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Immunology 3 for Micro Exam
Cell Mediated Immunity through Ontogeny
66
Immunology
Professional
10/29/2011

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Term
What composes the T-cell receptor, and what are it's characteristics?
Definition
αβ chains- it resembles the Fab portion of an antibody, but is univalent
-the TCR is never secreted
-MUST RECOGNIZE ANTIGEN IN CONJUNCTION WITH MHC
-has a V and a C region
-there is another gamma-delta chain styling, but the majority of TCR use the αβ style
Term
What function does CD3 have on T-cells?
Definition
CD3 is analogous to Igα and Igβ on B-cells
-the transmembrane part is responsible for bioactivity
-CD3 is responsible for T-cell activation and differentiation
Term
How is the signal cascade initiated on CD3?
Definition
ITAM is phosphorylated on CD3- this makes CD3 capable of binding to ZAP70- this initiates the signal cascade
Term
Where and how does T-cell development occur?
Definition
Progenitor T-cells are released from the BM and migrate to the thymus for education
-T CELLS MUST BE SELECTED FOR PRECISELY via positive and negative selection
Term
Where in the thymus are T-cells selected?
Definition
In the cortex- immature lymphocytes
Term
Where in the thymus are T-cells matured?
Definition
In the medulla- cells that survive selection become mature thymocytes
Term
What surface markings do progenitor T-cells have?
Definition
None- CD3, 4, and 8(-)
Term
What surface markings do pre T-cells have?
Definition
EVERYTHING- CD3,4,8 (+) also TCR(+)
Term
When does expression of TdT occur for recombination of the variable region of the TCR?
Definition
Through the time in the Thymic Cortex
Term
What shows up on the T-cells in the Thymic Cortex?
Definition
CD3 followed by the TCR
Term
Where does CD4 vs CD8 differentiation occur?
Definition
In the Thymic Medulla
Term
What does positive selection ensure?
Definition
That αβ TCR's will bind to self MHC
-that they can recognize MHC
Term
What does negative selection ensure?
Definition
-That there isn't TOO much affinity for MHC, otherwise they might kill normal self cells
-High-affinity cells are removed at this point
Term
Where does initial antigen contact happen?
Definition
Secondary Lymphoid Tissue (Spleen, LN, etc)
Term
What happens if a patient cannot make β-2 Microglobulin?
Definition
Remember, β-2 microglobulin is a component of the Class I MHC
- if it is absent, there can be no selection for CD8 cells so there are no cytotoxic T-cells
Term
What is the consequence of overactive T-cells?
Definition
Toxic Shock Syndrome
Term
What protein interaction is the second step after T-cell binds with antigen+MHC?
Definition
B7 on the APC interacts with CD28 on the T-cell
Term
What protein is constitutively expressed on dendritic cells?
Definition
B7- to interact with CD28
DENDRITIC CELLS ARE THE ONLY CELLS THAT CAN ACTIVATE NAIVE T-CELLS
Term
What do macrophages require to be able to activate naive T-cells?
Definition
IFN-γ and they can only do so after contact with antigen
Term
Name 3 Antigen Presenting Cells
Definition
Dendritic Cells (best), B-cells, Macrophages
Term
What is the major cytokine to activate macrophages?
Definition
IFN-γ
Term
What must T-cells find on macrophages for adhesion to occur?
Definition
CD28 on T-cells must find B7 on macrophages
Term
What 3 proinflammatory cytokines do macrophages release?
Definition
IL-1, IL-6, TNFα
Term
What other signal does the T-cell need for activation once binding with the macrophage occurs?
Definition
IL-1
Term
When activated, what receptor do Helper T-cells express?
What does it's binding cytokine cause?
Definition
IL-2 receptor; IL-2 causes T-cell proliferation
Term
What does ZAP70 become after it is recruited by the TCR?
Definition
A Tyrosine Kinase
Term
What happens if ZAP70 is constitutively turned on?
Definition
Acute Lymphocytic Leukemia
Term
What intracellular ion concentration increases when T-cell signalling occurs, and what does T-cell signalling lead to?
Definition
Intracellular calcium increases; activation of T-cells leads to cell division and cytokine production
Term
How do superantigens bind to the TCR?
Definition
Outside of the cleft, leading to a reduction in specificity- NUMEROUS T-cell clones are activated
Term
What is the superantigen made by Staph Aureas?
Definition
Toxic Shock Syndrome Toxin
Term
What type of reaction do intracellular parasites, bacteria, and fungi induce?
Definition
Delayed-type with TH1 and macrophage activation
Term
What are TH0 cells?
Definition
Precursors to differentiated helper T-cells
-can make any and all cytokines
-can differentiate into TH1 or TH2
Term
What are TH1 cells?
In what type of immunity are they found?
Definition
TH1 cells are associated with CELL MEDIATED IMMUNITY
-delayed hypersensitivity helps development of CD8 cytotoxic T-cells
-TH1 cells produce- IFN-γ, IL-2, TNF-Beta, IL-3, and GM-CSF
-TH1 cells use IFN-γ to downregulate TH2 cells
Term
What are TH2 cells?
In what type of immunity are they found?
Definition
TH2 cells are HUMORAL IMMUNITY-
-they work on EXTRAcellular pathogens
-help B-cells produce antibody
-induce CLASS SWITCHING
-proliferate eosinophils and mast cells
-produce: IL-4, IL-5 and IL-10
-down regulate TH1 by secreting IL-10
Term
What downregulates TH2 response?
Definition
IFN-γ
Term
What downregulates TH1 response?
Definition
IL-10
Term
What is required for clonal expansion of Cytotoxic T-cells, and their effector function?
Where does it come from?
Definition
IL-2 from activated TH1
Term
What does perforin do?
Definition
Punches holes in membranes by forming pores
Term
What are granzymes?
Definition
Enzymes that damage the target cell
Term
What cytokines are secreted by cytotoxic T-cells to induce apoptosis?
Definition
IFN-γ and TNF Beta
Term
What is the significance of Fas?
Definition
When FasL on cytotoxic T-cells binds with Fas on the target cell, apoptosis is induced
Term
What markers are found on Cytotoxic T-cells and what do these cells do?
Definition
TCR, CD3, CD8, CD2- they have specific antigen recognition at the TCR, requiring Class I MHC-
-use perforing and granzymes, when triggered by IFN-γ and TNF Beta, to kill the target cell
Term
What markers do NK cells have and what do these cells do?
Definition
CD16, CD56, CD2- cause ADCC by IgG- DOES NOT REQUIRE MHC
***IF MHC IS RECOGNIZED BY NK CELLS, APOPTOSIS IS INHIBITED***
Term
What markers are found on Macrophages and how do these cells act?
Definition
CD-14
-when prompted by TNF alpha, they secrete Nitric Oxide, enzymes, and oxygen radicals to destroy the pathogen
Term
What are Interdigitating Dendritic Cells?
Definition
the only cells capable of activating naive T-cells
Term
What are Follicular Dendritic Cells?
Definition
Helpers to forming memory and plasma cells
-DO NOT EXPRESS CLASS II MHC
-have long dendrites with C and Ab receptors
Term
How is antigen cleared from:
-tissues?
-blood?
-mucosa?
Definition
tissues- draining lymph nodes
blood- sent to spleen
mucosa- MALT
Term
What are the components/regions of a lymph node?
Definition
Remember, they have B-cell and T-cell areas
-afferent lymphatics (in)
-efferent lymphatics (out)
-post-capillary venules
Cortex, paracortex, medulla, germinal center
Term
Where in the lymph nodes do we find B-cells?
Definition
Cortex
Term
Where in the lymph nodes do we find T-cells?
Definition
Paracortex
Term
What happens in the LN germinal center?
Definition
Most proliferation, class-switching, and affinity maturation
Term
What can be found in the LN medulla?
Definition
Plasma cells secreting antibody
Term
What are antigens carried in to get to the spleen?
Definition
Splenic Artery
Term
Where in the spleen are B-cells found?
Definition
Marginal zone, arranged in follicles- when they meet antigen they form secondary follicles
Term
Where in the spleen can T-cells be found?
Definition
Around the artery in the Periarteriolar Lymphoid Sheath (PALS)
Term
What does the quantity of antigen-specific lymphocytes look like withing 24 hours of infection?
Definition
There are very few, because they have all rushed ot the LN or spleen to activate
Term
What directs the flow of B and T cells through secondary lymphoid tissue?
Definition
CAMs- Cell Adhesion Molecules-
Term
What specialized cells function as a secret door to the lymphatics for naive cells?
Definition
High Endothelial Venules (HEV's)
Term
What is Transmigration?
Definition
The movement of naive cells from blood to lymph
Term
What happens in rolling adhesion?
Definition
Selectins on the lymphocytes bind CD34 on vascular endothelium
Term
What is LAD?
Definition
Leukocyte Adhesion Deficiency- CAM (integrin) is missing
-CAM mediates tight binding, which is needed to get lymphocytes from blood to infected area
-super high WBC in blood, but NO PUS because they can't get to tissues
-recurrent bacterial infections and impaired wound healing
-first shows up in the umbilical stub
Term
What forms a separate secretory system in which plasma cells can secrete tons of IgA?
Definition
MALT
Term
What are the special cells through which antigen enters Peyers patches?
Definition
M-cells
Term
What type of epithelium contains M-cells?
Definition
Follicle-associated Epithelium (FAE)
Term
What happens in the mucosa after lymphocyte activation?
Definition
Lymphocytes enter lymph, go through mucosal nodes and the thoracic duct, and pass from the blood back to the lamina propria
-they become IgA secreting plasma cells
Term
What can be found in the lamina propria?
Definition
Large concentrations of activated T-cells, B-cells, and IgA plasma cells
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