Week 2 Lec: Lymphoid System Flashcards
All those physiological mechanisms that endow the animal with the capacity to recognize materials as foreign to itself and to neutralize, eliminate, or metabolize them with or without injury to its own tissues.
Immunity
The _______ is structured to recognize, respond to, and destroy a wide variety of invading organism that would otherwise be capable of promoting infections, harmful to the body.
immune system
The ability of an individual to resist infections by means of normally present body functions.
Natural Immunity
It is considered as first line of defense. Physical barriers such as our skin, and secretions.
External defense system
It is considered as second line of defense. The most important process is process of phagocytosis. It is incorporated with the different types of WBC such as the polymorphonuclear cells, monocytes, and macrophages.
Internal defense system
The type of resistance that is characterized by specificity for each individual pathogen, or microbial agent. Referred to as the 3rd line of defense.
Acquired Immunity
Lymphocytes represent _____ of the circulating WBCs.
20-40%
What is the second most common type of leukocyte?
Lymphocyte
The typical small lymphocyte is between _____ in diameter.
7 and 10 μm
Nucleus characteristics of lymphocyte?
a large rounded nucleus that may be somewhat indented
Color of lymphocyte when stained?
lighter blue appearance
Cytoplasm characteristics of lymphocytes?
- sparse
- few organelles
- no specific granules
- narrow ring surrounding the nucleus
Why are lymphocytes unique?
because they arise from a hematopoietic stem cell and are further differentiated in the primary lymphoid organs
2 main classifications of lymphocytes depending on where lymphocyte differentiation takes place?
Primary and Secondary Lymphoid Organs
Main function of Primary Lymphoid Organs?
maturation of B and T cells
Main function of Secondary Lymphoid Organs?
proliferation and differentiation of B and T cells
Lymphocyte circulation is complex and is regulated by different cell surface adhesion molecules and by chemical messengers called?
cytokines
They influence other activities of the cell.
cytokines
3 major populations of lymphocytes?
- T cells
- B cells
- Natural Killer cells
T cells account for how many percent in the total population of lymphocytes?
61-80%
B cells account for how many percent in the total population of lymphocytes?
20%
Natural killer cells account for how many percent in the total population of lymphocytes?
10-15%
Once T and B cells mature, they go to?
Secondary Lymphoid Organs
What is the precursor cell mainly associated with B, T, and NK cells?
common lymphoid precursor
Primary Lymphoid Organs consist of?
- Bone marrow
- Thymus
Secondary Lymphoid Organs consist of?
- Spleen
- Lymph nodes
- Mucosal-Associated Lymphoid Tissue (Appendix, Tonsils, Peyer’s Patches)
- Cutaneous-Associated Lymphoid Tissue
It consists of flat, long bones that is a source of hematopoietic stem cells.
Bone marrow
All lymphocytes arise from?
pluripotential hematopoietic stem cells
Aside from lymphocytes, it accounts for the different cell types such as RBC, WBC, macrophages and megakaryocytes/thrombocytes/platelets.
pluripotential hematopoietic stem cells
Weight of bone marrow in humans?
1,300-1,500 g (adult)
It fills the core of all long bones and is the main source of hematopoietic stem cells, which develop into different cell types.
Bone marrow
_____________ are released from the marrow and travel to additional primary lymphoid organs where further maturation takes place.
Lymphocyte stem cells
The mother cell of all cells.
hematopoietic stem cell
Hematopoietic stem cells give rise to what 2 different cell lines?
CLP (Common Lymphoid Precursor) and CMP (Common Myeloid Precursor)
Common Lymphoid Precursor gives rise to which cells?
- T cell
- B cell
- Dendritic cell
- Natural Killer cell
Common Myeloid Precursor gives rise to which cells?
- monocytes
- eosinophils
- basophils
- neutrophils
- erythrocytes
- platelets
It is an organ which is small, flat, bilobed organ found in the thorax, or chest cavity, right below the thyroid gland and overlying the heart.
Thymus
Weight of thymus at birth?
30 g
Weight of thymus at puberty?
35 g
A decrease in the size of thymus when it reaches its matured/maximum form is an example of what process?
atrophy
Each lobe of the thymus is divided into _____ filled with _____ that play a central role in this differentiation process.
lobules, epithelial cells
________ are acquired as the lymphocytes travel from the cortex to the medulla over a period of 2 to 3 weeks.
Surface antigens
Part of the thymus where T cells stay before they mature.
Cortex
Once matured T lymphocytes are formed, they are then released from the?
Medulla
Each lymphocyte spends most of its life span in ___________, entering the circulation only periodically to go from one secondary organ to another.
solid tissue
A specific lymphocyte may make the journey from blood to secondary lymphoid organs and back _____ times per day.
one to two
Largest secondary lymphoid organ.
Spleen
Dimensions and weight of the spleen?
12cm in length and weighs 150g in adult
A large discriminating filter that can remove foreign antigens and all RBCs from the blood.
Spleen
Spleen is located?
in the upper-left quadrant of the abdomen, just below the diaphragm
Spleen is surrounded by a?
thin connective tissue capsule
Splenic tissue can be divided into two main types?
- Red Pulp
- White Pulp
It makes up more than one half of the total volume, and its function is to destroy old red blood cells.
Red Pulp
In the red pulp of the spleen, blood flows from the arterioles into the red pulp and then exits by way of the?
splenic vein
It comprises approximately 20 percent of the total weight of the spleen.
White Pulp
The White Pulp comprises approximately ___ percent of the total weight of the spleen.
20
The White Pulp contains the lymphoid tissue, which is arranged around arterioles in a?
periarteriolar lymphoid sheath
Attached to the periarteriolar lymphoid sheath are?
primary follicles
It contains B cells that are not yet stimulated by an antigen.
primary follicles
Surrounding the PALS is a ___________ containing dendritic cells that trap antigen.
marginal zone
The marginal zone contains what cells that trap antigen?
dendritic cells
The most potent phagocytic cell and is considered as the best APC (Antigen Presenting Cell).
dendritic cell
Each day, an adult blood passes through the spleen approximately ___ times.
4
Why does the blood pass through the spleen ~4 times a day?
it allows lymphocytes and macrophages to constantly survey for infectious agents or other foreign matters
When B cells contained in the primary follicle are stimulated by an antigen, it results to a structure called?
germinal center
Tagalog term for lymph nodes?
kulani
Located along lymphatic ducts and serve as central collecting points for lymph fluid from adjacent tissues.
Lymph Nodes
Lymph Nodes are located along?
lymphatic ducts
Functions of lymph nodes?
- collecting points for lymph fluid from adjacent tissues
- contribute for the ideal environment of foreign antigens
Lymph nodes are especially numerous near?
joints and where the arms and legs join the body
Size of lymph node?
1 mm to 25 mm in diameter
Major purpose of lymph nodes?
filtration
The lymph fluid flows slowly through spaces called ______, which are lined with macrophages, creating an ideal location for phagocytosis to take place.
sinuses
The lymph fluid enters the lymph nodes via?
afferent lymphatic vessel
The lymph fluid exits the lymph nodes via?
efferent lymphatic vessel
Swelling of lymph nodes?
Lymphadenopathy
Region of lymph nodes: the outermost region. An aggregation of lymph nodes. Contains macrophages and aggregations of B cells in primary follicles, follicular dendritic cells, secondary follicles (germinal center), plasma cells, and memory cells.
Cortex
Consists of stimulated B cells and site where germinal center is seen.
Secondary follicles
They are fully differentiated lymphocytes found in the cortex of lymph nodes for antibody production and secretion.
Plasma cells
Region of lymph nodes: where T cells are found. Region between the cortex and medulla.
Paracortex
Region of lymph nodes: contains some T cells, B cells and numerous plasma cells.
Medulla
3 Mucosal-Associated Lymphoid Tissue?
- Appendix
- Tonsils
- Peyer’s Patches
Locations of Mucosal-Associated Lymphoid Tissue (MALT)?
- urogenital tract
- respiratory tract
- gastrointestinal tract
Located at the junction of the small and large intestines.
Appendix
Lymphoid tissue found in the mucous membrane lining of the oral and pharyngeal cavities that trap foreign particles. It responds to pathogens entering the respiratory and alimentary tract.
Tonsils
Located at the lower ileum of the intestinal tract.
Peyer’s Patches
A collective term for monocyte, macrophages, and dendritic cells (intraepidermal lymphocytes) in the epidermis. It also contains T cells. They are uniquely positioned to combat any antigens that enter through the skin.
Cutaneous-Associated Lymphoid Tissue (CALT)
True or false: Within each of the secondary organs, T and B cells are segregated and perform specialized functions.
True
B cells differentiate into memory cells and plasma cells and are responsible for?
Humoral Immunity or Antibody Production
T cells play a role in ________ , and as such, they produce sensitized lymphocytes that secrete ________.
Cell-Mediated Immunity, Cytokines
_______ are small polypeptides that regulate the functions of lymphocytes and other cells involved in the immune response.
Cytokines
These are proteins or antigens used to distinguish the developmental stage of each cell and serve as markers to differentiate T cells and B cells.
Surface Markers
Surface Markers have been detected by ___________, which are extremely specific antibodies made by cloning a single antibody-producing cell.
monoclonal antibodies
True or false: Several laboratories have developed monoclonal antibodies, and each used its own nomenclature for the set of antigens found.
True
Panels of antibodies from different laboratories were used for analysis, and antibodies reacting similarly with standard cell lines were said to define?
Cluster of Differentiation
CD marker for T cells?
CD 2, 3, 4, 8
CD marker for B cells?
CD 19, 21, 23
CD marker for NK cells?
CD 16, 56, 94
4 steps of B-Cells Differentiation?
- Pro-B cells
- Pre-B cells
- Immature B cells
- Mature B cells
(Pro-B cells) First step is the ______________ of an antibody molecule.
rearrangement of genes that code for the heavy and light chains
(Pro-B cells) The end result is a B lymphocyte programmed to produce a unique antibody molecule, which consists of ________________.
two identical light chains and two identical heavy chains
(Pro-B cells) Heavy Chains are coded on chromosome?
14
(Pro-B cells) Light Chains are coded on chromosome?
2 and 22
The pro-B cell has distinctive markers that include surface antigens?
- CD19
- CD45R
- CD43
- CD24
- c-Kit
(Pro-B cells) CD markers that will remain in the cell surface?
- CD19
- CD45R
- CD24
A tyrosine-specific phospate which is the main CD marker that can recognize Pro-B cells.
CD45R
(Pro-B cells) Intracellular proteins found at this stage are terminal __________ and recombination-activating genes _____ and ______, which code for enzymes involved in gene rearrangement.
deoxyribonucleotide transferase (TdT); RAG-1 and RAG-2
(Pro-B cells) These are DNA that live at certain possible recombination site.
RAG-1 and RAG-2
(Pro-B cells) Helps to join the pieces back together by incorporating additional nucleotides in the joining area.
terminal deoxyribonucleotide transferase/TdT
(Pre-B cells) The first heavy chains synthesized are the __________, which belong to the class of immunoglobulins called _____.
μ chains; IgM
Pre-B cells begin to form when?
rearrangement of heavy chain occurs
Pre-B cells also lose which CD markers?
- CD43 marker
- c-Kit
- TdT
Pre-B cells may also express μ chains on the cell surface, accompanied by an unusual light chain molecule called a?
surrogate light chain
(Pre-B cells) Surrogate light chains consist of __________ that are noncovalently associated with each other.
two short polypeptide chains
(Pre-B cells) Surrogate light chains consist of two short polypeptide chains that are __________ associated with each other.
noncovalently
(Pre-B cells) The combination of the two heavy chains with the surrogate light chains plus two very short chains, Ig-α/Ig-β form the?
pre-B cell receptor
Function of the pre-B cell receptor?
adheres to the bone marrow stromal cell membrane and transmits a signal to prevent rearrangement of any other heavy chain genes
True or false: It appears that all pre-B cells, whether expressing the μ heavy chains in association with surrogate light chains or not, survive and proceed to further differentiation.
False. Only pre-B cells expressing the μ heavy chains in association with surrogate light chains survive.
True or false: Once the pre-B receptor (pre-BCR) is expressed, neighboring pre-B cells may send signals for further maturation.
True
Rearrangement of genetic sequence coding for light chains on either chromosome 2 or 22 happens to form?
Immature B cells
Immature B cells are mainly distinguished by the appearance of _____ molecule on the cell surface.
IgM
(Immature B cells) In the reaarangement of light chains, Kappa chain is in line with chromosome _____.
2
(Immature B cells) In the reaarangement of light chains, Lambda chain is in line with chromosome _____.
22
(Immature B cells) True or false: Once surface immunoglobulins appear, μ chains are no longer detectable in the cytoplasm.
True
Other surface proteins that appear on the immature B cell include?
- CD 21
- CD 40
- major histocompatibility complex (MHC) class II molecules
Functions of the CD21 marker in immature B cells?
- acts as a receptor together with CD19
- a receptor for breaking down complement component C3 to become C3D, which acts as an adjuvant to increase humoral immune response
- receptor for Epstein–Barr virus (EBV), the causitive agent of infectious mononucleosis
Acts as coreceptor with CD21 that helps regulate further B cell development and activation.
CD19
Acts as an adjuvant to increase humoral immune response. It is mainly involved in the production of antibodies.
C3D
Immature B cells leave the __________ and proceed to seed the ______________.
bone marrow; spleen and other secondary lymphoid organs
In the spleen, immature B cells develop into mature cells known as?
marginal zone B cells
In addition to IgM, all mature B cells exhibit?
IgD
The mature B cells remain in the spleen in order to?
respond quickly to any blood-borne pathogens they may come into contact with
Other immature B cells become __________ which are found in __________ and other secondary organs.
follicular B cells; lymph nodes
If B cell is stimulated by antigen, it undergoes transformation to a ________, which eventually forms memory cells and antibody secreting plasma cells.
blast stage
Activated B cells exhibit identifying markers that include _____, which is found on both activated T and B cells and acts as a receptor for ________, a growth factor produced by T cells.
CD25; interleukin-2 (IL-2)
Characteristic of plasma cells?
- spherical or ellipsoidal cells
- between 10 and 20 μm in size
- characterized by the presence of abundant cytoplasmic immunoglobulin and little to no surface immunoglobulin
Represents the most fully differentiated lymphocyte.
Plasma Cells
Main function of plasma cells?
antibody production/secretion
True or false: Plasma cells are nondividing, and after several days of antibody production, they die without further proliferation.
True
It is estimated that approximately ___________ of the cortical cells die intrathymically before becoming mature T cells.
97 percent
Lymphocyte precursors called _________ enter the thymus from the bone marrow.
Thymocytes
Within the lobules of the thymus are two main zones?
- Outer cortex
- Inner medulla
Thymic stromal cells include _____________, all of which play a role in T-cell development.
- epithelial cells
- macrophages
- fibroblasts
- dendritic cells
In T-cell development, interaction with __________ under the influence of ___________ is critical for growth and differentiation.
stromal cells; cytokines
Cytokine involved in T-cell development.
IL-7
T-Cell Differentiation stages:
- Double-Negative Stage
- Double-Positive Stage
- Mature T-Cells
Rearrangement of the genes that code for the antigen receptor known as TCR begins at this stage.
Double-Negative Stage
Antigen receptor in Double-Negative Stage is called?
T-cell receptor complex (TCR)
Beta-Chain rearrangement in Double-Negative Stage: Signaling by the β chain also triggers the thymocyte to become _____ and _____.
CD4-positive (CD4+) and CD8-positive (CD8+) cells
The complex that serves as the main part of the T-cell antigen receptor.
CD3
Early thymocytes lack?
CD4-positive (CD4+) and CD8-positive (CD8+) cells
CD3 consists of ___________, six of which are common to all T cells.
eight noncovalently associated chains
Six chains common to all T cells.
- alpha and beta have constant and variable regions
- epsilon
- gamma
- zeta
- delta
The two chains associated in the T-cell receptor that recognizes antigens?
alpha and beta chains
Rearrangement of alpha chain takes place in what stage of T-cell development?
Double-Positive Stage
Two selection process in Double-Positive Stage?
- Positive selection
- Negative selection
When does the Double-Positive Stage start?
if there is complete expression of the CD3TCR complex
When the CD3-αβ receptor complex (TCR) is expressed on the cell surface, a _______________ takes place that allows only double positive cells with functional TCR receptors to survive.
positive selection process
In the positive selection process of the double-positive stage, T cells must recognize foreign antigen in association with ____________.
class I or class II MHC molecules
True or false: Any thymocytes that are unable to recognize self-MHC antigens die without leaving the thymus.
True
Takes place among the surviving double-positive T cells.
Negative selection
In negative selection of the double-positive stage, strong reactions with self-peptides send a signal to delete the developing T cell by means of ________, or programmed cell death.
apoptosis
The negative selection process is very rigorous, because only _________ of the double-positive thymocytes in the cortex survive.
1 to 3 percent
In mature T-cells, CD4+ T cells recognize antigen along with __________.
MHC class II protein
T helper cells consist of two subsets?
Th1 and Th2
TH1 is associated with?
gamma or type 2 Interferon and Tumor Necrosis Factor-beta
Role of TH2?
help B cells to produce antibodies against extracellular pathogens and produce interleukins 4, 5, 10, and 13
In mature T-cells, CD8+ T cells interact with antigen and _________.
MHC class I proteins
1/3 of the total T-cell population is associated with what cell?
CD8+
Activated T lymphocytes express receptors for_____, just as activated B cells do.
IL-2
Receptor for IL-2?
CD 25
Third major subclass CD4+ T-Cell population?
T-Regulatory Cells
T-Regulatory Cells possess which CD markers?
- CD4
- CD25
T-Regulatory Cells comprise approximately _________ percent of all CD4-positive T cells.
5 to 10
T-Regulatory Cells produce which cytokines?
IL-10 and transforming growth factor-beta
Third population lymphocytes?
Natural killer cells
5-10% circulating lymphocyte in the PB?
Natural killer cells
These lymphocytes are generally larger than T cells and B cells.
Natural killer cells
Characteristics of NK cells?
- 15 μm in diameter
- kidney-shaped nuclei with condensed chromatin
- prominent nucleoli
- higher cytoplasmic-nuclear ratio
- cytoplasm contains a number of azurophilic granules
They represent the first line of defense against virally infected and tumor cells.
Natural killer cells
Diseased and cancerous cells tend to lose their ability to produce?
MHC proteins
A second method of destroying target cells.
ADCC/Antibody-Dependent Cellular Cytotoxicity
They recognize and lyse antibody-coated cells through a process called?
ADCC/Antibody-Dependent Cellular Cytotoxicity
Type of WBC that is considered as ADCC?
Eosinophil
Cells coated with IgM are not subject to ADCC because?
IgM has no available Fc region
Primarily, _____ is the antibody responsible for ADCC.
IgG
A technique to separate mononuclear cells from other cells.
Density Gradient Centrifugation with Ficoll-Hypaque
The specific gravity for Density Gradient Centrifugation with Ficoll-Hypaque varies depending on the manufacturer, but ranges from?
1.077 to 1.114
Centrifugation for Density Gradient Centrifugation with Ficoll-Hypaque produces 3 distinct layers?
- Plasma
- Mononuclear cells
- RBC and Granulocytes
2 types of Cell flow cytometry?
- Forward Light Scatter
- Side Light Scatter
Forward Light Scatter identifies?
Cell Size
Side Light Scatter identifies?
Cellular Granularity
Lymphocytes are separated from whole blood and then mixed with a suspension of sheep red blood cells is performed in what test?
Rosette test/technique
E-rosette is in line with?
T cells
EAC/Erythrocyte Antibody Complement rosette is involved with?
B cells
Laboratory Techniques to Quantify and Identify Lymphocytes?
- Density Gradient Centrifugation with Ficoll-Hypaque
- Cell flow cytometry
- Immunofluorescence microscopy
- Rosette test/technique
An automated system for identifying cells based on the scattering of light as cells flow in single file through a laser beam.
Cell Flow Cytometry
In Cell Flow Cytometry, _____________ are used to screen of subpopulation of T and B cells.
Fluorescent antibodies
Components of Cell Flow Cytometry?
- Sample delivery system
- A laser for cell illumination
- Photodetectors for signal detection
- Computer based management system
2 types of IFA (Immunofluorescence Assay)?
- Direct Immunofluorescence
- Indirect Immunofluorescence
Uses monoclonal antibodies with a fluorescent tag fluorescein and phycoerythrin (490nm) rhodamine (545 nm).
Direct Immunofluorescence
Uses unlabeled antibody that first combines with the antigen by itself and a second antibody that is complexed with a dye.
Indirect Immunofluorescence
phycoerythrin nanometers?
490nm
rhodamine nanometers?
545 nm
