HCB Objectives 21

Note: T and B cell distribution in:
o MALT: T cells in mantle, B cells in germinal centers
o Lymph nodes: T cells in inner cortex, B cells in both mantle and
germinal centers of outer cortical lymphoid follicles
o Spleen: T cells in PALS surrounding central artery, B cells in
germinal centers
1.
Lymphocyte function: Lymphocytes are the main effector cells of the immune
system. Their function is to provide immunity in two different ways:
a. Humoral immunity: B lymphocytes which can differentiate into plasma cells
and release antibody into blood plasma
b. Cell-mediated immunity:
a. Helper T (CD4): organize an immune response by recruiting CD8 and
plasma B cells to site of infection via cytokines
b. Killer T (CD8): destroy infected cells/tumor cells
c. Suppressor T (CD8): suppress immune response
Accessory cell function: see blood lecture (objectives #8)
Function of IgA antibodies: the main antibody protecting mucosal surfaces
Function of IgG antibodies: the main antibody clearing antigens in deeper tissue
(if they penetrate past mucosal lining and IgA antibodies)
 Note: The other three antibodies:
o IgM antibodies are primary, naïve responses of virgin B cells
before they reach germinal centers of secondary lymphoid organs
o IgD antibodies are involved in B cell differentiation
o IgE antibodies are involved in parasitic infection and allergy
2.
IgA/IgM production/transport into saliva: produced by plasma cells in the
underlying connective tissue and transported into the epithelium via receptormediated transepithelial transport. Transepithelial transport is accomplished due
to the polymeric nature of IgA and IgM; they are recognized by poly-Ig receptors
which transport the antibody to the apical surface where they can be cleaved
(along with part of the receptor (secretory component) to prevent proteolysis) and
released into mucosal secretions.
3.
Lymphocyte pathway between blood and tissues: Lymphocytes originate in
the bone marrow (T cells will mature in the thymus) and will move to secondary
lymphoid organs before entering the bloodstream. They leave the bloodstream
via post-capillary venules and are recirculated into the bloodstream via the
lymphatic system. They are the ONLY white blood cell that will recirculate into
the bloodstream after entering the tissue.
White blood cell pathway between blood and tissues:
In general, all white blood cells except for lymphocytes enter into the lymphoid
organs from bone marrow and are sent into target tissues via post-capillary
venules where they will function and die
a. Macrophages: Macrophages start as monocytes in the bloodstream and
mature into macrophages when they enter tissue. They will either die in the
tissue after several months or enter the lymphatic system and live in lymph
nodes as antigen presenting cells
b. Eosinophils/neutrophils: These cells will leave the bloodstream and live in
the tissue for hours to days before dying
4.
Cells/mechanisms of immune protection for mucosal surfaces:
a.
IgA Antibodies: distributed into the lumen to cross-link pathogens or bind
pathogens and mucus promoting clearance of pathogen via mucus
secretion
 Note: antibodies in germinal centers undergo somatic hypermutation
whereby antibodies have high rate of point mutation causing
antibodies to improve their binding to an antigen
b.
Langerhans cells: cells in stratified squamous epithelia which sample
pathogens and deliver them to lymphoid follicles via lymphatic capillaries
c.
M cells: found in all follicle associated epithelium, M cells are specialized
epithelial cells that allow for transport of antigens across its surface. Once
antigens cross the surface, they are met by macrophages which can then
present antigen to lymphocytes
5.
Lymphoid follicles:
 Function: function as a secondary lymphoid organ, and thus, as an area of
immune response
 Structure: lymphocytes enter through high endothelial vessels, and drain
back into the bloodstream via lymphatic capillaries. Lymphoid follicles
are composed of an outer mantle and an inner germinal center (where B
cells are located).
Thymic lobules:
 Function: function as a primary lymphoid organ for T cell maturation,
and thus, are not involved in the immune response
 Structure: lobulated organ composed of a cortex and a medulla; cortex
has macrophages (for maturation purposes; destruction of self-attacking T
cells), thymocytes (pre-T lymphocytes), and epithelial reticular cells
(creates blood-thymus barrier to segregate foreign material from T cell
development). The medulla is the area where T cells enter the
bloodstream and has Hassall’s corpuscles (keratinized epithelial cells) that
are only found in the thymus
6.
Lymph nodes as filters of lymph: Lymph enters through afferent lymphatics
and flows through subcapsular sinuses. From the subcapsular sinuses surrounding
the node, the lymph flows through trabecular sinuses into the medulla of the
lymph node. The lymph then drains into the medullary sinuses (surrounded by
medullary cords of cortical material containing B and T lymphocytes as well as
macrophages and plasma cells) and leaves through the hilus in an efferent
lymphatic.
Spleen as filter of blood: Blood enters the spleen via the splenic artery and is
passed into the white pulp via trabecular arteries that dump into central arteries in
the white pulp. In the white pulp, lymphoid follicles and periarterial lymphatic
sheaths (PALS) generate immune an immune response to any pathogens. Blood
is spilled into spleen parenchyma via penicillar arterioles, and is picked up by
splenic sinusoids. The openings into splenic sinusoids are small and thus,
damaged or old RBCs will not be able to enter into them (splenic cords surround
the splenic sinusoids and contain macrophages which can present antigens to the
white pulp for an immune response). Healthy cells are allowed into the splenic
sinusoids and are sent through the pulp vein to the trabecular vein, and ultimately
leave the spleen via the splenic vein.
7.
Pathway for lymphocyte entry/exit from lymphoid tissue:
a.
Lymphocyte entry:
a.
MALT: lymphocytes enter via high endothelial venules
b.
Lymph nodes: lymphocytes enter via high endothelial venules into
lymphatic afferents
c.
Spleen: lymphocytes enter via penicillar arterioles
d.
Thymus: lymphocytes enter via high endothelial venules into the
outermost cortex
 Note: High endothelial venules are cuboidal vessels that
express receptor promoting lymphocyte entry into the tissue
b.
Lymphocyte exit:
a.
MALT: lymphocytes exit via lymphatic capillaries
b.
Lymph nodes: lymphocytes exit via lymphatic efferents
c.
Spleen: lymphocytes leave via lymphatic capillaries
d.
Thymus: lymphocytes leave via lymphatic capillaries