Host Defense Flashcards
What must happen for a microbe to cause disease?
Must evade the host immune system
How long does it take for the adaptive immune system to respond to an antigen? What about if it is a memory response?
7 days ish
3 days if memory
What is the cytopathic effect of viruses?
Lysing of cells once virus replicates within the cell
What indicates a successful virus infection?
Entry, replication, spread, transmission
Why can’t microbes enter through the skin?
Keratinization
What is the role of bile in immunity?
Destroys lipids of enveloped viruses
What is the role of the nasal turbinates in immunity?
Impeded virus entry (narrow and complicated path)
True or false: there are no major physical barriers to microbe entry through the eyes and GU tract
True
What are the two hepatitis viruses that are transmitted via the fecal-oral route?
A and E
What is the major cause of the common cold?
Rhinoviruses and adenoviruses
What is the viral family of RSV?
Paramyxoviridae
What are the two major viral causes of conjunctivitis?
Adenoviruses
Enteroviruses
What is the route of transmission for the MMR viruses?
Respiratory
What are the three major components of the innate immune system?
- IFN-alpha/beta
- Natural killer cells
- Macrophages
What is another name for type 2 IFN? What does this do?
IFN-gamma
Activates macrophages
What are the antiviral IFNs?
IFN alpha and beta
What are the roles of IFN alpha and beta? (4)
- Prevent infection of uninfected neighboring cells
- Increase MHC class I expression and antigen presentation
- Activate dendritic cells and macrophages
- Activate NK cells
What are the cells that produce IFN-alpha? IFN-beta?
IFN alpha = Leukocyte
IFN beta = Fibroblasts and other non-leukocytes
True or false: IFN alpha and beta have the same receptor on cells
True
What are the two pathways that IFN receptor binding can activate to inhibit protein synthesis and interrupt viral replication?
- induce 2’-5’ oligoadenylate synthetase to activate RNase L to degrade mRNA
- induce dsRNA depended protein kinase to phosphorylate eIF2 alpha and inactivate it
If IFN-alpha/beta activates 2’5’-oligoadenylate synthetase, what are the next two steps that lead to the inhibition of viral protein synthesis and replication?
Activation of RNase L, which degrades mRNA
If IFN-alpha/beta activates dsRNA-dependent protein kinase, what are the next two steps that lead to the inhibition of viral protein synthesis and replication?
eIF2-alpha is phosphorylated, inactivating it, and preventing viral protein synthesis/virus replication
What is the role of NK cells?
Lyse virus-infected cells early in viral infection
What activates NK cells?
The downregulation of MHC-class I
If a virus downregulates MHC class I proteins to avoid CTLs, how can the immune system counter this?
Upregulate NK cells
What is the role of IFNs in NK cell activity?
Enhanced activity
What is the first line of defense against virus infected cells?
NK cells
How is it that a lack of MHC class I activates NK cells?
MHC-class I has an inhibitory effect on NK cells. Lack of inhibition will thus activate it
What are the cells in the body that express class I MHC?
All nucleated cells except corneal epithelial cells
What is ADCC? What cells perform this?
Antibody dependent cell-mediated cytotoxicity–cross linking of IgG Fc receptors triggers it, and induces apoptosis/perforin mediated cel death
NK cells
Crosslinking of what type of antibody activates ADCC and NK cell killing of cells?
IgG
What are the two killing mechanisms that can be activated with ADCC?
Apoptosis or perforin mediated osmotic death
What are the antiviral effects of macrophages?
Production of TNF-alpha and NO to interfere with viral replication
What are the viruses that can infect macrophages? (5)
CMV Ebola AIDS Rubeola Rubella
(RACER)
What is the benefit to viruses if they can infect macrophages?
Facilitates viral spread
When in an infection is humoral immunity most important?
Early
What is the duration of the immunological memory at mucosal sites?
Short lived (months)
Where are most plasma cells locateD?
Bone marrow
Where do memory B cells reside? What happens when these cells encouter antigen?
Lymph nodes and the spleen
Differentiate into plasma cells
What are the three main funtions of antibody?
Opsonization
Neutralization
Complement activation
What is the role of antibodies in the expression of viral genes?
Downregulates the expression of viral genes inside infected cells following binding of cell surface viral glycoproteins (unknown MOA)
How do antibodies neutralize microbes?
Prevent the microbe from binding to the host target cell
What is the role of CD8+ T cells?
Cell mediated destruction during an established viral infection
How do CD8+ T cells kill?
Perforin mediated mechanisms or apoptosis
What chemical do CD8+ T cells produce to enhance immunity? How does it do this?
Increase TNF-alpha
Interferes with viral replication
How long does it take CD8 memory cells to become activated to prevent infection?
as little as 1 day
What MHC protein expresses endogenous proteins?
MHC class I
What happens to the CD8 cells once the infection is resolved? What happens to the rest?
95% die off
Remainder become memory cells
What is the major difference between memory B cells, and memory T cells?
T cells are dormant
B cells continually produce low levels of Ab to ward off recurrent infection
What is the half-life of serum Abs?
3 weeks or less
How long do most plasma cells live before dying?
several days
What are the mechanisms for long term antibody levels?
Periodic re-exposure to a virus leading to an asymptomatic chronic infection
What are the viral strategies for evasion of the immune system?
Antigen alteration through point mutations or reassortment of segmented RNA genomes
EBV viruses can remain latent in what cells?
B cells
Why is the CNS an ideal location for infections?
Immunologically privileged site
What percent of all neonates become chronic carriers of Hep B?
90%
What is the role of CTLs in hepatitis B infection?
CTLs will destroy hepatocytes, leading to cirrhosis
What is the molecular mimicry the some viruses can undergo?
Express proteins that are similar to endogenous ones to hide themselves
What are the bacteria that can survive in monocytes? (3) What is the advantage of this?
Listeria, mycobacteria, Chlamydia
Abs cannot get to them
How do macrophages attempt to rid themselves of intracellular bacteria?
Express IL-12, which activates NK cells to release IFN-gamma
What is the effect of IFN-gamma on macrophages?
Makes macrophages more efficient at killing intracellular bacteria, and produce NO
What is the effect of IL-12 on NK cells?
Encourages the release of IFN-gamma
True or false: some intracellular bacteria may be killed via the IFN-gamma released by NK cells, but adaptive immunity is generally required for eradication
True
What are the two cell types that can release IFN-gamma to macrophages to encourage the clearance in intracellular bacteria?
NK cells
Th1 cells
What is the result of the inability to kill mycobacteria?
Granuloma formation
What are the cells that mediate a granuloma formation? What are the roles of each of these?
Th1 cells and macrophages
Th1 cells secrete IFN-gamma,
Macrophages secrete IL-12 and wall off infection
What is the IL that stimulates the immune system to Th2 immunity?
IL-4
What is the IL that stimulates the immune system to Th1 immunity?
IL-12
How do granulomas impair bacterial replication? (3)
- Macrophages release NO
- Fibrosis and calcification of bacteria
- Decrease nutrient and oxygen supply
How can CTLs kill off intracellular bacteria?
If bacterial peptides are presented via MHC I, then CTLs will kill off cell
How do mycobacteria survive in macrophages?
Inhibit the fusion of phagosomes and lysosomes, and may scavenge ROS
How does listeria survive in macrophages?
Disrupts phagosome, and escapes into cytosol
What is tuberculoid leprosy?
TB Th1 mediated = granuloma formation + few bacteria present
What is lepromatous leprosy?
Th2 mediated response
What are the immunoglobin levels in tuberculoid leprosy? Lepromatous?
Tuberculoid = normal Lepromatous = hypergammaglobulinemia
What are the T cell levels in tuberculoid leprosy? Lepromatous?
Tuberculoid = Normal Lepromatous = low or absent
