Lymphoid organs and system. lymphoid tissues (Primary lymphoid organs) Thymus, B.M., (in embryonic...

Lymphoid organs

and

system

• lymphoid tissues (Primary lymphoid organs) Thymus,

B.M., (in embryonic course comprise Yolk sac, Liver and spleen)

• lymphoid tissues (Secondary lymphoid organs)

Lymph nodes, Liver Spleen, Lymphocytes, NK, MONO, MQ, DCs, NEUT, EOS,…..

• Immune response sites (Tertiary lymphoid organs)

Any where that immune system fight with organisms

Lymphoid OrgansLymphoid Organs

Th, CD3+, CD4+

Tc, CD3+, CD8+

B , CD19+, CD20+

NK, CD16+, CD56+

MQ, CD14+

DC, CD11c+

Production of naïve (in mice 1-3 months) lymphocyte is under equilibration with lymphocyte death with apoptosis (homeostasis)

Self- renewing

T Cells 80% of circulating lymphocytes Some of the types:

Cytotoxic T cells: attack foreign cells or body cells infected by viruses (“cell-mediated immunity”)

Regulatory T cells: Helper T cells and suppressor T cells (control activation and activity of B cells)

Memory T cells: produced by the division of activated T cells following exposure to a particular antigen (remain on reserve, to be reactivated following later exposure to the same antigen) Memory T cells (CD44 high) CD45RO whereas

Naive T cell express CD45RA receptor.

B Cells 10-15% of circulating lymphocytes Can differentiate into plasmocytes (plasma cells)

when stimulated by exposure to an antigen Plasma cells produce antibodies: soluble proteins

which react with antigens, also known as immunoglobulins (Ig’s)

“Humoral immunity”, or antibody-mediated immunity Memory B cells: produced by the division of

activated B cells following exposure to a particular antigen (remain on reserve, to be reactivated following later exposure to the same antigen)

NK Cells

5-10% of circulating lymphocytes Attack foreign cells, normal cels infected with

viruses, cancer cells that appear in normal tissues

Known as “immunologic surveillance”

What are T cells?

Migrate from marrow and develop in thymus Have antigen receptors on PM =

immunocompetent Mitosis produces clones

Clonal deletion destroys self-reactive clones

Good at destroying cells and stimulating B cells They do NOT secrete antibodies

as B cells do T cell types movie

DC

DC

T cells (helper and cytotoxic) “feel” cells Check for MHC (hotdog bun)

MHC = major histocompatibility complex

MHC-I on all cells MHC-II only on APCs HLA (human leukocyte antigen)

group = MHC

Dendritic cells known as professional APC

• Lymph nodes• Spleen• Thymus• Peyer’s patches• Tonsils• Red Bone Marrow• Appendix

Lymph Organs:Lymph Organs:

Part of the immune system that consists of 2 independent parts:

1. meandering network of lymphatic vessels

2. various lymphoid tissues and organs  

Lymphatic system is located within loose connective tissue systems of the body

The Lymphatic The Lymphatic SystemSystem

Lymphatic System

Consists of three parts1. A network of lymphatic vessels (lymphatics)

2. Lymph - a fluid

3. Lymph nodes

Lymphatic Capillaries

Absent from teeth, bone marrow and the CNS (Brain lacks immune system generally)

Lacteals: specialized lymph capillaries present in intestinal mucosa Absorb digested fat and deliver fatty lymph (chyle)

to the blood

Lymphatic System One way system: to

the heart Return of collected

excess tissue fluid Return of leaked

protein “Lymph” is this fluid Edema results if

system blocked or surgically removed

Lymph capillaries Have one way minivalves allowing

excess fluid to enter but not leave Picks up bacteria and viruses as well as

proteins, electrolytes and fluid

(lymph nodes destroy most pathogens)

Dynamics of Capillary Exchange

Figure 20.2a

Cervical nodesEntrance of rightlymphatic duct into vein

Internal jugular vein

Entrance of thoracicduct into vein

Thoracic duct

Cisterna chyli

Lymphaticcollecting vessels

Axillary nodes

Aorta

Inguinal nodes

Regionallymph nodes:

(a) General distribution of lymphatic collecting vessels and regional lymph nodes.

Drained by the rightlymphatic ductDrained by thethoracic duct

arteriolearteriole

venulevenule

lymphatic capillarieslymphatic capillaries

blood capillaries

blood capillaries

lymphatic vessel

lymphatic vessel

Fig. 22.04

Systemic Circulation

HEV; High endothelia venule that present in Lymph node and Pier patches but not in spleen.

Formation of Lymph

interstitial fluid

blood capillary

lymphatic capillary

tissue cell

What does the lymphatic system do? Return interstitial fluid

Capillaries only reabsorb 15% Funneled into subclavian veins

Absorb and transport lipids from intestines

Generate and monitor immune responses

lymphatic system movie

Lymphatic System: Functions Returns interstitial fluid and leaked plasma

proteins back to the blood Once interstitial fluid enters lymphatics, it is called

lymph Together with lymphoid organs and tissues,

provide the structural basis of the immune system

Antigen concentration and focusing√

Lymphatic Capillaries

Similar to blood capillaries, except Very permeable (take up cell debris, pathogens,

and cancer cells) Endothelial cells overlap to form one-way

minivalves, and are anchored by collagen filaments, preventing collapse of capillaries

   Form a 1-way system in which lymph fluid flows only toward the heart

   Vessels are similar to capillaries, but very permeable.

   They occur everywhere blood capillaries occur.

Lymphatic Lymphatic vesselsvessels

Lymph Lymph TransportTransport

• lacks pump for circulation• relies on activity of skeletal muscles and pulsation of nearby arteries for movement of fluid• 3L of lymph enters blood stream every 24 hrs• proteins easily enter lymphatic system• uptake of large particles such as cell debris, pathogens, and cancer cellslymph nodes where it is cleansed of debris and examined by cells of the immune system.

Lymph node anatomy

(FDC)

Cytokine determined anatomical distribution of immune cells in L.N. and CCR7 helps DC and Lym and CXCR5 for Ln-B to transfer to lymph nods. Cell migration through HEV carried out in Cortex area. LT-B is important in lymph node formation.

What is in the lymphatic system? Lymph nodes

Filters lymph fluid for antigens, bacteria, etc. B-lymphocytes made here Some T-lymphocytes and

macrophages congregate Afferent (more) and efferent

(less) vessels lymph fluid exits through hilum

Common site for cancer—Why? Hodgkin’s lymphoma: lymph

node malignancy Etiology unknown

Non-Hodgkin’s lymphoma: all other cancers of lymphoid tissue Multiplication/metastasis of

lymphocytes 5th most common cancer

The Lymphatic system

Afferent lymphaticvessels

Efferent lymphaticvessels

CapsuleTrabeculae

Hilum

Cortex• Lymphoid follicle (B cell rich zone)

• Germinal center• Subcapsular sinus

Medulla:• Medullary cord• Medullary sinus

(a) Longitudinal view of the internal structure of a lymph node and associated lymphatics

lymphatic capillaries

blood capillaries

lymphatic vessels

lymphatic node

one-way valves

Figure 20.2a

Cervical nodesEntrance of rightlymphatic duct into vein

Internal jugular vein

Entrance of thoracicduct into vein

Thoracic duct

Cisterna chyli

Lymphaticcollecting vessels

Axillary nodes

Aorta

Inguinal nodes

Regionallymph nodes:

(a) General distribution of lymphatic collecting vessels and regional lymph nodes.

Drained by the rightlymphatic ductDrained by thethoracic duct

Fig. 22.03

After Antigen stimulation Flow rate to Lymph node increase more than 20 times.

Spleen

Largest lymphoid organ Served by splenic artery and vein, which enter and

exit at the hilus Functions

Site of lymphocyte proliferation and immune surveillance and response

Cleanses the blood of aged cells and platelets, foreign matter, bacteria, viruses and debris

Stores breakdown products of RBC e.g. iron

Erythrocyte production in fetus (normally ceases after birth)

Structure of the Spleen

Two distinct areas White pulp around central arteries Mostly lymphocytes on reticular fibers and

involved in immune functions Red pulp in venous sinuses and splenic cords

Rich in macrophages for disposal of worn-out RBCs and bloodborne pathogens

(b) Diagram of spleen histology

SplenicarterySplenicvein Hilum

(a) Diagram of the spleen, anterior view

White pulp; Adjacent to artery and contain PALS, Follicle and marginal zone

Red pulp; Adjucent to tiny venule and contain RBC, MQ, DC, Ln, and plasmacell.

Red pulp area contains MQ that deleted opsonized bacteria such as Meningococcal, Pneumonococci

ThymusThymusLocated: on top of heart• Secretes hormones thymosin and thymopoeitin• Causes T-lymphocytes to function against specific pathogens in the immune response (called immunocompetent) • Most active during youth; it in size during childhood, by old age, it's mostly been replaced by fibrous and fatty connective tissue

ThymusDiffers from other lymphoid organs in

important ways It functions strictly in T lymphocyte maturation It does not directly fight antigens

The stroma of the thymus consists of star-shaped epithelial cells (not reticular fibers)

These thymocytes provide the environment in which T lymphocytes become immunocompetent

Thymus

Thymic lobes contain an outer cortex and inner medulla

Cortex contains densely packed lymphocytes and scattered macrophages

Medulla contains fewer lymphocytes and thymic (Hassall’s) corpuscles involved in regulatory T cell development

Figure 20.7

Cortex

Medulla

Thymic (Hassall’s)corpuscle

Immune system in skin

Langerhans cells after antigen capture immigrate to derma area. IEL contain TCD8+ cells.

MALT Mucosa-associated lymphatic tissue,

including Peyer’s patches, tonsils, and the appendix

(digestive tract) Lymphoid nodules in the walls of the bronchi

(respiratory tract) Protects the digestive and respiratory

systems from foreign matter

Mucosal Immune system (Three compartment)

A B

C

In mice 50% and in human 10% of such T cells are γδCD8+

Most T cells in lamina properia are activated CD4+

Aggregates of Lymphoid Follicles

Peyer’s patches Clusters of lymphoid follicles In the wall of the distal portion of the small

intestine Similar structures are also found in the

appendixPeyer’s patches and the appendix

Destroy bacteria, preventing them from breaching the intestinal wall

Generate “memory” lymphocytes

TonsilsSimplest lymphoid organsForm a ring of lymphatic tissue around the

pharynx Palatine tonsils—at posterior end of the oral cavity Lingual tonsils—grouped at the base of the tongue Pharyngeal tonsil—in posterior wall of the

nasopharynx Tubal tonsils—surrounding the openings of the

auditory tubes into the pharynx

TonsilsTonsils

Prevent pathogens in respiratory tract and digestive tracts from penetrating mucous membrane lining. The nature of immune response in moth is differ and comprise high titer Antibody response and tolerance in T cell response.

Tonsils

Contain follicles with germinal centers Are not fully encapsulated Epithelial tissue overlying tonsil masses

invaginates, forming tonsillar crypts Crypts trap and destroy bacteria and

particulate matter

Figure 20.8

Tonsil

Tonsillar crypt

Germinal centersin lymphoid follicles

Pharyngeal tonsil

Palatine tonsilLingual tonsil

Lymphocyte recirculation:

Lymphocyte homing (for specific sub-population) is selective process for specific tissue not for else (Antigen dependent).

Migration of Naïve T cells is differ from effector and memory T cells .

Cell migration is under Adhesion molecule control (Three

molecular family, selectins, Integrins and super Igs) .

HEV; High endothelia venule that present in Lymph node and Pier patches but not in spleen

First and loose binding with Selectins and strong binding with Integrins.

Naïve T cell express L-selectin but Effector T cells more P and E selectin and CD44 and Expression of CCR-7 decreased in activated T cells.

Ln B express CXCR-5 for migration into Lymph nodes and after stimulation loss it and export from Follicle and migrate to T cell area and express integrins for migrations.

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