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
What are the innate immune responses to intracellular bacteria/fungi/protozoa?
- Phagocytes
Neutrophils
Macrophages
- NK cells
- Cytokines
IL-12
IFN-y
What signals phagocytes to migrate into tissues?
N-formylmethionyl peptides, chemokines, or lipid mediators attach to seve a-helical transmembrane receptors
–> The cellular response is increased integrin avidity; cytoskeletal changes
–> Functional outcome is migration into tissues
What signals trigger phagocytes to kill bacteria?
Bacterial surface proteins/carbohydrates bind toToll-like receptors and mannose receptors
TLR –> Production of cytokines and/or Reactive oxygen intermediates leads to bacteria death
Mannose receptor –> phagocytosis of microbe into phagosome and fusion with lysosome+enzymes leads to bacterial death (using NO and ROIs)
What is the sequence/timeline of innate immunity activation with intracellular bacteria?
Neutraphils are activated first –> cytokines are released to bring macrophages to the sight of infection –> release of IL-12 activates NK cells –> NK cells release INF-y; further activating macrophages to kill phagocytosed microbes and positive feedback ensues
What adaptive immunity is used against intracelluar bacteria?
CD4+ T cells that develop into TH1 effectors
How do TH1 and TH2 effector cells become activated?
Naive CD4+ Tcells are activated by APCs by binding TCR to MHC Class 2 proteins as well as CD28 (Tcell) to costimulator B7 (APC)
–> activation leads to clonal expansion and differentiation of the Tcell
TH1: IFN-y producing; activates innate response further (macrophages)
TH2: IL-4, IL-5 producing
How do TH1 cells activate macrophages?
Tcell CD40L binds to macrophage CD40; TCR binds to MHCII and the TH1 cell is activated to release IFN-y
- -> IFN-y leads to activation of macrophage:
- Killing of phagocytosed microbes
- Secretion of cytokines (TNF, IL-1, IL-12, chemokines)
- Increased experssion of MHC and costimulators (B7 molecules)
What is the immune response to extracellular pathogens?
- Complement Activation (Innate)
Alternative Pathway
Mannose-binding lectin (MBL) pathway
- Phagocytes (Innate)
Neutrophils
Macrophages
- Bcell and Antibody Response (Adaptive)
- CD4+ TH cells
How does complement activation lead to the death of extracellular bacteria?
Classical (antibody) and lectin (mannose binding lecitin) pathways
Other than complement pathway, how else do antibodies mediate extracellular pathogen destruction?
IgG antibodies opsonize the microbe
- Abs bind to phagocyte Fc Receptor (FcyRI)
- Fc receptor signals activate phagocytosis
- Microbe is ingested and lysed
How do macrophages identify and kill bacteria on their own?
Macropohages express several receptors specific to bacterial constituents
–> i.e. Toll receptor, LPS receptor, mannose receptor, scavenger receptor, glucan receptor
Bacteria bidn to macrophage receptors
Macrophage engulfs and digests bound bacteria
What are functions of mamcrophage-produced cytokines (IL-1/IL-1/TNF-a) on the liver?
- *Release of acute-phase proteins**
- i.e. C-reactive protein, mannose-binding protein
Activation of complement and opsonization
What are functions of mamcrophage-produced cytokines (IL-1/IL-1/TNF-a) on the bone marrow epithelium?
Neutrophil mobilization leading to phagocytosis
What are functions of mamcrophage-produced cytokines (IL-1/IL-1/TNF-a) on the hypothalamus?
Increased body temperature leading to:
- *- Decreased viral and bacterial replication
- Increased antigen processing
- Facilitates adaptive immune response**
What are functions of mamcrophage-produced cytokines (IL-1/IL-1/TNF-a) on the fat and muscle?
Protein and energy mobilization to generate increased body temperature leading to:
- Decreased viral and bacterial replication
- Increased antigen processing
- Facilitates adaptive immune response
(same end results as hypothalamus)
What are functions of mamcrophage-produced cytokines (IL-1/IL-1/TNF-a) on dendritic cells?
TNF-a stimulates migration to lymph nodes and maturation
–> Initiation of adaptive immune response
