15 & 16- Lymphoid System Flashcards
(105 cards)
1
Q
The immune system consists of ___________ cells located ____________
A
lymphoid cells, located within all tissues of the body and lymphoid organs. Lymphoid cells constantly circulate via blood and lymphatic vessels
2
Q
The cells of the lymphoid system can generate __________
A
immune responses against various pathogens
3
Q
Molecules that are recognized by cells of the immune system are called ____________
A
Antigens (Ag)
4
Q
Cells of the immune system include (4 types)
A
- Lymphocytes
- Macrophages
- Dendritic Cells
- Granulocytes
5
Q
Describe Innate (natural) Immunity (4 things)
A
- Quickly mobilized, doesn’t require previous exposure to a pathogen (NONSPECIFIC)
- Cells mediating innate immunity include macrophages, dendritic cells and granulocytes
- Innate defenses are also provided by physical and chemical barriers of the skin and mucous membranes
- No memory, second response is always the same as the first response
6
Q
Describe Adaptive (specific) Immunity
A
- When innate defenses fail, the immune system develops a specific (adaptive) response that is mediated by lymphocytes
- This response is based on specific recognition of an antigen by the lymphocyte
- Only a small number of lymphocytes will recognize a particular antigen
- Generates immunologic memory (immune response is stronger and faster the second time)
7
Q
Clonal Expansion
A
Only a small number of lymphocytes will recognize an antigen. Upon antigen recognition these lymphocytes will become activated and start to divide, producing millions of identical effector cells (clonal expansion). This response requires more time to develop than the innate response.
8
Q
Adaptive Immune responses include (2 types)
A
- Cellular immune response- mediated by the T lymphocytes (require initial cell-cell contact)
- Humoral immune response- mediated by plasma cell-produced antibodies. Antibodies specifically bind to antigens and mark them for destruction.
9
Q
Nearly all antigens have to be processed by ____________
A
Antigen Presenting cells (APCs), before they can be recognized by lymphocytes
10
Q
APCs are found primarily in the ___________
A
skin, lymph nodes, spleen, and thymus. They are also associated with most mucosal epithelia
11
Q
APCs include (3 types)
A
- dendritic cells (ex: Langerhans cells in the skin)
- macrophages
- B cells
12
Q
Antigen processing is initiated when the __________
A
phagocytic APC ingests the antigen. The antigen (usually a protein) is broken down into small peptide-fragments in the cell
13
Q
The peptide-fragment produced by APC binds to the molecule called ____________
A
MHC and the Ag-MHC complex is transported to the APC surface. The Ag can be recognized by the lymphocyte only in the context of the MHC molecule (MHC= “plate” antigen is presented on)
14
Q
Lymphocytes are the effector cells of the __________
A
adaptive immune system
15
Q
Lymphocytes (5 facts)
A
- have a highly variable lifespan
- Approximately 70% of the population of lymphocytes circulates in the lymph or blood at any given moment
- Involved in immunologic surveillance of the body
- Morphologically, lymphocytes look similar
- They display cell surface receptors that facilitate the specific recognition of antigens
16
Q
Functionally, lymphocytes are classified
A
- T cells (T lymphocytes)
2. B cells (B lymphocytes)
17
Q
T lymphocytes (5 things)
A
- Responsible for cell-mediated immunity
- Differentiate in the thymus and account for the majority of circulating lymphocytes
- T helper Cells (Th cells, CD4+ on surface, secrete cytokines)
- T cytotoxic cells (Tc cells, CD8+ on surface, kills unwanted cells, like cells with viruses
- Regulatory T cells (CD4+, FoxP3- transcription factor; limit immune response, inhibitory cytokines)
18
Q
B lymphocytes (3 things)
A
- Responsible for humoral immunity
- Activated B cells differentiate into plasma cells (NOT a B cell, just a derivative of a B cell), which are antibody producing cells. Antibodies are SECRETED by plasma cells.
- Antibody (Ab) or immunoglobulin (Ig)
Immunoglobulin is a protein that interacts specifically with an antigen.
19
Q
Lymphoid cells spread throughout the body and the blood, lymph, and through __________
A
migration via connective and epithelial tissues
20
Q
Because lymphocytes have very little cytoplasm, their aggregates usually stain _______________
A
Blue with routine H&E
21
Q
Reticular and epithelioreticular cells constitute the ______________
A
stroma, that supports and organizes lymphoid cells (parenchyma) within the tissue
22
Q
Reticular cells (3 things)
A
- Present in the majority of lymphoid tissues and organs
- They produce reticular fibers (collagen type III) that form the 3D scaffold for lymphoid cells
- Reticular fibers are very thin, but can be visualized with silver stain
23
Q
Epithelioreticular cells (or epithelial reticular cells- 4 things)
A
- Stellate cells
- Present in thymus
- Produce keratin
- Joined by desmosomes
24
Q
Diffuse collections of lymphoid cells, ubiquitous (found everywhere) in the mucosa of many organ systems, forms _____________
A
diffuse lymphoid tissues (No border)
25
More densely packed, spherical clusters of lymphocytes are called _____________
Nodules
| Nodules are usually embedded in diffuse tissue, they are not covered by a capsule
26
Lymphoid nodules are NEVER present in the _________
Thymus
27
Lymphoid nodules are classified as
Primary nodule- homogenous in appearance and mostly formed by small B lymphocytes (dominant in nodules, still some helper T cells)
Secondary nodule- has a pale center and is darker at the periphery. They develop from primary nodules upon stimulation with Ag.
28
Primary lymph nodule is transformed into secondary nodule with presence of ___________
an antigen
29
Pale are in a secondary nodule is a __________
```
germinal center (light area with dark mantle- mantle has resting B cells, transient lymphocytes, they travel to another site in the body)
This is the area where activated B cells proliferate
```
30
B cell activation zone contains ____________
primary and secondary follicles
31
Primary follicle
naïve recirculating B cells & follicular DCs (dendritic cells)
32
Secondary follicle contains _____________
germinal center established by activated B cells
| mantle is the dark outer portion and it contains resting B cells
33
Organization of germinal center:
| Ag-activated B cells differentiate into ____________ in the ____________
centroblasts
| They undergo clonal expansion in the dark zone (mantle) During proliferation somatic hypermutations occur.
34
Organization of germinal center:
| Centroblasts differentiate into ____________ and move to __________
centrocytes & move to the light zone.
A subset of centrocytes undergoes Ig class- switch recombination (CSR).
35
Primary (central) lymphoid organs
Bone marrow, Thymus, Fetal liver
- Initial formation of lymphocytes occurs in the primary lymphoid organs
- AKAL: They generate initial diverse population of lymphocytes
- Lymphocytes in primary lymphoid organs DO NOT come in contact with foreign antigens
36
Secondary (peripheral) lymphoid organs (tissues)
MALT, Lymph nodes, Spleen
Lymphocytes migrate from primary to secondary lymphoid organs
Here (secondary L.Os) lymphocytes are activated by ENCOUNTERS WITH ANTIGENS
The spleen is a filter of blood; it reacts to blood-borne antigens
MALT (mucosal system) encounters antigens that entered fro the external environment passing through the specialized epithelial cells (M CELLS)
37
Immune responses occur in ______________
secondary lymphoid organs
Lymph nodes come in contact with antigens transported with lymph via the lymphatic vessels
38
More than 50% of the body's lymphoid tissue is located ____________
in the mucosal system of the digestive, respiratory and genitourinary tracts
-Gut- Associated Lymphoid Tissue (GALT), Bronchus- Associated Lymphoid Tissue (BALT)
39
Lamina Propria lymphocytes are mostly __________
activated T cells, but many activated B cells and plasma cells are also detected
-Lymphocytes are present in both the epithelium and the lamina propria
40
Majority of MALT is _________ in character
diffuse; but it can also aggregate into nodules
It also forms well defined structures: tonsils, Peyer's Patches, Vermiform appendix
41
Tonsils form a ring of lymphatic tissue at the entrance __________ called ___________
entrance of the oropharynx called Waldeyer's Ring
42
Tonsils are formed by:
- A mass of lymphatic tissue, both diffuse and nodular, located in the mucosa
- The outer (luminal) surface of the tonsil is covered by epithelium
- It invaginates into the underlying lymphatic tissue to for crypts or pits
- The lymphatic tissue is separated from underlying structures by an incomplete connective tissue capsule
- They have only EFFERENT lymphatic vessels
43
Secondary Lymphoid tissue (4 things it does)
* Facilitate the induction of adaptive immune responses
* Capture pathogens
* Facilitate encounters between APCs & lymphocytes
* Provide niches for the differentiation of immune effector cells
44
3 types of tonsils
Palatine, Lingual, Pharyngeal
45
Palatine Tonsils
- between the palatopharyngeal and palatoglossal arches at the posterior aspect of the oral cavity
- Paired and covered by stratified squamous epithelium
46
Lingual Tonsils
- on the base of the tongue
| - Paired and covered by stratified squamous epithelium
47
Pharyngeal Tonsils (adenoids)
- embedded in the posterior wall of the nasopharynx
- Unpaired and covered by pseudo stratified ciliated columnar epithelium with goblet cells (respiratory type epithelium)
- Can hypertrophy and obstruct the nasal openings
48
Peyer's Patches
large aggregations of lymphatic nodules in the mucosa and submucosa of the ileum
49
Vermiform Appendix
It's lamina propria is filled with lymphoid tissue, both diffuse and nodular
Lymphoid nodules penetrate the muscularis mucosae to occupy the submucosa
50
Lymph nodes are kidney-bean or oval-shaped structures that are located along the pathway of ___________
lymphatic vessels
51
The indentation on one side of the lymph node is called the
hilum
| -Blood vessels enter AND leave the node at the hilum, and lymphatic vessels LEAVE at the hilum
52
Lymph node is surrounded by a dense connective tissue capsule that ___________________
sends projections into the lymph node that are called trabeculae
- The stroma of reticular cells and fibers attaches to the capsule and the trabeculae
- Macrophages and dendritic cells are associated with the reticular fiber network
53
The parenchyma of a lymph node is primarily formed by ___________
diffuse and nodular lymphatic tissue and is divided into the cortex and medulla
54
The outer cortex of the lymph node is formed by _______
| part of the parenchyma
```
both diffuse (T cells) and nodular (B cells) lymphatic tissue
It is a B lymphocyte area
```
55
The inner cortex (deep cortex, paracortex) is formed by __________
(part of the parenchyma)
diffuse lymphatic tissue ONLY
| -It is the thymus-dependent area and contains T lymphocytes
56
Describe the medulla of a lymph node
- pale staining
- inner area of the node
- consists of diffuse lymphatic tissue that forms strands called Medullary Cords
57
Medullary Cords (of the medulla of a lymph node) contain
plasma cells, lymphocytes, and macrophages
58
The medullary cords are separated by lymphoid sinuses called medullary sinuses.
3 types of sinuses are found within a lymph node and are named based on their location:
1. Subcapsular (marginal) sinus- lies between the capsule and the lymphatic tissue of the outer cortex
2. Trabecular (cortical, intermediate) sinuses- lie between the trabeculae and the lymphatic tissue of the cortex
3. Medullary sinuses- found between the medullary cords
59
Lymph nodes are the only organs that possess ______________
both afferent AND efferent lymphatic vessels
60
In a lymph node, the afferent lymphatics:
bring lymph into the lymph node for filtering
- They come from other organs or other lymph nodes
- Many afferent lymphatics pierce the capsule of the lymph node at its periphery to drain into the subcapsular sinus
61
In a lymph node, the efferent lymphatics:
are few in number
-they are formed by the coalescence of the medullary sinuses
-they exit from the hilum of the node and carry lymph AWAY from the lymph node
-The efferent lymphatic of one lymph node may become the afferent lymphatic of the next lymph node in the chain
(because lymph is filtered by a series of lymph nodes as it courses through the lymphatic system)
62
Lymph flows _______
In one direction (toward the hilum)
Due to the presence of valves in both afferent and efferent lymphatics
63
The pattern of lymph flow through the node:
afferent lymphatics --> subcapsular sinus --> cortical sinus --> medullary sinus --> efferent lymphatic
Slide 35 of ppt for picture
64
Some lymphocytes enter the lymph nodes via lymphatics, but majority (90%) enters from __________
the blood stream in the deep cortex area
They cross the walls of the cuboidal-in-shape endothelium of the high endothelial post-capillary venules (HEV) via diapedesis
- They (HEV) have surface receptors for lymhopcytes and serve as a gate for circulating lymphocytes
- T lymphocytes stay in the deep cortex
- B lymphocytes migrate to the nodules of the superficial cortex
65
Lymphadenopathy
lymph node enlargement, it's a common consequence of infection
66
Lymphoma
primary tumor of lymphoid tissue
Examination of lymph nodes draining many malignant tumors is a routine part of the pathological assessment of tumor stage (whatever that means)
67
What does the spleen do? ( 4 things)
filters blood
detects blood borne antigens
removal and destruction of damaged RBCs and platelets
retrieval of iron from hemoglobin
68
Largest lymphoid organ
Spleen
69
The spleen has _________ connections with lymphatic vessels
no direct connections with lymphatic vessels
Lymphocytes enter and leave the spleen via blood vessels
70
The spleen is surrounded by ___________
a dense connective tissue capsule that extends into the organ with trabeculae
The trabeculae partially divide the parenchyma (the splenic pulp)
71
The spleen screens the entire blood volume for pathogens in _____
20-30 minutes (WOWZA!)
72
The spleen has a very well developed __________
reticular network, that forms a continuum with the trabeculae (splenic stroma)
73
Spleen is composed of _____________
```
white pulp (lymphoid tissue- leukocytes in spleen)
red pulp (site of removal of RBCs)
```
74
Again, no _________ crosses into the spleen
No lymph, just blood
75
Periarteriolar lymphatic sheaths (PALS) are _____
a cuff of lymphocytes that surrounds central arterioles running through the spleen. They are accumulations and contain mostly T cells
76
Lymphoid nodules are present at intervals along PALS, they contain mostly ___________
B cells
77
Marginal zone surrounds _____________
the follicle (?)
It is rich in macrophages
Blood borne antigens are filtered from the blood within the marginal zone.
78
Splenic artery branches into _________ (4 steps)
trabecular arteries, they follow the trabeculae
After they leave the trabeculae they are called CENTRAL ARTERIOLES and become surrounded by PALS
Some branches of the central arterioles end as marginal sinuses that supply the marginal zone
The central arterioles lose their PALS and terminate as small penicillar arterioles entering the red pulp
79
Red pulp contains
splenic sinusoids and splenic cords (cords of Billroth)
80
Splenic cords are supported by _____________ and contain _____________
reticular cells and fibers and contain T and B cells, macrophages, plasma cells, dendtiric cells, granulocytes, and RBCs
81
Macrophages of the red pulp _____________
phagocytose old RBCs and begin a breakdown of hemoglobin and the recycling of iron
82
Splenic sinusoids are lined by ______________
stave cells
loosely connected, elongated endothelial cells
Stave cells are oriented parallel to the blood flow. Spaces between endothelial cells allow blood cels to leave or enter the sinus
83
Closed circulation through the red pulp
capillaries branching from the penicillar arterioles connect DIRECTLY with the sinusoids, thus blood is ALWAYS within a blood vessel
84
Open circulation through the red pulp
capillaries from about 1/2 of the penicillar arterioles are open ended, thus blood enters the splenic cords.
In this case, ALL formed elements of blood must return to circulation by squeezing through the spaces between stave cells of the splenic sinusoid
Platelets, leukocytes, and young RBCs are flexible and can reenter the circulation, however old, stiff RBCs are blocked from reentry and removed by macrophages (BRILLIANT!)
85
Splenomegaly
enlargement of the spleen
Lots of causes of this. Causes of this include lymphoma, mononucleosis, or certain anemias.
Enlarged spleens may rupture, which can be life-threatening
86
Splenectomy
surgical removal of the spleen, is used as a therapy for traumatic rapture of the spleen
also used as therapy for some chronic disorders.
Splenectomy in adults usually has no clinical consequence
87
Location of Thymus
mediastinum (near the heart)
It as 2 lobes, subdivided into incomplete lobules
88
Mixed embryonal origin of thymus
Lymphoid cells (thymocytes) are generated in:
hematopoietic tissue derived from mesenchyme
89
Stroma is made of:
| thymus
epithelioreticular cells that develop from endodermal epithelium of the third laryngeal pouch
Hence, there are no reticular fibers in the thymus
(epithelioreticular cells make keratin, not reticular fibers)
90
The connective tissue capsule and trabeculae originate from:
| thymus
mesoderm
91
At birth, the thymus is _______________
fully functional and maintains its size until the time of puberty. With age, the thymus undergoes involution and becomes infiltrated by adipocytes, however it remains functional
92
With age, the thymus undergoes ____________
involution, and becomes infiltrated by adipocytes but it remains functional
93
The thymus is surrounded by a _______________
connective tissue capsule, which forms from trabeculae extending into the thymic parenchyma and divides it into lobules
-capsule and trabeculae contain blood vessels, nerves, efferent lymphatics, fibroblasts and reticular fibers
94
Describe thymic lobule cortex and medulla
Cortex: dark-staining basophilic, filled with thymocytes
Medulla: lighter-staining, there are less cells (significantly less cellular) and the cells are larger and have lighter nuclei and more cytoplasm
95
In the thymus, epithelioreticular cells:
provide the framework for developing T lymphocytes
Their function differs and different locations in the thymus
Currently, 6 types are recognized
Some epithelioreticular cells form Hassall's corpuscles, which are a characteristic feature of the thymus
96
Thymus is the site of
T lymphocyte development (thymic education)
97
Thymic education is a process of
maturation and differentiation of immunocompetent T cells from the lymphoid stem cells
98
The mature T cells have to possess the ability to recognize a variety of antigens presented in complex with _____________
MHC molecules, by antigen presenting cells (APCs)
99
Mature T cells have to be distinguish between ____________
self and foreign antigens
They have to "tolerate" self but have to initial an immune response agains the "foreign"
100
T cell precursors from ______________ enter ____________
from the bone marrow enter the corticomedullary junction of the thymus and migrate into the outer cortex (thymocytes)
101
Positive Selection
In the cortex, thymocytes that can interact with APCs (ex recognize self- MHC) are selected and are allowed to further mature and enter the medulla
Only about 10% of thymocytes survive and the rest undergo apoptosis
102
Negative Selection
In the medulla, thymocytes that would mount an immune response against the self are destined for apoptosis
Thymocytes that would not initiate an attack against the self are allowed to leave the thymus and populate secondary lymphoid organs as new T cells
```
Only about 2% of initial thymocytes survive (98% don't recognize our MHCs and apoptosis)
These thymocytes (apoptosed) are phagocytosed by macrophages, which are also present in the cortex
```
103
Thymocytes mature into T cells in the absence of ____________
any foreign antigens
104
Blood-thymus barrier
the physical barrier that prevents any contact between thymocytes and foreign antigens
105
Blood-thymus barrier is created by (3 things)
1. Endotheium of the capillary wall (continuous with tight junctions)
2. Macrophages in the surrounding perivascular tissue
3. Epithelioreticular cells with tight junctions (they surround the capillary wall in the cortex)
