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ADV IMMUNOLOGY FINAL
Terms in this set (77)
is the conserved surface component of Gram-negative bacteria.
• Lipopolysaccharide (LPS)
Host surface molecules responsible for lipopolysaccharide (LPS) sensing include:
o LPS binding protein (LBP)
is responsible for the vast majority of host transcriptional responses to lipopolysaccharide (LPS), although recent discoveries have revealed the existence of several ______-independent responses to LPS
Toll like receptor 4 (TLR4)-
are induced by and protect against viral infections, however, the two systems differ in the tissue expression of their receptor, resulting in different roles in vivo.
Type I and type III IFNs
Type I and III IFNs are produced following recognition of viral ligands, most prominently ____________, by a wide range of pattern recognition receptors.
can only survey the extracellular space and are expressed in a limited number of cell types
are expressed in almost all cells and are cytoplasmic RNA helicases that recognize non-self RNA motifs.
RIG-I and MDA5
While RIG-I-like receptors (RLRs) and mitochondrial antiviral signaling protein (MAVS) produce interferons (IFN) in response to _________, a parallel pathway detects intracellular viral DNA.
is an ER-localized protein that coordinates the type-I IFN response to viral DNA.
Stimulator of IFN genes (STING
TLR signaling not only induces global activation of dendritic cells through the upregulation of costimulatory molecules and secretion of cytokines, but also
acts locally in a phagosome-autonomous manner to enhance phagocytosis, degradation of pathogens, processing and presentation of antigens.
Following phagocytosis of pathogens, dendritic cells process the peptides for presentation
MHC CLASS II
One of the central tenets of TLR signaling is that all cellular responses to TLR ligands are mediated by either
MyD88- or TRIF-dependent signaling pathways.
The cytoplasmic domains of TLRs contain a Toll-interleukin 1 receptor (IL-1R) homology domain (TIR domain) that serves as a platform to recruit TIR domain containing adaptor proteins, such as MyD88 and TRIF, and the particular adaptor (MyD88 or TRIF) used determines which signaling pathway will be activated.
A pool of TLR9 constitutively resides in endolysosomes that is poised to initiate a rapid response to endocytosed viral and/or bacterial DNA.
Pattern Recognition Receptors (PRRs) that recognize Pathogen Associated Molecular Patterns (PAMPs) include:
o Toll-like Receptors (TLRs)
o NOD-like Receptors (NLRs)
o RIG-I like Receptors (RLRs)
o C-type Lectin Receptors of the Dectin family.
Organelles including ___________ have all been shown to serve as sites of viral protein localization and assembly of replication complexes.
endoplasmic reticulum (ER)
In contrast to plasma membrane localized PRRs such as TLRs and Dectins, ____ are cytoplasmic receptors.
All of the following are considered autoimmune diseases:
o rheumatoid arthritis
o systemic lupus erythematosus (SLE)
o Sjögren's syndrome
o multiple sclerosis.
Fc-receptor-bearing effector cells
the complement system
B cells produce antibodies that form complexes with target antigens, and the resultant immune complexes can engage ______
B cells coated with _____can be killed by one of two mechanisms:
o a cell-based mechanism called antibody-dependent cellular cytotoxicity (ADCC)
o when the complement membrane attack complex is assembled on the cell surface in a process called complement-dependent cytotoxicity (CDC).
B-cell activating factor (BAFF/BLyS) can provide a ___________ to B cells via binding to the BAFF receptor (BAFF-R).
Germinal centers (GCs) are transient structures that form within peripheral lymphoid organs in response to________________.
T cell-dependent antigen1
Within GCs, _________expressing high-affinity antibodies develop and differentiate into antibody-secreting plasma cells and memory B cells that mediate and sustain protection against invading pathogens.
• Within germinal centers, germinal center B cells proliferate at a rate that is unparalleled in mammalian tissues and their immunoglobulin variable region (IgV) genes are diversified by _______
Somatic hypermutation (SHM).
As a result of cellular stress, cellular damage, and non-physiological cell death, damage-associated molecular patterns (DAMPs) may be released from:
1.) degraded stroma (in the case of hyaluronate, for example),
2.) from the nucleus (in the case of high-mobility group box 1 protein (HMGB1), for example) and
3.) from the cytoplasm (for example, in the case of ATP, uric acid, S100 calcium-binding proteins and heat-shock proteins).
_________ are a specialized subset of CD4+ T cells that can suppress both innate and adaptive immune responses.
Regulatory T cells (TReg cells)
___________provide a crucial mechanism for the maintenance of peripheral self-tolerance, but may also limit the effectiveness of antitumor immune responses
Regulatory T cells (TReg cells)
TH2 cells produce ________ and they support ________and _________
- interleukin 4 (IL 4), IL 5 and IL 13,
- humoral immunity
-downregulate TH1 cell responses
Dendritic cells (DCs) initiate and shape both the innate and adaptive immune responses and recent evidence from clinical studies and experimental models implicates dendritic cells in the pathogenesis of ____________
most autoimmune diseases.
Medullary thymic epithelial cells (mTECs) are primarily responsible for the negative selection of autoreactive T cells in the thymus by expressing the transcription factor ___________, which drives the low-level expression of many tissue-specific self antigens for presentation to developing thymocytes.
autoimmune regulator (AIRE)
If dendritic cells take up and present self antigens to T cells in the context of pro-inflammatory mediators (such as interleukin 6 (IL 6), IL 12 and IL 23), they can promote _______________
the development of self-reactive effector CD4+ T cells and cytotoxic T lymphocytes (CTLs) that might contribute to pathological autoimmune responses.
The production of type I interferon (IFN) by plasmacytoid dendritic cells (pDCs) is a common mechanism of pathogenesis in:
type 1 diabetes
o systemic lupus erythematosus
CD4+ and CD8+ T cells are derived from a common precursor pool, in which each cell expresses both CD4 and CD8 proteins.
Each mature T cell generally retains expression of the co-receptor molecule (CD4 or CD8) that has an MHC-binding property that matches that of its ______
_________________ alert the immune system to active intracellular infection and target infected cells for destruction
MHC class-I ligands
________________ intercellular co-operation between haematopoietic cells in an immune response and help to combat extracellular infections.
Activation-induced cytidine deaminase (AID) is an essential enzyme to regulate:
- class switch recombination (CSR),
- somatic hypermutation (SHM)
- gene conversion (GC).
VDJ recombination is a site-specific recombination regulated by two recombinases, __________
RAG-1 and RAG-2.
The thymus provides the microenvironment essential for the development of T cells from__________
hematopoietic stem cells (HSCs).
Tiny numbers of _______________ enter the thymus, and after they encounter the thymic epithelium, they progress to the early thymic progenitor (ETP) stage of T cell fate specification.
thymic seeding progenitors (TSPs)
_________are still uncommitted and retain some myeloid, NK, and DC potential but little, if any, B cell lineage potential.
In T cell-dependent B cell responses, accumulating evidence shows that antigen-activated proliferating B cells begin to follow one of three fates by differentiating into __________________
extrafollicular short-lived plasma cells
germinal center-independent memory B cells
germinal center-dependent memory B cells.
• Upon antigen rechallenge, _____ memory B cells preferentially differentiate into plasmablasts.
whereas IgM+ memory B cells ______________
proliferate more and enter the germinal center reaction.
Memory B cells may express
is a highly conserved process that targets cellular contents to the lysosomal compartment for degradation.
Natural killer (NK) cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells and hence increasing evidences have pointed out the relevance of NK cells in organ-specific and systemic autoimmune diseases.
binds and cleaves the DNA at specific recombination signal sequences (RSSs) that flank each V, D and J gene segment.
The RSSs that flank each gene segment consist of conserved heptamer (7) and nonamer (9) elements separated by a less well conserved spacer region of either 12 or 23 base pairs, which defines the 12RSS and 23RSS, respectively. There is a strong preference for recombination between a 12RSS and a 23RSS, a restriction known as the 12-23 rule.
________________ exchanges the gene encoding the immunoglobulin heavy chain constant region (CH) with one of a set of downstream CH genes
Class-switch DNA recombination (CSR)
Class-switch DNA recombination (CSR) requires activation-induced cytidine deaminase (AID) and involves the generation of _______ in switch (S) regions (which lie upstream of the CH gene) followed by DSB repair.
DNA double-strand breaks (DSBs)
Activation-induced cytidine deaminase (AID) initiates class-switch DNA recombination (CSR) and somatic hypermutation (SHM) by
deaminating deoxycytosines in single-stranded DNA and supercoiled double-stranded DNA, both of which can arise during transcription.
The NLRP3 inflammasome is a cytosolic complex that regulates _______________.
processing and secretion of interleukins.
Degradation of Gram-positive bacterial cell wall peptidoglycan in macrophage and dendritic cell phagosomes leads to activation of
the NLRP3 inflammasome
The metabolic enzyme
__________ unexpectedly acts as a pattern recognition receptor that recognizes bacterial peptidoglycan and triggers activation of inflammasomes.
______________ are important controllers of autoimmunity, including type-1 diabetes.
T reg cells
T reg cells cause autoimmune diabetes by ____________
recruiting destructive T cells inside pancreatic islets.
_________ is upregulated in the heart of experimental autoimmune myocarditis rats.
___________knockdown improves heart function through regulation of TLR9 signaling in the experimental autoimmune myocarditis rats.
The ___________ of NADPH oxidase plays an essential role in suppressing intracellular multiplication of Salmonella in macrophages and in the regulation of both systemic and mucosal inflammatory responses to bacterial infection.
_________________are associated with the control of HIV replication.
Certain MHC class I alleles
Different MHC class I allele molecules differ in
how they present the epitopes that elicit effective HIV-specific T-lymphocyte responses
Adoptive cell transfer T cells are removed from a patient and modified so that they express receptors
specific to the patient's particular cancer.
______________directed to specific targets offers the possibility to endow the immune system with reactivities that are not naturally present.
The infusion of gene-modified T cells
Cell therapies are ultimately personalized in that, with rare exceptions, they are comprised of ___________
autologous, patient-derived T cells.
___________________ is produced by vascular endothelial cells to induce vasoconstriction, there is also immune-mediated ET-1 production induced by T cells upon activation through IFN-γ and TNF-α.
Although endothelin 1 (ET-1)
_____________ is a potent natural killer T-cell stimulator that also suppresses eosinophil production through interferon-γ-dependent induction of NO synthase and CD95.
The glycolipid α-Galactosylceramide
Omega-3 polyunsaturated fatty acids, well known to the public for their potential health benefits have immunoregulatory and immunosuppressive effects that through conflicting research _________
may or may not increase susceptibility to infection.
Cellular adaptation to low oxygen is mediated by hypoxia-inducible factors (HIFs). Natural killer (NK) cells infiltrate hypoxic tumor areas to kill cancer cells and deletion of HIF-1α in NK cells impairs tumor cell killing.
Neutralization of _________ ameliorates symptoms of experimental autoimmune myasthenia gravis in rats by decreasing effector T cells and altering humoral responses
_________ undergo terminal differentiation in the presence of IL-2 and IL-10 more readily than do naive B cells.
CD40-activated memory B cells
Severe asthma can be divided pathologically into two inflammatory subtypes based on the presence or absence of ____________.
The HIV envelope is a trimer composed of two antigens gp120 and gp41 that presents a variety of antibody neutralizing epitopes. However, the _________of the HIV genome gives the virus an extensive capacity to escape recognition by all known neutralizing antibodies.
Dendritic cells (DCs) act as antigen presenting cells to control immunity. Langerhans cells (LCs) are the only DC subset in the healthy epidermis. New antigen presentation by epidermal LCs results in either robust _____________________ and this decision-making depends on the activation state of the presenting LCs.
cytotoxic T lymphocytes (CTL) tolerance or CTL memory,
Malaria is caused by erythrocyte infection by the .
Plasmodium falciparum parasite.
Plasmodium falciparum-infected erythrocytes contain _______precipitates in the cytoplasm, which are released when the erythrocytes rupture. These _______precipitates induce maturation of dendritic cells.
BAFF-R and BCR signals cooperate to enable non-autoreactive immature B cells to differentiate into _____________
transitional B cells
and to be positively selected into the naïve B cell repertoire.
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