Lect 2 - -Lymphatic organs Flashcards
What is the function of The Immune System
distinguishing between self or non-self, dangerous or non-dangerous and responding to those with tolerance or elimination.
What is Immunohomeostasis?
maintenance of the genomic permanency
What is Antigen?
every structure (cells, molecules, microbes) that the immune system recognizes and responds to it
Steps of Innate immune system?
Cells → cellular immune response
(Monocytes - macrophages
Granulocytes
Dendritic cells
Mast cells)
Soluble molecules → humoral immune response
Complement proteins (glycoproteins, enzymes, receptors)
Steps of adaptive immune system
Cells → cellular immune response
(B lymphocytes
T lymphocytes)
Soluble molecules → humoral immune response (Antibodies)
Activation of the Innate System
-> What are some recognized structures?
Pathogen Associated Molecular Pattern (PAMP), or Damage-Associated Molecular Patterns (DAMP)
What are Receptors in Activation of the Innate System?
Pattern Recognizing Receptors (PRR).
(They are not clonal. They are the same on different cell types. )
Function of Major Histocompatibility Complex:MHC-I
MHC I displays endogenous antigens, or antigens from within the cell
- a diverse set of cell surface receptors expressed on all nucleated cells in the body, as well as platelets.
Function of Major Histocompatibility Complex: MHC-II
MHC II displays exogenous antigens, or antigens from outside the cell
- MHC class II molecules thereby are critical for the initiation of the antigen-specific immune response.
Origin of Antigens
originated from lipids join to CD1, peptide antigens join to MHC-I or MHC-II.
Antigen presentation
-> Antigen processing of endogenous proteins (the host cell synthesizes foreign proteins with tumour cell like characteristics in viral or bacterial infected cells).
proteasome (enzymes)
→ ER (peptide fragments join to MHC-I
→ Golgi
→ vesicular transport
→ appearance on the cell surface
Antigen presentation
-> Antigen processing of Exogenous proteins (the host cell synthesizes foreign proteins with tumour cell like characteristics in viral or bacterial infected cells).
endo- and lysosome system
→ protected MHC II - formed in the ER join to vesicular system
→ protein binds to MHC-II
→ appearance on the cell surface
The role of NK cells
NK cells express „Killer Activating Receptor (KAR) „ and „Killer Inhibitory Receptor” (KIR).
Steps of activation of NK cells
- Binding „self” MHC-I molecules to the KIRs inhibits the KARs.
- NK cell does not destroy self. Virus infected and tumour cells decrease the MHC-I expression to hide themselves from cytotoxic T-cells.
=> Therefore there is no enough MHC-I to activate the KIR so the NK cells attack.
(NK cells express „Killer Activating Receptor (KAR) „ and „Killer Inhibitory Receptor” (KIR). )
Does NK cells destroy itself? Why?
NK cell does not destroy self.
=> Virus infected and tumour cells decrease the MHC-I expression to hide themselves from cytotoxic T-cells.
=> Therefore there is no enough MHC-I to activate the KIR so the NK cells attack.
(NK cells express „Killer Activating Receptor (KAR) „ and „Killer Inhibitory Receptor” (KIR). )
Virus infected and tumour cells decrease the MHC-I expression to hide themselves from ____ (which type of cells?)
cytotoxic T-cells
What is CD (Clusters of Differentiation)?
The cell surface molecules that determine the type of the cell, the stage of the differentiation or activation.
Example of Cell line markers
1/ Hemopoietic stem cell CD34+
2/ T-helper cell - CD4+
3/ T-citotoxic-CD8+
2 types of cell line markers
- Maturation markers
- Activation markers
Examples of maturation markers
Tymocytes in the thymus CD1+, mature T lymphocyte does not express this
What are Cytokines?
small peptides or glycoproteins that regulate the cell functions in the immune system through receptor mediated pathways.
What are Lymphokines?
cytokines produced by lymphoid cells.
5 types of Antibodies – Immunoglobulins (Ig)
1/ IgM
2/ IgD
3/ IgG
4/ IgA
5/ IgE
Identify the 5 types of antibodies
What is IgM?
naive B cell antigen binding receptor
What is IgD?
naive B cell antigen binding receptor
What is IgG?
„switched” B cell antigen binding receptor (opsonisation, complement activation, maternal immunity)
What is IgA?
„switched” B cell antigen binding receptor (mucosa immunity)
What is IgE?
„switched” B cell antigen binding receptor (immediate hypersensitivity)
What does it mean when it comes to Diversity of the Antigen Binding Receptors?
Genetic mechanism that results in diversity and specificity is the somatic recombination of genes that code the antigen binding site of the immunoglobulins and T-cell receptors.
What is B-cell Receptor (BCR)?
membrane bound immunoglobulin molecule with signal transduction chains
BCR: membrane bound immunoglobulin molecule with signal transduction chains.
-> BCR reacts with _____
soluble or corpuscular antigens
Antigen-activated B-cells may follow two pathways which are ____ and ____
1/ T-dependent activation
2/T-independent activation
How does T-dependent activation occur?
T-cell-independent antigen, B cells will proliferate and differentiate into short-living (SL) plasma cells and release low-affinity antibodies (first-line defence)
How does T-independent activation occur?
(2) T-cell-dependent antigen, B cells proliferate, undergo somatic hypermutations and isotype class switch, and differentiate into either long-living (LL) plasma cells releasing high-affinity antibodies and memory B cells.
T-cell Receptor (TCR) coded by ___
genes belonging to the Ig super-family
T-cell Receptor (TCR) recognize only ___
linear sequence of peptide fragments that join to MHC molecules!!!
Is TCR-MHC-antigen binding enough for T-cell activation? Why?
TCR-MHC-antigen binding is not enough for T-cell activation.
-> Co-stimulatory molecules are necessary!!!
What are included in cellular immune response?
- Production of cytokines (lymphokines) – activation of macrophages
- Regulation of inflammatory and cytotoxic processes
- Defense against intracellular pathogens
What are the 2 responses relating to T-cell classes?
- Cellular immune response
- Humoral immune response
What are included in humoral immune response?
- Production of lymphokines – activation of B cells
- Differentiation into plasma cells
- Defense against extracellular pathogens
What is included in regulation of immune response?
Production of lymphokines
The role of T-cell classes
Destroys virus or intracellular pathogen infected or tumour cells (perforin, granular enzymes.)
3 Organization Levels of the Immune System
- Cells: cells of the innate and adaptive immune system
- Tissues: blood and lymphatic tissues
- Organs: lymphatic organs
Organization of Lymphatic Organs
-> What are the 2 Primary (central) lymphatic organs?
- Bone marrow
- Thymus
Organization of Lymphatic Organs
-> Primary (central) lymphatic organs
-> The role of Bone marrow
formation of T and B lymphocyte and maturation of B-cells
Organization of Lymphatic Organs
-> Primary (central) lymphatic organs
-> The role of Thymus (thymus gland)
maturation of T-cells
Organization of Lymphatic Organs
-> What are the 5 Secondary (peripheral) lymphatic organs?
- Mucosa Associated Lymphatic Tissue (MALT: antigen in the mucosa)
- Skin Associated lymphatic Tissue (SALT), antigen in the skin)
- Lymph and lymph node (antigen in tissues)
- Spleen (antigen in the blood)
- Gastriontestinal tract (digestive tract) GALT
Organization of Lymphatic Organs
-> The role of Secondary (peripheral) lymphatic organs
„meeting with the antigens”
→ activation of B and T cells
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
Diffuse lymphoid elements (lymphocytes)
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
Aggregated lymph nodules (pl. Payer’s plaque)
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
Lymph node
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
Solitary lymph nodule or follicle
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
Epithelium related lymphatic tissue : tonsils
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
spleen
Different Forms of Lymphatic Tissue
-> Identify this form of lymphatic tissue
Thymus
Types of lymphatic organs
Capsulated lymphatic organs
Primary Lymphatic Organ: Thymus
-> What is the arterial supply?
a. thoracica interna, a. pericardiophrenica, a. thyroidea sup. et. inf.
Primary Lymphatic Organ: Thymus
-> What is the venous supply?
v. brachiocephalica
Primary Lymphatic Organ: Thymus
-> What are the included lymph vessels?
only efferents!!!
-> Anterior mediastinal lymph nodes
Primary Lymphatic Organ: Thymus
-> What is the Vegetative innervation?
n. vagus, sympathetic innervation
Histology of the Thymus
-> Identify
Pseudo-lobules
Thymus, foetal H&E
-> Connective tissue trabeculae (interlobular septum) divide the lobes into ______
(pseudo)lobules.
Histology of the Thymus
-> Each lobule has a peripheral darkly stained region called (1)___ and a central light area called the (2)____
- cortex
- medulla
Histology of the Thymus
-> Each lobule has a peripheral darkly stained region called (1)___ and a central light area called the (2)____
- cortex
- medulla
Cells of the Thymus
-> Which thymus cells are included cortex?
(5) cortical epithelial reticular cells secreting thymoxatin, thymosin, thymopoietin
(2) nurse cells (expressing MHC-II and T lymphocytes called thymocytes develope among their processes)
(9) macrophage
Cells of the Thymus
-> Which thymus cells are included in Cortico-medullary junction?
(6) medullary epithelial reticular cells (larger than the cortical ones, PTH, CRP, insulin)
(7) dendritic cells (APC from the bone marrow), macrophages, eosinophils
Cells of the Thymus
-> Which thymus cells are included in Cortico-medullary junction?
(6) medullary epithelial reticular cells (larger than the cortical ones, PTH, CRP, insulin)
(7) dendritic cells (APC from the bone marrow), macrophages, eosinophils
Cells of the Thymus
-> Which thymus cells are included in medulla?
(6) medullary epithelial reticular cells, Hassal- body (keratinized epithelial cells type VI), macrophage, dendritic cells, Hammar myoid cell
Type VI Epithelial Reticular Cells, Hassal body
-> Identify
Type VI Epithelial Reticular Cells, Hassal body
-> Identify
Type VI Epithelial Reticular Cells, Hassal body
-> Identify
What is Hassel body?
concentrically located flattened, eosinophilic, epithelial reticular cells connected with desmosomes.
What are accumulated in the centre of Hassal body?
Keratohyalin and cytokeratin
Dendritic Cells (DC)
-> Identify
1/ Lymphocyte
2/ Dendritic cell
Where do Dendritic Cells (DC) originate from?
the bone marrow
Identify this cell
Dendritic Cell (DC)
Maturation of T cells
-> T progenitor (pro-T) cells from the bone marrow enter the Thymus through ____
the venules of the cortico-medullary junction
Maturation of T cells
-> T progenitor (pro-T) cells from the bone marrow enter the Thymus through the venules of the cortico-medullary junction
→ They move into the ____ region and intensively proliferate.
subcapsular
Maturation of T cells
-> T progenitor (pro-T) cells from the bone marrow enter the Thymus through the venules of the cortico-medullary junction
→ They move into the subcapsular region and intensively proliferate.
-> Do they express CD8 or CD4?
They do not express neither CD8 nor CD4 receptor, double negative T cells (DN)
Maturation of T cells
-> T progenitor (pro-T) cells move into the subcapsular region and intensively proliferate
-> They do not express neither CD8 nor CD4 receptor, double negative T cells (DN)
-> What will make them expressing CD8 and CD4?
Environmental signal molecules induce the expression of TCR-s (genetic recombination) and CD4 and CD8, double positive T cells (DP)
Maturation of T cells
-> T progenitor (pro-T) cells move into the subcapsular region and intensively proliferate
-> They do not express neither CD8 nor CD4 receptor, double negative T cells (DN)
→ They migrate toward ____
the medulla
Maturation of T cells
-> T progenitor (pro-T) cells move into the subcapsular region and intensively proliferate
-> They do not express neither CD8 nor CD4 receptor, double negative T cells (DN)
→ They migrate toward the medulla and meet with their own ____
MHC molecules presented by nurse cells, epithelial reticular cells, dendritic cells, macrophages).
Maturation of T cells
-> T progenitor (pro-T) cells move into the subcapsular region and intensively proliferate
-> They do not express neither CD8 nor CD4 receptor, double negative T cells (DN)
→ They migrate toward the medulla and meet with their own ____
the venules of the cortico-medullary junction
Maturation of T cells
-> T progenitor (pro-T) cells move into the subcapsular region and intensively proliferate
-> They do not express neither CD8 nor CD4 receptor, double negative T cells (DN)
→ They migrate toward the medulla and meet with their own MHC molecules presented by nurse cells, epithelial reticular cells, dendritic cells, macrophages).
-> Those thymocytes that recognize at least one of the MHC-s (MHC restriction) will survive.
-> Others (90%) die by apoptosis.
-> This process is called ___
Positive selection
Barriers in the Thymus
-> Identify
Barriers in the Thymus
-> Tightly arranged _____ form a closed sheath under the capsule, around the trabeculae and vessels to form an inpermeable barrier to macromolecules to protect the thymocytes from contact with foreign antigens.
subcapsular epithelial cells (3)
Barriers in the Thymus
-> Tightly arranged subcapsular epithelial cells (3) form a closed sheath under the capsule, around the trabeculae and vessels to form an inpermeable barrier to macromolecules to protect ____ from contact with foreign antigens.
the thymocytes
Barriers in the Thymus
-> Tightly arranged _____ form a closed sheath under the capsule, around the trabeculae and vessels to form an inpermeable barrier to macromolecules to protect the thymocytes from contact with foreign antigens.
subcapsular epithelial cells (3)
Barriers in the Thymus
-> Tightly arranged sub-capsular epithelial cells (3) form a closed sheath under the capsule, around ___ and ____ to form an impermeable barrier to macromolecules to protect the thymocytes from contact with foreign antigens.
the trabeculae and vessels
What are the 5 Layers of blood-thymus barrier?
- Epithelial reticular cells (contacted with each other by desmosomes and tight junctions, type I)
- Basal lamina of the epithelial reticular cells
- Perivascular connective tissue septa with macrophages
- Basal lamina of the endothels
- Capillary endothels
General Features of Peripheral Lymphatic Organs
-> Name of lymphoid cells
B and T lymphocytes, plasma cells, NK cells,
General Features of Peripheral Lymphatic Organs
-> Name of accessory cells
Macrophages and dendritic cells
The role of of follicular dendritic cells (FDC)
- bind native antigens
- help the differentiation of B-cells in the germinal center of the lymphatic nodule (B- dependent area)
The role of dendritic cells (interdigitating dendritic cell)
It present MHC-II joined antigens to the Th cells in the T- dependent area of lymphatic organs, (eg. Langerhans cells of the skin, interstitial dendritic cells in the connective tissue)
What are some Vessels characterize peripheral lymphatic organs?
- blood vessels (with high endothelial venules, HEV)
- lymph capillaries
Special formations of of Peripheral Lymphatic Organs?
lymphatic nodules (follicles)
Reticular cell
-> Identify
What does primary follicles contain?
reticulum cells, resting naive B-lymphocytes (antigen free environment, e.g. intrauterine life)
What do secondary follicles contain?
- Cap (like the primer follicle).
- Germinal centre (centrum germinativum): dark zone - B lymphoblasts (centroblasts), dividing forms light zone-smaller centrocytes , follicular dendritic cells, macrophages
Which reaction occur in germinal center?
B-cell activation
Germinal Centre - Reaction: B-cell activation
-> Identify
Germinal Centre - Reaction: B-cell activation
-> Identify (red squares)
tingible body macrophage
Why are there two types of dendritic cell ???
Naive B-cells, macrophages, follicular dendritic cells are the main cell types in the ____
Follicle
naive T cells, dendritic cells, macrophages are located in the ____
interfollicular areas.
Identify
General Features of Tonsils
-> What does MALT – Mucosa Associated Lymphatic Tissue contain?
- Lymphoepithelial tissue
- Lymphoreticular tissue
- Crypts
What is Lymphoepithelial tissue?
the epithelium is infiltrated with lymphatic cells
What are the characteristics of Lymphoreticular connective tissue with lymphatic nodules?
- The follicles are B-dependent areas.
- Among the follicles, T-dependent areas are with blood vessels (HEV), and lymph capillaries.
What are crypts (fossula, lacuna)?
epithelial invaginations (increasing the surface for immune response)
Histology of Lingual Tonsil
-> Identify
- Crypt lined with stratified squamous non-keratinized epithelium
- Mucosa-associated lymphoid tissue (MALT)
- Germinal center
- Skeletal muscle fibers
- Seromucous accessory salivary glands (lingual salivary glands)
Histology of Palatine Tonsil
-> Type of epithelium
stratified squamous non-keratinizing epithelium infiltrated with lymphoid cells.
Histology of Palatine Tonsil
-> are the crypts deep?
Crypts are deep and branched
(during bacterial infection (strepto- or staphylococcus) the crypts are filled with neutrophils → pus
Histology of Palatine Tonsil
-> What is Hemicapsule?
a band of dense connective tissue acting as a capsule separating the lymphoid tissue from the subjacent structure
Histology of Palatine Tonsil
-> Function of hemicapsule
barrier against to spread infections (area for tonsillectomy)
Histology of Palatine Tonsil
-> Embryology
-> Palatine tonsil is a derivative of ____
The 2nd pharyngeal pouch
Histology of Palatine Tonsil
-> Identify E and F
E - Epithelium: stratified squamous non-keratinizing epithelium infiltrated with lymphoid cells.
F - Follicles (Lymphoreticular connective tissue with follicles)
Histology of Pharyngeal Tonsil
-> Describe the epithelium
ciliated pseudostratified columnar epithelium (with islands of stratified squamous non-keratinizing epithelium on the top of the folds and in the pits) infiltrated with lymphoid cells.
Identify
MALT: Peyer’s Patches
What is lymph?
: interstitial (extracellular) fluid with some red blood cells and lymphoid cells.
What is Lymph capillary?
thin endothelial cells formed tubes covered by basal lamina and connective tissue fibers
Does lymph capillary contain valves? Why?
It contains valves that determine the direction of the lymph flow
What are lymphatic ducts?
the largest lymph vessels (intima: endothel, elastic fibers, media: circular smooth muscle cells, adventitia: spiralry organized smooth muscle cells mixed with connective tissue fibers
Lymphokinetic motion and pressure gradient
Capillary →extracellular fluid→lymph capillary→ vasa lymphatica→ lymphatic duct →large vein
Lymph and Blood Circulation
-> How can fluid go from lymph capillary to large veins?
Lymph capillary → vasa lymphatica → lymphatic duct → large veins
Lymph node
-> Identify
Lymph node
-> What does the cortex contain?
dense parenchyma with follicles and less sinusoids
Lymph node
-> What does the paracortex contain?
dense parenchyma less sinuses, no follicles
Lymph node
-> What does the medulla contain?
lymph sinusoids, with parenchyma (medullary cords) extending from the cortex
Identify
Reticular cells
Lymph node
-> identify
1 - medulla
2 - cortex
Lymph node
-> Identify
1/ medullary cord
2/ medullary sinus
3/ trabecule
4/ follicle
Identify 1 -> 3
What does cortex contain?
follicles (B dependent area) with follicular dendritic cells and follicular macrophages, interfollicular zone (T-dependent area as the paracortex),
What does paracortex contain?
T lymphocytes , dendritic cells, macrophages, HEV
Identify MS and MC
MC - medullary cord
MS - medullary sinus
Identify MS and MC
MC - medullary cord
MS - medullary sinus
Medulla
-> What does medullary cord have?
B cells
Few T cells
Plasma cells
Medulla
-> What does medullary sinus have?
flat reticular cells (sinusendothel) covered vessels in which lymph and cells are located (lymphocytes, plasma cells, macrophages)
Write down Lymph route
vasa afferentia
-> marginal sinus (subcapsular)
-> trabecular sinus
-> medullary sinus
-> vasa efferentia
Write down blood circulation
Blood circulation: (enter through the hilus) artery → capillary → postcapillary venule (HEV) → hilar vein
Where are High Endothelial Venule located?
Mainly in paracortex
Describe endothelium of High Endothelial Venule
The cuboidal or low columnar endothelial cells with large lightly stained nucleus.
-> Circulating lymphocytes leave the blood circulation (homing, 15-20 thousand cells/second!)
Structure of the spleen
- Peritoneum (mesothel)
- Capsule: dense connective tissue (collagen, elastic fibres, myofibroblasts, smooth muscle cells)
- Trabeculae: similar to the capsule (but more elastic fibre among collagen) blood and lymph vessels, nerves
- Red pulp
- White pulp
Spleen
-> Identify
- Red pulp
- White pulp with splenic nodules
What does Red Pulp Sinusoid contain?
- Blood cell
- Hoop fibers
- Stave cells
What does storm of red pulp contain?
reticular connective tissue (reticular fibres with reticulum cells)
Spleen - Red pulp
-> Sinuses are separated by ____
splenic Cords of Billroth
What do splenic Cords of Billroth have?
(The Cords of Billroth (also known as splenic cords or red pulp cords) are found in the red pulp of the spleen between the sinusoids)
- reticular fibres
- reticulum cells
- macrophages, plasma cells
- granulocytes
- thrombocytes
- red blood cells (red colour of the pulp).
Red pulp of spleen
-> identify
1 - cell in transit
2 - sinusoids
3 - endothelium
4 - cell in transit
Spleen
-> Where can you find white pulp?
White pulp (lymphoreticular connective tissue) around the central artery
What does white pulp (lymphoreticular connective tissue) contain?
- PALS: periarterial lymphoid sheath.
- Follicles (splenic nodule, Malpighian follicle)
- Marginal zone