Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
59 Cards in this Set
- Front
- Back
- 3rd side (hint)
|
Differentiate between opsonic and non-opsonic phagocytosis.
|
Opsonic: Mediated by deposition of proteins (antibodies, complement) on microbes. Leukocytes recognize them and phagocytose. More efficient.
Non-opsonic: Mediated by cell-surface receptors that recognize specific CHO sequences (TLRs). |
|
|
|
Phagocytosis of apoptotic corpses...
|
is non-immunogenic. There is NO inflammation.
ANTI-inflammatory signal is sent by TGF-beta. |
|
|
|
Describe phago-lysosomal fusion.
|
Filamentous actin around phagosome depolymerizes.
Lysosome fuses with phagosome. Lysosomal enzymes chew up contents (lysozyme, lactoferrin, proteases, defensins). |
|
|
|
What is an ANTI-inflammatory cytokine?
|
TGF-beta
|
|
|
|
What do lysosomes contain?
|
Lysozyme
Lactoferrin Proteases Defensins |
|
|
|
How does oxidant-dependent killing work?
|
O2 is converted to superoxide anion (O2-) by NADPH oxidase.
Next, O2- is converted to H2O2 (hydrogen peroxide). Finally, myeloperoxidase converts H2O2 and Cl to make HOCl (bleach). This is toxic to our cells, too. |
|
|
|
How do we defend ourselves against H2O2?
|
Catalase. This protects our cells from hydrogen peroxide, so it only attacks microbes. Except when they have catalase, which sucks for us.
|
|
|
|
What happens when you lack NADPH oxidase?
|
Can't make reactive oxygen species (O2-).
Result is chronic granulomatous disease (CGD). |
|
|
|
How do bacteria fight back against phagocytosis?
|
Modify phagocytic receptors to prevent phagocytosis: Pseudomonas aeruginosa
Disrupt ingestion phase of phagocytosis: Yersinia Escape phagosome and enter cytoplasm: Listeria, Shigella Stall phagosome maturation: M. tuberculosis, Legionella Resistant to lysosomal enzymes: Salmonella |
|
|
|
What is chronic granulomatous disease (CGD)?
|
Lack of NADPH oxidase.
Can't make reactive oxygen species to kill bacteria and fungi, so granulomas are formed. |
|
|
|
What does complement do?
|
1) Opsonization by C3a
2) Leukocyte chemoattraction by C3b 3) Lysis of pathogens (C5-9; terminal complement complex) |
3 things!
|
|
|
How does complement get activated?
|
1) Classical pathway: antigen-antibody complexes
2) Lectin pathway: lectin binds to pathogen surface, activates C3/C5 convertase, which activates complement 3) Alternative pathway: pathogen surfaces activate C3/C5 convertase, which activates complement. 3) |
3 more things!
|
|
|
Describe the structure of MHC Class I molecules.
|
MHC I expressed on all nucleated cells.
Has one alpha-chain plus beta-2 microglobulin (for stability). Antigenic peptides are derived from the cell's cytoplasm, usually |
|
|
|
Describe the structure of MHC Class II molecules.
|
Expressed on APCs (dendritic cells, macrophages, and B cells).
Has one alpha-chain and one beta-chain. Antigenic peptides are usually derived from the endocytic compartment after phagocytosis (i.e., from the environment). |
|
|
|
What type of receptor are chemokine receptors?
|
G protein-coupled.
|
|
|
|
What does the Scavenger receptor A family recognize? What do they mediate?
|
Gram-positive and -negative bacteria.
Mediate non-opsonic phagocytosis. |
|
|
|
Which complement proteins opsonize bacteria?
|
C3b
C3bi |
|
|
|
Which complement proteins are chemoattractants?
|
C3a
C4a C5a |
|
|
|
Which complement fragments form the "terminal complement complex"?
|
C5-9
|
|
|
|
What enzymes is responsible for cleaving C3 and C5?
|
C3/5 convertase
|
|
|
|
What is chronic granulomatous disease (CGD)?
|
Lack of NADPH oxidase. Most common mutation is in GP91phox channel protein used to make O2-.
Unable to make reactive oxygen species. Subsequent granuloma formation. 1/250,000 live births in U.S. Recurrent infection with catalase-positive organisms (Staph, Mycobacteria, Klebsiella, Pseudomonas, Nocardia, Burkholderia, Serratia) and fungi (Aspergillus, Candida). Granulomas, abscesses, and lymphadenitis usually result in clinical presentation in first 2 years of life. |
|
|
|
What does superoxide dismutase make?
|
Hydrogen peroxide (H2O2) from O2-.
|
|
|
|
What does myeloperoxidase make?
|
HOCl (bleach) from H2O2 and Cl2.
|
|
|
|
What types of things (besides reactive oxygen species) are present in the phagolysosome?
|
- Reactive nitrogen species (NO3-)
- Lysozyme (disrupts peptidoglycan in cell wall) - Defensins (highly + proteins that intercalate into membrane, disrupting it) |
|
|
|
Where are defensins made, besides by phagocytes?
|
Cells in the crypts of the gut make defensins and secrete them into the lumen.
Defensins are highly + molecules that intercalate into bacterial cell walls and disrupt them. |
|
|
|
What happens in apoptosis that makes it a non-inflammatory process?
|
Phagocytic corpses are ingested by macrophages.
An ANTI-inflammatory signal, TGF-beta, is released, which prevents their ingestion from triggering an inflammation response. |
|
|
|
What does TGF-beta do?
|
TGF-beta induces apoptosis via the SMAD or DAXX pathways.
It is an anti-inflammatory cytokine, so apoptotic corpses do not induce an immune response. |
|
|
|
What happens with immunoglobulin and TCR genes before they're rearranged?
|
They are inactive (no mRNA transcripts are made).
|
|
|
|
What does TLR-2 recognize?
|
TLR-2 recognizes bacterial lipoglycans.
|
|
|
|
What do TLR-3, TLR-7, and TLR-8 recognize?
|
TLRs 3, 7, and 8 recognize viral nucleic acids (double-stranded RNA, etc.)
|
|
|
|
What does TLR-4 recognize?
|
TLR-4 recognizes LPS (endotoxin).
|
|
|
|
What does TLR-5 recognize?
|
TLR-5 recognizes flagellin, a component of bacterial flagellae.
|
|
|
|
What does TLR-9 recognize?
|
TLR-9 recognizes unmethylated CG-rich (CpG) oligonucleotides.
|
|
|
|
Where are toll-like receptors (TLRs) located?
|
- Cell surface
- Endosomes (to recognize bacterial components that have been ingested) |
|
|
|
What does activation of TLRs do?
|
TLR activation causes:
Transcription factor expression, especially: - NF-kB (nuclear factor kappa-B), which promotes cytokine expression - IRF-3 (interferon response factor 3), which promotes Type I interferon expression (Type I interferons are anti-viral; IFN-alpha, IFN-beta) Chemokine expression: - IL-8 - MCP-1 - RANTES Upregulation of endothelial adhesion molecules - E selectin Upregulation of co-stimulatory molecules - CD80/86 |
|
|
|
What is NF-kB?
|
NF-kB is a transcription factor that increased transcription of cytokines.
NF-kB is upregulated by toll-like receptor activation. |
|
|
|
What does IRF-3 do?
|
IRF-3 (interferon response factor 3) increases production of anti-viral interferons (Type I interferons).
|
|
|
|
What is iNOS, and where is it located?
|
Inducible nitric oxide synthase (iNOS) is located in phagocytic phagolysosomes. iNOS makes arginine into nitric oxide (NO), which is antimicrobial.
|
|
|
|
What happens to phagocytes in response to f-Met peptides and chemokines?
|
- Upregulation of integrin avidity (to facilitate diapedesis)
- Cytoskeletal changes - Activation! |
|
|
|
What is ADCC, and how does it work?
|
ADCC = antibody-depending cellular cytotoxicity.
NK cells recognize antibody-coated pathogens and kill them. |
|
|
|
What are ITAMs?
|
ITAMs are immunoreceptor tyrosine-based activation motifs.
ITAMS occur on the cytoplasmic tails of activating NK cell receptors and certain T cell receptors. When a ligand activates the cell's receptor, the ITAMs are phosphorylated on their tyrosine residues. Phosphorylated ITAMs bind tyrosine kinases, which are then phosphorylated, triggering a signaling cascade. In NK cells, this cascade leads to cytotoxic granule exocytosis (perforin, granzyme) and IFN-gamma release (to call in phagocytes). |
|
|
|
What makes IL-12? What does it do?
|
IL-12 is made by activated macrophages.
IL-12 actives NK cells to kill stressed/infected cells. |
|
|
|
How do inhibitory receptors of NK cells work? What are ITIMs, and how do they facilitate inhibitory signals?
|
Inhibitory receptors are linked to ITIMs (immunoreceptor tyrosine-based inhibitory motifs).
ITIMs are phosphorylated, then phosphorylated cytoplasmic protein tyrosine phosphatases. Tyrosine phosphatases de-phosphorylate signaling molecules, blocking the activation of NK receptors. Since inhibitory receptors are activated by "self" MHC molecules, self MHC shuts down NK cell activation, preventing healthy cells from being killed. |
|
|
|
Name some inhibitory receptors of NK cells.
|
Inhibitory receptors of NK cells:
- KIRs (killer cell immunoglobulin-like receptors) - CD94/NKG2 |
|
|
|
What cytokines activate NK cells?
|
NK-activating cytokines:
- IL-12 - IL-15 - IFNs (Type I interferons) |
|
|
|
How does the lectin pathway of complement fixation occur?
|
A plasma protein, mannose-binding lectin, attaches to terminal mannose residues on microbial glycoproteins.
Mannose-binding lectin triggers complement cleavage and opsonization. |
|
|
|
What cells secrete IL-12? What does it do?
|
IL-12 is secreted by macrophages and dendritic cells.
IL-12 stimulates T cells and NK cells to increase IFN-gamma production. IL-12 also causes T cells to differentiate into Th1 cells. |
|
|
|
Very high levels of what cytokine cause septic shock?
|
TNF (tumor necrosis factor)
|
|
|
|
What is an example of an acute-phase protein? How does it work in infection?
|
C-reactive protein (CRP) is an acute-phase protein made by the liver.
CRP binds to phosphorylcholine on microbes, opsonizing them for phagocytosis by macrophages. Macrophages have a receptor for CRP. |
|
|
|
What is an adjuvant, and why is it necessary when vaccinating?
|
Adjuvants are administered with protein vaccines because the immune system needs a "second signal" for activation.
Many good adjuvants are microbial products. These stimulate the cytokines necessary for a good second signal and immune system mobilization against the protein antigen. |
|
|
|
How does C3d work in B cell activation?
|
Complement fixation generates C3d, which attaches to bacteria.
C3d is recognized by the CR2 receptor on B cells. B cells recognize 1) microbial antigens, and 2) C3d on microbes; this causes B-cell activation. |
|
|
|
What is MHC restriction?
|
T cells can only see peptides when bound to that individual's own MHC molecules.
|
|
|
|
What are epidermal dendritic cells called?
|
Langerhans cells.
|
|
|
|
Where do mature dendritic cells go?
|
Mature dendritic cells take their antigens to the T cell-rich areas of the lymph nodes and spleen.
|
|
|
|
What activates dendritic cells? What happens to activated dendritic cells?
|
Inflammatory cytokines (TNF and IL-1) activate dendritic cells.
Activated dendritic cells lose their adhesive molecules for epithelial cells. Activated dendritic cells start producing CCR7, which is a receptor for chemokines produced by the T cell zones of lymph nodes. Thus, activated dendritic cells begin moving toward lymph nodes. |
|
|
|
What is CCR7?
|
CCR7 is a receptor for chemokines produced by T cell areas of lymph nodes.
CCR7 is expressed on the surface of activated dendritic cells, so activation causes them to move to the lymph nodes. CCR7 is also expressed by naive T lymphocytes, promoting their entry into the lymph nodes. When APCs and T cells are both present in the lymph nodes, they can meet. |
|
|
|
What stimulates dendritic cells that reside in the lymph nodes?
|
Soluble antigens in the lymph.
|
|
|
|
What stimulates dendritic cells in the spleen?
|
Blood-borne antigens stimulate spleen dendritic cells.
|
|
|
|
What are some receptors that are important in innate immunity?
|
G-protein coupled receptors: cytoskeletal changes, increased integrin avidity. Ligands = f-Met, chemokines, lipid mediators
Toll-like receptors: production of cytokines and chemokines (ex: CD14/TLR4 for LPS) Lectins: phagocytosis (ex: mannose-binding lectin) |
|
