Immunology Flashcards
What organisms infect interstitial spaces, blood, and lymph?
What protective immunity is present?
Extracellular environment
Organisms:
Viruses
Bacteria
Protozoa
Fungi
Worms
Protective Immunity:
Antibodies
Complement
Phagocytosis
Neurtralization
What organisms infect epithelial surfaces?
What protective immunity is present?
Extracellular environment
Organisms:
Neisseria gonorrhoeae
Mycopasma spp.
Streptococcus pneumoniae
Vibrio Cholerae
Escherichia Coli
Helicobacter pylori
Candida Albicans
Worms
Protective Immunity:
Antibodies (esp. IgA)
Antimicrobial peptides
What organisms infect Cytoplasm?
What protective immunity is effective?
Intracellular Environment
Organisms:
Viruses
Chlamydia spp.
Rickettsia spp.
Listeria monocytogenes
Protozoa
Protective Immunity:
Cytotoxic Tcells
NK cells
What organisms infect vesicles?
What protective immunity is effective against them?
Intracellular environment
Organisms:
Mycobacterium spp.
Salmonella typhimurium
Yersinia pestis
Listeria spp.
Legionella pneumophila
Cryptococcus neoformans
Leishmania
Histopasma
Trypanosoma spp.
Protective Immunity:
T cell and NK cell dependent macrophage activation
What is the immune response to viruses?
- Obligatory intracellular parasites -
Block/prevent infection:
Type I Interferons (Innate)
Neutralizing Antibodies (Adaptive)
Eliminate Infected Cells:
NK cell killing of infected cells (Innate)
T cell killing of infected cells (Adaptive)
How do Type I interferons protect against viral infections?
Type I Interferons inhibit viral replication and activate host defenses
Infected cells produce interferons when dsRNA binds to a pattern recognition receptor (TLR3)
- *- Induction of “antiviral state” in infected cells to block viral replication
- Increased expression of Class I MHC molecules on infected cells, killing by CTLs
- Increase expression of ligands for receptors on NK cells**
What are the two major types of interferons?
- -> IFN-a = Mononuclear phagocytes “leukocyte interferon”
- -> IFN-ß = “fibroblast interferon” (most cells have ability to produce IFN-ß)
How do NK cells identify infected cells?
Stimulation of NK cells with IFN-a and IFN-ß favors the development of the cells’ killer functions (where as IL-12 favors production of cytokines - i.e. IFN-y which activates macrophages)
NK cells have activating and inhibitory cell-surface receptors
NKG2D (activating R) are present on all human NK cells - the ligands for this receptor are only presented on virally infected cells (or stressed by other trauma); inducing cell lysis
Healthy cells resist attack because they produce ligands to the inhibitory receptor on NK cells
- Infected cells produce these ligands as well, but the activating ligands overpower the inhibitory signal
What is used by NK cells to kill virus-infected cells?
- Perforin: pore forming protein (also released by CTLs) inserts itself into infected cell membrane leading to lysis
- Granzymes: serum proteases that induce apoptosis
After activation by the activating ligand, NK cells release their granules
–> Granzymes enter infected celsl through perforin holes and activate caspases (apoptosis ensues)
How do cytotoxic T cells identify virus infected cells?
Virus infects cell –> viral proteins are synthesized in teh cytosol
–> peptide fragments of viral proteins are bound by MHC class I protein in ER –> bound peptides are transported by MHC Class I to the cell surface
–> TCRs on CD8+ Tcells bind to MHC Class I proteins with corresponding antigen presentation –> activating release of cytotoxic effector molecules
What cytotoxic effector molecules are utilized by CTLs?
Other molecules released upon binding to MHC1?
Cytotoxic molecules:
Perforin
Granzymes
Granulysin
Fas Ligand
Others:
IFN-y
TNF-ß
TNF-a
How does FasL activate apoptosis for virus infected cells?
Engagement of FasL (on CTLs) with Fas (expressed on infected cell) leads to activation of apoptosis pathways
What is the general difference between NK cell killing and CTL cell killing?
NK cells prevent infected cells from replicating; prevent spread of infection
CTLs actively kills infected cells specifically and stops infection
How do neutralizing antibodies inhibit viral infections?
Block virus binding and entry into host cells with neutralizing antibodies produced by B cells
*only for protection against 2nd+ infection or and infection after immunization
–> B cells haven’t been activated or made into memory B cells prior to initial infection
If CD8+ T cells actively kill virus infected cells and B cells produce antibodies against future infections, why are CD4+ T cells necessary for immunity to viruses?
They stimulate B-cells into proliferation, to induce B-cell antibody class switching, and to increase neutralizing antibody production
