Infectious Disease - Immunology - Regulation; Hypersensitivity; Vaccines; Tumors Flashcards
CD___ is the main IL-2 receptor.
CD25 is the main IL-2 receptor.
Treg cells have a ________ affinity for MHC II receptors presenting _____ antigens.
Upon binding these proteins, they do what?
Treg cells have a high affinity for MHC II receptors presenting ‘self’ antigens (endogenously synthesized proteins that have been picked up by APCs after leaking from dead cells).
Suppress the T cell response to reduce likelihood of autoimmunity (peripheral tolerance)
True/False.
MHC II can sometimes present ‘self’ antigens.
True.
These are endogenously synthesized proteins that have been picked up by APCs after leaking from dead cells.
__________ tolerance involves inactivation of overactive T cells in the thymus.
__________ tolerance involves TReg cells supressing immune activity in the periphery.
Central tolerance involves inactivation of overactive T cells in the thymus.
Periperal tolerance involves TReg cells supressing immune activity in the periphery.
True/False.
Central tolerance in the thymus basically answers the question, ‘does the T cell bind MHC too tightly?’
True.
Peripheral tolerance — TReg cells sense _______ cells and inhibit T cell activity.
Peripheral tolerance — TReg cells sense self cells and inhibit T cell activity.
What is neonatal immune tolerance?
It is only relevant in what conditions?
The neonate becomes tolerant to anything it is exposed to at birth in non-inflammatory conditions
Why is neonatal tolerance important?
The neonate is exposed to maternal antigens en masse during delivery and breastfeeding — it would be detrimental if the child developed immune activity against normal body proteins
B7-CD28 interactions lead to IL-___ production.
B7-CD28 interactions lead to IL-2 production.
What receptor, when expressed, decreases immune activity by binding B7 (on APCs) with a higher affinity than CD28?
What interleukin is especially down-regulated via this process?
CTLA-4;
IL-2
Why do TReg often protect tumor cells from T cells and NK cells?
How do they accomplish this?
The tumor cells display ‘self’ antigens;
PD-1 receptor binding
True/False.
PD-1 receptor activity promotes the killing of tumor cells by T cells and NK cells.
False.
PD-1 receptors (when activated by PD-L1) inhibit the killing of tumor cells.
Anti-tumor immune activity can be increased by the administration of ___-__ inhibitors.
Anti-tumor immune activity can be increased by the administration of PD-1 inhibitors.
(PD-1 activity decreases the killing of tumor cells because they are self cells.)
What cell type displays the Foxp3 transcription factor?
Defects in this surface receptor cause what condition?
TReg cells;
IPEX
(immunodysregulation polyendocrinopathy enteropathy X-linked syndrome)
IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) is caused by a mutation in what TReg surface receptor?
How is this condition treated?
Foxp3;
immunosuppressive medications (lethal if not treatment not begun in early childhood)
What rare X-linked disorder is characterized by pervasive autoimmunity affecting multiple organs?
IPEX
(immunodysregulation polyendocrinopathy enteropathy X-linked syndrome)
B cells generally require ___ cells to enable them to mount autoimmune responses against self antigens.
B cells generally require TH cells to enable them to mount autoimmune responses against self antigens.
(I.e. virtually all autoimmunity is mediated by T cells.)
What general cell type mediates virtually all autoimmunity?
T cells
(B cells generally require TH cells to enable them to mount autoimmune responses against self antigens.)
Most autoimmune conditions are precipitated by some sort of _____________ event (e.g. stress, infection) that increases immune activity by increasing IL-_____ secretion.
Most autoimmune conditions are precipitated by some sort of inflammatory event (e.g. stress, infection) that increases immune activity by increasing IL-2 secretion.
Autoimmunity is mostly mediated by what specific cell type?
TH1 cells
What routes of antigen intake are typically tolergenic?
What routes are typically immunogenic?
Oral and IV routes;
subcutaneous, IM, intradermal
What amount of antigen load (low, intermediate, high) is most likely to promote an immune response?
Intermediate
(1. Small amount of antigen –> tolerance (probably mimics normal dying of cells releasing small amounts of antigen at a time
2. High amounts of antigen –> tolerance (clonal exhaustion)
3. Intermediate amount of antigen –> immunogenicity)
1. Small amount of antigen –> __________ (tolerance/immunogenicity).
2. Intermediate amount of antigen –> __________ (tolerance/immunogenicity).
3. High amounts of antigen –> __________ (tolerance/immunogenicity).
1. Small amount of antigen –> Tolerance (probably mimics normal dying of cells releasing small amounts of antigen at a time).
2. Intermediate amount of antigen –> Immunogenicity.
3. High amounts of antigen –> Tolerance (clonal exhaustion).
Why do very small amounts of antigen often not lead to immune responses?
Why do very large amounts of antigen often not lead to immune responses?
Mimics normal dying of cells releasing small amounts of antigen at a time;
clonal exhaustion
__________ exposure to an antigen leads to clonal exhaustion leads to __________.
Persistent exposure to an antigen leads to clonal exhaustion leads to tolerance.
True/False.
Persistent exposure to an antigen can lead to tolerance.
True.
Due to clonal exhaustion.
________ ________ — an antigen-recognizing T cell accidentally activates a B cell that produces antibodies against a similar ‘self’ antigen.
Molecular mimicry — an antigen-recognizing T cell accidentally activates a B cell that produces antibodies against a similar ‘self’ antigen.
Molecular mimicry — an antigen-recognizing ___ cell accidentally activates a ___ cell that produces antibodies against a similar ‘self’ antigen.
Molecular mimicry — an antigen-recognizing T cell accidentally activates a B cell that produces antibodies against a similar ‘self’ antigen.
All of the following are example causes of autoimmunity:
Molecular __________
Increased ______ antigens present on MHC II
_________proliferation / decreased _____________
All of the following are example causes of autoimmunity:
Molecular mimicry
Increased ‘self’ antigens present on MHC II
Lymphoproliferation / decreased supression
Autoreactive antibodies bind cells, and then NK CD___ are cross-linked as they bind the antibody ___ the cell is then killed.
Autoreactive antibodies bind cells, and then NK CD16 are cross-linked as they bind the antibody FC the cell is then killed.
Delayed hypersensitivity:
- Allergen is sensed in skin by a ________ cell.
- The above cell travels to a lymph node where it activates a ________ cell.
- This cell now enters the bloodstream and looks for signs of inflammation, at which point it enters the tissue.
- The cell is now activated by a ________ and begins releasing cytokines.
- Eosinophils follow the cytokines to the area.
Delayed hypersensitivity:
- Allergen is sensed in skin by a dendritic cell.
- The above cell travels to a lymph node where it activates a TH2 cell.
- This cell now enters the bloodstream and looks for signs of inflammation, at which point it enters the tissue.
- The cell is now activated by a macrophage and begins releasing cytokines.
- Eosinophils follow the cytokines to the area.
Delayed hypersensitivity:
- Allergen is sensed in skin by a dendritic cell.
- The above cell travels to a __________ where it activates a TH2 cell.
- This cell now enters the bloodstream and looks for signs of __________, at which point it enters the tissue.
- The cell is now activated by a macrophage and begins releasing cytokines.
- __________ follow the cytokines to the area.
Delayed hypersensitivity:
- Allergen is sensed in skin by a dendritic cell.
- The above cell travels to a lymph node where it activates a TH2 cell.
- This cell now enters the bloodstream and looks for signs of inflammation, at which point it enters the tissue.
- The cell is now activated by a macrophage and begins releasing cytokines.
- Eosinophils follow the cytokines to the area.
How long does a delayed hypersensitivity reaction (type IV HSR) typically take to manifest?
24 - 48 hours
Are antihistamines effective at mediating type IV hypersensitivity?
No
True/False.
Delayed (type IV; cytotoxic) hypersensitivity is mediated by CD8 T cells and mast cells only.
False.
Delayed (type IV; cytotoxic) hypersensitivity responses are all mediated by T cells (the type varies with infectious agent).
TH1 cells mainly activate what cell type(s)?
TH2 cells mainly activate what cell type(s)?
TH17 cells mainly activate what cell type(s)?
Macrophages & TC cells (pain, inflammation)
Eosinophils & B cells (itch, allergic inflammation)
Neutrophils (pain, pyogenic inflammation)
TH1 cells mainly activate what cell type(s)?
Macrophages & TC cells (pain, inflammation)
TH2 cells mainly activate what cell type(s)?
Eosinophils and B cells (itch, allergic inflammation)
TH17 cells mainly activate what cell type(s)?
Neutrophils (pain, pyogenic inflammation)
Which cytokine is the main inducer for a TH0 cell to become a TH1 cell?
IL-12
Which cytokine is the main inducer for a TH0 cell to become a TH2 cell?
IL-4
Which cytokines are the main inducers for a TH0 cell to become a TH17 cell?
IL-6, TGF-β
Which cytokine is the main inducer for a TH0 cell to become a TReg cell?
TGF-β
TH1 cells mainly activate macrophages and TC cells in response to what infection type(s)?
TH2 cells mainly activate eosinophils and B cells in response to what infection type(s)?
TH17 cells mainly activate neutrophils in response to what infection type(s)?
Viruses (pain, inflammation)
Helminths, ticks, mites (itch, allergic inflammation)
Bacteria (pain, pyogenic inflammation)
PPD testing mainly involves T___ cells.
PPD testing mainly involves T<strong>H</strong>1 cells.
Allergic dermatitis mainly involves T___ cells.
Allergic dermatitis mainly involves TH2 cells.
Autoinflammation mainly involves T___ cells.
Autoinflammation mainly involves TH17 cells.
An individual who has no pre-sensitization / previous immune experience with mosquitoes is bitten by one.
Can this individual undergo a type I hypersensitivity reaction?
Why or why not?
No.
No IgE for mast cells has been produced yet as no B cell maturation has occurred as the the antigen has not been encountered before.
Mast cell degranulation releases histamine, serotonin, heparin, eosinophilic chemotactic factors, _______ase, leukotriene ___, prostaglandin ___, IL-___, and TNF-α.
Mast cell degranulation releases histamine, serotonin, heparin, eosinophilic chemotactic factors, tryptase, leukotriene C4, prostaglandin D2, IL-4, and TNF-α.
Why do degranulating mast cells release IL-4?
To promote TH2 cells and IgE production
Why do degranulating mast cells release PGD2?
Strong chemokine for eosinophils, basophils, and TH2 cells
Why do degranulating mast cells release leukotriene C4?
Increased vascular permeability and bronchoconstriction
True/False.
Eosinophils are one of the most toxic and destructive cell types in the body.
True.
Name the cell type that can synthesize and release all the following:
Pre-formed: Major basic protein, (name of cell) cationic protein, (name of cell)-derived neurotoxin, (name of cell) peroxidase
On-demand: IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, TNF-α
Eosinophils
Pre-formed: Major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase
On-demand: IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, TNF-α
Describe how immediate allergic reactions may change in response to the following levels of interaction with an antigen:
No previous contact
Few previous encounters
Multiple previous encounters
Very many previous encounters
Describe how delayed allergic reactions may change in response to the following levels of interaction with an antigen:
No previous contact
Few previous encounters
Multiple previous encounters
Very many previous encounters
Why can antigens be immunogenic if taken up through the skin and tolergenic if taken up orally?
Cancer defenses against immunity are often mediated by de-differentiation to immature, more stem-cell-like forms:
1. Low immunogenicity (downregulated ____/peptide; absence of co-stimulation for self-antigens –> _______ of T cells; no _______ molecules; absence of inflammation)
2. Recruiting Tregs
3. Antigenic modulation — antibody binding surface antigen leads to endocytosis and destruction of antigen by tumor cell
4. Immunoediting — selective changes in expressed antigens
5. Creation of a physical barrier to immune activity (encapsulation)
Cancer defenses against immunity are often mediated by de-differentiation to immature, more stem-cell-like forms:
1. Low immunogenicity (downregulated MHC/peptide; absence of co-stimulation for self-antigens –> anergy of T cells; no adhesion molecules; absence of inflammation)
2. Recruiting Tregs
3. Antigenic modulation — antibody binding surface antigen leads to endocytosis and destruction of antigen by tumor cell
4. Immunoediting — selective changes in expressed antigens
5. Creation of a physical barrier to immune activity (encapsulation)
Cancer defenses against immunity are often mediated by de-differentiation to immature, more stem-cell-like forms:
1. Low immunogenicity (downregulated MHC/peptide; absence of co-stimulation for self-antigens –> anergy of T cells; no adhesion molecules; absence of inflammation)
2. Recruiting _____
3. Antigenic modulation — antibody binding surface antigen leads to _______ and destruction of antigen by tumor cell
4. Immunoediting — selective changes in expressed antigens
5. Creation of a physical barrier to immune activity (encapsulation)
Cancer defenses against immunity are often mediated by de-differentiation to immature, more stem-cell-like forms:
1. Low immunogenicity (downregulated MHC/peptide; absence of co-stimulation for self-antigens –> anergy of T cells; no adhesion molecules; absence of inflammation)
2. Recruiting Tregs
3. Antigenic modulation — antibody binding surface antigen leads to endocytosis and destruction of antigen by tumor cell
4. Immunoediting — selective changes in expressed antigens
5. Creation of a physical barrier to immune activity (encapsulation)
Cancer defenses against immunity are often mediated by de-differentiation to immature, more stem-cell-like forms:
1. Low immunogenicity (downregulated MHC/peptide; absence of co-stimulation for self-antigens –> anergy of T cells; no adhesion molecules; absence of inflammation)
2. Recruiting Tregs
3. Antigenic modulation — antibody binding surface antigen leads to endocytosis and destruction of antigen by tumor cell
4. Immunoediting — selective changes in expressed __________
5. Creation of a _________ barrier to immune activity (en_____lation)
Cancer defenses against immunity are often mediated by de-differentiation to immature, more stem-cell-like forms:
1. Low immunogenicity (downregulated MHC/peptide; absence of co-stimulation for self-antigens –> anergy of T cells; no adhesion molecules; absence of inflammation)
2. Recruiting Tregs
3. Antigenic modulation — antibody binding surface antigen leads to endocytosis and destruction of antigen by tumor cell
4. Immunoediting — selective changes in expressed antigens
5. Creation of a physical barrier to immune activity (encapsulation)
