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Immunology Lec. 13-15
Terms in this set (138)
Th1 cells do what?
stimulates cellular immunity
Th2 cells do what?
important in mucosal immunity and parasitic infections
Th17 cells do what?
Tfh cells do what?
follicular helper cells that help B-cells
Treg cells do what?
Regulatory T-cell that suppress T-cells
What are the cytokines that develop Th1 cells?
IL-12 and IFN-gamma
Th1 cells are generated during infections with __________
What are the primary cytokines secreted by Th1 cells?
What cytokine causes Th1 cells to replicate into clones that leave the lymph node and go into circulation?
What cytokine is secreted whenever the Th1 cells encounter their cognate antigen peptide on MHC II molecules on the surface of APCs?
Th1 cells become activated where?
What allows Th1 and Th17 cells to exit blood vessels in areas of inflammation?
They acquire a different set of LFA adhesion molecules
What activated Th1 cells encounter their cognant peptide on _________ of infected macrophage in the area of inflammation, they will secrete copious amounts of _____ that will activate the infected ________ further, and help them kill the intracellular bacteria.
1) MHC II molecules
What cytokine will activated macrophages secrete that will stimulate Th1 cells further, creating a positive feedback?
Through the action of what 4 important cells will the Cell-Mediated Immunity help kill/eliminate viral, bacterial and protozoal infected cells?
1) Th1 cells
4) NK cells
Which part of the Th1 cells recognizes that peptide presented by macrophages on their MHC II molecule?
If a person has had TB before, what cells will they have that are sensitized to tuberculin?
Memory Th1 cells
When PPD is injected intradermally, ________ cells pick up the PPD, break it down in ________ and present PPD derived peptides on their _______ molecules.
-- MHC II
During a TB test, the memory Th1 cells recognize and bind to the PPD __________ complex, become activated and secrete ____; which in return causes the DC to secrete _______ and _______ cytokines (TNF-alpha, IL-12)
-- Pro-inflammatory and Vasoactive
People that get leprosy have a deficiency of what cells?
What are the cytokines that favor the development of Th2 cells?
IL-4 and IL-5 are produced by what cells?
Activated mast cells and T-cells (not by DCs)
When do mast cells release IL-4?
1) Chitin, a polysaccharide present on fungal, helminth parasites, and insects
2) Airborne allergens that cross the mucosal epithelial cells in very low doses
When do mast cells release IL-5?
When pathogens infect mucosal epithelial cells
What causes naive Th cells to develop into Th2 cells?
What type of T-cell is primarily involved in mucosal immunity?
DCs move into the mucosal associated lymphoid tissues and present peptides derived from chitin/allergen/pathogen on their ____ molecules.
Th cells that recognize the chitin/allergen/pathogen in the presence of _____ or ____ become activated and develop into Th2 cells?
IL-4 or IL-5
What cytokines do activated Th2 cells secrete?
What cytokine will help B-cells whose BCR recognize chitin or allergen, to switch from producing IgM to producing IgE?
Which cytokine will help B-cells whose BCR recognize pathogens, to switch from producing IgM to IgA?
IL-4 switches IgM into what?
IL-5 switches IgM into what?
What do you call the process in which a T-cell is bound by the cytokine it secreted itself?
How are Th2 cells "locked" onto an IL-4 or IL-5 secreting cell?
By autocrine stimulation--the cytokines released by the cell bind back on itself
In the lymphoid follicles, the _____ cells will help B-cells replicate into clones, secrete IgM initially, and eventually help them switch to secreting IgE (IL-4) or IgA (IL-5)
What are the cytokines that favor the development of Th17 cells?
TGF-beta (transforming growth factor beta)
Which cytokines must be ABSENT for Th17 cells to develop?
IL-4 and IL-12
_____ is induced during almost all infections, particularly minor extracellular fungal and bacterial infections.
If an infection is serious, and it results in abundant IL-12 secretion, then Th17 cells will switch to what kind of cell?
If an infection causes abundant release of IL-4 by mast cells, then Th17 will switch to what kind of cell?
What is the primary cytokine that is secreted by an activated Th17 cell?
What is a pro-inflammatory cytokine that promotes inflammation indirectly?
How does IL-17 indirectly promote inflammation?
IL-17 acts on receptors present on fibroblasts, epithelial cells, and keratinocytes in tissue, causing these cells to release chemokines. The chemokines will attract neutrophils to the area of infection causing inflammation.
Th17 become activated upon encountering their pathogen-derived peptide presented by _______ on DCs secreting ____ and ____ in the lymph node ______.
When do Th17 cells secrete IL-17?
When they re-encounter their cognate peptide on MHC II on macrophages that have phagocytosed the same pathogen.
What is the primary function of Th17 cells?
To protect against extracellular pathogens through the stimulation of neutrophil response that helps clear such pathogens.
T or F: In most instances, Th17 cannot clear infections on their own, and need help from other Th cells.
False, they can clean up infections on their own most of the time.
What cytokine favors the developtment of Tfh cells?
What are Tfh cells?
Follicular helper T-cells
Where in lymphoid tissues are Tfh cells activated?
T-cell rich paracortical area
When are Tfh cells activated?
When they encounter their cogante peptide on MHC II molecules presented by DCs secreting IL-6 primarily.
What do activated Tfh cells do?
They migrate to the lymphoid follicles and help B-cells replicate and manufacture antibodies.
Tfh cells can secrete cytokines characteristic of either ____ or _____ cells.
Th1 or Th2
If ____ predominates, then the Tfh cells will secrete ______ that will encourage B-cells replicating in the secondary follicles to produce strongly opsonizing antibodies (IgG).
If ___ predominates, then Tfh cells will secrete ____ which will cause the B-cells in the secondary follicles to produce other antibody classes (IgA, IgE)
Which type of T-helper cell help replicating B-cells in the lymphoid follicles to divide and manufacture high affinity antibodies?
How do you explain how B-cells, during an infection, can switch from producing strong opsonizing antibodies to non-opsonizing strongly neutralizing antibodies?
Because of the ability of Tfh cells to secrete both Th1 or Th2 type cytokines.
What cytokine favors the development of regulatory T-cells (Treg)?
What cytokines must be absent in order for Treg cells to develop?
IL-6 and other pro-inflammatory cytokines such as IL-12
What are the 4 receptors that Treg cells carry?
Which T-helper cells are called "FoxP3 positive" cells?
What will a Th cell turn into if it encounters its cognate peptide in the presence of TGF-beta plus IL-6?
a pro-inflammatory Th17 cell
What will a Th cell turn into if it encounters its cognate peptide in the presence of TGF-beta alone?
What cytokines to Treg cells secrete?
What do TGF-beta and IL-10 do?
They suppress the inflammation and the immune response; therefore, they prevent unwanted immune responses
How do TGF-beta and IL-10 suppress the immune response?
-- These cytokines act by blocking the production of both IL-2 and receptors for IL-2
--They also block the expression of B7 on antigen presenting cells--B7 is the co-receptor for activation of T-cells through CD28
The presence of IFN-gamma and IL-12 blocks _____ secretion and prevents the differentiation of Th0 and Th17 into Th2.
What are the 3 effector T-cells?
What are the secondary lymphoid organs?
Lymph nodes, spleen, Peyer's patches
What does the B-cell rich area of a secondary lymphoid organ contain?
B-cells and FDCs equivalent to primary lymphoid follicles of lymph nodes
What does the T-cell rich area of a secondary lymphoid organ contain?
T-cells and IDC equivalent to paracortex of LN
What is the red pulp in the spleen composed of?
Red blood cells
What is the white pulp in the spleen composed of?
Is it the white or red pulp that has a central arteriole in the spleen?
Central arteriole is surrounded by a periarteriolar lymphoid sheath (PALS) made up of _______.
Lymphoid follicles in the spleen are made up of what cells?
What is the marginal zone in the spleen composed of?
Macrophages and dendritic cells--these pick up antigen and migrate to the other zones when activated
What does MALT stand for?
Mucosal Associated Lymphoid Tissues
GALT stands for?
Gut Associated Lymphoid Tissues
NALT stands for?
Nasal Associated Lymphoid Tissues
BALT stands for?
Bronchial Associated Lymphoid Tissues
The slowing down and contact of lymphocytes with high endothelial cells activates the T-cell integrin molecule ________.
LFA-1 binds to intercellular adhesive molecules _________, _____, and _____ present on the high endothelial cells, bringing the naive T-cell to a stop in the HEV
ICAM-1, ICAM-2, ICAM-3
What is the process of a cell squeezing through endothelial cells to exit a vessel called?
What happens to BCRs once they have attached to an antigen?
They are endocytosed into the B-cell
When a B-cell has recognized and endocytozed its cognate Ag, it goes into a "rested state" until what occurs?
Until it is co-stimulated by a Th cell
What will happen to a B-cell that remains in a "rested state" for too long?
It will get in a state of Anergy, and may eventually undergo apoptosis
What are the 2 criteria that Th cells need to activate a B-cell?
1) it must already be activated or "armed" by a DC
2) It was activated by a peptide (on the MHC II of DCs) orginating from the same Ag recognized by the BCRs (i.e. the B-cell must be presenting the same peptides on its MHC II molecules)
The B-cell acts as an ____ during activation.
APC (antigen presenting cell)
The resting B-cell is stimulated into proliferating via cytokine _____ released by the Th2 cell.
Where in the lymph node does B-cell activation by Th2 cells take place?
What antibody will B-cells make under the influence of IL-4?
what is the first Ab manufactured by the newly activated B-cell?
Which regions on an Ab is switched to form a different isotype?
The constant heavy regions
Do paratopes change when an Ab changes to a different isotype?
No, they stay the same
How many Constant heavy regions do IgM Abs have?
How many Constant heavy regions do IgG Abs have?
Which antibody isotype is known to be strongly opsonizing?
In the presence of which cytokine will B-cells switch from making IgM to making IgG? Which Th cell makes this cytokine?
What are some things that IgG Abs do?
1) Strongly opsonize bacteria
2) activates complement system
3) stimulate phagocytosis
4) induce ADCC
In the presence of which cytokine will B-cells switch from making IgM to IgE and IgG2?
What is IgG2 good at?
What are the 2 function of IgE?
1) attach to mast cells and induces allergies
2) Excellent at fighting parasitic infections
Which cytokines make B-cells switch from making IgM to IgA?
IL-5 and TGF-beta
What is IgA important for?
Which Ab is a pentomer?
When B-cells are first activated in the medulla, some will leave the LN and become IgM secreting ______ cells.
Which cells are in germinal centers?
What is another name for the rapidly dividing B-cells in the dark zone of the germinal centers?
When does isotype switching occur?
during period of active proliferation of B-cells
During division in the dark zone, the hypervariable regions (HVR) of the BCRs undergo a high rate of mutation, known as _______.
B-cells that have undergone somatic hypermutation move to the center of the ________ follicle.
What are the B-cells that have undergone somatic hypermutation and have moved into the center of a secondary follicle called?
Centrocytes interact with which type of cells?
Where is antigen concentrated on a FDC?
on the iccosomes
Centrocytes bind to where on the FDCs?
they bind to the antigen concentrated on the iccosomes
In order for the centrocytes to continue proliferating, they have to be _______ by ____, otherwise they undergo apoptosis.
re-stimulated by antigen
What cell looks like an octopus?
What are the "beads" on the tentacles of the FDC?
Antigen:antibody complexes= iccosomes
T or F: FDC processes antigens.
False- they DO NOT process antigen, they capture and present it in the form of an iccosome
How long does antigen remain attached to the FDC in the form of iccosomes?
Iccosomes are ingested by activated _______ whose _____ attach to the antigen on them.
When the centrocytes with "mutated" HVRs on their BCRs encounter the Ag on iccosomes, what 3 things can happen?
1) they can no longer recognize the Ag
2) they recognize the Ag "as before"
3) they bind to the Ag more avidly than before
What will happen to centrocytes whose BCR do not recognize the Ag?
They will undergo apoptosis
The B-cell with BCRs that have the ______________ are more likely to take up the Ag, present them as peptides via their MHC II molecules, and be stimulated by Th cells.
highest avidity for the Ag
Centrocytes with their peptides displayed on MHC II molecules migrate to the periphery of the ______
Re-activated B-cells can do 3 things:
1) undergo another round of rapid division
2) move out of the follicle and become plasma cells
3) become memory cells
How do B-cells become re-activated once they move the the periphery of the germinal center?
TCRs of Th2 cells bind to the peptide-MHC II combo, and the cytokine IL-4 reactivates it.
This "fine tuning" of BCRs for their cognate antigen results in a collection of B-cells that will produce very high affinity Ab. This process is referred to as _________.
Affinity maturation allows antibodies to change which regions?
Fc region (class switching)
Fab region (somatic hypermutation)
What is essentially the end result of affinity maturation?
a B-cell that is better adapted to fight the pathogen
At the end of an infection, what is the fate of most activated B-cells?
They undergo apoptosis
What cells are referred to as "antibody factories"?
About how many antibodies can a plasma cell produce?
~10,000 per second
Where are a few locations that plasma cells release their antibodies?
In the medullar cords of a lymph node, and also directly into the blood stream from the bone marrow.
Where do memory B-cells circulate?
From lymphoid tissues into the blood circulation, and back to the lymphoid tissues
Memory B-cells constantly come in contact with which cells where they are re-exposed to antigen?
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