immuno molecules Flashcards
TNF principle cell source
macrophages, T cells
TNF cellular targets and biologic effects
Endothelial cell: activation (inflammation, coagulation) Neutrophils: activation Hypothalamus: fever Liver: synthesis of acute phase proteins Muscle:catabolism (cachexia) Fat: catabolism (cachexia) Many cell types: apoptosis
IL-1 source
Macrophages, endothelial cells, some epithelial cells
IL-1 targets and effects
Endothelial cells: activation (inflammation and coagulation)
Hypothalamus: fever
Liver: synthesis of acute phase proteins
Chemokines source
Macrophages, endothelial cells, T lymphocytes, fibroblasts, platelets
Chemokines targets and effects
Leukocytes: chemotaxis, activation
IL-12 source
Macrophage, dendritic cells
IL-12 targets and effects
NK cells: IFN-gamma synthesis, increased cytolytic activity
T cells: IFN-gamma synthesis, increased cytolytic activity, TH1 differentiation
IFN-gamma source
NK cells, T lymphocytes
IFN-gamma targets and effects
Activation of macrophages,
stimulation of some antibody responses
IFN-alpha source
Macrophages
IFN-alpha targets and effects
All cells: antiviral state, increased class I MHC expression NK cells: activation
IFN-beta source
Fibroblasts
IFN-beta targets and effects
All cells: antiviral state, increased class I MHC expression NK cells: activation
IL-10 source
Macrophages, T cells (mainly TH2)
IL-10 targets and effects
Macrophages: inhibition of IL-12 production, reduced expression of costimulators and class II MHC molecules
IL-6 source
Macrophages, endothelial cells, T cells
IL-6 targets and effects
Liver: synthesis of acute phase proteins
B cells: proliferation of antibody-producing cells
IL-15 source
Macrophages, others
IL-15 targets and effects
NK cells: proliferation
T cells: proliferation
IL-18 source
Macrophages
IL-18 targets and effects
NK cells: IFN-gamma synthesis
T cells: IFN-gamma synthesis
What cytokines are produced by macrophages
TNF, IL-1, Chemokines, IL-12, IFN-gamma, IFN-alpha, IL-10, IL-6, IL-15, IL-18
What cytokines target macrophages? What is the effect of each?
IFN-gamma: activation
IL-10: inhibition of IL-12 production
What cytokines are produced by T cells?
TNF, chemokines, IFN-gamma, IL-10, IL-6
What cytokines are produced by endothelial cells?
IL-1, chemokines, IL-6
What cytokines are produced by some epithelial cells?
IL-1
What cytokines are produced by fibroblasts?
Chemokines, IFN-beta
What cytokines are produced by platelets?
Chemokines
What cytokines are produced by NK cells?
IFN-gamma
Which cytokine does this? Endothelial cell: activation (inflammation, coagulation) Neutrophils: activation Hypothalamus: fever Liver: synthesis of acute phase proteins Muscle:catabolism (cachexia) Fat: catabolism (cachexia) Many cell types: apoptosis
TNF
Which cytokine does this?
Endothelial cells: activation (inflammation and coagulation)
Hypothalamus: fever
Liver: synthesis of acute phase proteins
IL-1
Which cytokine does this?
Leukocytes: chemotaxis, activation
Chemokines
Which cytokine does this?
NK cells: IFN-gamma synthesis, increased cytolytic activity
T cells: IFN-gamma synthesis, increased cytolytic activity, TH1 differentiation
IL-12
Which cytokine does this?
Activation of macrophages,
stimulation of some antibody responses
IFN-gamma
Which cytokine does this? All cells: antiviral state, increased class I MHC expression NK cells: activation
IFN-alpha
IFN-beta
Which cytokine does this? Macrophages: inhibition of IL-12 production, reduced expression of costimulators and class II MHC molecules
IL-10
Which cytokine does this?
Liver: synthesis of acute phase proteins
B cells: proliferation of antibody-producing cells
IL-6
Which cytokine does this?
NK cells: proliferation
T cells: proliferation
IL-15
Which cytokine does this?
NK cells: IFN-gamma synthesis
T cells: IFN-gamma synthesis?
IL-12, IL-18
What are the systemic effects of IL-1beta?
Fever and production of IL-6
What are the local effects of IL-6?
Lymphocyte activation and increased antibody production
What are the local effects of IL-8?
Chemotactic factor recruits neutrophils, basophils, and T cells to site of infection
What are the local effects of IL-12?
Activate NK cells and induces CD4 T cells to differentiate to TH1 cells;
These then release IFN-gamma cells, which activates macrophages
TLR2 ligands
bacterial lipopeptides (with TLR1), bacterial peptidoglycan
TLR1 ligands
bacterial lipopeptides (with TLR2)
TLR4 ligands
LPS (lipopolysaccharide) (MD2 on external side of transmembrane protein)
TLR5 ligands
bacterial flagellin
TLR6 ligands
bacterial lipopeptides (with TLR2)
TLR3 ligands
dsRNA (endosome)
TLR7 ligands
ssRNA (endosome)
TLR8 ligands
ssRNA (endosome)
TLR9 ligands
CpG DNA (endosome)
gram positive bacterial ligands
lipoteichoic acid
What are opsonins?
small complement proteins that deposit on microbes and enhance their uptake by phagocytes bearing complement receptors
what are chemotactic factors?
small complement proteins that attract immune cells
What are anaphylatoxins?
small complement proteins that cause degranulation of mast cells/basophils and release vasoactive substances
What are 3 ways of complement activation?
classic, alternative, and lectin pathway
describe the classic complement activation pathway
activated by antigen-antibody complex
describe the alternative complement activation pathway
activated by microbial cell wall
describe the lectin complement activation pathway
interaction of microbial carbohydrates with mannose-binding protein in the plasma activates this
What are some key points on neutrophils:
1st cell to arrive;
respiratory bursts and release of granules controls bacterial growth
What are some key points on eosinophils?
contain cationic granule proteins; fight helmithes and other multicellular parasites
What are some key points on NK cells?
kill infected host cells via cytolytic mediator perforin
What site does neutrophils and monocytes enter tissue at?
post-capillary venules, except parenchymal tissues (liver, lungs, kidney) where all blood cells enter through capillaries
IL-8 target and effect
chemoattractant for neutrophils
what are microbicidal mechanisms for neutrophils?
cathepsin G, defensins, BPI, lactoferrin, lysozyme
Describe cathepsin G
a Ser protease that digests collagen and proteoglycans
Describe Defensins
inserted into membrane of microbes to destabilize ion channels
describe lysozyme
splits bacterial cell wall
What are MCP1, MIP1alpha and beta?
Macrophage inflammatory proteins:
chemoattractants for monocytes
Which cytokines activate macrophages directly?
IFN-gamma, TLR-ligands
Which cytokines inactivate macrophages and cause antiinflammatory responses?
IL-13, IL-4
Describe fMet
N-formylmethionyl peptide is present in prokaryotes and not in eukaryotes;
bind to 7transmambrane receptor proteins and cause increased integrin avidity in neutrophils and macrophages MIGRATION INTO TISSUES
What are the direct functions of NK cells?
recognize infected and distressed cells;
release granules to kill them
What are the indirect functions of NK cells?
secrete IFN-gamma (macrophage)
What activates NK cells?
failure to detect Ag expressed on healthy cells (MHC-I) class one major histocompatibility complex
What is KIR?
killer-cell immunoglobulin-like receptor; is the inhibitory receptor which is activated by no change in MHC-I;
upon inactivation NK cells go to town
describe CD4
Th cells express this and it “directs” Th cells to Ags presented by class II MHC (dendritic cells and macrophages APCs)
Describe CD8
directs Cytolytic T cells to Ags presented by class I MHC (all cells that express Ags from virus or other microbe inside of them)
describe haptens
require carrier molecules to be immunogenic, rxn with specific antibodies when homologous carriers are not employed, interact with specific antibody even if the hapten is monovalent, they cannot stimulate secondary antibody responses without carriers
Which interleukin is the main regulator of the complement protein production?
IL-6
acute phase proteins (hepatocytes)
describe granzyme b
serine protease (NK cells and CTL)
What are the enzymes used by phagocytes to kill.
NADPH oxidase, superoxide dismutase, myeloperoxidase, glutathione reductase, G6PD
fc receptor
binds to antibody which is bound to the pathogen
IgA
mucosal immunity, neonatal passive immunity
IgD
Naive B cell antigen receptor
IgE
Mast cell activation (immediate hypersensitivity)
IgG
opsonization, complement activation, antibody dependent cell mediated cytotoxicity, neonatal immunity, feedback inhibitor of B cells
IgM
Naive B cell antigen receptor, complement activation
Antibody neutralization
neutralize viruses, bacterial toxins (LPS), and other harmful substances by blocking their interaction with cell surface receptors
Antibody agglutination
cross-linking occurs because Abs possess two identical Ag-binding sites; therefore microbes can be agglutinated into mesh-like structures called immune complexes
Antibody activation of complement
Abs can trigger an activation of complement cascade via classical pathway
Antibody opsonization
Abs can bind to Fc receptors on macrophages and neutrophils that enhances phagocytosis
Antibody degranulation
Mast cells, basophils, eosinophils: IgE binding to Fc receptors on the cells
antibody-dependent cell-mediated cytotoxicity (ADCC)
Fc receptors on NK cells; Ab-tagged killing of tumor cells and virus infected host cells
Gram-positive bacteria receptor
TLR-2
Gram-negative bacteria receptor
TLR-4
Which cells use class II MHC proteins?
Dendritic cells: present to naive T cells
Macrophages: present to activated (effector) T cells
B cells: present to activated (effector) T cells
Which cells cannot recognize antigens unless they are associated with MHC molecules?
T cells
Which cells end up expressing class I MHC more than others?
Neutrophils
What are the 3 genes which encode for class I MHC?
human leukocyte antigen (HLA)
HLA-A
HLA-B
HLC-C
Which cells does class I MHC present Ag to?
CD8+ T cells
CTL
What are the 3 genes which encode for class II MHC?
DR
DP
DQ
What cells does class II MHC present Ag to?
CD4+ T helper cells
What length of peptides does class II MHC bind to?
13-25 amino acids
What length of peptides does class I MHC bind to?
8-11 amino acids long
What is the main structural difference in the binding site on class I vs class II MHC?
Class I has two alpha1 domains
Class II has an alpha and a beta domain which presents the peptide
What is the functional difference between class I and class II MHC?
class I: alarm CD8 cells about danger occurring inside the cells (pathogen inside of cell) class II: alarm CD4 cells about danger happening outside of the cells (phagocytes uptake the pathogen)
What is the function of the invariant chain?
class II MHC needs to be synthesized and stored “at ready” in a endosome. It order to keep it from binding to it’s own proteins during synthesis the invariant chain is bound until removed by HLA-DM (in presence of alien peptides)
Which cells do not express class I MHC?
non-nucleated cells and cells that have class II MHC
Which cells express class II MHC?
dendritic, mononuclear phagocytes, B cells, endothelial, thymic epithelium
what is the difference between the beta microglobulin and the beta chain (MHC)
beta microglobulin is a smaller part of the class I MHC dimer Beta chain is the second half of the class II MHC dimer
What is required to keep MHC molecules stable?
the displayed peptide keeps the molecule stable, without it the MHC complex falls apart
What is the exception from the rule regarding class I MHC?
Ags taken up from outside can be presented by class I MHC
what are plasma cells?
formerly b cells; secrete Abs from lymphoid organs
What is needed to activate B cells?
It does not need antigen presenting cells
What are the surface Ig’s
IgM, IgD
What Ag can BCRs recognize?
any Ag (lipid, protein, carb, DNA)
What is needed to activate T cells?
First: APC must present with MHC;
Second: APC must costimulate the T cells
Describe CD3
identification marker for all T cells
What is the difference between resting and active APCs?
resting: not expressing costimulatory molecules to activate T cells
active: is expressing high levels of MHC and costimulatory molecules
describe the immunological synapse
The TCR and MHC comlex is weak; so upon binding a chemokine signals to integrins on the T cell and APC to bind
What are the integrins involved in the immunological synapse?
LFA-1 and ICAM-1
What is the costimulatory pair of proteins between the T cell and the APC
B7 and CD28
What is the specific marker of B cells?
CD19
What are the two mechanisms of B cell activation?
protein Ags activate B cells with the assistance of T helper cells (thymus dependent TD)
other Ags are activated without help (thymus independent: TI)
What is the ligand that Th2 cells use to activate B cells?
CD40
CD40L
what is the most important function of TLRs
activate macrophages
what is the most important function of TLRs
activate macrophages
what molecule is an anaphylatoxin?
C5a
describe the steps in the classical pathway of complement activation
Ab and Ag bind, attract C1; C1 cleaves C2 and C4; C4b (covalent) C2a bound to bacteria; C3 convertase, C3b bound to bacteria as opsonin tag C3b+C3=C5 convertase