immunology

Bursa of Fabricius

where does B cell mature in birds

Bone marrow

Where does B cell mature in primates and rodents?

Intestinal lymphoid tissue

Where does B cell mature in rabbits and ruminants?

Thymus

Where does T CELLS mature?

Thymus

Located in the thoracic cavity in front and below the heart.

Cortex

What do you call the outer part of each lobule in the thymus?

Hassall’s corpuscles

What can you find the in the Thymus’ medulla (round layered bodies)

Thymulin

Zinc-containing peptide secreted by epithelial cells

Thymulin

Partially restore T-cell function in thymectomized animals

Hassall’s corpuscles

Regulate thymic activity since they produce a growth factor called ‘‘THYMIC STROMAL LYMPHOPROTEIN (TSLP)

THYMIC STROMAL LYMPHOPROTEIN (TSLP)

Activates thymic dendritic cells that can stimulate regulatory T cells

Bursa of Fabricius

Round sac above the cloaca

Bursin

What do you call the hormone extracted from the bursa that activates B cells but not T cells?

Apoptosis

What do you call the negative selection of self-reactive B cells in bursa?

Peyer’s patches

Lymphoid organs located in the walls of the small intestine.

Ileal PPs

\-site for B cell proliferation in PP

\-major source of B cells

Lmyphoglandular Complexes

present in the wall of the large intestine and cecum in horses, ruminants, dogs, and pigs. They consist of submucosal masses of lymphoid tissue penetrated by radially branching extensions of mucosal glands.

Secondary Lymphoid Organ

\-Responds to a huge diversity of organs than an animal may encounter.

\-Includes antigen-specific lymphocytes can encounter their target antigens.

\-Arise late in fetal life and persists in adults.

\-Enlarges in response to antigenic stimulation

\-Facilitates antigen trapping and provides the optimal environment for the initiation of immune responses

\-Connected to both the blood and lymphoid systems

Lymph nodes

\-Are round or bean-shaped filters strategically placed on lymphatic vessels in such a way that they can sample antigens carried in the lymph.

Subscapular sinus

\-is located immeadiately under the connective tissue capsule in the lymph nodes

Peripheral cortex

Central medulla

Paracortex

The interior of lymph nodes is divided into what three regions:

Peripheral cortex

Where do B cells predominate and arranged in aggregates called follicles.

Lymph node medulla/ Central medulla

contains lymph-draining sinuses separated by medullary cords containing many plasma cells, macrophages, and memory T cells.

Germinal centers

sites where B cells grow, mutate, and mature. They are ovoid clusters of cells divided into a light and dark zone.

Somatic mutation

What do you call the process where B cells proliferate and undergo a process in germinal centers

B Light zone

\-site where immunoglobin class switching memory B cell formation

\-rich in antigen-trapping follicular dendritic cells and CD4+T cells

HEVs (High Endothelial Venule)

Paracortical cord, lined with tall, rounded endothelial cells Surrounded by concentric layers of fibroblastic reticular cells

Perivenular channel

What do you call the narrow space in HEV

Conduits

consists of collagen fibers ensheathed by fibroreticular cells ( not continuous)

Reticular fibers

\-provides a scaffolding of the lymph node

\-serve as conduits for the rapid transmission of signaling molecules

Chemokines

\-Small proteins which stimulate the migration of cells

\-Control the relocation and recirculation of lymphocytes ensuring they end up in the right place.

Facilitate the interactions between antigen presenting cells and antigen sensitive T and B cells

What is the principle function of 2ndary lymphoid organs such as lymph nodes?

Both B and T cells are highly active and motile

What is the interesting feature of secondary lymphoid organs?

Bone marrow→ thymus→ secondary lymphoid ogans→sites of microbial invasion

Trace the movement of cells in Lymphocyte circulation

T cells

\-constantly circulate around the body in the blood and tissue fluid and are the predominant lymphocytes in blood

\-as they travel, they survey the body for foreign antigens and preferentially home to sites of microbial invasion and inflammation.

HEV in lymph nodes

T cells that have not previously encountered antigens (“naïve” T cells) bind to where?

Endothelial cells

What cells in lymphocyte circulate that is not joined by tight junctions but are linked by discontinuous “spot-welded” junctions.

T cells

What cells leave the bloodstream through conventional blood vessels in tissues and are then carried to lymph nodes through afferent lymphatics.

BLOODSTREAM→ afferent

LYMPH NODES→ efferent

T cells leave the bloodstream through ________ lymphatic

T cells leave the lymph nodes through ________ lymphatic

Thoracic duct

What do you call the largest lymph vessels

85% T cells

5% B cells

10% dendritic cells

Afferent lymph percentage in sheep

75% T cells

55 B cells

10% dendritic cells

Efferent lymp percentage

Cortex→ Medulla→ Periphery→ Efferent Vessels→ drain the region between between nodules

Trace species differences lymph nodes flow

conventional

What structure is mesenteric lymph nodes

Inverted structure

What structure is mediastinal lymph node?

Conventional

What structure is bottlenose dolphins and striped dolphins?

Hemolymph nodes

\-Structures similar to lymph nodes

\-Ruminants, elephants and some rodents (rats)

\-Function is unclear

\-Sinuses contain numerous red cells

\-Cortex- containing germinal centers and B cells.

\- T cells predominate at the center in association with lymphatic sinuses.

\-Carbons trapped in IV

Spleen

\-Filter blood-borne pathogens and antigens

\-Filtering process- removes antigenic particles

\-Blood-borne microorganisms, cellular debris, and aged blood cells

\-Stores red cells, and platelets, recycle iron and undertakes red cell production in the fetus.

Red pulp

\-used predominantly for blood filtering and for red cell storage, called the red pulp.

\-It contains large numbers of antigen-presenting cells, lymphocytes, and plasma cells.

\-specialize in removing aged red blood cells and so regulate iron recycling.

Spleen

\-rich in both B and T cells where immune responses occur

\-separated from the red pulp by a region called the marginal zone. not supplied with lymphatic fluid, although it does possess efferent lymphatics.

Lymphoid tissue in the digestive system

The largest pool of lymphocyte

Tertiary Lymphoid Organ

\- Lymphoid structures in response to microbial colonization and chronic immune stimulation

\-Masses of lymphocytes with discrete T and B cells

Angiogenic factors

What trigger the production of lymphatics and HEV’s in Tertiary Lymphoid Organ

Inflammation

\-The sum of the host’s defenses to infectious or noxious stimuli

\-To bring immune cells to the area of concern

\-To inactivate and or destroy invaders

\-To start repairs

\-itis”

VASODILATION

INCREASE IN CAPILLARY PERMEABILITY

INFLUX OF PHAGOCYTES

CHEMOTAXIS

Major events of an Inflammatory Response

Vasodilation

\-Blood vessels widen allowing more blood to flow through.

Erythema

This is the engorgement of the capillary network

Increases in capillary permeability

\-Facilitates the influx of fluids

\-EDEMA

Diapedesis

The passage of blood cells through the unruptured wall of a blood vessel into the surrounding tissues.

Influx of phagocytes

\-Margination in which there is the adherence of these phagocytic cells to the endothelial wall.

Chemotaxis

This is the migration and recruitment of inflammatory cells and stem cells in response to tissue damage for wound healing and tissue maintenance and repair.

PAMPS (Pathogen-associated molecular patterns)

DAMPS (Damaged-associated molecular patterns)

2 types of signal trigger the body’s innate defenses

PAMPS (Pathogen-associayed molecular patterns)

What signal trigger that the presence of invading microorganisms is detected by sensing their characteristic surface molecules or nucleic acids.

DAMPS (Damaged-associated molecular patterns)

\-Cells detect molecules released from damaged tissues and broken cells.

\-Also called alarmins

Sentinel cells

Where can we find the PRRs?

PAMPS

\-Essential molecules that are common to many different organisms

\- Needed for microbial survival

\- Widely distributed

Walls of G+ bacteria (chains of peptidoglycan)

G+ bacteria (lipoteichoic acid)

G- bacteria (Peptidoglycan with a layer o LPS)

Acid-fast- covered in glycolipid

Yeast - B-glucan-rich cell wall

Example of PAMPS

Toll-like receptors

\- The critical first line of defense against bacterial, viral, and fungal invaders

\- Plays a vital role in microbial sensing.

\-Found in sentinel cells

Macrophages

Mast cells

Epithelial cells

Example of TLRs

Cytokines

What proteins that regulate the activites of cells involved in the defense of body produces?

caspase-1

Cytokines are produced as an inactive precursor and then activated by what enzyme?

Inflammasomes

What triggers Caspase-1?

increase leukocyte production

Bacterial LPS binding to TLR4 on these stem cells stimulates what production.? ( feature of bacterial dss)

Polymorphic variations

What influence animal resistance to infections?

Enteric disease

TLRs trigger the initial steps in resistance to microbial invaders. If they are ineffective, an animal may show increased susceptibility to infections. For example, what is the name of disease common in German Shepherd dogs.

\-if several single-nucleotide polymorphisms (SNPs) in the TLR4 and TLR5 genes were associated with the occurrence of this disease. It is likely that in German Shepherd dogs

\-mutations in their TLR4 and TLR5 genes reduced their ability to defend against intestinal bacterial invasion.

\-This predisposes to enteric infections, as shown by diarrhea

Retinoic acid-indusicble gene (RIG)-1-Like receptors -RLR’s

\-Another family of PRRs

\- Detect viral double-stranded viral RNA molecules

\-Their detection is through RLRs and activates capsases and triggers the production of type 1-interferon.

\-Triggers the prodcution of cytokines and defensins

NLRs - Nucleotide-binding oligomerization domain (NOD)-like receptors

Another family of PRRs

• Different location with RLRs

• Detect intracellular PAMPS

NOD 1

What NLR binds to bacterial peptidoglycans?

NOD 2

What NLRs muramyl peptide and serve as a general sensor of intracellular bacteria

NOD 3

What NLRs binds to diverse ligands including many viral nucleic acids and inorganic matter such as silica, asbestos and alum

Caspase-11

What enzyme that causes cell death by pyroptosis

Bacterial LPS

\-Ubiquitous structural components of the cell walls of bacteria especially G- bacteria

\-TLR4 does not bind directly

\-MD-2 (myeloid differentiation factor)

\-LPS-binding protein (LBP)

\-CD14

What 3 proteins bind to TLR?

it decreases the specificity of these reactions and enables both rough and smooth strains of bacteria to be recognized

What happens when The CD14 interacts with TLR4

Binding of LPS to the CD4/TLR4/MD2

\-complex activates your macrophages and triggers cytokine production

Bacterial Peptidoglycan

\-Polymers of alternating N-acetyl glucosamine and N-acetyl muraminic acid- major constituents of the cells walls of G+ and G-

\-Several PRRs can recognize these peptidoglycans

TLRS, NODs, CD14

Bacteria DNA

\-Consists of dinucleotide, unmethylated cytosine guanosine (CpG).

\

dinucleotide, unmethylated cytosine guanosine (CpG).

These can bind and trigger TLR9

Deoxyguanosine (dG) nucleotides

Binds to TLR9 and trigger the production of cytokines such as TNF-a, IL-6, IL-12

Viral Nucleic Acid

Consists of a nucleic acid core surrounded by a layer of proteins called capsid and possibly lipid envelope

TLR9-dsDNA CpG DNA

intracellular bacteria in Viral Nucleic Acid

TLR8 and TLR7

\-Detects ssRNA in Viral Nucleic Acid

vesicular stomatitis

TLR7 and TLR8 recognize single-stranded RNA viruses such as _____________

.TLR3- sRNA, some ssRNA and some dsDNA

Reovirus Viral Nucleic Acid

TLR7 and TLR9

uses MyD88- signaling pathways and trigger production of inflammatory cytokines and type I IFNs.

TLR3

uses TIR-domain containing adaptor protein inducing IFN- β (TIRF)

\-Activates the transcription factor for IRF3 that then activates the genes for inflammatory cytokines and IFN-β

Damaga associated molecular patterns DAMPS

\-Caused by physical trauma and tissue damage

\-Also called as alarmins-

\- May be released when cells die intracellularly or generated when the connective tissue is damaged (extracellular)

\- Have potent antimicrobial properties.

\-Others recruit and activate cells of the innate immune system and promote adaptive response

.DNA-rich in unmethylated CPG

When cells die, broken mitochondria may release large amounts of this DNA that can bind TLR9 and trigger inflammation.

High Mobility group box protein-1 (HGMB1)

\- Potent trigger to inflammation

\-Secreted by macrophages that have been activated by lipopolysaccharides or by cytokines

\- Binds to TLR1 and TLR4- sustain and prolongs inflammation

\-Stimulates secretion of inflammatory cytokines from macrophages, monocytes and neutrophils and endothelial cells.

Cytokine IL-33

\-Stored in the nucleus and released when cells die

\-Potent DAMP