Exam 1 Flashcards
(82 cards)
1
Q
Lymphoid tissues are composed of:
A
bone marrow (where all immune cells are made), spleen and lymph nodes
2
Q
Sequential steps of the immune system:
A
Innate: -barrier protection/breach -innate sensing -phagocytosis & oxidative burst -anti-microbial proteins/cells -antigen processing and presentation Adaptive: -T cell activation -B cell activation -Generation of high-affinity soluble antibody -T-cell mediation inflammation and pathogen clearance -development of memory B and T cells.
3
Q
- Primary lymphoid are:
- Secondary lymphoid are:
- Tertiary lymphoid are:
A
- fetal liver, bone marrow
- spleen, lymph node, MALT (mucosal associated lymphoid tissue)
- tissue-resident immune cells (lamina propria in the gut)
4
Q
Bone marrow is a:
A
pluripotent hematopoietic stem cell
5
Q
Common lymphoid progenitors are:
A
B cells (produce plasma cells), T cells, NK-cells, ILC, and immature dendritic cells.
6
Q
Common myeloid progenitors produce:
My-loid = most cells of the immune system
A
immature dendritic cells, neutrophils, eosinophils, basophils, unknown precursor mast cells, monocytes (macrophages)
7
Q
Macrophage:
A
phagocytosis and activation of bactericidal mechanisms. Antigen presentation
8
Q
Eosinophil:
A
killing of antibody coated parasites
9
Q
dendritic cell
A
antigen uptake in peripheral sites and antigen presentation
10
Q
basophil
A
allergic responses and anti-parasitic
11
Q
neutrophil
A
phagocytosis and activation of bactericidal mechanisms
12
Q
mast cell
A
release of granules containing histamine and active agents.
13
Q
The inflammatory innate response
A
1) Pathogens enter wound
2) Platlets from blood release blood-clotting proteins at the wound site
3) Mast cells secrete factors that mediate vasodilation and vascular constriction. Delivery of blood, plasma and cells to injured areas increases
4) Neutrophils secrete factors that kill and degrade pathogens
5) Neutrophils and macrophages remove pathogens by phagocytosis.
6) Macrophages secrete hormones called cytokines that attract immune system cells to the site and activate cells involved in tissue repair.
7) Inflammatory response continues until the foreign material is eliminated and the wound is repaired.
14
Q
T helper cells recognize complex of bacterial peptide with … and …
A
MHC Class 2
activates macrophages
15
Q
Cytotoxic T cell recognizes complex of viral peptide with … and …
A
MHC Class 1
kills infected cells
16
Q
Cause of cystic fibrosis
A
mutation of gene; CF patients produces such thick mucus that cilia can’t move around, leading to lung infection and inflammation.
17
Q
Anti-microbial peptides
A
made by neutrophils and epithelial cells; are short, cationic peptides. Are differentially active against different micro-organisms.
18
Q
Lysozyme
A
cleaves B1,4-linkage between GlcNAc and MurNAc in bacterial peptidoglycan
19
Q
Defensins
A
are brought into the lipid bilayer by the electrostatic and transmembrane electrical field. These peptides form a pore.
20
Q
Defensins, cathelicidins and histatins are activated by:
A
proteolysis to release an amphipathic antimicrobial peptide.
21
Q
CLR
A
transmembrane proteins localized at the plasma membrane recognize glycans from the wall of fungi and some bacteria. Activates kinase SYK and CARD9/Malt1/BCL10
22
Q
NLR Subfamilies: -A) NLRPs: -B) AIM2: -C) NOD1/NOD2:
A
cytoplasmic sensors
- A) recognize bacterial, viral, parasitic and fungal PAMPs and cell damage
- B) detects viral and bacterial DNA
- C) recognize bacterial peptidoglycan
23
Q
TLR
A
transmembrane proteins localized either at the plasma membrane or in the endosomes. Broad range of specificity recognizing proteins, nuc acids, glycans, etc. Activation of MAP kinase, NFkB and IRF pathways.
24
Q
RLR
A
cytoplasmic sensors of viral RNA
- signal through mito adaptor protein -MAVS
- triggers antiviral responses including the production of type 1 IFN.
25
TLRs activate ... transcription factors to induce expression of inflammatory cytokines and type 1 IFNs
NFkB, AP-1 and IRF
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Transmission of signal from plasma membrane to nucleus (TLRs):
TLR --> Adaptor --> kinase or Ub --> phos-TF --> translocation to the nucleus --> inflammation and IFN-1 genes
27
Cells need cytosolic PRRs:
TLRs are restricted to certain myeloid cell types. And cytosolic PRRs are more broadly expressed.
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Cytosolic (intracellular) PRRs are:
NLRs (bacterial, cell damage) and RLRs (viral RNA), and cytosolic DNA sensors
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NLRs:
NFkB and MAPK
30
NOD1/NOD2 receptors
intracellular sensors of bacterial infection and cell damage. NOD proteins reside in the cytoplasm in an inactive form. Binding of bacterial ligands induces RIP2 recruitment and then activation of TAK1 and NFkB activation.
31
NLRP
react to infection or cell damage through an inflammasome to induce cell death and inflammation (pyroptosis). The inflammasome activation requires 2 signals (priming and activation).
32
The RIGI-like receptors (RIGI/MDA5):
detect cytoplasmic viral RNAs and activate MAVs to induce type 1 interferon production and proinflammatory cytokines
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Cytosolic DNA sensors:
signal through Sting to induce production of type 1 IFNs. Cells are protected by CGAS when dividing by having CGAS bind to the nucleosome
34
When pathogens are found in the cytosol
A) peptides bind to:
B) and are presented to:
C) which results in:
A) MHC Class 1
B) Effector CD8 T cells
C) cell death
35
```
When pathogens are found in the intravesicle:
-degraded in endocytic vesicles
A) peptides bind to:
B) and are presented to:
C) which results in:
```
```
A) MHC class 2
B) effector CD4 T cells
C) macrophages are activated to kill intravesicular pathogen
```
36
```
When pathogens are found in extracellular space:
-degraded in endocytic vesicles
A) peptides bind to:
B) and are presented to:
C) which results in:
```
A) MHC class 2
B) effector CD4 T cells
C) Activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins.
37
Class 1 pathway:
- all nucleated cells
- antigen presentation to CD8 t cells
- cytosolic proteins degraded by the proteasome in the cytosol.
38
Class 2 pathway:
- DCs, macrophages and B cells (APCs)
- presentation to CD4 T cells
- proteins are degraded in endosomes and lysosomes
- can present endogenous proteins through autophagy
39
Cross presentation
DC presents Ag via class 1 pathway to CD8 T cells.
40
Cross presentation is needed because:
* many viruses do not infect APCs. Many tumor cells don't activate APCs.
* many viruses + tumors develop mechanisms to stop direct antigen processing in the host cell, thus cross-presentation provides an effective way of separating antigen from these inhibitory processes.
41
MHC is polygenic and polymorphic. For MHC polymorphism, most individuals will be ... and this is ... This is why siblings sometimes cannot be tissue donors..
MHC haplotype:
Naming: HLA-A*O2
heterozygous and codominant.
the particular combination of MHC alleles on a single chromosome.
```
A= gene
O2 = allele group
```
42
A) Syngenic (inbred strains)
B) Outbred
C) congenic
D) Example: The strain C57BL/6 was designated H-2^b haplotype and said to possess the "b" alleles at each MHC loci. Thus it is: H-2^b = K^b, D^b, L^b, I-A^b and I-E^b
A) identical at all genetic loci
B) different set of alleles at each loci
C) genetically identical except at a single loci
43
MHC restriction:
T cells could only be activated by APCs that shared MHC alleles with the mouse in which the T cells originated. MHC genotype "restricts" the antigen specificity of the T cells.
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Human class 1 MHC
HLA-A, HLA-B, HLA-C
| --> antigen presentation to CD8+ cells
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Human class 2 MHC:
HLA-DP, HLA-DQ, HLA-DR
| --> antigen presentation to CD4+ cells
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HLA-DM and HLA-DO:
regulate loading peptides
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Mouse class 1 MHC:
K, D, L (H-2D, H-2K, H2L)
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Mouse class 2 MHC:
A, E (I-A, I-E)
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cytokines
direct the growth, development, maturation, activation and life span of immune cells.
interferons, TNF, interleukins, transforming growth factor B and colony stimulating factors.
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chemokines
direct the movement of WBCs in the body
CC, C, CXC, CX3C
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Cytokines that mediate and regulate innate immunity:
IL1, TNF-alpha, IL6, IFN-a/B/gamm. These act on endothelial cells and leukocytes to stimulate innate responses.
52
Cytokines that mediate and regulate adaptive immunity:
IL2, IL4, IL5, TGF-B. Act on lymphocytes to stimulate and regulate adaptive responses.
53
Stimulators of hematopoiesis
stem cell factors, M-CSF and MG-CSF. These act on bone marrow to stimulate growth and differentiation of leukocytes and lymphocytes.
54
Interleukins:
A) IL-1
B) IL-2
C) IL-4
cytokines produced by one leukocyte acting on another leukocyte.
A) Inflammasome/inflammation
B) T cell proliferation
C) B cell switch (IgG--> IgE)(allergic)
55
TNF
- large superfamily of cytokines
- TNF-a is a major inflammatory cytokine involved in activating immune cells during infection and inflammation
- drives cell death
56
Colony stimulating factors (CSFs)
essential for differentiation of immature leukocytes in the bone marrow.
57
Inflammatory chemokines
produced in response to infection or injury and direct the migration of leukocytes into the infected or damaged site. CCL2 attracts monocytes while CXCL8 attracts neutrophils.
58
Hemostatic chemokines
control the migration of cells during the normal development and maintenance of tissues and lymphoid organs.
59
Angiogenic chemokines:
some chemokines promote (CCL2) or inhibit the development of blood vessels.
60
Inflammatory chemokines need:
chemokine, integrin and cell adhesion molecule (CAM) to recruit an innate cell from circulation
61
Acute phase response
- cytokines made by macrophages and dendritic cells induce a systemic reaction known as the acute phase response
- elevation of body temperature, IL6 (endogenous pyrogens) --> prostaglandin E2 --> hypothalamus --> fever
- these cytokines also act on liver hepatocytes that produce acute-phase proteins in the blood.
Activated macrophages secrete many cytokines and chemokines
62
Complement Pathway
- more than 30 proteins produced by the liver
- circulate in an inactive state
- complement destroys microbes in 3 main ways:
1) inflammation
2) opsonization (phagocytosis
3) cytolysis (membrane attack)
63
Apoptosis
programmed cell death, casp3/7 activation, non-inflammatory
extrinsic: by transmembrane death receptors, including FasL, TNFR1, Apo1/Apo3
intrinsic: release by signaling factors from mitochondria.
64
Pyroptosis
-inflammasome mediated cell death, casp 1/11
Upon recognition of DAMPs and PAMPs, NLRs induce the assembly of the inflammasome, which is comprised of NLR, ASC and caspase 1 to drive activation of caspase 1 and IL18 and induce py
Gasdermin D cleavage fragment form pores on the membrane for release of cytokines and cell lysis
65
Necrosis
-unnatural cell death in tissue due to lack of blood flow; caspase independent
66
Monocytes and macrophages
- monocytes circulate in the blood, bone marrow and spleen
- migrate from blood to tissues during infection
- produce inflammatory cytokines and take up cells and toxic materials
- differentiate into inflammatory DCs or macrophages
67
Macrophage main functions
- major phagocytes resident in most tissues
- derived from progenitor cells or from circulating monocytes
- express many PRRs
- During infection: efficient at phagocytosis and production of inflammatory cytokines
- participates in wound healing by removing apoptotic cell debris and promoting anti-inflammatory response
- macrophages kill microbes in phagolysosomes.
- MTB blocks phagosome-lysosome and replicates in vacuoles. MTB exploits macrophages for replication.
68
G-coupled protein receptors (GPCRs) -other receptors that signal phagocytic killing of microbes
- largest, most diverse group of membrane receptors
- inform cells about presence/absence of life-sustaining light/nutrients in their environment
- GPCRs on phagocytes link microbe recognition with increased efficiency of intracellular killing LfMLF receptor. Protein synthesis in bacteria is typically initiated with an N-formylmethionine (fMet) residue, an amino acid present in prokaryotes, but not eukaryotes.
69
Neutrophils
phagocytosis and activation of bactericial mechanisms
- most abundant WBC
- very short life span
- acts as first line of defense: migrates through blood vessels to enter the site of infection
- phagocytosis and kills pathogens
- neutrophils die and release extracellular contents to make NETs (neutrophil extracellular traps). these NETs contain DNA and activate IFN.
70
Selectin
selected lectin; allows leukocytes to roll along the vascular endothelial surfaces
71
Drugs good at preventing immune cell infiltration in tissues?
Glycoproteins (E selectin, P-selectin) and CXCL8/IL8, Integrins and ICAM1
72
Conventional DCs
- specialized antigen processing and presenting cells
- high phagocytic activity as immature cells and high cytokine-producing capacity as mature cells
- present in large numbers in peripheral tissues
- highly migratory --> move from tissues to T cell and B cell zones of lymphoid organs via afferent lymphatics and high endothelial venules
- regulate T cell responses both in the steady state and during infection
73
Immature dendritic cells reside in the ... Dendritic cells migrate via lymphatic vessels to regional lymph nodes. Mature dendritic cells activate naive T cells in lymphoid organs such as lymph nodes.
peripheral
74
Plasmacytoid DCs (Type 1 IFN producing cells)
- circulate through the blood and lymphoid tissues
- selectively express TLR7 and TLR9 and are specialized in rapidly secreting massive amounts of type 1 IFN following viral stimulation.
- can promote the function of natural killer cells, B cells, T cells and myeloid DCs through type 1 IFNs.
75
Follicular DCs
-reside in the primary B-cell follicles and germinal centers of lymphoid tissues.
Functions:
- organize histoarchitecture of lymphoid follicles
- capture and retain antigens for presentation to B cells
- engulfment of apoptotic bodies
76
Natural Killer Cells
- release lytic granules that kill some virus infected cells
- similar to cytotoxic T cells, but with broader specificity
- cytotoxic w/o prior sensitization, releases granules and cytokines immediately upon activation
- killing activity can be enhanced by type 1 IFN
- multiple roles in innate immunity (A-tumor/A-viral)
77
NKCs - 2 ways of recognizing a target
A) Activating
B) Inhibitory
A) recognize host-encoded molecules induced or transformed on infected cells or non-self ligands
B) recognize self ligands, such as MHC Class 1.
78
Perforin
- found exclusively in the cytoplasmic granules of killer cells.
- perforin KO mice are more susceptible to tumors and infection
- pore forming protein of plasma membrane or endosome allowing granzymes to enter target cell cytoplasm
79
Granzyme B:
- protease located in cytoplasmic granules of killer cells
- cleaves after Asp residues in caspase 3 and 7
- kills bacteria directly
80
Innate lymphoid cells (ILCs)
- growing family of immune cells that mirror the phenotypes and functions of T cells.
81
1) NK cells are innate counterparts to:
2) ILC1, ILC2 and ILC3:
ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins, termed cytokines that direct the developing immune response.
1) cytotoxic CD8+ T cells
| 2) innate counterparts of CD4+ T helper cells
82
Complement System:
A) Opsonization
B) Cell lysis
C) Inflammation
A) C3B activates macrophages and via phagocytosis, engulfs microorganisms
B) C5b initiates membrane attack complex, which ruptures bacterial cell wall
C) C3a and C5a activate mast cells and basophils, which cause large amounts of inflammation.
