Specific Immune Responses (Adaptive/Acquired Immunity) Flashcards
1
Q
What are the 7 characteristic features of adaptive immunity that enable it to perform its physiologic function of host defense?
A
1- Specificity 2- Diversity 3- Specialization 4- Clonal expansion 5- Memory 6- Self-limitation 7- Self-tolerance
2
Q
T or F?
Humoral immunity protects against intracellular pathogens, whereas cell-mediated immunity protects against extracellular pathogens and bacterial exotoxins.
A
FALSE.
Humoral immunity protects against extracellular pathogens and bacterial exotoxins, whereas cell-mediated immunity protects against intracellular pathogens.
3
Q
T or F?
Different classes of microbes elicit variable immune responses; or the same microbe can elicit different immune responses during different stages of its infections.
A
TRUE.
4
Q
T or F?
Self-limitation refers to immune responses usually waning with time after antigenic stimulation, allowing the immune system to respond to new invaders.
A
TRUE.
5
Q
What is the definition of passive immunity?
A
This is the transfer of preformed antibodies or immune cells (adaptive immunity) to a naive (nonimmune) individual.
6
Q
What is the definition of active immunity?
A
This is immunity acquired actively following natural infection of immunization by vaccines. It is mediated by humoral and cell-mediated immune responses.
7
Q
What is the physiologic function of the humoral immune response?
A
To defend against extracellular organisms and microbial toxins.
8
Q
T or F?
Immunoglobulins against surface antigens on bacteria and viruses may confer protection from disease.
A
TRUE.
9
Q
T or F?
A humoral immune response to antigens from inside viable bacteria and viruses (eg, bacterial ribosomes) are protective because they are accessible to immunoglobulins.
A
FALSE.
A humoral immune response to antigens from inside viable bacteria and viruses (eg, bacterial ribosomes) are NOT protective because they are INACCESSIBLE to immunoglobulins.
10
Q
Immunity is transferable from one individual to another by ____ ____.
A
Immune serum.
11
Q
Passive humoral protection provides ______ (immediate/delayed?) protection; however, because the Igs are decaying steadily while no new ones are being formed, passive protection is _____-_____ (short-term/long-term?)….
A
1) Immediate.
2) short-term (only a few weeks).
12
Q
Is there a memory response in passive humoral protection?
A
No.
13
Q
If Igs from another species are used, what kind of reaction might we see in the passive humoral protection?
A
Hypersensitivity reactions.
14
Q
What are the 5 sources of passive humoral protection?
A
1) Hyperimmune serum.
2) Colostrum.
3) Transplacental transfer.
4) Egg yolk.
5) Albumen (egg white).
15
Q
T or F?
Passive humoral protection can be used for both prophylactic and therapeutic purposes.
A
TRUE.
16
Q
Active humoral immunity develops _____ (slowly/quickly?) over a period of ___to___; however, it tends to persist usually for ___or___.
A
1) Slowly.
2) days to weeks.
3) months or years.
17
Q
Is there a memory response in active humoral immunity?
A
Yes, active humoral immunity usually demonstrates a memory response.
18
Q
What kind of treatment is active humoral immunity mainly used for?
A
Active humoral immunity is used mainly for prophylaxis.
19
Q
What are the 4 phases of antibody production?
A
1) Lag phase.
2) Log (exponential) phase.
3) Plateau (stationary) phase.
4) Decline phase.
20
Q
1) What is the lag phase of antibody production? 2) Can antibody to the antigen be detected in the serum during this phase?
A
1) It includes the time required for: B cells and T cells to recognize the antigen; to undergo clonal expansion; and to differentiate.
2) No.
21
Q
What happens during the log (exponential) phase of antibody production?
A
Antibody titer [concentration] rises exponentially.
22
Q
What happens during the plateau (stationary) phase of antibody production?
A
Antibody titer stabilizes; secretion and degradation of antibody are balanced.
23
Q
What happens during the decline phase of antibody production? Why?
A
Antibody titer declines due to natural catabolism of antibodies and clearance of immune complexes (Ag-Ab complexes) from the circulation by the mononuclear phagocytes.
24
Q
What is the threshold antibody titer?
A
The minimum antibody titer required for disease protection.
25
T or F?
The threshold antibody titer does not vary from disease to disease; it is uniform.
FALSE.
The threshold antibody titer varies from disease to disease.
26
What is the responding B cell in the primary antibody response? In the secondary antibody response?
The responding B cell in the primary response is the naive B cell. The responding B cell in the secondary response is the memory B cell.
27
How long is the lag phase in the primary antibody response? In the secondary antibody response?
The lag phase in the primary response is usually 5-10 days. The lag phase in the secondary response is usually 1-3 days.
28
How long does it take to get to the threshold titer in the primary antibody response? In the secondary antibody response?
It takes about 3-4 weeks to get to the threshold titer in the primary response. It takes about 1-2 weeks to get to the threshold titer in the secondary response.
29
T or F?
The peak antibody level in the primary antibody response is low; whereas the peak antibody level in the secondary antibody response is about 100-1000x higher.
TRUE.
30
T or F?
The antibody isotypes for both the primary and secondary antibody responses is mainly IgM > IgG.
FALSE.
The antibody isotypes in the primary antibody response is mainly IgM > IgG.The antibody isotypes in the secondary antibody response is mainly IgG > IgM.
31
Which antibody response (either primary or secondary) has the higher Ig affinity (the affinity maturation)?
The secondary antibody response has a higher Ig affinity than the primary response.
32
CMI (cell-mediated immunity) is an immune response mediated mainly by what kind of accessory and T cells?
CMI is an immune response mediated mainly by antigen specific T cells and other nonspecific accessory cells (NK cells, macrophages) of the immune system.
33
What can one use to transfer CMI to naive (nonimmunized) individuals?
CMI can be transferred to naive (nonimmunized) individuals with LYMPHOCYTES.
Remember: it CANNOT be transferred with plasma or serum.
34
What are the 3 functions of CMI?
1) Destruction of virus-infected cells, tumor cells, or allografts.
2) CMI inhibits organisms such as fungi, parasites, and intracellular bacteria.
3) Mediates delayed-type hypersensitivity (DTH; Type IV hypersensitivity).
35
What are cytotoxic T cells (cytolytic T lymphocytes, CTLs)?
They are CD8+ T cells that target cells expressing peptide epitopes in association with MHC class 1 molecules.
36
T or F?
The interaction of a CD8+ CTL with a target cell involves multiple T cell membrane proteins that recognize different ligands on the target cell.
TRUE.
37
What does LFA-1 (CD11a/CD18) on the CD8+ CTL bind to on the class 1 MHC-expressing target cell?
ICAM-1
38
What does TCR (a/b TCR) on the CD8+ CTL bind to on the class 1 MHC-expressing target cell?
The peptide and Class 1 MHC molecule.
39
What does LFA-3 (CD58) on the target cell bind to on the CD8+ CTL?
CD2.
40
What does CD28 on the CD8+ CTL bind to on the class 1 MHC-expressing target cell?
B7-1/B7-2.
41
Cytosolic proteins are degraded into peptides that associate with _____1_____ for presentation to __2__.
1) Class 1 MHC molecules.
| 2) CTLs.
42
As a rule of thumb, host cells that present peptide-MHC 1 complexes to CTLs are referred to as _____ _____.
TARGET CELLS
| not antigen-presenting cells
43
What are the 3 sources of cytosolic proteins?
1) Foreign antigens such as viruses or other intracellular pathogens.
2) microorganisms internalized into phagosomes.
3) Cellular proteins such as faulty or damaged proteins, regulatory proteins, etc.
44
Where are cytosolic proteins degraded into small peptides?
In proteasomes.
45
What do proteins have to be tagged with in order for proteosomes to target them for degradation?
Proteins must be tagged with molecules of a small invariant protein called ubiquitin in order to be attacked by proteosomes.
46
What mediates the energy-dependent transport of peptides from the cytosol into the endoplasmic reticulum where MHC class 1 proteins are assembled?
It is mediated by a heterodimeric protein located in the ER membrane called TAP (Transporter associated with Antigen Processing).
47
What happens to cells that lack functional TAP?
Class 1 MHC molecules are not loaded with peptides; leading to their degradation in the ER.
48
T or F?
A number of viruses code for proteins that inhibit TAP, which forces peptide delivery to class 1 MHC molecules, thereby preventing presentation of viral antigens to CTLs.
FALSE.
A number of viruses code for proteins that inhibit TAP, which BLOCKS peptide delivery to class 1 MHC molecules, thereby preventing presentation of viral antigens to CTLs.
49
What is tapasin? What does it do?
Tapasin is a TAP-associated protein, which is a key molecule in the assembly of class 1 MHC molecules. It links the TAP protein to newly synthesized class 1 MHC molecules.
50
What does a mutation in the tapasin gene lead to?
A mutation in the tapasin gene leads to the expression of unstable class 1 MHC molecules on the cell surface.
51
In the ER, peptides ___1___ amino acids long bind to the cleft of MHC class 1 molecules. Longer peptides that cannot bind to the cleft are trimmed to the correct size by what enzyme___2___?
1) 8-10 amino acids long.
| 2) Endoplasmic Reticulum AminoPeptidase (ERAP) enzyme.
52
T or F?
Peptide-MHC 1 complex is released from tapasin and moves through the golgi into exocytic vesicle. Fusion of exocytic vesicle with the plasma membrane and expression of peptide-MHC 1 complex on cell surface is recognized by antigen-specific CTL.
TRUE.
53
T or F?
CTLs are NOT fully differentiated when they exit the thymus.
TRUE.
54
What can undifferentiated CD8+ T cells (aka pre-CTLs or naive CD8+ T cells) NOT do?
These cells cannot lyse target cells even though the express functional TCRs that are specific for a particular foreign antigen.
55
What 2 signals are required for the differentiation of pre-CTLs to effector CTLs?
1) Recognition of MHC 1-associated peptides (signal 1).
| 2) Co-stimulators (signal 2).
56
Pre-CTL is activated by virus-infected _____ ___ expressing peptide-MHC class 1 complex on its surface.
Professional APC.
57
What does the activated pre-CTL produce?
IL-2.
58
What does the activated pre-CTL proliferate in response to? What is the final outcome of this? What kind of cell does the pre-CTL become?
The activated pre-CTL produces IL-2 and proliferates in response to it (autocrine effect), eventualy differentiating into armed or effector cytotoxic CD8+ T cells.
59
T or F?
Professional APC can also present peptides from ingested virus-infected (often apoptotic) cells, which move from the cytosol to the phagosome; a process called cross-priming or cross-presentation.
FALSE.
Professional APC can also present peptides from ingested virus-infected (often apoptotic) cells, which move from the PHAGOSOME TO THE CYTOSOL; a process called cross-priming, or, cross-presentation.
60
Which T cell may provide the cytokines that stimulate pre-CTL differentiation?
CD4+ T cells.
61
T or F?
Both the pre-CTL and the CD4+ T cell must recognize an antigen on the surface of the same professional APC in order for the CD4+ T cell to stimulate the pre-CTL with its own cytokines.
TRUE.
62
What do differentiated CTLs have that contain proteins used in killing target cells?
Membrane-bound cytoplasmic granules.
63
What cytokines do CTLs secrete? What do they do?
CTLs acquire the ability to secrete cytokines ( eg, IFN-y, TNF, low level IL-2, and lymphotoxin), which activate phagocytes and induce inflammation.
64
T or F?
Effector CTL cells in circulation encounter target cells that express the same MHC class 1-associated peptides that triggered the proliferation and differentiation of pre-CTLs and bind to them using specific TCRs and accessory molecules.
TRUE.
65
What is the result of TCRs binding to peptide epitopes?
1) The clustering of the TCRs and...
| 2) The generation of biochemical signals that activate the CTL.
66
T or F?
Co-stimulators and cytokines, which are required for the differentiation of pre-CTLs into active CTLs, are necessary in triggering the effector function of CTLs.
FALSE.
Co-stimulators and cytokines, which are required for the differentiation of pre-CTLs into active CTLs, are NOT necessary in triggering the effector function of CTLs.
67
T or F?
Activation of the CTL results in the release of granule contents onto the target cell.
TRUE.
68
What are the most important granule proteins in the mechanisms of cell killing?
The most important granule proteins are...
1) Perforin 1
2) Granzymes (granular enzymes [fragmentins]).
69
What is perforin? How are polyperforins formed?
Perforin is a pore-forming protein present as monomers in the granules of CTLs. Interaction with Ca2+ ions in the extracellular environment results in the polymerization of the monomers to form tubular pores called polyperforins.
70
What do polyperforins do to target membranes?
Polyperforins insert themselves into the target membranes so that they form transmembrane channels.
71
What happens if there are sufficient amounts of polyperforins on target membranes?
If a sufficient amount of polyperforins - and therefore, transmembrane channels - are on the target membranes, the target cell will be unable to exclude water and ions; leading to osmotic swelling and death.
(High concentrations of calcium that enters the cell may also trigger apoptosis)
72
What molecule is released via exocytosis by CTLs, which enter target cells mainly through the perforin-created membrane channels, and proteolytically cleave and activate caspases?
Granzymes.
73
What are caspases? What do they do?
Caspases are intracellular proteases that cleave several substrates and induce target cell apoptosis.
74
T or F?
Nucleases can be activated in apoptosis that degrade viral DNA, preventing the assembly of virions and the infection of nearby cells.
TRUE.
75
What is Fas ligand (FasL)? What does it do?
Fas ligand (FasL), aka, CD95L is a membrane protein expressed by activated CTLs that binds to Fas protein (CD95), which is expressed on various cells. The interaction also results in activation of caspases and apoptosis of target cells.
76
Although CTLs can program target cells to die within __1__, target cell death may take several __2__.
1) Minutes (~ 5mins)
| 2) Hours (2-6hrs).
77
T or F?
The highly polar release of the effector molecules (ie, CTLs orient their secretory apparatus to focus it on the point of contact with a target cell) ensures that the CTL itself and non-antigen expressing nearby cells ("innocent bystander" cells) are killed.
FALSE.
The highly polar release of the effector molecules (ie, CTLs orient their secretory apparatus to focus it on the point of contact with a target cell) ensures that the CTL itself and non-antigen expressing nearby cells ("innocent bystander" cells) are NOT killed.
78
T or F?
As the antigen is eliminated, many of the effector CTLs die by apoptosis, returning the immune system to its basal state of rest.
TRUE.
79
What are the only surviving cells (as in, the cells that survive even after the antigen is eliminated from the body) that are generated during the immune response?
Long-lived memory CD8+ T cells.
80
What large granular lymphocytes (LGLs) originate in bone marrow; represent 5%-10% of lymphocytes found in the peripheral blood and spleen; are rare in other lymphoid organs; and do NOT recirculate?
NK cells.
81
T or F?
NK cells do not possess antigen receptors; are not subject to MHC restriction; and have no memory.
TRUE.
82
What cytokines enhance NK cell proliferation and cytolytic activity? What produces the cytokines in this list that are produced in response to infection?
NK cell proliferation and cytolytic activity are enhanced by IL-2, IL-12, IL-15, IFN-a, IFN-B, and IFN-y.
IL-12, IL-15, and IFN-a are produced by macrophages in response to infection.
83
What does KIRs and KARs stand for? What expresses them? What else does this cell express?
NK cells express CD16 (FcyRIII), CD2, CD11a/CD18, Killer-cell Immunoglobulin-like Receptors (KIRs), and Killer-cell Activatory Receptors (KARs).
84
What are the main functions of NK cells?
The main functions of NK cells are to recognize and kill certain tumor cells and virus-infected cells and to secrete IFN-y, which activates macrophages to destroy intracellular parasites.
85
NK cells are an _____ (early/late?) component of the host response to virus infection.
Early.
86
What cytokines appear first in the host response to virus infection? What cell(s) follows them? What do these cytokines + cell(s) function to do together?
IFN-a and IFN-b appear first, followed by a wave of NK cells, which together control virus replication before antigen-specific CTLs become fully active.
87
T or F?
NK cells kill target cells that express, or, overly express MHC class 1 proteins.
FALSE.
NK cells kill target cells that FAIL to express, or, REDUCED MHC class 1 proteins.
88
T or F?
Some viruses produce virokines that can down-regulate MHC class 1 expression and some tumor cells often do not express MHC class 1 molecules.
TRUE.
89
What do KARs do?
KARs on NK cells recognize carbohydrate molecules on self cells. This recognition event triggers NK cells to kill target cells.
90
What do NK cells use to kill target cells when stimulated by KARs?
NK cells kill target cells using exocytosed perforin 2 and granzymes when stimulated by KARs.
91
Interaction of KIRs with MHC class 1 molecules expressed by the target cells _____(stimulates/inhibits?) killing by NK cells in a DOMINANT WAY.
Inhibits.
92
What is Granulysin? Where is it present? What does it do?
Granulysin is an anti-microbial peptide present in the granules of NK cells and CTLs. When released, it kills a wide variety of extracellular bacteria, fungi, and parasites; some pass through the perforin channels and kill microbes in the target cell.
93
What does ADCC stand for? What does it represent?
ADCC stands for Antibody-Dependent Cell-mediated Cytotoxicity.
It represents that NK cells cal also kill target cells coated with IgG via their CD16 receptor (FcyRIII).
94
What are inflammatory macrophages? What can they become?
Monocytes moving into inflamed tissues are referred to as inflammatory macrophages because of their enhanced activities. Inflammatory macrophages can be stimulated further to become activated macrophages.
95
What can activated macrophages do that resting macrophages cannot?
Activated macrophages to perform some function(s) - eg, synthesis of nitric oxide (NO) - that cannot be performed by resting macrophages.
96
How are macrophages activated? What cell(s)/cytokine(s) are involved?
Activation of inflammatory macrophages consists of quantitative changes in the expression of various proteins.
Macrophages are activated by CD40L-CD40 interactions and by IFN-y produced by the TH1 cells and NK cells.
97
What microbial substance is a potent activator of macrophages via binding to CD14 receptors on the macrophage?
Bacterial endotoxin (LPS) is a potent activator of macrophages (binds to CD14 receptor on macrophages).
98
T or F?
Various microorganisms such as viruses, protozoa, bacteria, and fungi can replicate within the macrophages and kill the macrophages.
TRUE.
99
How can the macrophage protect itself against microbes that attempt to replicate inside the macrophage, and therefore, kill the macrophage?
Macrophage activation itself can protect against these microbes. The response is NONSPECIFIC and activated macrophages are capable of destroying a wide range of normally resistant intracellular parasites.
100
T or F?
Macrophages are nonspecific and activated ones are capable of destroying a wide range of normally resistant intracellular parasites.
TRUE.
101
What enzyme(s) is increasingly synthesized in response to macrophage activation? What does this enzyme(s) do?
Macrophage activation results in increased synthesis of NADPH oxidase, which catalyzes the generation of reactive oxygen intermediates (ROI) and the production of inducible NO synthase, which stimulates the synthesis of nitric oxide (NO).
102
T or F?
ROI and NO are not potent microbicidal agents.
FALSE.
ROI and NO ARE potent microbicidal agents.
103
T or F?
Activated macrophages contain increased amounts of lysosomal enzymes.
TRUE.
104
What do the TH2 cell-secreted cytokines IL-4 and IL-10 do?
These cytokines, which are secreted by the TH2 cells, antagonize (cross-regulate) TH1 cytokines (eg, IFN-y) that promote macrophage activation and the inflammatory response.
