Lecture 26/27: Lymphoid Flashcards
What does CD stand for? What does it mean?
Cluster of differentiation: a particular cell type displays some cell surface marker that is useful for identification purposes
What is necrosis?
When a cell bursts and dies in an uncontrolled process
What cleans up the mess after necrosis?
Macrophages
What does necrosis cause?
An inflammatory response because the cell membrane ruptures and spills cellular contents into the milieu
What is apoptosis?
Cell suicide in a controlled process
What can induce apoptosis?
Fas ligands
What are the body’s 3 lines of defense? In order.
- Physical/biochemical barriers 2. Innate/non-specific immunity 3. Adaptative/specific immunity
Describe the body’s physical/chemical barriers. Examples?
Obstacles to prevent pathogens from gain foothold on/in body: sloughing off skin cells, acidic pH in stomach and reproductive system, flushing of urinary tract, tears, mucus, cilia, commensals (bacteria to help with digestion)
Describe the innate/non-specific immunity.
Evolutionary primitive defense mechanism
Does the innate/non-specific immunity have immunologic memory?
NOPE
When does the innate/non-specific immunity join the fight?
When a pathogen enters the body
Describe adaptive/specific immunity.
More recent evolutionary development charged with discriminating between biological components that are self and non-self
What are the 3 basic characteristics of adaptive/specific immunity that distinguish it from innate/non-specific immunity?
- Specificity 2. Diversity 3. Memory
What are the 2 mechanisms of adaptive immunity?
- Humoral: B-cell mediated 2. Cellular: T-cell mediated
How does the number of Natural Killer cells change after a surgery? When is this most severe? What does this do?
Considerably decreases in number and function Most severe 3 days post-op Makes it easier for metastatic cells to seed new locations
What is the suppression of NK cells proportional to?
The extent of the surgical intervention
Describe humoral adaptive immunity.
- Antigen presented to B lymphocyte 2. B cell surface antibody reacts with antigen 3. B cell undergoes clonal expansion 4. B cell proliferates to form 2 different cell types: plasma cells and memory B cells
What is another name for B cells?
B lymphocytes
Describe how the plasma cell created by the B cell works.
It has lots of RER to secrete soluble antibodies
For how long does the plasma cell created by the B cell survive?
Weeks - months
How can one recognize a plasma cell histologically?
Large cytoplasm filled with RER
Is the memory B cell terminally differentiated?
NOPE
Is the plasma cell terminally differentiated?
YUP
What is the purpose of the memory B cell?
Produce a rapid response if the same antigen is presented again
Do the memory B cell lose its proliferative potential?
NOPE
Where do B cells go once they are released by the bone marrow?
Lymph nodes and spleen
Where do stem cells destined to become T cells go once they are released by the bone marrow?
Thymus where they mature
What happens to the thymus as you get older?
It atrophies
Describe the structure of IGs.
2 heavy chains + 2 light chains connected by disulfide bonds
What is the purpose of the variable portions of an IG? Where are they located?
Provides a certain degree of specificity for antigens On each heavy chain and each light chain (at the tip of the Y)
Where does the variable portions of IGs come from?
Somatic recombination: 3 different exons coding for heavy and light chains shuffle in order to code for novel combinations of variable portions of the antibody
What does the DNA coding for heaving and light chains consist of?
- Variable-region exons 2. Joining-region exons 3. Diversity-region exons
What are the 5 types of IGs?
- IgG 2. IgM 3. IgA 4. IgD 5. IgE
What are the 3 functions of IgGs?
- Opsonization
- Neutralization
- Protect newborn
Which are the first antibodies to be produced in an initial immune response? Ie: which IGs constitute the primary response?
IgMs
What IG is dominant in the secondary response?
IgG
Which lag is longer: lag between exposure and primary response or lag between recurrent exposure and secondary response?
Lag between exposure and primary response
What is the function of IgAs? How come?
Protect the surface of mucosas as they resist proteolysis because tagged with a “secretory component” to protect itself from lysosomal degradation within the epithelial cell while being transcytosed through it (removed for it to become fully functional again)
What is the function of IgDs?
Receptors to antigens triggering B cell activation
What are the 2 functions of IgEs?
- Participate in allergies 2. Lyses parasitic worms
What 3 Igs are monomers?
- IgG 2. IgD 3. IgE
What Ig is a pentamere?
IgM
What Ig is a dimer with a secretory component?
IgA
Which Ig is the secretory one? Across what is it secreted?
IgA secreted across lining epithelium
Where is IgA made? Example?
Plasma cells in MALT: lining of GI tract, lungs (pleural cavity), tonsils
What do all 5 types of Igs have in common?
All have same core structure of 2 heavy and 2 light chains
What are the 5 ways in which antibodies engage pathogens?
- Agglutination 2. Opsonization 3. Neutralization 4. Cytotoxicity 5. Complement activation
Describe agglutination.
Antibody binds antigen = fewer antigens
Describe opsonization.
Antibody binds antigen = antigen marked for phagocytosis
Describe neutralization.
Antibody binds antigen = blocks their pathogenic adhesion mechanisms + inactivates their toxins
Describe cytotoxicity.
Antibody binds parasitic worms = induces macrophages and eosinophils to inondate the worm with chemical agents
What are CD8+ T cells also called?
Cytotoxic T-cells
What are CD4+ T cells also called?
Helper T-cells
How is the T cell activated?
When the T cell receptor on the surface of T cells interacts with an antigen presented on an MHC (major histocompatibility complex)
What type of T cell does MHC 1 interact with?
Cytotoxic T cells
What type of T cell does MHC 2 interact with?
Helper T cells
What is another name for cytotoxic T cells?
Cytotoxic lymphocytes
What happens when the cytotoxic T cell is presented an antigen on MHC 1?
Memory T cells and cytotoxic T cells are produced
What do cytotoxic T cells do to the virally infected cells of the body? 2 options.
- They use perforin to lyse infected cells 2. They use Fas ligand to initiate apoptosis of the infected cell
What happens when the helper T cell is presented an antigen on MHC 2?
Helper T cell activated and produces interleukins inducing B cells to become active and proliferate/differentiate
What is a potential therapy for a patient who has severe combined immunodeficiency (no B or T cells)? What are the risks?
Viral vectors = gene threapy
Have oncogenic risks though because these would randomly enter the genome and sometimes disrupt other normal genes
What does the HIV virus do?
Destroys HELPER T cells: titer declines during latency period until reaching a critical level where infections occur and lead to death
What type of antibodies on the B lymphocytes recognize antigens that are presented?
IgDs
What are the 3 cell types in innate immunity? List what each includes.
- Mastocytes
- Granulocutes: neutrophils and eosinophils
- Agranulocytes: monocytes, macrophages, NK lymphocytes
What is the function of mast cells?
They participate in innate immunity and liberate compounds that modulate inflammation.
What do NK lymphocytes do?
Destroy pathogens
What is this?
Natural Killer cell
How can one reduce surgical stress? Purpose?
Robotic surgery to not decrease too many NK cells
What is the oldest vertebrate class that had adaptive immunity? What does it include?
Sharks with immunoglobulins, gene rearrangement mechanisms, T cell receptors, and MHCs
What are the 2 functions of the lymphoid system?
- Recognize antigens
- Inactive/Eliminate antigens
What are the 4 types of antigens?
- Foreign material
- Microorganisms
- Cancer cells
- Organ transplants
Where does the synthesis of B cells and T cells start?
Bone marrow
Where do B cells mature?
Bone marrow
Where are B cells produced during the 2 trimester of pregnancy?
Fetal liver
Which is the most common Ig?
IgG
What are these?
Plasma cells (from B cells)
Where are IgEs located?
Surface of mastocytes and basophils
Where are IgMs located as monomers?
Surface of B cells
What is the production of T cells stimulated by?
Cytokines secreted by basophils, B cells, macrophages, hassal’s corpuscles in thymus
Describe complement activation.
Antibody binding to initial protein of complement system = complement cascade = produces membrane attack complex with transmembrane channels to cause cell lysis
What is another name for cytokines?
Lymphokines
What is PD-1?
A cell surface receptor on T cells which down-regulate the immune system by preventing the activation of T cells
What are PD-1’s ligands?
PDL-1 and PDL-2
What do PD-1 inhibitors do? What are they used to treat?
Activate the immune system to attack tumors = used to treat cancer
THIS IS INHIBITING THE INHIBITOR
What were the 6 milestones of cancer discoveries?
- Surgery (helped with robotics and anesthetics)
- Radiation therapy
- Hormonal therapy
- Chemotherapy
- Gene therapy
- Immunotherapy
What are supressor T cells?
T cells with PD-1 receptors
What are examples of APCs?
Macrophages, dendritic cells, langerhans cells, osteoclasts …etc
Does apoptosis create an immune response?
NOPE
What is a side effect of HIV drugs?
Accelerated aging
What are the 2 types of lymphoid organs?
- Central
- Peripheral
What is the lymphoid system responsible for?
Surveying the body for pathogens and producing immune cells
What is the central lymphoid system made of? What do these two have in common?
- Thymus: site of T cell maturation
- Bone marrow: site of B cell maturation
They are both encapsulated
What does encapsulated mean?
Surrounded by connective tissue
Where do B and T cells go once they mature in the central lymphoid organs?
The peripheral lymphoid organs
What are the 2 types of peripheral lymphoid organs? List what each includes.
- Encapsulated: lymph nodes and spleen
- Unencapsulated: single nodules, aggregated nodules, diffuse lymphoid tissue, MALT
What is the role of the encapsulated lymphoid organs?
Filtering the 2 types of fluid found in the body:
- Lymph nodes: lymph
- Spleen: blood
What is MALT? What % of all lymphoid tissue does it comprise? What is its role?
Mucosa Associated Lymphoid Tissue
85%
Conducts antigen surveillance along mucosal tracts: lungs, GI tract, reproductive tract, oral cavity
What are nodules?
Unencapsulated group of lymphocytes (peripheral lymphoid organ)
Describe the B and T cell composition of the lymph nodes.
- B cells in cortical nodules = superficial cortex
- T cells in paracortex
Describe the B and T cell composition of the spleen.
- B cells in lymphoid nodules
- T cells in PALS = PeriArterial Lymphatic Sheath
Describe the lymphocyte composition of the blood.
[T cell] >>>> [NK cells] > [B cell]
Describe the B and T cell composition of the lymph.
[T cell] >>>> [B cell]
Describe the B and T cell composition of the mucosal tissues = unencapsulated perypheral lymphoid organs.
[B cell] >>>> [T cell]
Are the B and T cells localized in specific spots in the blood, lymph, and mucosa?
NOPE
Where is diffuse lymphoid tissue found?
Small intestine
What are the 4 components of diffuse lymphoid tissue?
- Lamina propria
- Lymphocytes (mainly B)
- Eosinophils
- Plasma cells
What is the lamina propria?
The connective tissue that lines the mucosa underneath the surface epithelium
What is another name for solitary nodules?
Follicles
Where are solitary nodules found?
- Lymph nodes
- MALT
What are the 2 types of solitary nodules? What does each contain? How does each stain?
- Primary nodules: naive B cells
⇒ one color density w/ H&E
-
Secondary nodules:
- Cap/Mantle: naive B cells (around germinal center stains darker)
- Germinal center (two color density w/ H&E because more sytoplasm): activation of immune cells:
- B cells
- Helper T cells
- Dendridic cells
- Tingible bodies
What do tonsils contain? What is around them?
Germinal centers, which are greater in number during an oral infection
- At bottom: the cap
- At top: non-keratinized epithelium
Where are Peyers patches found? What do they contain? What are they used for? Describe how this works.
Found in lamina propria of the ileum of the small intestine, contaning primary nodules
Used for antigen surveillance: M/Microfold cells between surface epithelial cells of the small intestines transport the antigen to lymphocytes inside the Peyer’s patch (eg: macrophages for stimulation of B and T cells)
What are the 3 aggregated nodules?
- Tonsils
- Peyers patches
- Vermiform appendix
Describe the encapsulation of aggregated nodules.
Incomplete = considered unencapsulated
What are the 4 capsulated lymphoid organs?
- Bone marrow
- Spleen
- Lymph nodes
- Thymus
What are solitary nodules?
Aggregation that is not surcomscribed to connective tissue capsule
What are diffuse lymphoid tissues? Where are these usually found?
Cluster of lymphocytes (typically found in the mucosa)
What is the order of complexity of lymphoid organs?
- Circulating Lymphocytes
- Diffuse Lymphoid Tissues
- Solitary Nodules
- Aggregated Nodules (incompletely encapsulated)
- Specific Organs (encapsulated)
Where is the Vermiform appendix located? How does it change as a person ages?
McBurney’s point
The amount of immune tissue inside it declines, adipose replaces
What is the main function of the thymus?
T cell maturation
What are the 2 major components of
Where do T cells mature in the thymus?
Begin to mature in cortex and continue to be modified in the medulla
What are the epithelial reticular cells of the thymus?
Cells that form the microframework of the thymus and act as a scaffolding for T cells to hang on while they mature
What % of T cells are self-recognizing? How do we protect them from attacking us?
95% (VERY INEFFICIENT)
Blood-thymus barrier which separates the processes in the thymus from causing problems to the rest of our bodies + they are not released and destroyed
What are Hassal’s corpuscles? What do they secrete?
Remnants of keratinized epithelial reticular cells located in the thymus (medulla) ONLY
Secrete cytokines to promote chemotaxis
Label this shit.
How does the number of T cells in the thymus change with age? What is this called?
Decreases and replaced with adipose tissue
Thymic involution
What are the 3 immune organs that are replaced with adipose tissue with age?
- Bone marrow
- Thymus
- Appendix
What are the 4 functions of the lymph nodes?
- Filter lymph
- Antigen surveillance
- Recognize activated lymphocytes in the blood
- Release more lymphocytes in the blood during infection
How many lymph nodes do we have in our body? What are they in line with?
>500
Lymph vessels
Why are lymph nodes biopsied for? What sometimes happens to them?
Tumor cell metastasis to look for tumor cell-related surface markers
Surgeons will remove them after removing a tumor if cancer cells are suspected there
What are 3 areas of the body that are rich in lymph nodes?
- Neck
- Mediastinum (central compartment of the thoracic cavity)
- Retroperitonium
What is the pathway of the lymphatic fluid as it travels through the lymph node? 5 steps
Show it on the image.
- Afferent lymphatics
- Subcapsular sinus
- Trabecular sinus
- Medullary sinus
- Hilium/Efferent lymphatics
Does blood travel through the lymph nodes? How?
Yes, but in the opposite direction as the lymph:
Post-Capillary High Endothelial Venules (HEVs) in the paracortex are made of cuboidal cells (rather than squamous), which allows lymphocytes in the blood to squeeze between them to activate other lymphocytes in the lymph nodes
What are the 4 functions of the spleen?
- Filtering blood
- Mounting immuse responses against pathogens in blood
- Storing platelets
- Performing hematopoiesis (residual function from fetus) if damaged bone marrow
Describe the passage of blood through the spleen.
- Central artery or arteriole
- White pulp
- Marginal zone sinuses
- Red pulp: splenic cords
- Red pulp: venous sinusoids
- Hepatic portal vein
What is the white pulp of the spleen composed of?
Lymphocytes:
- B cells in lymphoid nodules (periphery of white pulp)
- T cells in PALS
How does white pulp stain? Why?
Dark purple because lymphocyte nuclei
What is included in the marginal zone?
Lymphocytes
What are the 2 parts of the red pulp of the spleen?
- Splenic cords
- Venous sinusoids
How does the red pulp of the spleen stain? Why?
Lighter because of RBCs that do not have nuclei
What are the 3 functions of the splenic cords?
- Platelet storage
- Iron storage
- Hematopoiesis
What to note about the central artery?
It’s NOT CENTRAL in the white pulp
Describe the marginal zone sinuses.
Very loose blood vessels without muscles
What happens as blood goes through the venous sinusoids? Describe the 2 types of circulations.
Older or sickled RBCs are filtered out by macrophages
2 circulations:
- Open: 90% of flitration, SLOW: Direct contact between blood and sinusoid parenchyma
- Closed: 10% of filtration, FAST: Discontinuity between blood and sinusoid parenchyma
Where are the PALS in the spleen?
Around the perimeter of the central artery
What must all RBCs pass before going back into the blood? Purpose?
Sinusoidal wall
Only healthy cells can pass
Where is somatic recombination seen in lymphocytes?
- Variable portions of Igs made by B cells
- T cell receptors
What can be said of all peripheral lymphoid organs?
They contain lymphoid nodules
