Exam #1 Flashcards
1
Q
VLA-4
A
High affinity integrins on monocytes that interact with VCAM-1 (high affinity integrin ligand) on the luminal side of the endothelium.
2
Q
Caspase-1
A
Enzyme that activates IL-1 (combines with NLRP-3 to form inflammasome).
3
Q
DAMPs
A
(Damage Associated Molecular Patterns)
Released from damaged or necrotic cells.
4
Q
CC- chemokines
A
Chemokines that are generally associated with monocyte recruitment (in addition to lymphocyte recuitment; as are the CXC- chemokines).
The chemokines of the CC and CXC subfamilies are produced by leukocytes and by several types of tissue cells, such as endothelial cells, epithelial cells, and fibroblasts
5
Q
IRF-3
A
(Interferon Regulatory Factor): Antiviral transcription factor in TLR signalling pathway —>Induces production of type-1 interferon (e.g. IFN-alpha/ß/gamma) in the nucleus.
Induces antiviral state.
L3 #26
6
Q
CH50
A
Hemolytic units –Used to quantify complement activity; the dilution of serum which lyses 50% of standardized suspension of AB-coated RBCs.
7
Q
NKG2D
A
NK activating receptor –Activated by “MHC-like” molecule that is expressed in response to cellular stress.
8
Q
IL-4 and IL-13
A
Cytokines the activate macrophages in the absence of strong TLR signals, inducing the macrophages to function in reducing inflammation and in tissue repair.
9
Q
IKK-gamma/NEMO
A
Signalling intermediate in TLR pathway that activates NF-kB; defects prevent activation of NF-kB, resulting in depressed responses to TLR signals (L3, #21).
10
Q
PNAd
A
Peripheral node addressin –Ligand on HEVs that bind L-selectin expressed on T cells and facilitates their migration into the LN stroma.
11
Q
Digestion of antibody with PAPAIN yields what?
A
Fab (x2) and Fc (x1) #25
12
Q
G-CSF (Granulocyte Colony-Stimulating Factor)
A
Produced at site of infection; increased neutrophil production by bone marrow.
13
Q
IL-1
A
Chemokine released by MPGs, DCs, FBs, endothelial cells, etc. that activates endothelial cells. Stimulates endothelium to express E and P selectin
14
Q
FRs
A
Framework regions –relatively conserved regions outside the CDRs on which hypervariable regions are suspended. #19
15
Q
Two co-stimulators for T cell activation
A
CD80 (B7-1), CD86 (B7-2).
Expressed by DCs, MPGs, and activated B cells
16
Q
ADCC
A
Antibody-dependent cell-mediated cytotoxicity: NK cells bind to antibody-coated cells via the affected cells antibody receptor (CD16).
17
Q
IL-1 and TNF-alpha
A
Pleiotropic inflammatory cytokines that activate endothelium. Released by macrophages upon PAMP/DAMP recognition stimulation.
18
Q
IL-8 (CXCL8) functions (3)?
A
Chemotactic factor that recruits NEUTROPHILS, basophils, and T cells to site of infection.
19
Q
LPS
A
(Lipopolysaccharide): PAMP of gram-negative bacteria. Human TLR4 recognizes LPS on gram-negative bacteria.
20
Q
CCL2
A
Chemokine secreted by macrophages and activated endothelium; presented/expressed on luminal side of endothelium where it can be sensed by monocytes (via chemokine receptor CCR2) and stimulate them to express the high affinity integrin (VLA-4).
21
Q
- ) Perforin
2. ) Granzymes
A
- ) Method of NK cell induced apoptosis –Perforin creates pores in endosome to deliver granzymes to cytoplasm of target cell.
- ) Activates apoptotic pathway of target cell.
22
Q
PRRs
A
(Pattern Recognition Receptors)
Mediates PAMP recognition.
23
Q
Regulatory T cells CD
A
CD-4, CD-25
24
Q
IRAK-4
A
IL-1 receptor associated with kinase 4; is a critical kinase downstream of TLRs and IL-1 receptor (defects manifest in early life with severe invasive bacterial infections).
25
M2 (Alternatively Activated Macrophages)
Macrophages activated by cytokines such as IL-4 and IL-13, in the absence of strong TLR signals, and function in reducing inflammation and in tissue repair.
26
C1 INH
C1 Inhibitor – Stops activation of the classical pathway by interfering with the C1q component.
27
IFNg (gamma)
Produced by activated NK cells; activates macrophages to boost intracellular killing.
28
MCP
Membrane cofactor protein – A cofactor for the proteolysis of C3b into inactive fragments (displaces Bb from C3b); a process that is mediated by a plasma enzyme called *factor 1*.
*Prevents C'-mediated damage to host cells*
29
E and P Selectin
Adhesion molecules expressed by endothelium after stimulation by IL-8. Interacts with neutrophils to cause low affinity binding and rolling of the neutrophil.
30
Helper T cell CD
CD3, *4*
31
Selectin Ligands; also, E-, P-, and L-Selectin
Low affinity ligands (e.g. CLA-1 on T cells) expressed by neutrophils (or lymphocytes) that bind with E and P selectin, creating low affinity binding.
Selectin: Adhesion molecules expressed by endothelium after stimulation by IL-8. Interacts with neutrophils to cause low affinity binding and rolling of the neutrophil.
P-selectin (CD62P): Expressed on platelets and activated endothelium.
E-selectin (CD62E): Expressed on activated endothelium.
L-selectin (CD62L): expressed on leukocytes.
32
CXCR1 and 2
IL-8 receptor on neutrophils.
33
CXCR5
Chemokine receptor expressed by naive B cells, attracting them to the follicles of LNs. CXCR5 binds to CXCL13, produced *only in the follicles of LNs*
34
C3a
Complement C-activation product that is chemotactic for neutrophils, mast cell degranulation (making C3 an *anaphylotoxin*), and increases vascular permeability.
*C3 gradient attracts neutrophils*
35
IFN-gamma
Key cytokines involved in activating macrophages. Known as *immune interferons*
36
IL-6 functions (2)?
Lymphocyte activation, increased AB production.
37
LFA-1, MAC-1
High affinity integrins on neutrophils that interact with ICAM-1 (high affinity integrin ligand) on the luminal side of the endothelium. Part of the ß2 integrin family.
38
IL-1ß function (4)?
Activates vascular endothelium, activates lymphocytes, local tissue destruction, increases access for all effector cells.
39
Fc
Fragment Crystalline: Portion of antibody composed only of remaining heavy chains below the antigen-binding region (#22).
• Macrophages will recognize the Fc portion.
40
CCR2
CCL2 chemokine receptor on macrophages/monocytes.
41
CD-18
Gene responsible for the expression of LFA-1 and MAC-1 ß2 integrins; deficiency of which causes LAD1.
42
Isotypes
```
One of five types of antibodies. Differences between constant regions due to usage of different constant-region genes (e.g. IgM, IgE, IgG, etc.)
Each different isotype performs a different set of *effector functions,* but its SPECIFICITY REMAINS THE SAME!
#43
```
43
NLRs
(Nod-Like Receptors): Type of PRR – Microbial products, damaged tissues.
44
TLR4
Human TLR that recognizes LPS on gram-negative bacteria.
45
IL-10
```
Suppresses activation of macrophages to reduce/suppress inflammation.
#22
```
46
Fab
```
Fragment antigen-binding: Fragment of antibody that contains an entire light chain attached to the variable and first constant domain of the heavy chain.
#21
```
47
Kd
```
A measure of *affinity* —> Molar concentration of an antigen required to occupy 1/2 of the available antibody molecules in solution.
*LOWER Kd = HIGHER affinity*
#47
```
48
NLRP-3 (Nod-like Receptor)
Senses bacterial products as well as substances that indicate cell damage and death (e.g. Intracellular crystals (urate, silica); changes in cytosolic ATP and ion concentrations; lysosomal damage).
LOCATION: Cytosol of phagocytes, epithelial cells, and other cells.
p.55
49
L-Selectin (CD62L)
Surface receptor/Selectin expressed by lymphocytes (B and T cells) – mediates HEV endothelial adhesion and lymphocyte migration into LN stroma.
50
Biological effects of C5a?
Mast cell degranulation (anaphylotoxin), chemotactic for neutrophils, *STIMULATION OF OXIDATIVE METABOLISM*, LEUKOTRIENE RELEASE.
51
IFN-alpha
Leukocyte interferon.
52
IL-1
Inflammatory cytokine produced by macrophages in response to infection. They induce chemokines which ultimately result in inflammation and fever.
53
Biological effects of C2b?
Edema
54
Polymorphism
The existence of two or more alternative forms, or variants, of a gene that are present at stable frequencies in a population. Each common variant of a polymorphic gene is called an allele, and one individual may carry two different alleles of a gene, each inherited from a different parent. The MHC genes are the most polymorphic genes in the mammalian genome, some of which have thousands of alleles.
p.485
55
CCL19 and CCL21
Chemokines produced by stromal cells in the T cell region of LNs (parafollicular region). Attracts activated DCs and naive T cells that express the chemokine receptor CCR7.
56
TNF-alpha functions (6)?
Activates vascular endothelium and increases vascular permeability – which leads to increased entry of IgG, complement, and cells to tissues, and increased fluid drainage to LNs.
57
NF-KB
(Nuclear Factor): Nuclear factor (TF) involved in TLR pathway for acute inflammation, and also stimulates adaptive immunity —> Increases expression of cytokines, adhesion molecules, and costimulators.
*If not activated, prevents the whole signalling pathway*.
L3 #26, #3njp
58
IFN
Type 1 Interferons (IFNs) – Large family of related cytokines that mediate the early innate response to viral infections.
L6, #18
59
What is the most variable region of the Ig molecules and contributes most to antigen binding?
```
CDR3.
#17
```
60
MBL
Mannose-Binding Lectin – An acute-phase reactant produced by the liver during periods of inflammation.
*Initiates the Lectin Pathway* #19 L5
61
CDR
```
Complementarity-determining regions: Short stretches of hypervariability concentrated with the variable regions of Igs.
*Each variable region of the light or heavy chains contains THREE CDRs*
#17
```
62
Inflammasome
Cytosolic NLRP-3 and caspase-1 complex; disregulation of which causes autoinflammatory syndromes characterized by uncontrolled and spontaneous inflammation.
*Caspase-1 activates IL-1ß, which activates the vascular endothelium*.
63
DAF
Decay Accelerating Factor – Disrupts the C3 convertase in the alternative and classical/lectin pathways.
*Prevents C'-mediated damage to host cells*
64
cDC
Conventional dendritic cell – Captures antigen in peripheral tissue and presents it to adaptive immune cells in draining lymph node.
*Produce TNF and IL-6 to induce T cell response against most antigens*
65
B cell CD
CD19, 20, 21
66
FasL, Fas
FasL = Cell surface ligand engaged by NK cells that bind to the death receptor Fas and, upon activation/engagement by NK cells, induce apoptosis in the targeted cell.
67
Name three cytokine pyrogens
```
IL-1, IL-6, TNF-alpha
#22
```
68
Cytotoxic T cell CD
CD 3, *8*
69
ITIMSs
Inhibiting receptors on NK cells (active when MHC class-1 are present); engage MHC class-1 and inhibit NK (#47, L4).
70
PAMPs
(Pathogen Associated Molecular Patterns)
| Shared among broad groups of microbes/pathogens – *NOT ON HOST CELLS*
71
ITAMs
Activating receptors on NK cells (active when MHC class-1 not present); engage stress/virus induced surface molecules (#46, L4).
72
IL-8 (CXCL8)
Chemokine secreted by macrophages and activated endothelium; presented/expressed on luminal side of endothelium where it can be sensed by neutrophils (via chemokine receptor CXCR1 and CXCR2) and stimulate them to express high affinity integrins (LFA-1, MAC-1).
SUPER IMPORTANT!
73
Antibody Receptor (CD16)
NK activating receptor – Activated by antibodies bound to cells.
74
TLRs
(Toll-Like Receptors): Major family of PRRs. Mammalian TLRs are involved in responses to a wide variety of molecules that are expressed by microbial but not by healthy mammalian cells. The ligands that the different TLRs recognize are structurally diverse and include products of all classes of microorganisms. Examples of bacterial products that bind to TLRs are LPS and lipoteichoic acid, which are constituents of the cell walls of gram-negative bacteria and gram-positive bacteria, respectively, and flagellin, the protein subunit component of the flagella of motile bacteria.
p.56
75
Biological effects of C4b?
Opsonin, removal of immune complex
76
IL-1ß
Activated by caspase-1 and secreted to induce inflammation and cause fever. Activates vascular endothelium and lymphocytes, and induces local tissue destruction (#37, L4). Induces production of IL-6.
77
ICAM-1 (neutrophils) and VCAM-1 (monocytes)
Integrin ligand expresse on the luminal surface of endothelium; interacts with MAC-1 and LFA-1 (or VLA-4) to produce high affinity interaction between endothelium and neutrophil.
78
Where are the two types of TCRs mainly found and how do they recognize their AG (w/ regards to molecular composition of AG and whether or not it need MHC presentation)?
1.) Alpha-beta: Lymphoid tissue – Recognizes AG only in the context of cell-cell interaction and *in correct MHC context.*
2.) Gamma-delta: Mucosal surfaces – Recognizes protein and non-protein AG in an *MHC-independent manner*.
#57, 61
79
ß2 integrins
Includes LFA-1 and MAC-1; expression mediated by CD18 gene.
80
CXC- chemokines
Chemokines that are generally associated with neutrophil recruitment (in addition to lymphocyte recruitment; as are CC- chemokines).
*The chemokines of the CC and CXC subfamilies are produced by leukocytes and by several types of tissue cells, such as endothelial cells, epithelial cells, and fibroblasts*
81
Most dendritic cells arise from the _______ lineage
```
Myeloid lineage
#8, L7
```
82
IL-7
Hematopoietic cytokine that induces proliferation of B and T lymphocytes; produced by fibroblasts and bone marrow stromal cells.
Secreted by *thymic cortical cells*; required for early T cell development in the thymus.
83
IL-12 functions (2)?
Activates NK cells, induces differentiation of CD4 T cells into TH1 cells.
84
Biological effects of C4a?
Stimulates inflammation, chemotactic for neutrophils.
85
GM-CSF and M-CSF
Colony-stimulating factors that stimulate production of monocytes by the bone marrow.
86
M1 (Classically Activated Macrophages)
Macrophages activated by microbes through TLRs or by key cytokines (e.g. IFN-gamma, #32).
87
CRP
C-reactive protein: Acute phase protein made in the liver; production induced by IL-1, 6, and TNF-alpha – Binds to phosphorylchlorine on microbes and coats the microbes for phagocytosis by macrophages, which express a receptor for CRP.
*CRP can also trigger the classical pathway*
L6, #12
88
Monocyte/macrophage CD
CD-14
89
CCR7
Chemokine receptor expressed by activated DCs; causes them to migrate from peripheral tissue to LN for antigen presentation. CCR7 binds CCL19 and CCL21 produced in the T cell region of LNs (paracortical region).
*Naive T cells also express CCR7 and are drawn to LN*
90
IFN-ß
Fibroblast interferon – fibroblasts, epithelial cells, etc.
91
Biological effects of C3b?
Opsonization, phagocyte activation, *immune complex removal*
92
Which cells arise from a common *lymphoid* progenitor?
B cells, T cells, NK cells.
93
IL-12
Cytokine produced by activated macrophages – activates NK cells, which then produce IFNg, which activates macrophages further and boosts intracellular killing.
*Important in shaping the adaptive immune response (even though it is an innate cytokine)*
94
1. ) Dendritic cells arise from which type of precursors?
| 2. ) Where do they present?
1. ) Myeloid precursors in the bone marrow.
| 2. ) Lymphoid organs, epithelia of the skin, GI and respiratory tracts.
95
IFN-alpha and beta
Key cytokines involved in viral infections – They increase the capacity to present antigen to the cells of the adaptive immune system (e.g. they increase MHC class 1 expression and antigen presentation in all cells.
96
Idiotypes
```
Differences due to rearranged Vh and Vl genes (differences in light and heavy genes of the variable regions).
*Refers to antigen specificity*
#43
```
97
IFN-gamma
Immune interferon – produced by certain activated T cells, NK cells. Important in the activation of *MACROPHAGES*
98
T cell CD (in general)
*CD3*, CD2
99
pDC
Plasmacytoid dendritic cell – Found in draining LNs; recruited to sites of inflammation, where they become activated and produce large amounts of Type 1 Interferons.
*Induce T cell response against viruses*
100
Allotypes
```
Differences due to different alleles at the same constant region genes (i.e. polymorphic differences in C-region genes between individuals).
*Influenced by parental genetics*
#43
```
