Immune System

Part A

Lymphoid tissue- major component is lymphosytes

-        includes thymus, bone marrow, lymph nodes, and spleen

Lymphoid nodules- tonsils, appendix, Peyer’s patches, small lymphatic collections in the GI tract, respiratory, and urinary tracts

Embyrology- all derived from mesoderm except thymus (meso- and endo-)

FUNCTION- IMMUNE SURVEILLANCE and DEFENSE  (distinguiaton between self and non-self)

I.                 Lymphoid tissue and the immune response

A.     lymphatic tissue

1.     specialized form of connective tissue

2.     contains large numbers of lymphocytes

3.     supporting network- reticular cells and reticular fibers

B.     Lymphocytes (main component)

1.     T-lymphocytes (T-cells)

a.     mediate cellular immunity

b.     protects individual from MICROORGANISMS, TUMOR CELLS, AND VIRUSES

c.      Maturation- thymus

d.     Antigen contact®activated T-cells

e.     Three different types of T lymphocytes

1.Helper T cells

a.     assist B and T cells in carrying out an immune response

b.     PRIMARY FUNCTION- secrete lymphokines in response to foreign Ag

2.Suppressor T-cells

a.     suppress B-cell activity

3.Natural Killer cells (NK)

a.     10-15% of circ. Lymphocytes

b.     MAIN FUNCTION: kill virus infected cells and malignant cells

2.     B-Lymphocytes (B-cells, Plasma cell, and B memory cells derived from)

a.     mediate humoral immunity

b.     mature into plasma cells which secrete antibodies (Ab)

c.      Ab work to destroy or inactivate foreign antigens

d.     Maturation- UNCERTAIN; Bursa in Birds, may be bone marrow or gut related lymphoid tissue in humans

e.     When the come into contact with antigen (Ag)®B cells®Plasma Cells which secrete immunoglobulins(Ig)

f.       B memory cells PROGRAMMED to respond to 2nd exposure

3.     Both originate from stem cells present in the bone marrow

4.     Five classes of Ig- IgG, IgA, IgM, IgE, IgD

C.    Antigen presenting cells (APCs)

1.     responsible for antigen presentation to lymphocytes

2.     Mononuclear phagocyte system

3.     Derived from the bone marrow

4.     Ex. Macrophages, Langerhans cells, dendritic cells, epithelial cells of the thymus

II.               Circulation

A.     Lymphatic vessels

1.     begin as capillaries in loose conn. Tissue

2.     most numerous in skin and mucous membranes

3.     vessels MORE permeable than capillaries

B.     Lymph passes through various organs where the antigens in the lymph can come into contact with the lymphocytes, thus initiating an immune response.

1.     enter organ via AFFERENT, leave via EFFERENT (typically)

2.     Some Lymphocytes remain in the dependent areas of the organ

C.    Vessels empty into the thoracic duct®venous system (at junction of jugular and subclavian veins)®bloodstream

1.     come back into the lymphatic system via postcapillary venules in the lymph nodes

2.     Recirculation includes all organs but the thymus and the bone marrow

III.              Thymus

A.     Bi-lobed primary lymphoid organ

B.     Lies in the superior mediastinum

C.    MOST ACTIVE IN CHILDHOOD (bad things happen if removed when a child, not as debilitating a when removed from an adult)

D.    T CELLS ONLY!

E.     Capsule

1.     made up of thin loose connective tissue

2.     penetrates into the parenchyma thus forming the lobes

3.     contain blood vessels and EFFERENT vessels (NO AFFERENT!)

4.     nerves

F.     “Lymphoepithelial organ”- because of embryonin development from endoderm-derived epithelial reticular cells and lymphocytes

G.    Cortex

1.     Closely packed Pre-T-lymphocytes also called thymocytes (Immature)

a.     produced and accumulate in the cortex

b.     most die in the cortex

c.      enter medulla from cortex

2.     Epithelial reticular cells

a.     stellate appearance

b.     connected together by desmosomes at the end of long, cytoplasmic processes

3.     macrophages

4.     NO LYMPHOID NODULES OR FOLLICLES

H.    Medulla

1.     epithelial reticular cells

a.     Hassall’s corpuscles- flattened epithelial reticular cells which have degenerated; may have keratinization; concentric; varying size; UNKNOWN FUNCTION

2.     LARGE, immature T-lymphocytes

3.     Macrophages

I.       Blood-Thymus Barrier

1.     Arteries enter through the capsule, branch and follow the conn. Tissue septae into the organ.  These give off capillaries which drain into the venules of the MEDULLA

2.     Sheath of reticular epithelial cells surround small vessels in the CORTE

a.     Prevents antigens from entering the cortex and messing up the T-lymphocyte development

3.     NO LYMPH BECAUSE NO AFFERENT lymphatics

4.     Immature t-lymphocytes enter the circulation from the thymus via postcapillary venules

J.      Thymic function

1.     development of the T-lymphocytes

2.     growth factors for proliferation and differentiation (thought to be produced by reticular epithelial cells)

a.     Thymosin a

b.     Thymopoietin

c.      Thymolin

d.     Thymic humoral factor

3.     Macrophage phagocytize the non-differentiating thymocytes (Immature Ts in the cortex)

IV.             Lymph Nodes

A.     Round or kidney -shaped

B.     Distributed throughout body along vessels

C.    All lymph passes through at least one node before entering the circulatory system®AFFERENT AND EFFERENT

D.    Afferent enter along convex surface

E.     Efferent leave from concave depression termed the hilum

F.     Arteries enter and veins leave the node via the hilum as well

G.    Parenchyma

1.     diffuse and nodular lymphoid tissue

H.    Capsule

1.     dense connective tissue capsule

2.     sends conn. Tissue septae into the organ

I.       Cortex (inner and outer)

1.     AFFERENT lymphatic enter into the subcapular sinus located under the capsule

a.     this sinus connects to the medullary sinuses via cortical or paratrabecular sinuses

2.     Outer cortex

a.     primarily lymphoid nodules composed of B-lymphocytes along with macrophages, plasma cells, and reticular cells

J.      Follicles

1.     Primary follicles- aggregates of small B-lymphocytes

2.     Germinal center- changes the primary follicle into a secondary follicle

3.     Mantle zone- surrounds the germinal center

4.     Dendritic Reticulum Cells- found in the germinal center

a.     trap antigens on their surface

b.     present to B-lymphocytes

5.     B-lymphocytes in the germinal center are proliferating (may see mitotic figures)

6.     Tingible body macrophages

a.     also found in the germinal center

K.     Medulla

1.     composed of medullary cords of lymphatic tissue separated by medullary sinuses (contain lymph)

2.     Cords contain BOTH B & T lymphocytes, macrophages, plasma cells

3.     Place where plasma cells are formed®where Ab production takes place

L.     Circulation of Lymph

1.     AFFERENT Lymphatic vessels®Subcapsular sinus®cortical sinuses®medullary sinuses®EFFERENT Lymphatic vessels

2.     Lymphatic vessels- contain one way valves

M.    Function

1.     Filtering of lymph before circulatory system entrance

a.     Phagocytic cells- remove bacteria and foreign particles

b.     APCs- trap foreign antigens

2.     B-cells may recognize the antigen with or withour T-cell hel

a.     ACTIVATED B-Cells migrate into the germinal center and begin multiple itotic divisions to give rise to Ag-specific immature lymphoblasts

3.     B-Lymphocytes give rise to Memory B cells and Plasma Cells

a.     Plasma cells- secrete Ab in the Medullary cords

b.     Memory B Cells migrate and wait for spec. Ag

4.     T lymphocytes can become activated via low concentration of cytotoxic T lymphocytes in the body

5.     Enlarge due to localized antigenic response

Part B

I.                 Spleen

  • Upper right quadrant of abdomen
  • Site of destruction of aged or abnormal RBCs and platelets
  • defense against foreign microorganisms
  • Major Antibody production site

A.     General Organization

1.     Capsule- dense irregular

a.     trabeculae extend into parenchyma (also occurs at the hilum)

2.     Parenchyma- Splenic pulp (red and white)

3.     NO CORTEX OR MEDULLA

4.     Medial surface indented and houses the hilum

5.     Hilum- vessels and nerves pass in and out

6.     Lymphatic vessels present in only 2/3 of all spleens

7.     Support- reticular fibers

B.     Splenic Circulation

1.     Splenic artery- enters at hilum- branches into trabecular arteries(follow trabeculae)

2.     Trabecular arteries branch and eventually enter splenic pulp as central arteries

3.     Periarterial sheath- lymphocyte composed sheath that surrounds the central arteries

a. may form actual follicles

4.     Capillaries carry blood to the splenic sinusoids (not understood)

5.     Emptys from sinusoids®veins of red pulp®trabecular veins®splenic veins®hilum

C.    White Pulp

1.     diffuse lymphoid tissue- primarily lymphocytes

2.     deeply basilic(due to lymphocytes); when fresh-pale white or grey

3.     Periarterial Lymphatic Sheath

a.     parallels the course of the central arteries

b.     primarily T lymphocytes

c.      look for artery

4.     Lymphoid Nodules

a.     cheifly B lymphocytes

b.     germinal centers; mantle zones (B cells); marginal zones (B and T cells)

c.      Splenic nodules or Malpighian corpuscles

D.    Perifollicular zone

1.     interface between red and white

2.     consists of sinuses and loosely arranged B lymphocytes

3.     role- filtering of blood and initiation of immune response

4.     macrophages

5.     maturing plasma cells may be present which will enter the red

E.     Red Pulp

1.     Fresh- Red; also red histo. (due to massive amount of RBCs)

2.     Splenic cords

a.     also called Cords of Billroth

b.     reticular fiber meshwork containing reticular cells, lymphocytes, macrophages, RBCs, Plasma cells, and granulocytes

c.      Important immune function—plasma cells

3.     Splenic sinuses

a.     lined by special endothelial cells

b.     carry venous blood

c.      cells surrounded by thick rings of reticular fibers

d.     small spaces exist- allow things to pass through easily

e.     Macrophages- highly phagocytic; filter out damaged cells and foreign particles

II.               Tonsils

  • Lymphoid organs formed of INCOMPLETELY encapsulated aggregates of lymphoid nodules
  • Beneath the epithelium of the mouth and pharynx
  • DO NOT filter lymph

A.     Palatine Tonsils

1.     located in the lateral wall of the oropharynx

2.     Stratified squamous epithellium- form invaginations called crypts.

3.     Dense collections of lymphoid nodules; many germinal centers; single layer underneath the epithelium.

4.     Partially encapsulated at the basal surface

5.     Debris in the crypts can cause infection and inflammation (tonsillitis)

B.     Pharyngeal Tonsil (Adenoid)

1.     posterior nasopharynx

2.     atrophies with age

3.     ciliated, pseudostratified columnar epithelium (respiratory type)

4.     occasional patches of stratified squamous

5.     Usually NO CRYPTS

6.     Inflammation obstructs nasal breathing

C.    Lingual tonsils

1.     small, numerous aggregates of lymphoid nodules

2.     base of the tongue

3.     stratified squamous epithelium

4.     Each has a SINGLE crypt

V.               III. Unencapsulated Lymphoid tissue

  • lamina propria of gastrointestinal, upper respiratory, and urinary tracts
  • NO CAPSULE
  • Structure of the lymphoid follicle is same as in lymph nodes (primarily B lymphocytes®Plasma Cells)
  • MALT- Mucosa-Associated-Lymphoid-Tissue
  • GALT- Gut- ALP
  • BALT- Bronchial- ALP
  • The major antibody produced by the plasma cells is IgA, which is secreted onto the mucosal surface; protects against foreign antigens which enter the upper resp. or GI tracts; Prevents adherence of certain microbes and neutralizes bacterial toxins and viruses

Peyer’s Patches

A.     Diffuse lymphoid tissue

B.     Contains large aggregates of confluent lymphoid nodules which are present in the wall of the ileum

C.    Approx. 10-200 nodules

D.    Approx 30 patches in the adult

E.     Covered with epithelium composed of M CELLS(microfold)

1.     have numerous pits

2.     contain lymphocytes

3.     take up microorganisms and Foreign Ag and transport them to the underlying lymphocytes which then migrate to the lymph nodes and initiate an immune response

4.     GALT- produces secretory IgA as a first line of defense

Appendix

A.     small fingerlike blind projection off the cecum of the large intestine

B.     contains numerous lymphoid nudules in the mucosa and submucosa

C.    more in a later lecture

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