Immunology exam 1 Flashcards

(103 cards)

1
Q

Pro B cells

A

The earliest identifiable cells of the B-cell lineage. The main event in the pro-B stage in the rearrangement of the heavy chain genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Early Pro B cell

A

Joining of D (H) and J (H) segments occurs at this stage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Late Pro B cell

A

Joining of a V (H) segment to the rearranged DJ (H)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Large Pre-B cell

A

successfully rearranged a heavy chain gene and make a mu heavy chain, they have stopped have stopped heavy chain rearrangement. Light chain not yet rearranged

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Small Pre- B cell

A

Rearrangement of light chain genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Immature B cell

A

VDJ rerranged, VJ rearranged, mu heavy and lambda or kappa light chain IgM on surfance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Stromal Cell in B cell Dev- functions

A

1) Make specific contact with the developing B cells through the interaction of adhesion molecules and their molecules. 2) Produce growth facts that act on the attached B cells ex: membrane-bound stem cell factor (SCF), which is recognized by Kit on maturing B cells, growth factor IL-7 that is a cytokine that acts on late pro-B and pre-B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Nonproductive rearrangements

A

Gene rearrangements that do not translate into a useful protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

RAG1 and RAG2 - recombination-activating genes

A

Proteins that is needed for DNA rearrangement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

E2A and EBF

A

Transcription factors responsible for changing gene expressions of RAG1 and RAG2. Also cause the expression of Pax-5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Pax-5

A

Transcription factor that is responsible for switching on the genes for many proteins that are expressed only in B cells, including Ig alpha and a cell surface protein called CD19, which in mature B cells forms part of the B cell co-receptor that helps the cell respond to antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

B cell dev: 1st checkpoint criteria

A

1) Make a mu heavy chain, mu chain must demonstrate ability to combine with a light chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

VpreB and Lambda5

A

Two proteins synthesized by pro B cells which bind to mu heavy chains in a manner that mimics the light chain. Vpre B = variable region , Lambda5 - constant region , together they form the surrogate light chain. Transcription of their gene is controlled by E2A and EBF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

pre B cell receptor

A

Receptor made from heavy chain, surrogate light chain, IgBeta, IgAlpha . When receptor is formed it allows a pro B cell to become a pre B cell. Also prevents B cells from making more than one functional mu chain by signaling for transcription of the RAGE genes to stop and signals for RAG proteins to be degraded and the for the structure of the chromatin of the heavy chain locus to be rearranged into a state that resists gene rearrangement (leads to allelic exclusion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Allelic exclusion

A

when one of two copies of a gene is expressed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

B cell dev: 2nd checkpoint

A

Light chains that bind the existing mu heavy chain and assemble a functional B cell receptor will live

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

B cell dev: self tolerance - negative selection

A

Immature B cells in bone marrow are exposed to self antigen expressed by stromal cells, hematopoietic cells and macromolecules circulating the blood plasma. During this process, immature B cells are only expressing IgM on their surfaces.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

B cell dev: receptor editing for autoreactive B cells

A

When the immature B cell binds to self antigen in the bone marrow, the B cell will reduce the amount of IgM on its surface and maintain expression of the RAG proteins, which permits the B cell to continue rearranging its light chain loci and will remove the original light chain. If all light chin possibilities end, then cells will die.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Clonal Deletion

A

The selective death of developing lymphocytes and the consequent removal of their self- reactive receptor specificities from the B cell repertoire

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

B cell dev: anergy

A

If immature B cell binds to soluble monovalent self antigens, they will become inactivated and unresponsive to their specific antigen and be development arrest called anergy. Anergic cells make both IgD and IgM, but unlike in mature B cells, the IgM is prevent from assembling a functional B cell receptor and is retained in the cell. IgD is on the cell surface but it does not activate B cell on antigen binding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Central Tolerance

A

Immunological tolerance developed in a primary lymphoid organ- the bone marrow in the case of B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Peripheral Tolerance

A

Immunological tolerance induced to antigens outside the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

CCL21 and CCL19

A

Chemokines that attract immature B cells to enter the secondary lymphoid tissue through the walls of HEVs. CCL21 is secreted by stromal cells in the lymph node cortex AND dendritic cells within lymph node. CCL21 binds CCR7 receptor on B cells. CCL19 is expressed by dendritric cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

CXCL3

A

Chemokine secreted by follicular dendritic cells located in primary lymphoid follicles. They that attracts B cells into primary follicle where they interact with proteins on FDCs that signal their final maturation into mature B cells. Surface proteins on B cells called lymphotoxin binds to receptor on FDC to preserve the integrity of its network.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Primary Lymphoid Follicle
Ares within lymph nodes that consists principally of B cells enmeshed in a network of specialized stromal cells called follcular dendritic cells.
26
BAFF (B cell activating factor in the TNF Family
Made by several cell types in secondary lymphoid organs and is bound by the BAFF receptor expressed by B cells. It promotes B cell survival
27
B cell maturation
Maturation first involves the alternative splicing of the heavy chain mRNA so that the cell makes IgD as well as IgM. This is followed by a shift from an excess of IgM over IgD on the cell surface to an excess of IgD over IgM
28
Secondary lymphoid follicle
Similar to primary lymphoid follicle except with a germinal center. At the germinal center, the activated B cells become large proliferating lymphoblasts called centroblasts; these mature into more slowly dividing B cells called centrocytes, which have undergone isotype switching and somatic hypermutation.
29
Germinal center
located within secondary lymphoid follicle. It is where affinity maturation occurs. Also the resting location for memory B cells.
30
complement
Plasma proteins constitutively produced by the liver and are present in the blood, lymph, and extracellular fluid
31
C3bBb
An alternative C3 convertase which works right at the surface of the pathogen. A larger proportion of the C3b fragment it produces become fixed to the pathogen.
32
iC3Bb
Soluble C3 convertase. C3 spontaneously hydrolyzes which activates C3 to bind factor B. Cleavage of B by the serine protease factor D produces the soluble C3 convertase which then activates C3 molecules by cleavage.
33
Properdin (factor P)
Increases the speed and power of complement activation by binding to the C3 convertase C3bBb on microbrial surfaces and preventing its degradation
34
Factor H
Complement control protein that binds to C3b and facilitates its further cleavage to a form called iC3b by the plasma serine protease factor I.Fragment iC3b cannot assemble a C3 convertase
35
Decay-accelerating Factor (DAF) / Membrane co-factor protein (MCP)
Both are complement control proteins located at the membrane of human cells that binds to C3b component of the alternative C3 convertase, cause its dissociation and inactivation. MCP can also make C3b susceptible to cleavage and inactivation by factor I
36
Complement receptor 1 (CR1)
Receptor on macrophage that binds to C3b fragments on pathogens that make phagocytosis more efficient. It also protects the surface of the cells its expressed on by making them susceptible to Factor I
37
Opsonization
Coating of pathogen with protein that facilitates phagocytosis
38
CD59 and Homologous restriction Factor (HRF)
Prevent the recruitment of C9 by the complex C5b, C6, C7 and C8
39
C3a and C5a
They increase inflammation at the site of complement activation through binding to receptors on several cell types. They can induce anaphylactic shock, which is an acute inflammatory response that occurs simultaneously in tissues throughout the body so they are referred anaphylatoxins.
40
alpha2- macroglobulins
A glycoprotein is a protease inhibitor present in human secretions and plasma. It lures a protease with a bait region that is allowed to cleave. This activates alpha2- macroglobulin to covalently attach to the protease via its thiosester and it also undergoes a conformational change by which it envelops the protease. (Defense mechanism against protease prodcued by pathogens)
41
defensins
Human antimicrobial peptides that are rich in positively charged arginine residues and which characteristically have three intra-chain bonds. There are two classes: alpha and beta defensins. They are synthesize as part of longer, inactive polypeptides that are then cleaved to release the active fragment.
42
alpha-defensins
Are expressed mainly by neutrophils, the predominant phagocytes of innate immunity and by Paneth cells
43
beta- defensins
Are expressed by a broad range of epithelial cells, in particular those of the skin, the respiratory tract and the urogenital tract.
44
Lectins
Receptors and plasma proteins that recognize carbohydrates. These can be present on macrophages that will aid in phagocytosis of pathogen
45
Scavenger receptor
A phagocytic receptor of macrophages that is not a lectin; it binds to an assortment of ligands that share the property of being negatively charged.
46
Recepter- mediated endocytosis
A process of engulfment initiated by the binding of these macrophage receptors to their microbial ligands in which the receptor bound pathogen is surrounded by the macrophage membrane and internalized into endosome or phagosome.
47
Phgolysosomes
Is formed when phagosomes fuses with lysosomes which are loaded with degradative substances that destroy pathogens
48
cytokines
Small proteins that are made by a cell in response to an external stimulus and influence other cells by binding to a specific receptor on their surfaces. Can be produced by macrophages when it receives signal by toll-like receptors that pathogen is present which will recruit other immune system cells.
49
Toll-like receptors
A family of signaling receptors, each of which is specific for a different set of microbial products.
50
Toll-like receptor 4 (TLR4)
Expressed by macrophages and has specificity for LPS and related compounds present on the outside of gram-negative bacteria. In present of infection it can activate the expression of cytokine genes that can induce innate immune responses. Cytokines that induce inflammation are known as inflammatory cytokines. TLR4 is a homodimers of a single polypeptide
51
Location of TLR
TLRs that sense proteins, carbohydrates, and lipids characteristics of microbial cell surface, are located on the surfaces of human cells. TLRs that detect nucleic acids of pathogens reside in the membranes of endosome within cytoplasm.
52
Activation of TLR4: Involving MyD88
LPS is detected by the complex of TLR4, CD14 and MD2. The activated receptor binds the adaptor protein MyD88 which binds protein kinase IRAK4. IRAK4 will phosphorylate itself and dissociates from the complex and phosphorylates another adaptor protein TRAF6 which will eventually lead to the activation of a kinase complex called the inhibitor of kB kinase (IKK). IKK phosphorylaes IkB , causing its dissociation from the comples NFkB. NFkB can now move into the nucleus where it directs the activation of cytokine gene and other adhesion molecules that will intensity macrophage's effector function
53
Activation of TLR3 and TL4: Involving TRIF and TRAM
After TLR3 or TLR4 have detected their ligands, they will form a complex with adaptor proteins TRIF and TRAM. This will phosphorylate TRAF3 and create a kinase cascade. Phosphorylation of IRF3 in the cytoplasm will allow it o enter the nucleus where it directs the transcription of the genes for type I interfererons and cytokines
54
IL6
Cytokine that causes fever and induces acute- phase protein production by hepatocytes
55
TNF- alpha
Activates vascular endothelium and increase vascular permeability, which leads to increase entry of complement and cells to tissue and increased fluid drainage to lymph nodes. It also cause fever mobilization of metabolities and shock
56
IL-1Beta
Activates vascular endothelium, activates lymphotes, local tissue descrution, increase access of effector cells. It also causes fever and production of IL6
57
CXCL8
A chemokine (Chemoattract cytokine) that recruits neutrophils and basophils to site of infection
58
IL-12
Activates NK cells
59
Chemokine
Messengers that direct flow of leukocyte traffic . Two major families are defined on the basis of pairs of cysteine residues, which are either adjacent (CC) or separatedby another amino acid (CXC)
60
CXCRI and CXCR2
Chemokine receptors on neutrophiles that bind CXCL8 coming from infected tissue.
61
Binding of chemokine to chemokine receptors on leukocyte
1) The leukocyte's adhesive properties are altered so that it can leave the blood and enter the tissue 2) the leuckocytes movement is guided toward the center of infection along a gradient of the chemokine.
62
Natural Killer cells (NK cells)
Lymphocytes that specialize in defense against viral infections
63
Neutrophils
Short lived granulocyte that have phaogcytic activity. They are the most abundant WBC and are excluded from healthy tissue and leave the blood in response to inflammatory mediators released by infected sites.
64
The adhesion molecules of immune system
1) selectins - carbohydrate binding proteins which have specificity for the oligosaccharide of different vascular addressins 2) Vascular addressins 3) Integrins- binds to proteins 4) Immunoglobulin superfamily
65
Extravasation
The process by which neutrophils migrate out of blood capillaries and into tissues
66
Neutrophil granules
Phagosomes containing pathogens fuse with azurophilic ( primary) granules and specific (secondary) granules. Primary granules contians proteins and peptides that can disrupt and digest microbes. The specific granules contains lactoferrin that compete with pathogens for iron and copper. They also contain NADPH oxidase, an essential enzyme for neutrophil function that is assembled in the phagosome after fusion of the phagosome with the azurophilic and specific granules.
67
NADPH oxidase
Produces a superoxide radical that are converted into hydrogen peroxide. It raises the pH and activates the antimicrobial peptides and proteins and attacked trapped pathogens in phagosomes.
68
Kill of pathogens by neutrophils
1) Bacteria is phagocytosed 2) phagosome fuse with primary and secondary granules 3) pH of phagosome rises, antimicrobial response is activates and pathogen is killed 4) pH of phagosome decreases,fuses with lysosome which allows acid hydrolases to degrade pathogen completely 5) neutrophil dies and is eaten by macrophage
69
pyrogens
Molecules that induce fever
70
Acute phase response
A systemic effect of IL1, IL6 and TNF-alpha that changes the spectrum of soluble plasma proteins secreted by hepatocytes in the liver
71
Acute phase proteins
Proteins whose synthesis and secretion is increased during the acute - phase response. Two acute phase protein called mannose- binding lectin and C-reactive protein enhance fixation of complement at pathogen surfaces
72
Mannose Binding lecting (MBL)
A calcium dependent lectin that binds to mannose-containing carbohydrates of bacteria, fungi, protozoans and virues. It circulates in plasma as a complex with two serine protease zymogens: MBL-associated serine protease (MASP) 1 and 2. Two molecules each of MASP-1 and MASP-2 is associated with MBL. When MBL binds to pathogen, one molecule of MASP-2 is induced to become enzymatically active and cuts itself. It then cuts the second MASP-2 molecule. Substrates for the activated MASP-2 protease are the C4 and C2 complement components. C4 is similar to C3 and C2 is similar to factor B.
73
Classical C3 convertase
C4 molecule interacts with MASP-2 and is cleaved into C4b and C4a fragments. C4b is fixated to pathogen surface. When a C2 molecule interacts with MASP-2, it is cleaved into a larger C2a and a smaller C2b. Larger C2a binds to a pathogen bonded C4b. The complex of C4b and C2a known as C4bC2a is a C3 convertase. It is a component of both the classical and lectin pathway. The classical convertase binds and cleaves C3 to yield C3b which attaches to pathogen surface. This in turn activates factor B to assemble molecules of the alternative C3 convertase, C3bBb
74
C-reactive protein (CRP)
It contains 5 identical subunits that form a pentamer. When CRP binds to phosphocholine components of LPS on pathogen surfcae, it can also interact with C1, the first component of the classical pathway of complement activation. C1 has similar structure to MBL but instead of MASP 1 and 2, it has C1r and C1s. CRP binds to C1 stalk and causes one molecule of C1r to cut intself, the other molecule of C1r and both molecules of C1s. Now C1s becomes an active proteases that cleaves C4 , leading to formation of C4bC2a
75
Type I interferon
Cytokines made when human cells becomes infected by a virus. It interferes with viral replications of infected cells, and signals nearby uninfected cells that they too should prepare to resist a viral infection.
76
Type 1 interferon production
Type 1 interferon production is induced by intracellular events that follow viral infection or the triggering of TLR3. Infection or ligand sensing triggers the phosphorylation of the transcription factor IRF3 in the cytoplasm which dimerizes and enters the nucleus to help initiate transcription of the Interferon-beta (IFN-b) gene which also requires the transcription factors NFkB and AP-1
77
Interferon response
When interferon binds to its receptor, the intracellular Jak1 and Tyk2 kinases associated with the receptor , it initiates reactions that changes the expression of different genes.
78
Effects of interferon response
1) induce resistance to viral replication in all cells 2) Increase expression of ligands for receptors on NK cells 3) activate NK cells to kill virus infected cells
79
Interferon producing cells (IPCs) or natural interferon producing cells (NIPCs)
These cells secrete up to 1000x more interferon than other cells
80
Stimulation of NK cells
Stimulation of NK cells with type 1 interferons favors the development of the cell's killer function. Stimulation with IL-12 favors the production of cytokines. One of the main cytokines is IFN-gamma (aka Type 2 interferon). Its function is to activate macrophages that will produce more IL-12 so it is positive feedback. Macrophages can activate T cells thus activating the adaptive immune response.
81
NK receptors
Most NK cell recepotrs have extracellular ligand-binding regions that are made up immunoglobulin domains or lecti-like domains. There an inhibitory and activating type of both receptors. Activating receptors have short cytoplasmic tails and charged amino acid residues in the transmembrane domain that facilitates interaction with intracellular signaling proteins. Inhbitory receptors have long cytoplasmic tails that caontain a short amino acid sequence motif called immunoreceptor tyrosine based inhibitory motif (ITIM), which binds protein phosphatases that act to inhibit the activating pathway
82
NK receptor: NKG2D
NKG2D is a lectin like receptor that binds to ligands called MIC-A and MIC-B, cell surface proteins that produced in response to stress. Healthy cells resists attack by NK cells because signals generated from inhibitory receptors dominate those generated from activating receptors. NK cells attack the virus -infected cell because the signal generated by NKG2D interacting with MIC proteins tips the balance to activation.
83
Clonal selection
The process by which pathogens select particular lymphocytes for expansion
84
Clonal expalnsion
The proliferation of selected clones
85
Dendritic cells
A type of phagocytic cell leukocyte that reside in tissues and are specilized in the uptake and breakdown of infection agents. The presence of infection causes dendritic cells to differentiate into mobile cells that transport bacteria and their antigens through the lymph to the secondary lymphoid tissues.
86
MHC class I
Binds CD8 T-cells and processes intracellular antigens.It is expressed on all cells
87
MHC class II
Binds CD4 T cells and processes extracellular antigens. It is only expressed on professional APCs ( DC, macrophages, B cells)
88
Immunoglobulin domains
a single motif of about 100-110 amino acids long and folds up into a compact and exceptionally stable protein.
89
Ab domains
Heavy chain- constant IgG, IgD, IgA have 3 constant domains IgM, IgE have 4 contant domains Light chain: All have 1 constant domain Only 1 variable domain for both heavy and light chian
90
Ab structure
1) Light and heavy chain each have 3 hypervariable regions (CDRs) so they are totaly of 6 CDR 2) CDR are flanked between less variable framework region 3) Made of 4 polypeptides
91
Switch sequence or switch region
Highly repetitive sequences that flank the 5' side of each C gene, with the exception of gamma gene, that mediate recombination
92
Somatic hypermutation
Occurs after gene rearrangement. It randomly introduces point mutations at a high rate throughout the V region.
93
Activation induced cytosine deaminase (AID)
Enzyme that is made in proliferating B cells. AID converts cytosine in single stranded DNA to uracil. During transcription, when the two DNA strands become temp separated, AID converts cytosine into uracil. Other enzymes then act to convert the uracil to any of the 4 normal DNA bases
94
T cell receptor complex
CD3 proteins and squiggly line chian remain in stable association with the T cell receptor. In this complex, CD3 proteins and sqiggly chain transmits singals to the cells interior after antigen has been recognized by the alpha and beta chain of the TCR . The alpha and beta chain has short tail that cannot signal.
95
Calnexin
A calcium dependent lectin that retains MHC class I heavy chains ( alpha) in the ER till beta2- microglobulin binds
96
Peptide loading complex of MhC 1
ERp57 and tapasin - bridging proteins that bind to both mhc clas I and the TAP-1 subunit of the peptide transporter Protein disulfide isomerase ( PD-1) - stabalizes the disulfide bond of the alpha2 domain of the class I heavy chain Calreticulin- resembles soluble calnexin and has similar chaperone function
97
Endoplasmic reticulum aminopeptidase (ERAP)
An enzyme that removes amino acids from the amino terminal end of the peptide on MHC 1 to improve fit
98
Transporter associated with antigen processing (TAP)
A protein embedded in the ER membrane that transports peptides across the ER membrane
99
Invariant chain
Associates with alpha and beta chain of MHC 2 to prevent it from bindin peptides present in the ER. It also delivers the MHC 2 to endocytic vesicles where they bind peptides. The vesicles called MHC class II contain proteases that selectively cleave the invariant chain which will leave a small fragment covering the peptide binding site called Class II associated invariant chain peptide (CLIP)
100
HLA-DM
Removes CLIP and helps the binding of peptide to mhc II. When HLA-DM binds to mhc II it causes CLIP or weakly bound peptides to be released
101
Cross presentation
It allows extracellular antigens to be presented by MHC I. Two possible ways 1. Phagocytosis of dead, infected cells by APC allows complexes of MHC I and viral peptides to be transported from the dead cell to the membranes of intracellular vesicles inside the APC to the cell surface 2) extracellular viral proteins are deliver by endocytic vesicles to proteasome degradation and presented by the usual mhc I pathway
102
S protein, clusterin, and factor J
Soluble proteins that inhibit C5b, C6 and C7 binding to cell membrane
103
Immunoglobulin
Membrane bound form of antigen receptor of B cells