Innate Immunity Flashcards
(166 cards)
1
Q
What is cross-presentation
A
The process where dendritic cells (DCs) present extracellular antigens on MHC class I to CD8 T cells, initiating a cytotoxic T cell response.
2
Q
What happens to a DC when infected by a pathogen
A
An infected dendritic cell becomes dysfunctional, does not migrate to the lymph nodes, and thus fails to present antigens to CD8+ T cells, impairing the adaptive immune response initiation.
2
Q
Markers of Cross-presenting DCs in Mice
A
Cross-presenting DCs in mice are identified by the expression of surface molecules such as CD24, Clec9A, XCR-1, and CD8α.
3
Q
Role of Infected Tissue Cells in Immune Response
A
Infected tissue cells process pathogen or viral antigens internally but cannot effectively present these antigens to CD8+ T cells, failing to initiate an immune response
4
Q
Function of Cross-Presenting Dendritic Cells
A
Specialized in capturing and processing antigens from infected cells or tissues through a unique pathway for presentation on MHC class I molecules and migrating to lymph nodes for T cell activation.
5
Q
How does Cross-Presentation activate CD8+ T cells?
A
Cross-presenting DC presents antigens to CD8+ T cells in lymph nodes, activating them to seek and destroy cells infected with the same pathogen, crucial for fighting viral infections and tumour immunity
6
Q
How do T cells recognise antigens?
A
T cells recognise antigens as short, linear sequences of amino acids presented on MHC molecules.
7
Q
MHC Class I
A
MHC Class I presents endogenous antigens to CD8+ T cells
8
Q
How are proteins processed for Class II MHC presentation?
A
Proteins are taken up into endocytic vesicles, degraded in acidic multilamellar bodies by enzymes like cathepsins, generating peptides
9
Q
Role of Acidic Proteases in Antigen Processing
A
Acidic proteases like cathepsin L or S generate peptides from antigen proteins, crucial for MHC class II antigen presentation.
10
Q
Function of GILT in Antigen Processing
A
GILT breaks disulfate bonds
11
Q
Function of AEP in Antigen Processing
A
AEP unlocks tertiary structures, enhancing antigen processing for MHC presentation
12
Q
MHC class II
A
MHC Class II presents exogenous antigens to CD4+ T cells.
13
Q
Roles do CIIV play in antigen processing and presentation
A
Sorting compartment -newly internalized antigens meet MHC for peptide loading, less acidic to facilitate this interaction (than late endosomal)
14
Q
Roles do MIIC play in antigen processing and presentation
A
MIIC is an advanced, late-stage compartment for final antigen processing; its acidic environment optimizes protease activity for peptide generation.
15
Q
What is the function of the invariant chain in MHC class II processing?
A
Invariant chain guides MHC II through the ER and Golgi to endosomal compartments, preventing premature peptide binding by occupying the peptide-binding groove with its CLIP region, ensuring proper MHC II folding and transport.
16
Q
Describe the sorting signals within the invariant chain that direct MHC class II
A
contains dileucine, tyrosine-based, and di-acidic motifs as sorting signals, directing MHC class II molecules from the ER through the Golgi to endosomal/lysosomal compartments for antigen processing.
17
Q
How does HLA-DM facilitate MHC class II processing?
A
HLA-DM removes CLIP from the MHC II groove, stabilizing the complex for high-affinity peptide loading onto the peptide-binding groove (PBG), ensuring that MHC II presents the most immunogenically potent peptides.
18
Q
What leads to B cell anergy and its significance?
A
B cell anergy occurs when B cells bind self-antigen but don’t receive T cell help, preventing autoantibody production and autoimmunity by making the B cell functionally unresponsive.
19
Q
How do viruses interfere with MHC class II processing?
A
Viruses may inhibit class II molecule expression, interfere with MHC II trafficking, or disrupt viral antigen processing, evading detection and impeding the adaptive immune response.
20
Q
MHC II chain synthesis
A
alpha and beta, which are synthesized in the ER where they bind to the invariant chain, facilitating the folding and prevention of binding to the ER.
21
Q
Invariant chain guide
A
MHC II molecules through the Golgi apparatus to the endosomal/lysosomal compartments
22
Q
CLIP
A
maintaining the integrity of the peptide binding groove during transport.
23
Q
anergy/ anagenic
A
prevents immune cells from attacking host tissues
24
Viral Interference with MHC II processing
inhibit the expression of class II molecule
interfere with intracellular trafficking of MHC class II
disrupt the normal processing of viral antigens that should be loaded.
25
What does the surface expression of pMHC indicate in antigen-presenting cells?
Surface expression of pMHC indicates that MHC class II molecules have processed and bound a peptide and are displayed on the surface of an APC for T cell recognition.
26
How do dendritic cells balance MHC class II molecules and pMHC surface expression in a steady state?
In the steady state, DCs balance new MHC class II synthesis with surface pMHC expression through recycling, avoiding unnecessary T cell activation and autoimmunity.
27
Why are B cells considered efficient in antigen presentation via MHC class II?
B cells, being MHC II+, have a low rate of ubiquitination and can efficiently present antigens internalized through their B cell receptor, making them more effective than other APCs.
28
ubiquitination
Ubiquitination is a cellular process where a ubiquitin protein is covalently attached to a target protein
29
Describe the components and functions of the regulatory particles (19S or PA700) of the proteasome.
Regulatory particles are cap-like structures responsible for recognizing polyubiquitinated proteins, unfolding them, and translocating them into the core for degradation. They include a base with ATPases for energy and a lid for ubiquitin removal.
30
What are the regulatory particles of the proteasome
19S or PA700
31
Describe the efficiency of the MHC class I antigen presentation process
The process is rapid but relatively inefficient, with only a small proportion of total protein molecules being presented.
32
What is the structure of the core particle (20S Proteasome)?
The core particle is a barrel-shaped structure with four stacked rings: two outer alpha rings and two inner beta rings, with only the beta rings having proteolytic sites
33
what is the core particle of the proteasome
20S
34
Function of
Ubiquitination
Ubiquitination regulates various cellular processes, including protein degradation by the proteasome, signal transduction pathways, cell cycle control, DNA repair mechanisms, and immune responses.
35
How does ubiquitination signal for protein degradation?
Proteins tagged with a polyubiquitin chain are recognized and degraded by the proteasome. This process removes damaged, misfolded, or unnecessary proteins from the cell.
36
What is the structure of the B cell receptor (BCR)
membrane-bound immunoglobulin molecule that recognizes antigens and an associated heterodimer of Ig-alpha and Ig-beta proteins, which transduce signals into the cell upon antigen binding.
37
How does the BCR recognize antigens?
BCR recognizes antigens through its variable region, which can bind to a specific part of an antigen called an epitope. This interaction triggers B cell activation and the immune response.
38
How do B cells present antigens to T cells?
After antigen binding, B cells internalize the BCR-antigen complex via endocytosis. The antigen is processed and presented on MHC class II molecules to T helper cells, leading to B cell activation and antibody production.
39
What happens when the BCR is engaged by its specific antigen?
B cell activation, proliferation, and differentiation into plasma cells that secrete antibodies or memory B cells.
40
What is the significance of the low rate of ubiquitination in B cells?
preserve the BCR and MHC class II molecules on the cell surface, ensuring effective antigen presentation and sustained interaction with T helper cells.
41
What is monoubiquitination and its typical outcomes for substrate proteins?
Attaching a single ubiquitin molecule to the substrate protein. This modification can affect protein activity, location, or interactions
42
What are the implications of ubiquitination in diseases?
Aberrations in ubiquitination processes can lead to diseases, including cancer, neurodegenerative disorders, and immune system dysfunctions. For example, malfunction in the degradation of cell cycle regulators can contribute to cancer, while impaired degradation of proteins can lead to conditions like Parkinson's disease.
43
How do immunoproteasomes differ from standard proteasomes?
Immunoproteasomes have slightly different subunits in the beta rings specialized for generating peptides for MHC Class I presentation, enhancing the immune response.
44
Standard Proteosome structure
beta subunits β1, β2, and β5 responsible for caspase-like, trypsin-like, and chymotrypsin-like proteolytic activities
45
Immunoproteasomes structure
they replace the subunits with β1i, β2i, and β5i, altering the cleavage specificity to produce peptides more suitable for MHC Class I presentation.
46
What triggers the formation of immunoproteasomes?
Immunoproteasomes are induced by interferon-gamma (IFN-γ) during immune responses, particularly under conditions of inflammation or infection, enhancing the cell's ability to present antigens and stimulate CD8+ T cell responses.
47
What role do immunoproteasomes play in antigen presentation?
optimize the peptides for binding to MHC Class I molecules, facilitating efficient recognition by CD8+ T cells and enhancing the cellular immune response.
48
How are immunoproteasomes relevant to diseases?
implicated in autoimmune diseases, where their altered peptide processing may lead to the presentation of autoantigens. They also play a role in cancer immunity, where enhancing their activity could improve antigen presentation and tumor cell recognition by the immune system.
49
What is the significance of immunoproteasome inhibitors?
therapeutic agents for autoimmune diseases by potentially reducing the presentation of autoantigens. They may also affect cancer treatment by altering the immune system's ability to recognize and destroy cancer cells.
50
autoantigens
normal proteins or molecules found within the body that are mistakenly recognized as foreign by the immune system, leading to an autoimmune response.
51
how does autoantigens occur
Molecular Mimicry, post-translational modifications, Loss of Immune Regulation, Genetic Susceptibility (HLA types), enviromental triggers (altered self antigens)
52
Describe the structure and roles of the alpha and beta subunits in the proteasome
Alpha subunits form the gate to the proteasome's inner chamber where beta subunits, containing protease activities, degrade proteins into peptides. ATPases facilitate substrate unfolding and entry.
53
What is the typical length of peptides processed by the proteasome for MHC I presentation, and how are they further trimmed?
Proteasome generates peptides 8-10 amino acids long, which can extend up to 25 amino acids. Aminopeptidases in the cytosol further trim peptides for MHC I presentation.
54
Describe the TAP complex's role in antigen processing for MHC I.
TAP1 and TAP2 form a complex that transports cytosolic peptides into the ER, using ATP for translocation. The complex is upregulated by interferons and associates with tapasin to optimize peptide loading onto MHC I.
55
What is the role of calnexin, calreticulin
Calnexin and calreticulin bind to MHC I molecules for proper folding
56
Role of Tapasin
Tapasin bridges MHC I to TAP and ensures high-affinity peptide loading
57
role of Erp57
Erp57 works with tapasin to aid folding.
58
Explain the role of tapasin's N-terminal in MHC I peptide loading
Tapasin's N-terminal connects to the alpha2 and alpha3 domains of MHC I and is vital for high-affinity peptide loading. It is a transmembrane glycoprotein located on the ER.
59
How does tapasin contribute to the optimization of MHC I peptide loading
Tapasin acts as a bridge between TAP and MHC I, working with Erp57 to optimize peptide loading and enhance the immune response.
60
What is the function of ERAP-1 in MHC class I antigen processing?
ERAP-1 trims peptides within the ER to the optimal length for binding to the MHC class I peptide-binding groove, crucial for creating epitopes recognized by T cells. It is inducible by IFN-γ.
61
Describe the process of MHC class I molecule surface expression post-peptide loading.
After peptide loading, the pMHC I complex is transported to the cell surface via the Golgi, where it can be recognized by CD8+ T cells, triggering an immune response
62
How can viruses interfere with MHC class I pathways, and what role does brefeldin A play?
Viruses may evade immune detection by downregulating peptide loading complexes or degrading MHC class I molecules. Brefeldin A, a drug, can inhibit MHC class I transport from the Golgi to the ER, highlighting the pathway's significance, especially in the context of cancer research
63
Where is polymorphism most common in MHC class I molecules
Variation or polymorphism in MHC class I molecules typically occurs in the peptide-binding groove, influencing the range of peptides that can bind.
64
Explain the process and significance of cross-priming by dendritic cells
Cross-priming involves dendritic cells presenting peptides on MHC class I that are typically presented on MHC class II, initiating a CD8+ T cell response. It enables CD8+ T cell activation against pathogens not directly infecting APCs and is critical for robust immunity.
65
Why is cross-presentation crucial for the immune response?
Cross-presentation allows dendritic cells to process and present exogenous antigens from non-APC-infected cells or tumors on MHC class I, broadening the immune response to include CD8+ T cells against diverse pathogens.
66
What is the role of WDFY4 in antigen presentation?
WDFY4 is implicated in the cross-presentation pathway, guiding the routing of antigens for MHC class I presentation and ensuring a comprehensive immune defense
67
What is the role of the phagosome in antigen presentation
maintains a neutral pH using NADPH oxidase and V-ATPase, essential for antigen processing. Misfolded proteins are removed by retrotranslocons, allowing antigens to reach the cytosol for proteasomal degradation. Resulting peptides are transported back into the ER via TAP, loaded onto MHC I molecules, and presented on the cell surface to activate CD8+ T cells
68
Non-specific Phagocytosis
Non-specific phagocytosis engulfs particles indiscriminately,
69
Receptor-mediated Phagocytosis
eceptor-mediated phagocytosis uses specific receptors like Mannose R, DC-SIGN, and CLEC9A to recognize and ingest pathogens or dying cells, adding specificity to immune responses.
70
What is the significance of CD91 in the immune system?
CD91 is involved in cross-presenting antigens from extracellular proteins and clearing apoptotic debris. It recognizes heat shock protein-peptide complexes, facilitating their uptake by dendritic cells for T cell presentation.
71
Describe the function of Tim3 in the immune system
found on immune cells, mediates the phagocytosis of apoptotic cells by binding to phosphatidylserine. This leads to antigen clearance or presentation and can promote immune tolerance or activation depending on the context
72
Exosomes in Antigen Presentation
small vesicles released by cells, carrying MHC-peptide complexes among other contents. APCs, like dendritic cells, use exosomes to present antigens to T cells, influencing the immune response.
73
What is the function of the Golgi body?
process and packages proteins and lipids. It modifies proteins received from the rough ER and sorts and dispatches them to their destination
74
Why are mitochondria referred to as the powerhouse of the cell
Mitochondria generate ATP through cellular respiration, providing the necessary energy for cellular functions.
75
What are the roles of the rough and smooth ER?
The rough ER synthesizes proteins, while the smooth ER is involved in lipid synthesis and detoxification processes.
76
What is the role of the nucleus in a cell?
The nucleus contains genetic material (DNA) and coordinates cell activities such as growth, metabolism, and reproduction.
77
What is the primary function of ribosomes
Ribosomes are the site of protein synthesis, translating mRNA into polypeptide chains.
78
How do cells respond to inflammation
During inflammation, cells respond to pathogens or threats by migrating to the infection site and initiating immune responses, such as releasing cytokines and chemokines
79
Describe the process of phagocytosis
like macrophages and dendritic cells recognize pathogens via PRRs or opsonins and engulf them. The formed phagosome fuses with a lysosome to degrade the contents.
80
Differentiate between pinocytosis and micropinocytosis
Pinocytosis ("cell drinking") ingests extracellular fluid and solutes. Micropinocytosis is a variant where cells form small vesicles to sample the environment
81
What molecules are involved in clathrin-mediated endocytosis
This pathway involves LDLR for cholesterol, TfR for iron import, EGFR for cell growth, insulin receptors, GPCRs, integrins for matrix interactions, and more, ensuring cellular uptake of specific molecules.
82
LDLR
for cholesterol
83
TfR
iron import
84
EGFR
Cellular growth
85
How are vesicles formed in clathrin-mediated endocytosis?
Clathrin and adapter proteins assemble into a coated pit that invaginates and separates from the membrane to form a vesicle.
86
Heat shock proteins (HSPs)
proteins that are produced by cells in response to stressful conditions, such as heat, cold, UV light, and during fever or infection- can be taken u by DC
87
opsonins
molecules that enhance phagocytosis by marking foreign particles such as bacteria for destruction by phagocytic cells
88
IgG opsonins
IgG antibodies are well-known opsonins that bind to antigens on the surface of pathogens. The Fc region of the antibody is recognized by Fc receptors on the surface of phagocytes, facilitating the uptake and destruction of the pathogen.
89
What are caveolae, and where are they found?
Caveolae are small, flask-shaped invaginations in the plasma membrane, found in endothelial and muscle cells. They're involved in endocytosis and signal transduction.
90
Describe caveolins and their role in caveolae formation
Caveolins are integral membrane proteins that form the coat of caveolae. CAV1, CAV2, and CAV3 are types of caveolins, with CAV1 and CAV2 expressed together, and both CAV1 and CAV3 being essential for caveolae formation
91
What are cavins, and what role do they play in caveolae
Cavins are cytosolic proteins crucial for stabilizing caveolae structures, including several types (1,2,3,4), with each playing a specific role in caveolae dynamics and membrane curvature
92
What are the components of the cytoskeleton and their functions?
The cytoskeleton comprises intermediate filaments (mechanical strength), microtubules (vesicle transport, cell division), and actin filaments (cell movement, shape). Each component contributes uniquely to cellular structure, transport, and motility
93
How does actin polymerization contribute to cellular processes?
ATP-dependent process, is crucial for cell movement, shape, intracellular transport, and division. It involves the growth of actin filaments (F-actin) from monomers (G-actin), driven by proteins like formins and the ARP2/3 complex.
94
What role does actin polarity play in cellular functions
Actin filaments have inherent polarity with a fast-growing 'barbed' end and a slower-growing 'pointed' end. This polarity is essential for directional movement and force generation within cells, influencing processes like migration, division, and signal transduction
95
How is actin depolymerization regulated, and what are its implications?
Actin depolymerization is regulated by ATP hydrolysis, converting ATP-bound actin to ADP-bound actin, which has a lower affinity for filaments. Proteins like cofilin accelerate disassembly, influencing filament turnover and cell responsiveness
96
What are Fc Receptors (FcRs), and how do they function in receptor-mediated phagocytosis?
receptors on phagocytes that recognize the Fc region of antibodies. Different Fc receptors bind to various classes of antibodies (IgG, IgA, etc.), leading to the internalization and clearance of pathogens that have been opsonized (coated) with antibodies.
97
Describe the role of Complement Receptors in phagocytosis.
Complement Receptors (e.g., CR1, CR3, CR4) bind to complement proteins opsonized on pathogens. For instance, CR1 binds to the complement component C3b, enhancing the phagocytosis of microbes by signaling the phagocyte to engulf the complement-coated pathogen.
98
What are Scavenger Receptors, and what ligands do they recognize?
Scavenger Receptors bind a broad spectrum of ligands, including modified LDLs, anionic polymers, and bacterial polysaccharides. They play a crucial role in clearing cellular debris, oxidized lipids, and in pathogen clearance
99
How do Mannose Receptors (MR) contribute to pathogen recognition?
Receptors recognize specific sugar residues like mannose, fucose, and N-acetylglucosamine, commonly found on the surface of many pathogens but absent on human cells. MR facilitates the phagocytosis of fungi, bacteria, and viruses by binding to these sugars.
100
What is Dectin-1, and what does it recognize?
Dectin-1 is a receptor that primarily recognizes β-glucans, components of fungal cell walls. It mediates the phagocytosis of fungal pathogens, triggering an immune response to fungal infections.
101
Describe the role of DNGR-1 (CLEC9A) in receptor-mediated phagocytosis.
recognizes dead and dying cells by binding to exposed actin filaments in these cells, playing a role in the clearance of cellular debris. It also potentially facilitates the cross-presentation of antigens from dying cells, contributing to the immune response.
102
What is the structure and function of Microtubules?
part of cytoskeleton made from alpha and beta tubulin subunits, forming hollow tubes with polarity. They maintain cell shape, enable intracellular transport, and segregate chromosomes during division. Their dynamics are regulated by GTP.
103
How do motor proteins function on microtubules and actin filaments?
How do motor proteins function on microtubules and actin filaments?
104
What roles do microtubules play in cell movement?
facilitate cell movement by polymerizing actin at the leading edge, creating force for plasma membrane protrusion. They also enable adhesion to the extracellular matrix and coordinated release, driven by cellular signaling.
105
Describe actin dynamics in cell movement.
Actin filaments, regulated by accessory proteins like profilin, formins, and ARP2/3, support structural integrity, cell movement, and division. They polymerize for forward movement and depolymerize for retraction, aiding in cellular navigation.
106
How is ATP hydrolysis involved in motor protein function?
Motor proteins exhibit random Brownian motion until binding to a microtubule, triggering ADP release and ATP binding. ATP hydrolysis causes a conformational change, propelling the protein along the microtubule for intracellular transport and division.
107
How does myosin facilitate cell movement?
Myosin transforms ATP to mechanical energy, moving along actin filaments. It undergoes a cycle of binding, ATP hydrolysis, and power strokes, moving forward and enabling cell contraction and migration.
108
How do myosins contribute to cell adhesion and migration
In stress fibers, myosin contracts the cell rear, aiding migration. Focal adhesions connect the cytoskeleton to the extracellular matrix, while talin and vinculin mediate integrin activation for cell adhesion and movement.
109
What are the roles of Golgi body, mitochondria, ER, nucleus, and ribosome in cell response to inflammation?
These organelles process proteins/lipids, generate ATP, synthesize proteins/lipids, contain genetic material, and synthesize proteins, respectively. They enable cells to respond and migrate to infection sites during inflammation.
110
Explain the myosin movement cycle.
The cycle starts with myosin binding to actin, then ATP binding causes it to release. ATP hydrolysis shifts it to a high-energy state. The power stroke moves myosin along actin, propelling it and repeating the cycle.
111
phagocytosis mechanisms in immune response.
Phagocytosis involves immune cells engulfing pathogens via receptors like Fc and complement receptors.
112
endocytosis mechanisms in immune response.
Endocytosis includes pinocytosis for fluid uptake and clathrin-mediated for specific molecule internalization, crucial for cellular response and immunity.
113
What is the role of immature DCs in tissue surveillance?
Immature dendritic cells (DCs) patrol peripheral tissues, sampling the environment for antigens through macropinocytosis and phagocytosis. This allows them to capture antigens from both self-tissues (for tolerance induction) and pathogens (for initiating immune responses).
114
How do steady-state DCs migrate to lymph nodes?
Steady-state DCs express CCR7, a chemokine receptor that responds to CCL19 and CCL21 chemokines from lymphatic tissues. This guides them towards lymphatic vessels, through which they migrate to lymph nodes, maturing en route to prepare for effective antigen presentation to T cells.
115
What changes occur in DCs as they migrate to lymph nodes?
As DCs migrate, they undergo maturation, characterized by the upregulation of MHC molecules, co-stimulatory molecules (like CD80/CD86), and cytokines. This prepares them to effectively present antigens to T cells upon arrival in the lymph node
116
How do DCs induce tolerance or immunity
Depending on the context of the antigen (self-antigen for tolerance or pathogen-associated for immunity), DCs can either induce immune tolerance to prevent autoimmunity or initiate an adaptive immune response.
117
What functions do quiescent DCs perform?
capture antigens and express MHC class II molecules at low levels, with minimal co-stimulatory molecules, primarily inducing tolerance. They become activated upon encountering pathogenic antigens or inflammatory signals.
118
How do quiescent DCs contribute to immune tolerance?
With their non-activated state and low levels of co-stimulatory molecules, quiescent DCs are more likely to induce tolerance when they present antigenic peptides to T cells, either leading to anergy or the development of regulatory T cells.
119
What triggers the activation of quiescent DCs?
Quiescent DCs become activated upon encountering pathogenic antigens or inflammatory signals, upregulating co-stimulatory molecules, cytokines, and chemokine receptors such as CCR7, which directs their migration to lymph nodes for naive T cell activation.
120
Describe the surveillance role of quiescent DCs.
The quiescent state of DCs allows for continuous surveillance of the body's tissues without triggering unnecessary immune responses against self-antigens, crucial for preventing autoimmunity and maintaining immune surveillance.
121
What are conventional dendritic cells (cDCs)?
key subtype of DCs, crucial for initiating immune responses. They are divided into cDC1, which are specialized in cross-presenting antigens to CD8+ T cells and producing IL-12, and cDC2, which are adept at activating CD4+ T cells and are involved in responses to a broader range of pathogens.
122
What is the primary function of plasmacytoid dendritic cells (pDCs)?
ability to produce large amounts of type I interferons in response to viral infections, playing a critical role in antiviral immunity and tolerance.
123
monocyte-derived dendritic cells (moDCs) formed?
generated during inflammation when monocytes are recruited to tissues and differentiate into DCs in response to infection or tissue injury, performing functions similar to conventional DCs.
124
What distinguishes Langerhans cells
Langerhans cells are specialized dendritic cells found in the epidermis, identified by the expression of langerin (CD207). They activate T cells upon migrating to lymph nodes after encountering antigens.
125
Describe follicular dendritic cells (FDCs).
located in B cell areas of lymphoid tissues, presenting antigen to B cells. They play a role in B cell memory and the germinal center reaction but do not present antigen to T cells.
126
What are semi-mature lymph dendritic cells?
found in peripheral tissues and are in a state between immature and fully mature. They capture antigens but do not provide strong co-stimulatory signals, often leading to T cell anergy or tolerance in the absence of inflammatory signals
127
How do DCs influence Th1 responses?
DCs can influence the immune response direction; IL-12 production by DCs can drive a Th1 response, important for fighting intracellular pathogens.
128
How do DCs influence Th2 responses?
presence of IL-4 can influence DCs to promote a Th2 response, typically against extracellular pathogens and associated with allergies and asthma.
129
What is the role of IL-4 in dendritic cell function?
IL-4 can modulate dendritic cell function to favor Th2 cell activation, which is significant for responses to extracellular parasites and conditions like allergy and asthma. DCs are influenced by the IL-4 in their environment rather than producing it themselves.
130
Describe the importance of IL-2 in the context of DC and T cell interaction.
IL-2 is crucial for T cell growth and survival. A lack of IL-2 can lead to T cell anergy or the development of regulatory T cells, especially when DCs don't provide adequate stimulation, contributing to immune tolerance.
131
How are monocytes recruited to sites of inflammation or tissue injury?
Monocytes are recruited through the action of chemokines, cytokines, and PAMPs, which activate endothelial cells to adhere to circulating monocytes.
132
Describe the process of monocyte activation and migration.
Activated by inflammatory signals, monocytes express integrins and adhere to the endothelium, then migrate into tissues through diapedesis.
133
What role does the local environment play in monocyte differentiation into DCs?
Inflammatory cytokines like GM-CSF and IL-4 in the tissue microenvironment initiate monocyte differentiation into DCs by activating specific transcription factors
134
Explain the differentiation and maturation changes in monocytes as they become DCs.
Monocytes lose CD14 expression, express high levels of MHC II and co-stimulatory molecules (CD80, CD86), and develop dendrites crucial for T cell interaction
135
What functions do differentiated moDCs serve in the immune response?
process and present antigens to T cells, can migrate to lymph nodes to activate naïve T cells, and elicit strong Th1 responses against intracellular pathogens.
136
Where are Langerhans cells located, and how do they migrate?
Located in the epidermis, capture antigens and migrate to lymph nodes when activated, using langerin (CD207) for antigen capture and presentation
137
What distinguishes conventional dendritic cells from Langerhans cells?
found in almost all tissues and are classified into cDC1 and cDC2, each playing unique roles in antigen presentation and immune response initiation.
138
Describe the function and immune response roles of Langerhans cells.
Langerhans cells initiate immune responses against pathogens entering through the skin and maintain tolerance to self-antigens, preventing autoimmunity.
139
How do conventional dendritic cells contribute to the immune response?
Conventional DCs act as immune sentinels, with cDC1s presenting to CD8+ T cells and cDC2s activating CD4+ T helper cells, shaping adaptive immunity.
140
Compare the tissue residency and renewal of Langerhans cells and conventional dendritic cells
tissue-resident and self-renew within the epidermis, whereas conventional DCs often arise from bone marrow precursors and can be replenished from circulating monocytes.
141
What is the significance of understanding DC subsets in disease and therapy?
aids in developing targeted immunotherapies to enhance immunity against pathogens or induce tolerance in autoimmune diseases and transplants.
142
What initiates the germinal center reaction in B cells?
The germinal center reaction is initiated when a B cell recognizes an antigen through its B cell receptor (BCR), becomes activated, and migrates to the edge of a follicle within a lymph node or spleen to interact with helper T cells
143
What processes do B cells undergo in the germinal center?
In the germinal center, B cells undergo somatic hypermutation and class switch recombination. These processes generate B cells with higher affinity BCRs and allow B cells to switch the class of antibody they produce.
144
Describe the role of somatic hypermutation in the germinal center.
involves introducing mutations in the variable region of immunoglobulin genes in B cells, potentially increasing the affinity of the antibodies they produce for their specific antigen.
145
How does affinity maturation occur in the germinal center?
Affinity maturation occurs as FDCs present antigens to B cells in the form of immune complexes. B cells with higher affinity receptors capture more antigen and receive survival signals, leading to their selection
146
What is class switch recombination, and how is it influenced?
Class switch recombination is a process where B cells change the type of antibody they produce (e.g., from IgM to IgG). This process is influenced by cytokines in the microenvironment and interactions with helper T cells.
147
What are the outcomes of high-affinity B cells in the germinal center?
High-affinity B cells can differentiate into plasma cells, which secrete large quantities of antibodies, or into memory B cells, which provide rapid and effective responses upon subsequent antigen exposures.
148
What is the significance of memory B cells from the germinal center reaction?
Memory B cells are long-lived cells that do not immediately secrete antibodies but can quickly do so upon re-exposure to their specific antigen, providing long-lasting B cell immunity.
149
Why is the germinal center reaction crucial for vaccines?
The germinal center reaction produces high-affinity antibodies and establishes long-lasting B cell immunity, making it essential for the effectiveness of many vaccines aimed at generating a pool of memory B cells for rapid future responses.
150
MHC class II HLA
(HLA-DP, HLA-DQ, and HLA-DR).
151
MHC class I HLA
HLA-A, HLA-B, and HLA-C
152
What is the primary function of MHC Class I genes (HLA-A, HLA-B, and HLA-C)?
present peptide fragments derived from intracellular proteins (e.g., from viruses or tumor cells) to CD8+ T cells, facilitating the immune response against these antigens.
153
How do MHC Class II genes (HLA-DP, HLA-DQ, and HLA-DR) function in the immune system?
MHC Class II genes encode molecules that present peptides from extracellular sources (like engulfed bacteria) to CD4+ T cells.
crucial for initiating helper T cell responses, leading to antibody production by B cells, activation of cytotoxic T cells, and orchestration of the immune response through cytokine release.
154
What role does genetic diversity in MHC genes play in the immune system?
contributes to the uniqueness of each individual's immune response and increases the population's ability to respond to various pathogens. However, it poses challenges in clinical settings like organ transplantation, where HLA allele matching between donor and recipient is crucial for transplant success.
155
Describe the role of HLA-DR in the immune system
HLA-DR molecules, part of MHC Class II, are crucial for presenting extracellular pathogen-derived peptides to CD4+ T cells. This interaction activates CD4+ T cells, which then help orchestrate the immune response, including cytokine production, enhancement of CD8+ T cell function, and B cell antibody production.
156
How does HLA-DR contribute to immune surveillance and regulation?
HLA-DR molecules play a vital role in immune surveillance by presenting a broad array of peptides for T cell recognition, thus monitoring for pathogens or abnormal cells. They regulate the specificity and direction of the immune response, promoting infection clearance, immune memory, and self-tolerance to prevent autoimmunity.
157
How can variations in HLA-DR alleles affect health?
Variations in HLA-DR alleles can influence an individual's susceptibility to autoimmune diseases, response to infections, and the outcome of organ transplantations due to their central role in immune activation and regulation.
158
Treg Mechanisms of Suppression
Cytokine Deprivation: consume IL-2 through high-affinity IL-2 receptors, depriving effector T cells of this growth factor.
Direct Cell-Cell Contact: Through CTLA-4, directly suppress effector T cell function by interacting with costimulatory molecules on APCs.
Secretion of Inhibitory Cytokines: secrete cytokines such as TGF-β and IL-10, which have broad anti-inflammatory and immunosuppressive effects
159
Therapeutics of Tregs
treatment of autoimmune diseases, graft-versus-host disease (GVHD), and in the context of organ transplantation to promote tolerance to the transplanted organ
160
Inducible Tregs (iTregs)
iTregs in the presence of TGF-β and IL-2. This process is especially important in mucosal tissues where TGF-β levels are often high due to the local environment. iTregs contribute to the pool of Tregs that mediate tolerance.
161
what metabolic status' can activate tregs
high concentrations of certain metabolites or low oxygen levels (hypoxia) in tissues can enhance Treg function
162
Treg in gut
Signals such as short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fibers can promote the expansion and function of Tregs in the gut- prevent autoimmunity
163
PD-1 co-inhibitor signal
PD-1 interaction with its ligands (PD-L1 and PD-L2) can inhibit T cell receptor (TCR) signaling
164
CTLA-4 co-inhibitor signal
CTLA-4 competes with CD28 for CD80/86, reducing co-stimulatory signals required for effector T cell activation, thus functioning as a mechanism of suppression.
165
Treg co-stimulatory molecules
CD28 (CD80,86 ligands) , ICOS (for survival and poliferation)
