[DISCUSSION] MODULE 3 Flashcards
• Developmental history of
the immune system
during evolution
PHYLOGENY
• Development of the
immune system as a
comparative relation of
man and other animals
PHYLOGENY
→ most developed
and most complex
immune system
MAN
Man: most developed & most
complex immune system
EVIDENCES:
- Demonstrable hallmarks
- Well-developed immune system organs
- Cells are highly specialized
- Well developed complement system
- Separate function of humoral and cellular
immunity - Ability to reject graft and mount the
response is reasonably developed at birth
• Developmental history of
the immune system
within a species
ONTOGENY OF THE IMMUNE SYSTEM
FUNCTIONS OF LYMPHOID TISSUES
- To provide an environment for the
maturation of the immune system’s
immature cells
2.To concentrate lymphocytes into organs
that drain areas of antigen insult
3.To permit the interaction of different
classes of lymphocytes
4.To provide an efficient vehicle for the
disbursement of antibodies and other
soluble factors from lymphocytes and
other immune cells.
– A tissue in which lymphocytes are found
LYMPHOID TISSUE
– Diffuse arrangements of individual cells to encapsulated organs
LYMPHOID TISSUE
– Organized cylindrical clusters of lymphocytes
LYMPHOID FOLLICLES
Organized cylindrical clusters of lymphocytes that, when gathered into groups, are called
lymphoid patches
– Usually groups of follicles that are surrounded or encapsulated by specialized supporting tissues and membranes
LYMPHOID ORGANS
Lymphocytes develop central tolerance is establised
Primary Lymphoid Tissues
All lymphocytes arise from HSCs in the bone marrow and B cells mature in this site
Primary Lymphoid Tissues
T cells migrate from the bone marrow to the thymus and mature in this site
-Bone marrow
-Thymus
Thymus
T
lymphocytes
(%)
B lymphocytes
(%)
100
0
Blood
T
lymphocytes
(%)
B lymphocytes
(%)
80
20
Lymp nodes
T
lymphocytes
(%)
B lymphocytes
(%)
60
40
Spleen
T
lymphocytes
(%)
B lymphocytes
(%)
45
55
Bone marrow
T
lymphocytes
(%)
B lymphocytes
(%)
20
90
• the primary site of
hematopoiesis in the
adult human.
BONE MARROW
BONE MARROW
– about (?)% myeloid
lineage cells
60–70
BONE MARROW
– (?)% erythroid lineage
cells
20–30
BONE MARROW
– (?)% lymphoid lineage cell
10
BONE MARROW
– remainder consisting of
(1) plus
various other (?)
such as stromal cells and
adipocytes
- mast lineage cells
- non-hematopoietic cell types
• Where immature T cells
complete their development.
THYMUS
• Sites for antigen-driven immune cells
SECONDARY LYMPHOID TISSUES/ORGANS
• Antigen-dependent lymphocyte
differentiation occurs
SECONDARY LYMPHOID TISSUES/ORGANS
• Major site for the interaction of lymphocytes with antigen during a primary adaptive response
Lymph nodes
• Occur along the entire length of lymphatic system
but are clustered in a few key regions
Lymph nodes
• Bean-shaped, encapsulated structures 2- 10 mm in diameter
Lymph nodes
• Contain large numbers of lymphocytes, FDCs and
APCs
Lymph nodes
– Contains large numbers of resting B cells,
FDCs and macrophages arranged in lymphoid
follicles
Cortex
– Home to many T cells and thymic DCs
Paracortex
• Antibody-secreting plasma cells
Medulla
• Most antigens escaping
the innate immune response, (?) make their way into the tissues, are collected in the lymphatic system and are channeled into local lymph nodes.
MALT and
SALT
• Most antigens escaping
the innate immune response, MALT and
SALT make their way into the tissues, are collected in the (?) and are channeled into local lymph nodes.
lymphatic system
• Most antigens escaping
the innate immune response, MALT and
SALT make their way into the tissues, are collected in the lymphatic system and are channeled into (?).
local lymph nodes
SEVERAL WAYS BY WHICH AN
ANTIGEN CAN ACCESS THE
BLOOD CIRCULATION:
- Directly into the blood (e.g.,
drug injection, insect/snake
bites). - Overwhelming local infection
can result in penetration of
underlying blood vessels by
the pathogen. - Systemic infection contained
by the lymph nodes pours into
the efferent lymph, and
eventually dumped into the
blood.
• Abdominal organ that traps blood-borne
antigens
Spleen
• Entire blood volume of the adult courses
through the spleen 4x daily
Spleen
• Each arteriole in the spleen is encased by a
PERIARTERIOLAR LYMPHOID SHEATH (PALS)
Spleen
– Cylindrical arrangement of tissue
PERIARTERIOLAR LYMPHOID SHEATH (PALS)
– Populated mainly by mature T cells
PERIARTERIOLAR LYMPHOID SHEATH (PALS)
– Containing low numbers of plasma cells,
macrophages and conventional DCs
PERIARTERIOLAR LYMPHOID SHEATH (PALS)
Spleen
• Tissue surrounding the PALS contains:
– Lymphoid follicles
– Surrounding the follicles is the:
– MARGINAL ZONE
• Resting B cells and macrophages
Lymphoid follicles
• Contains particular B cell subsets
MARGINAL ZONE
– Contain splenic arterioles with their PALS, the follicles and the marginal zone
WHITE PULP
– Abundant erythrocytes
RED PULP
– Consists of splenic cords and venous sinuses and surrounds the white pulp
RED PULP
FUNCTION OF THE RED PULP:
– Filtering of particulate material from the blood
– Disposal of senescent or defective erythrocytes
and leukocytes
MALT (Mucosa-associated lymphoid
tissues)
– NALT (Nasopharynx-associated lymphoid tissue)
– BALT (Bronchi-associated lymphoid tissue)
– GALT ( Gut-associated lymphoid tissue)
• Tonsils
NALT (Nasopharynx-associated lymphoid tissue)
• Peyer’s patches
• Appendix
GALT ( Gut-associated lymphoid tissue)
LYMPHOID TISSUE ORGANIZATION
-Diffuse lymphocytes
-Follicle
-Patch
-Organ
Primary and Secondary Lymphoid
Tissues
-BALT
-NALT
-GALT
-SALT
-Thymus
-Bone marrow
-Lymp node
LYMPH NODE
-Afferent lymphatic vessels
-Cortex
-Paracortex
-Medulla
-Lymphoid follicle
-Capsule
-Subcapsular sinus
-Efferent lymphatic vessel
SPLEEEEEEEEEENNNNN!!!
-Lymphoid follicles
-Arteriole
-Marginal zone
-PALS
-Capsule
-Trabeculae
-Hilus
-Efferent lymphatic vessel
Components of NALT and BALT
-Ciliated epithlial cell
-Mucus
-Commensal organisms
-Nose hairs
-Lingual tonsil
-Palatine tonsil
-Goblet cell
-M cell
-Trachea
-lambda gamma T cell
-Esophagus
-Submucosal gland
-Bronchus
-Pharyngeal tonsil
-Plasma cell
-alpha beta T cell
-Macrophage
-Interfollicular region
-Follicle
-Immature DC
• With the SALT, protect the body at all surfaces that interfere with the external environment
MALT (Mucosa-associated lymphoid
tissues)
• Populations of mature T & B lymphocytes, DCs, NK and macrophages
MALT (Mucosa-associated lymphoid
tissues)
• Comprises small populations of leukocytes in
the epidermis and dermis
SALT (Skin-associated lymphoid tissues)
• EPIDERMIS → (?)
Langerhans cells
• DERMIS →(?)
T cells, dermal DCs, macrophages
– Entire network of vessels and ducts that
collects and channels the lymph and its
contents throughout the body
Lymphatic system
– Connected to the blood circulation
Lymphatic system
• (?) empties the lymph into the right subclavian vein
Right lymphatic duct
• (?) connects with the left subclavian
vein
Thoracic duct
LYMPHATIC SYSTEM
-Right lymphatic duct
-Right subclavian vein
-Lymphatic vessels of mammary gland
-Cistema chyli
-Lymphatic vessels of lower limb
-Cervical lymph nodes
-Thoracic duct (left lymphatic duct)
-Lymphatic vessels of upper limb
-Left subclavian vein
-Axiliary lymph nodes
-Intestinal and mesenteric lymph nodes
-Abdominal lymph nodes
-Inguinal lymph nodes
-Popliteal lymph nodes
• function in cell-mediated immunity
T CELLS
T CELLS
• function in cell-mediated immunity:
– delayed hypersensitivity
– graft rejection
– graft-versus-host reactions
– defense against intracellular organisms (such as
tubercle bacillus and Brucella)
– defense against neoplasms
• majority of circulating lymphocytes are (?) that have a life span of months to years
T cells
• Perform in humoral immunity
B CELLS (and their progeny)
• minor population (10%–20% of the
lymphocytes)
B CELLS (and their progeny)
• probably have a short life span measured in days (with the exception of memory B cells)
B CELLS (and their progeny)
• distinguished by the presence of
considerable Ig on their surface membranes
B CELLS (and their progeny)
• Markers to differentiate T cells and B cells
SURFACE MARKERS ON
LYMPHOCYTES
• Distinguish the developmental stages of the 2 types of cells
SURFACE MARKERS ON
LYMPHOCYTES
• Detected by monoclonal antibodies
SURFACE MARKERS ON
LYMPHOCYTES
• CLUSTER OF DIFFERENTIATION
– Numerical designation
– Reference in standardizing names of membrane
proteins found on all wbcs
– Currently numbers more than 350
– Human Cell Differentiation Molecules (Dec.
2004)
B CELL DEVELOPMENT
TWO PHASES:
- Maturation phase
- Differentiation phase
– Hematopoietic stem cell (HSC) divides and eventually generates mature naïve B cells
Maturation phase
– Antigen independent
Maturation phase
– Begins in the bone marrow
Maturation phase
– Ends with mature naïve B cells taking up
residency in the secondary lymphoid tissues
Maturation phase
(?) divides and
eventually generates mature naïve B cells
Hematopoietic stem cell (HSC)
Maturation phase
– MAJOR DEVELOPMENTAL STAGES:
• HSC → MPP → CLP → Pro-B cell → Pre-B cell →
Immature naïve B cell → Transitional B cell →
Mature naïve B cell
/MFECh
Differentiation phase
Two stages:
a. Activation of a mature B cell by its
specific antigen
b. Generation of antigen-specific plasma cells and memory B cells
(?) → recognized by the presence of a surface molecule called CD45R
Earliest B cell precursor
(?) → first hematopoietic cells clearly recognizable as being of the B cell lineage
Early pro-B cells
• Identified by their expression of certain B lineage markers and their Ig genes are still in the germline configuration
PRO-B CELLS (Progenitor B cells)
(?) have yet to undergo V(D)J
recombination
Igh, Igk, Igl loci