17 - Infectious diseases and vaccines Flashcards
(39 cards)
intermediate host
vector. Carries infection from one organism to another
ticks, fleas, flies, mosquitoes
vector-borne infection
infection carried by an intermediate host, which helps the pathogen get past the physical barriers of defence (epithelial sufaces on skin, f.ex)
lipopolysaccharide
endotoxin produced by some bacteria.
stimulates macrophages or endothelial cells to produce cytokines (IL-1, IL-6 and TNF-alpha (tumor necrosis factor))
peptidoglycan
in cell wall of many bacteria
activates the alternative complement pathway, leading to oponization and phagocytosis or lysis
what do viruses typically induce the production of?
interferons, which can inhibit viral replication by inducing an antiviral respose in neigbouring cells
NK cells also kill virus infected cells (and others)
sepsis
infections entering the bloodstresm
septic shock
if sepsis occurs, the pathogen spreads all over the body, and the subsequent immune response can do more damage than the pathogen itself
what determines which immune tools are availible and best suited for pathogen detection and elemination?
(type of pathogen), entry site and ultimate location
mucosal or barrier infections are typically controlled by…
Th2-Type responses
most infectious agents enter though …
mucosal routes (mouth, eyes, nose, urogenical tract). Tricky, as the mouth has to be in contact iwth food, commensal microbes (expected and essential). Can’t kill them all, has to have some tolerance, but can’t let other bad microbes penetrate the epithelial cell lining of the body either; must limit the amount of bad microbes that enter.
MALT
mucosal-associated lumphoid tissue
se chap 13
what does a Th2 type response mean?
- activation of ILC2
- Th2 specific cytokines (IL-4 and -13)
- IgE capable of recognizing surface epitopes of the pathogen
- cells expressing IgE receptor (mast cells, basophils, eosinophils)
- dimeric IgA (dIgA), found most abundantly at mucosal surfaces, serves important role in neutralizing pathogens and maintaining barrier integrity. Binding of IgA to pathogens can block them from attaching to epithelial cells (neutralization), and thus aid passively in the elimination of the infectious organism (without inducing inflammation)
what does Th2 type response work against
particularly helminths (worms)
What two main types of infection can happen once the pathogen has breached the barrers?
intra- and extracellular
extracellular infections
intestinal fluis or bloodstream. Can remain local or spread (via circulatory or lymph).
immune mediators vary, but can include PRRs on phagocytic cells, complement, antimicrobial compounds, cytokines (activate immune cells), and antibody (IgG, mIgA, IgM). Often Tfh, Th17 and/or Th2
Intracellular infections
most diffucult for IS to find and destroy
not recognized by Ab (antibodies) once inside the cell (but can be before entry)
eradication of infectious organisms that occupy endosomal spaces inside ost cells requires a strong Th1 pathway response.
DTH = delayed type hypersensitivity relies on cytokines secreted by Th1 cells (like IFN-gamma) to activate macrophages that can digest these vesicle-bound agents and overcome common pathogen-induced immune evasion of phagosome-lysosome fusion.
PRRs
Eradication of cytosolic infections requires strondg and comprehensive cell-mediated immunity; activated pAPCs (frequently DCs), CD4+ T cells that can licence DCs for cross-presentation (often Th1 type) and CD8+ T cells.
DTH
DTH = delayed type hypersensitivity relies on cytokines secreted by Th1 cells (like IFN-gamma) to activate macrophages that can digest these vesicle-bound agents and overcome common pathogen-induced immune evasion of phagosome-lysosome fusion.
Antiviral innate response
- complement activation via innate pathways
- PRR recognize PAMPs
- PRR signaling induces IFN-alpha and -beta (type I interferons) and NK activation
- IFN alpha/beta binding tor eceptors -> antiviral activiry + resistance to viral replicatoin. Through JAK-STAT (leads to production of new transcripts, one of which encodes an enzyme for viral RNA degradation). IFN binding also induces dsRNA-dependent protein kinase (PRK) (leads to inactivation of protein synthesis. binding also induces lytic activoty in NK cells, enhanced by IL-12 (produces by DCs early in response to viral infection)
- triggering of adaptive IS
viruses neutralized by Ab
Ab crucial for blocking spread and secondary infection
exposure ideally leads to production of Ab, especially those who localize to areas with viruses; surface or mucosal IgA and circulating IgG are often most protective.
during secondary response, Ab most effective if located by the viral entry, and bind to virus so it struggels with binding to and entering host cells (neutralizing Ab). oral polio vaccine = example
can also happen after viral attachment. Ab bind to epitopes necessary for fusion of viral envelope and cell membrane, thus blocking entry. If Ab is of a complemet-activating isotype, lysis of enveloped virions may ensue.
Ab or complement may also agglutinate viral particles and function as an opsonizing agent to facilitate Fc or C3b receptor-mediated phagocytosis of the free virions
Some isotypes of Ab bound to infected target cells can trigger ADCC by NK
How are IgG and IgA generated=
during primary response when viruses or virions are recognized in extracellular spaces (as virus spreads from dcell to cell/infected cells burst).
Neutralizing Ab
bind to viruses to prevent them from binding to and entering cells
humoral immune responses to viruses
- Antibody (esp IgA) blocks binding of virus to host cells, thus preventing infection or reinfection
- IgG, IgM and IgA Ab block fusion of viral envelope with host cells plasma membrane
- IgG and IgM Ab enhance phagocytosis of viral particles (opsonization)
- IgM Ab agglutinates viral particles
- complement activated by IgG or IgM Ab mediates opsonization by C3b and lysis of enveloped viral particles by membrane-attack complex
cell mediated immune responses to viruses
IFN-gamma secreted by Th or Tc cells has direct antiviral activity (induces antiviral state in nearby cells)
cytotoxic T lymphocytes kill virus-infected self cells
NK (activated by IFN-y and IL-2) and macrophages kill virus-infected cells by Ab-dependent cell mediated cytotoxicity (ADCC)
cell mediated virus clearance
Ab important in acute phases of infection, but can’t eliminate established infection.
Both CD8+ and CD4+ are needed
activated Th1 produce cytokines (IL-2, IFN-gamma, TNF-alpha).
IFN-gamma induces antiviral state in nearby cells
IL-2 help activate cytotoxic T lymph precursors, generating effector population of cytotoxic cells.
both IFN-gamma and IL-2 activate NK cells
Th1 cells directed against the same pathogen (though not always the same epitopes) are required in order to licence pAPCs for cross-presentation, allowing activation of naïve CD8+ T cells
