lecture 10 Flashcards
host immune response
- innate immunity
- adaptive immunity
- passive immunity
innate immunity
- no antigen specificity
- no memory
- first line of defense because they are:
- -constantly present
- -operational immediately after viral infection
- -only immune defense available for first few days after viral infection
innate immunity: important primary physical and chemical defenses
- GI tract
- respiratory tract
innate defense of GI tract
- mucous membrane of oral cavity and esophagus are refractory to viruses
- acidity of the stomach
- alkalinity of the intestine
- layer of mucous covering gut
- lipolytic activity of bile
- proteolytic activity of pancreatic enzymes
- defensins (host defense peptides) with antiviral activity- modulate host immune response
respiratory tract innate defenses
- mucociliary blanket
- temperature gradient: between nasal passages (33c) and alveoli (37C), plays important role in localization of infection, rhinovirus which infect nasopharynx and cause common cold replicate well at 33 C but grow poorly at 37, influenza shows inverse temp presence
natural killer cells (NK cells)
-mediate death of virus infected cells via apoptosis
cell 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) which cause phagocytosis, chemotaxis, inflammatory mediators, interferons
interferons
- group of cytokines (complex glycoproteins) that are secreted in somatic cells in response to viral infections and other stimuli
- possess potent antiviral, immunomodulating, and anti-cancer properties
- not specific for virus
- RNA are stronger inducers of interferon than DNA
- orally inactive, should be administered parenteral (injection)
types of interferons we care about
- type-I
- type-II interferon
- type-III
- IFN-alpha
- IFN-beta
Type 1 interferons
- many types
- inhibit virus replication in host cells
- activate NK cells to kill infected cells
- increase expression of MHC-I molecules and antigen presentation
- stimulate different monocytes in dendritic cells
- maturation of dendritic cells
- stimulates memory T cell proliferation
IFN-alpha
- leukocyte interferon
- produced in large quantities by plasmacytoid dendritic cells
IFN-beta
- fibroblast interferon
- secreted by virus infected fibroblast
type II interferon
- only one type, IFN-y
- mostly immunoregulatory
- produced by antigen-stimulated T cells and NK cells
type-III interferon
- at least 3 types identified: IFN-lambda 1, IFN lambda 2, IFN lambda 3
- recently discovered
- expressed in response to viral infections and activation of TLRs
- primarily function as immunoregulator
adaptive immunity
- humoral and cellular components
- humoral mediated principally by abs released from B lymphocytes
- cellular immunity mediated by T lymphocytes
- adaptive immunity is antigen specific, takes time (several days) to develop, mediated by lymphocytes that possess surface receptors specific to each pathogen
- long-term memory after infection
- internal viral antigens elicit protective cell mediated immune response
- surface cell antigens elicit protective humoral and CMI responses
antibody mediated immunity (humoral immunity)
-antibodies may be directed against viral proteins or free virions (capsid or envelope) or against viral proteins expressed on surface of infected cells
antiviral effects of antibodies
- virus neutralization
- opsonization
- clumping of viruses (immunocomplex formation)
- activation of complement system
- antibody dependent cell mediated cytotoxicity
virus neutralization
-neutralizing antibodies prevent virus attachment and entry into host cells, they bind to viral capsid or host envelope
opsonization
- coating of virions with antibodies
- antibody coated virion is recognized and phagocytosed by macrophages, and sometimes by neutrophils
cell-mediated immunity
- CD4+ recognizes microbial antigen in phagocyte
- CD8+ recognizes infected cell containing microbial antigen
- causes activation of macrophages, inflammation, stimulation of B lymphocytes, killing of infected cells
evasion of immune response
- antigen plasticity
- antigen multiplicity
- negative cytokine regulation
- downregulation of MHC class I pathway
- inhibition of complement activation
- evasion of neutralizing antibodies
- latency
- cell-to cell spread of viruses
- inhibition of apoptosis
antigen plasticity
- rapid changes in the structure of viral antigen, may be result of mutation, reassortment, or recombination
- due to change in antigen structure, virus may become resistant to immunity generated by previous infection
antigenic multiplicity
-antigenic variants with little or no cross reactivity
negative cytokine regulation
- virokines: homologs of cytokines/interferons produced by virus
- viroceptors: some viruses incode proteins that are homologous to the receptors
