, Factor D, Properdin (Factor P)
What is C3-Convertase and C5-Convertase composed of in the Alternative Complement Pathway?
C3-Convertase: C3bBb
C5-Convertase: C3bBbC3b
Note: C3-Convertase is stabilized by Factor P (Properdin) C3bBbP
What complements make up the Membrane Attack Complex (MAC)? What is its function?
C5b, C6, C7, C8, and polymeric C9
Functions to create holes in the membrane and can kill/damage pathogen/cell
What is the order of complements coming in in the Classical/Lectin Complement Pathways? Just up until C5-convertase.
C4 then C2 then C3
What complements are primarily responsible for: Cell Lysis, Opsonization and the Activation of Inflammatory Response?
Cell Lysis: MAC (Membrane Attack Complex)
Opsonization: C3b
Activation of Inflammatory Response: C3a and C5a
What is an opsonizing agent/opsonin?
A molecule that enhances phagocytosis by marking an antigen for an immune response or dead cells for recycling.
What are C3a and C5a also known as? What is their job?
They are also known as chemoattractants.
They activate inflammatory response by: smooth muscle contraction, mast cell degranulation, vasodilation (local edema, local influx of antibody and complement), neutrophil activation.
How are particulate antigens removed?
Antigens are percolated with IgG and C3b (opsonization). Then the circulating red blood cells (with C3b receptors) recognize the antigens. They are then removed in the spleen/liver.
Are the complement pathways part of the innate or adaptive immune system?
Innate primarily but can be innate or adaptive depending on the activator.
What is humoral adaptive immunity mediated by?
Mediated by antibodies secreted by antigen-activated B Cells and their progeny plasma cells.
What are the 2 types of humoral immune responses and explain the difference between the 2.
- Primary Humoral Immune Response - has never been exposed to the antigen before.
- Secondary Humoral Immune Response - has had exposure to the antigen previously.
How does secondary humoral immune response differ from primary humoral immune response?
- Shorter lag phase
- Greater magnitude
- Class-switched IgG (IgG has stronger, longer reaction than IgM (opposite is true in primary))
What are Paratopes?
Part of an antibody which recognizes an antigen; the antigen-binding site of an antibody.
It is a small region (15-22 amino acids) in the FAB (Variable region) of the antibody
What is an Epitope? Where is it found?
Epitope are antigen determinants.
They are found on antigens.
Antigens may be multitalented (have more than one epitope). If they are multivalent, they may have multiple different epitope or one repeated epitope.
What are Paratopes found on?
Antibodies
B-Cell Receptors (BCRs)
T-Cell Receptors (TCRs)
(Antigen Presenting Cells)
Which antigen presenting cells can recognize native antigen proteins without any processing or Major Histocompatibility Complex (MHC)?
B-Cell Receptors and Antibodies are capable of this. T-Cell Receptors are not.
What must antigens have in order for T-Cell Receptors to recognize them?
The antigen must be processed and on Major Histocompatibility Complex (MHC). T-Cell Receptors are unable to recognize a native protein antigen (B-Cell Receptors and Antibodies can).
Briefly describe the structure of an antibody?
~ Y-shaped
Has 2 heavy and 2 light chains.
The top of the Y tends is the light chain (Fab) and the stem is the heavy chain (Fc).
What does Ig stand for? What is it?
Immunoglobulin.
An antibody.
What are Papain and Pepsin? What is their purpose?
They are proteases.
They cleave antibodies in different regions. Where they cleave can have different clinical applications.
Why is veterinary virology important?
Because viruses cause high rates of mortality and morbidity in animals and birds.
Viral diseases in animals and birds cause tremendous financial losses to the livestock and poultry industries –> can hamper the economic development of a country.
Some viruses are zoonotic.
Describe the structure of a virus.
Nucleic acid genome (DNA or RNA - single or double-stranded) surrounded by a protein coat (Capsid) and in some cases also surrounded by an additional layer (Lipid Envelope)
Do viruses possess cellular organelles? Can viruses create their own energy or make proteins by themselves?
No. Viruses contain no standard cellular organelles.
No. Viruses cannot make energy or proteins by themselves and have to rely on a host cell.
What type of parasites are all viruses?
Obligate Intracellular Parasites.
Outside of a living cell, viruses are inert, dormant particles. Inside the cell the virus hijacks and utilizes cell machinery to produce proteins and nucleic acid for the next generation of virus.
How do viruses replicate?
They do not have the genetic capability to replicate by division.
Virus reproduction resembles an assembly line in which various parts of the virus come together from different parts of the host cell to form new virus particles.
What is a capsid of a virus? What is composed of?
A capsid is the protein shell of a virus that encases the viral nucleic acid/genome.
A capsid is composed of capsomeres held together by non-covalent bonds.
The capsid and the virus nuclei acid (DNA or RNA)/genome is referred to as what?
Nucleocapsid.
What is the lipid envelope of a virus? What is it composed of? What is often present at the surface of the envelope?
Additional layer in some viruses that covers the capsid.
It is usually made from lipid belayer derived from the host cell.
Glycoproteins are present on the surface of the envelope and often appear as spikes.
What is a naked virus?
A non-enveloped virus.
It only has a capsid enclosing the nucleic acid.
What is an enveloped virus?
Viruses that contain the additional layer (lipid envelope) enclosing the protein capsid which then encloses the nucleic acid.
Define Pleomorphism.
The ability of some viruses to alter their shape or size.
What are the steps of virus replication?
- Attachment
- Penetration
- Uncoating (injects nucleic acid into the cell)
- Synthesis of Viral Nucleic Acid and Protein (replicates using host cell machinery)
- Assembly and Maturation (New viral nuclei acid are packaged into viral particles)
- Release in large numbers (host cell may be damages in process)
What are the potential impacts that virus replication in a host cell can have on that host cell?
- Cell Death - lysis, alteration of cell membrane, apoptosis (cell suicide)
- Fusion of Cells, Mulinucleated (hybrids via mitosis)
- Transformation of a cell into a Malignant one
- No apparent changes to infected cell. Latent, persistent or chronic infection.
What are the steps of Apoptosis?
Normal Cell –> Condensation –> Fragmentation –> Apoptic Bodies
What is the organization responsible for viral taxonomy (classification of viruses)?
ICTV - International Committee on Taxonomy of Viruses
Their classification system is followed worldwide.
They are the only body charged by the International Union of Microbiological Societies with the task of developing, refining, and maintaining a universal virus taxonomy.
What are the 5 main ways that viruses are transmitted?
- Direct Contact Transmission - direct physical contact with infected/susceptible host
- Indirect Contact Transmission - contaminated inanimate object (fomites)
- Common Vehicle Transmission - fecal contamination of water/food, viral contamination or meat/meat products.
- Airborne Transmission
- Vector (Arthropod)-Borne Transmission - mosquitoes, ticks
What is vertical transmission?
Infection that is transferred from mother to embryo or fetus or newborn before, during or after parturition.
What are the main ways that one can diagnose/detect a virus/viral disease?
- Diagnosis by gross evaluation and histopathology (clinical signs, necropsy, histopathology)
- Detection via cultivation/isolation (cell/tissue culture, inoculation in eggs)
- Electron Microscopy
- Serology (ELISA, Fluorescent Antibody Staining, Immunohistochemical Staining)
- Detection of Viral Nucleic Acids (RT-PCR, PCR, Virus Genome Sequencing)
What is serology?
Detection of viral antigen or host antibody against virus.
What are the 3 main ways of doing serology?
ELISA
Fluorescent Antibody Staining
Immunohistochemical Staining
What is ELISA? What does it stand for?
Enzyme-Linked ImmunoSorbent Assay
Means of serology.
What are the main methods for detection of viral nucleic acids?
RT-PCR (Reverse Transcription (RT); Polymerase Chain Reaction (PCR)) - only for RNA viruses
PCR
Quantitative PCR
Virus Genome Sequencing (reading virus genes)
What are the main treatments for viruses?
- Antiviral Drugs
- Immune System Stimulation (interferons)
- Synthesize antibodies or administration of natural antiserum (antibodies)
How do antiviral drugs treat viruses?
They interfere with the ability of a virus to infiltrate a target cell or target different stages of replication/synthesis of components required for replication of the virus.
What are interferons?
A class of proteins that has antiviral effects and modulate functions of the immune system.
What are the 3 main types of virus vaccinations? Which is most effective and why?
- Live-attenuated Virus Vaccines
- Non-Replicating Virus Vaccines
- Vaccines produced by recombinant DNA and related technologies.
Live-attenuated virus vaccines are the most effective because they stimulate cell-mediated immunity (T-cells) whereas the others only stimulate humoral response.
What are the 4 main ways to prevent/control viruses?
- Vaccination
- Proper Hygiene and Sanitation
- Eliminate Arthropod Vectors
- Quarantine and Culling
What are the 2 main ways to eliminate arthropod vectors?
- Biological control - eg predatory fish that eat mosquito larvae
- Chemical Control - eg insecticides
Define Pathogenicity.
The ability of a virus to cause disease in the host
Define Pathogenesis
The manner/mechanism of development of a disease
Define Virulence
Quantitative or relative measure of the degree of pathogenicity of the infecting virus
Define avirulent
Not virulent (not harmful to the host)
Is virulence an absolute property of a virus? Explain.
No, virulence depends on many variables:
Factors related to virus: genetic variation, route entry into host, affinity of virus or host organs, dose of infection, immune-evasion
Factors related to host: species, host immunity, physiological factors (age, hormones, nutrition status, stage of cell differentiation), fever
Other factors: Environment, Dual Infections
What is LD50?
Lethal Dose 50.
It is the dose of virus required to cause death in 50% of animals.
If the LD50 of one virus is LOWER than another this means that it is __________ virulent.
MORE
What are the 4 main routes of entry of viruses into a host?
- The skin - needs cut/breach, transcutaneous injection (bite of Arthropods, bite of infected animal, contaminated objects (needle))
- Mucous Membrane - conjunctiva (eye), oropharynx (throat), genitourinary tract, rectum
- Gastrointestinal Tract - virus in contaminated food/water
- Respiratory Tract
Describe the spread of a virus in the host beginning with the epithelium. Think layers..
- Local spread of virus of epithelial surfaces - causes localized infection, may or may not proceed to subepithelial layer, if they proceed viruses should overcome local host defense
- Subepithelial Invasion and Lympatic Spread - in subepithelial tissues, viruses get access to lymphatic, phagocytic cells and tissue fluids - may help carry virus to bloodstream.
- Bloodstream and Spread of virus via Bloodstream - viremia
- Spread via Nerves
Define Viremia. What are the 2 types of viremia.
The presence of virus in the blood.
Two types:
1. Primary Viremia
2. Secondary Viremia
What is primary viremia? What are the 2 ways that it can happen.
Primary Viremia is the initial entry of the virus into the blood.
It can happen via:
1. Spread of virus infection to blood from the subepithelial layer/lymphatics
2. Directly injected into the blood, through bite of mosquitoes, syringes
What is secondary viremia?
Virus has replicated/multiplied in major organs and once again entered circulation
What is a disseminated infection? What is a systemic infection?
Disseminated infection is an infection that spreads beyond the primary state of infection.
Systemic infection is if a number of organs/tissues are infected.
What are the 3 ways that viruses spread via nerves?
- Through peripheral nerves
- Through receptor neurons in the nasal olfactory epithelium
- Can cross blood-brain barrier and infect CNS
What is a neurotropic virus?
Viruses that can infect neural cells.
What is a neuroinvasive virus?
Viruses that can enter the CNS (brain and spinal cord) after infection of a peripheral site
What is a neurovirulent virus?
Viruses that cause disease of nervous tissue, manifested by neurological symptoms and often death.
What is Tropism?
The specificity/affinity of a virus for a particular host.
What is a pantropic virus?
A virus that can replicate in more than one host organ/tissue.
List some virus-cell interactions (mechanisms of viral injury and disease).
Inhibition of host-cell nucleic acid synthesis
Inhibition of host-cell RNA synthesis (transcription)
Inhibition of host-cell protein synthesis
Cytopathic effects of “toxic” viral proteins
Interference with cellular membrane function
List the possible outcomes of viral injury.
- Cell lysis/bursting (following release of new viruses, after viral replication is complete)
- Apoptosis (mechanism of cell suicide that the host activates as a last resort to eliminate viral factories before new virus production is complete)
- Oncoviruses - cause cancer
- Persistent Infection - don’t cause immediate death of infected host cells but cause persistent infection. Viruses remain latent of dormant in host cell for long periods escaping detection by the host immune system
- Immunosuppression.
Describe the difference in virus shedding between acute and persistent infections.
Acute Infection - intensive shedding over a short time period
Persistent Infection - shed at lower titles for months to years
List and define the different skin injuries that a virus can produce.
- Vesicles - fluid filled sac
- Ulcers - opening in the skin, caused by sloughing of necrotic tissue, extending past the epidermis
- Nodules - solid tumorous mass
- Warts - benign skin growths that appear when a virus infects the top layer of skin
- Erythema - reddening of skin
Describe how viruses “injure” the GI tract.
Ingestion or from blood (systemic infection) –> destruction of intestinal enterocytes –> malabsorption, diarrhea –> dehydration, acidosis, hemoconcentration
List some ways viruses can cause damage to the central nervous system.
Lytic (destruction/bursting) infections of neurons. Neuronal necrosis (necrosis is death of body tissue) Neuronophagia (killing/devouring or neuronal cells by phagocytic cells) Perivascular Cuffing (inflammatory cells around blood vessels in CNS).
List the 2 ways viruses cause damage to the hemopoietic system?
- Damage to endothelium - hemorrhages.
2. Disseminated intravascular coagulation (DIC) - clots form throughout the body followed by hemorrhages