Lecture 5 2/6/24 Flashcards
What factors impact whether or not an animal is resistant to infection?
-genetics
-endocrine
-age
-other factors
How does genetics play a role in resistance to infection?
related but different species can have slightly different genes that make them more (or less) resistant
How do corticosteroids impact viral immunity?
they are immunosuppressive
Why are pregnant animals often immunosuppressed?
due to the hormones that maintain pregnancy
How can nutrition play a role in viral immunity?
affects:
-mucous membrane and skin integrity
-phagocytes
-immune response
What affects can obesity have that impact immune response?
-pro-inflammatory
-immunosuppressive
How do polymicrobial infections impact viral immunity?
-deplete immune resources
-skew immune response
-alter pathology
Why are elderly animals more prone to infection?
-waning adaptive immunity
-innate immunity in higher gear, leading to more inflammatory responses
Why are young animals more prone to infection?
-immature immune systems
-B and T cells that function less optimally
-lack protective Ab titers
-some cell types are more susceptible at a younger age
How does colostrum protect a neonate?
-vaccinating mother leads to secretion of IgA into colostrum
-gut absorption of IgA leads to some level of protection
Why can maternal antibodies be a problem?
-interfere with vaccination and reduce vaccine efficacy
-prevent vaccination from mounting a memorable immune response
What is the window of susceptibility?
time at which maternal antibody level is no longer sufficient at protecting from infection, but is still high enough to prevent a protective vaccine response
What is the purpose of “boosting” a vaccine?
intent is to increase coverage of infant animals that may be in or out of the window of susceptibility, since we do not know exactly when the window is
Why is an antibody titer not always representative of a young animal’s actual immune status?
maternal antibodies can be picked up on a titer and cannot be differentiated from the animal’s own immune response
What are toll-like receptors?
pattern recognition receptors that recognize pathogen-associated molecular patterns
Which toll-like receptors are involved in viral immunity?
-TLR3
-TLR4
-TLR7
-TLR9
Which RNA helicases in the cytoplasm of host cells are able to recognize viral RNA intermediates?
-RIG-1
-MDA5
What are the characteristics of interferon?
-PRRs alter gene expression to produce type 1 interferon
-virus-infected cells produce type 1 interferon to protect neighboring cells
-type 1 interferon is released in paracrine manner to induce an antiviral state in nearby uninfected cells
What are the characteristics of NK cells?
-first cells to respond to viral infection
-activated within hours
-produce large amounts of IFN-gamma, which leads to macrophage activation
How do NK cells kill?
-NK cells express both activating and inhibitory receptors
-balance of receptors controls release of toxic granules
-lack of activation of an NK cell’s inhibitory receptors leads to NK cell degranulation
What are the characteristics of macrophages?
-release cytokines that activate NK and CD8+ T cells following virus phagocytosis
-restrict viral spread by inactivating extracellular virions via free radicals and nitric oxide
What are the general characteristics of adaptive immunity?
-requires antigenic priming
-can take days to activate
-results in memory generation
What are the three components of the adaptive immune response?
-B cells
-CD8+ T cells
-CD4+ T cells
What are the functions of antibodies produced by B cells/plasma cells?
-block viruses from interacting with host receptors/neutralization
-opsonize viruses to trigger phagocytosis via macrophages
-bind viral antigens on host cell surface to target them for ADCC by NK cells
-activate complement
How can antibodies neutralize a virus?
-interfere with virion binding to cell receptors
-block uptake into cells
-prevent uncoating of genomes within endosomes
-lyse enveloped viruses via complement pathway
What are the steps of antibody/complement opsinization?
-microbe is opsonized by antibody
-opsonized microbe bind to phagocytic receptors
-phagocyte receptor signals activate the phagocyte
-opsonized microbe is phagocytosed and killed
What are the steps of ADCC?
-antibody binds to virus proteins expressed on cell surface
-NK cell receptors recognize BOUND antibody
-NK cells kill the antibody-coated cell
How do enveloped viruses evade antibodies?
-bud from internal membrane, so no viral proteins on plasma membrane
-cell-to-cell spread through syncytia formation
-heavily glycosylated receptors
-rapid mutation of receptors
How do persistent viruses evade antibodies?
latency within cells
How do CD4+ T cells help CD8+ T cells?
-virus enters APC and exogenous antigens are presented to CD4+ T cell
-CD4+ T cell helps CD8+ T cell via cytokine production
-activated CD8+ T cell kills virus-infected cell
How do CD4+ T cells help B cells?
-virus binds to IgM on B cell surface
-viral antigens are loaded onto MHCII molecules and presented to CD4+ T cell
-CD4+ T cell helps B cells via cytokine production
-B cells differentiate into plasma cells
How do TH1 responses differ from TH2 responses in viral immunity?
-TH1 cytokines promote viral clearance through cell-mediated immunity
-TH2 cytokines promote viral persistence
What are the characteristics of CD8+ T cells?
-effector function is to kill viral-infected cells
-T cell receptor recognizes viral peptide loaded on MHCI
-only kill infected cells, not extracellular virions
-generally effective against most viral diseases
How can viruses evade T cells?
-encode proteins resistant to proteasome-mediated lysis and prevent MHC loading
-encode proteins that prevent transport of peptides into ER to prevent MHC loading
-down-regulation of MHCI
What are the characteristics of memory in adaptive immunity?
-allows adaptive immunity to remember a pathogen after the initial contact
-key concept in vaccine strategy and design
-allows immune system to recognize pathogen faster and more efficiently
What happens if the immune response is too weak/innappropriate?
-induction of TH2 response leads to less robust CD8+ T cell response
-wrong cytokine can be fatal
-CD8+ T cell response can take too long
What happens if the immune response is too aggressive?
-too much inflammation
-potential for a cytokine storm
