Download lymph nodes - Molecular Immunology

Innate and Adaptive Immunity
Types of
Adaptive
Immunity
Lecture 2
Cells and Tissues
of the Immune
System
OVERVIEW OF THE IMMUNE SYSTEM
Cells: lymphocytes, macrophages & monocytes, dendritic
cells, granulocytes. All arise from pluripotent
hematopoietic stem cells in bone marrow.
Organs: lymph nodes (found in various locations), thymus,
spleen - these constitute the lymphoid organs
Thymus and bursa (bone marrow) are called central
lymphoid organs
Peripheral Lymphoid Organs: Except lymph nodes,
spleen, and tonsils, liver, intestine and skin are also
are also important parts of the immune system.
Hematopoiesis
Pluripotent
Lymphocytes
Lymphocytes
• B Cells
• T Cells
• NK Cells
Origin of T Cells
Jacques Miller found that removal of thymus (thymectomy) from
neonatal mice resulted in fewer lymphocytes and no antibody to
sheep red blood cells (1962). Later on, in thymectomized animals,
the ability to reject allografts and to mount delayed
hypersensitivity responses was drastically reduced.
By the mid-1960s, immunologists were convinced that there were
indeed two separate arms of the immune system: one dealing
exclusively with the production of circulating antibodies (humoral
immunity), and another that is involved in the delayed
hypersensitivity-type reactions and graft rejections (cell-mediated
immunity). To have a good immune response, both have to exist.
Classes of Lymphocytes
Null Cells (NK Cells)
• Do Not Express Classical Lymphocyte
Markers
• Predominantly NK Cells (CD56)
• Eliminate Tumor Cells and Virally
Infected Cells
• Express Low Affinity FcRIII (CD16)
• Using CD16 They Can Carry Out ADCC
• Reduction of MHC I Can Activate Them
A T Cell ?
A B Cell?
Immune Cells Can Be Analyzed by Flow Cytometry
Phenotypic Markers to Distinguish
Lymphocyte Subsets
B Cell
CD19+
T Helper
CD4+
T Cytotoxic
CD8+
Phases of
Lymphocyte
Activation
Naive
Activated
Effector
T vs B Cells
T cells
Ag receptor
TCR related to Ig
but not Ig
Ag recognition
in context of MHC
on APC or accessory cells
Functional
Th (helper) and
subsets Tc (cytolytic)
B cells
BCR is membrane-bound Ig
(plus accessory molecules)
can recognize Ag alone
subsets of B cells only
subtly different in function
Secrete
Cytokines
Ig (as Ab) and cytokines
When
activated
Become (proliferating)
lymphoblasts
Become lymphoblasts, then
become plasma cells
Accessory Cells
• Mononuclear Phagocytes
– Monocytes and Macrophages
• Dendritic Cells
Monocytes and
Macrophages
• Functions
– Phagocytosis
– Antigen processing and
presentation (APCs)
– Activation of T cells
Origin and Development of
Macrophages
MONOCYTES AND MACROPHAGES
Monocytes are immature macrophages; monos circulate in blood & accumulate at sites of inflammation. Macrophages may differentiate in tissue in
absence of antigen (Kupffer cells in liver, e.g.) or differentiate in response to
inflammation. They are Ag-presenting cells (APC). Also phagocytose
microbes; contain bacteriocidal mechanisms.
•mono in blood smear
•Wright-Giemsa
macrophage in tissue, H&E
stain
Monocyte
Activated Mac
MONOS AND MACS CONTINUED
*Express CD14, a receptor for a wide variety of bacterial envelope molecules: LPS,
components of bacterial cell walls. Ligation of CD14 leads to macrophage
activation.
*Are activated by T cell derived cytokines such as interferons: leading to increased
phagocytosis and microbicidal activity (increased activity of degradative enzymes,
nitrogen and oxygen free radical production and prostaglandins etc.).
*Express receptors for Ab (FcR) and complement.
*Act as scavengers for apoptotic cells, cell debris and senescent cells (e.g., Kupffer
cells in the liver bind "old" erythrocytes).
Dendritic Cells
• Transport Antigens to L. nodes
• Initiation of T Cell Responses
Dendritic Cell Subsets
Follicular DCs
• Do Not Express MHC II Molecules
• Found in Lymph Follicles (Rich in B
Cell)
• Express FcR For Antibodies and
Complement
• Ag-Ab Complex Shown To Last
Very Long (weeks to months)
(Myeloid DC)
Granulocytes
Neutrophil
Eosinophil
Basophil
Lymphoid Organs
• Primary (Generative)
Lymphoid Organs
– maturation site of
lymphoid cells
– bone marrow, bursa of
Fabricius, thymus,
• Secondary Lymphoid
Organs
– efficient at trapping and
concentrating foreign
substances
– site of Ag-driven
proliferation and
differentiation; e.g. Ab
production
– spleen, lymph nodes,
diffuse tissues, payers
patch, tonsils
Organs Of Immune System
• Primary Lymphoid Organs
– Bone Marrow and Thymus
– Maturation Site
• Secondary Lymphoid Organs
– Spleen, lymph nodes,
– MALT (mucosal associated lymph tissue)
– GALT (gut associated lymph tissue)
– Trap antigen, APC, Lymphocyte
Proliferation
ORGANS OF THE IMMUNE SYSTEM
PRIMARY LYMPHOID ORGANS
Primary lymphoid organs are where lymphocytes arise and mature in the
absence of antigenic stimuli. They are the bone marrow and thymus.
Bone marrow: Source of all hematopoietic progenitor (stem) cells, site of B cell
maturation post-birth in mammals.
About 1 in every 10,000 to 15,000 bone marrow cells
is thought to be a stem cell.
In the blood stream 1 in 100,000 blood cells.
Chicken Bursa
PRIMARY LYMPHOID ORGANS: THYMUS
Thymic epithelial cells are derived from the third pharyngeal pouch.
The thymus is the site where T cells develop.
It gradually enlarges during childhood but after puberty it undergoes a process of involution.
The thymus is arranged into an outer cortex and an inner medulla. Immature lymphoid cells in the
cortex. Mature T cells are in the medulla from where mature T lymphocytes enter the circulation.
SECONDARY LYMPHOID ORGANS
Peripheral lymphoid organs: lymph
nodes, spleen, tonsils, adenoids, and
lymphoid tissue associated with other
organ systems (gut, skin, mucosa).
LYMPH NODES: filter lymphatic fluid; sites
of Ag presentation & cell traffic
LYMPH NODES
Lymph nodes have a fibrous capsule from which trabeculae
extend towards the center, forming a framework for the
lymphatic parenchyma (cortex, paracortex, and medulla).
1 - cortex (B Cells) 2 - paracortical zone (T Cells)
3 – medulla(T, B, Mac) 4 - medullary cords
5 - lymphoid follicle of the cortex
6 - capsule
7 - subcapsular sinus
8 - cortical sinus 9 - medullary sinus
LYMPH NODES, CONTINUED
Functions of structural elements of lymph nodes
Lymph  afferent lymphatics,
sinuses lined with macrophages 
efferent lymphatic (ultimately all
drain into the portal vein).
Lymphocytes enter the node
primarily from the blood via HEV 
efferent lymphatics.
DCs migrating from tissue enter the
node into the T cell areas.
B cells entering nodes from blood
must cross the T rich area in transit to
the B cell rich areas thus optimizing
T-B cooperation.
Subcapsular
Sinus
LYMPH NODES, CONTINUED
SPLEEN
Stained with haematoxylin and eosin
1 - lymphoid follicle (white pulp)
2 - red pulp
3 - capsule
4 - trabeculae (connective tissue)
The spleen serves two major functions:
*It is responsible for the destruction of old red blood cells (RBCs) - this
occurs in the red pulp;
*It is a major site for mounting the immune response - the white pulp.
The spleen behaves like a lymph node, but instead of filtering lymph, it
filters blood.
Has the hematopoiesis function in mice.
INSIDE THE SPLEEN
White pulp
Red pulp
Mouse splenic CD3 expression
inperiarteriolar lymphocyte sheath of white
pulp and in scattered cells in red pulp.
MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT)
Lymphoid tissue found at the gastrointestinal tract, respiratory tract and
urogenital tract.
MALT consists of aggregates of lymphocytes, macrophages, DCs, and other
accessory cells.
GUT-ASSOCIATED LYMPHOID TISSUE (GALT)
This is comprised of:
* tonsils, adenoids (Waldeyer's ring)
* Peyer's patches
* lymphoid aggregates in the appendix and large intestine
* lymphoid tissue accumulating with age in the stomach
* diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut
SKIN-ASSOCIATED LYMPHOID TISSUE (SALT)
Skin is
an active participant in host defense.
It has the capability to generate and
support local immune and inflammatory
responses to foreign Ags that enter the
body via the skin.
Cells of SALT include keratinocytes,
Langerhans cells (immature DCs found in
skin), intraepiethelial T cells, and
melanocytes.
Langerhans cells form a continuous
epidermal meshwork: they capture Ag,
then migrate to draining lymph nodes,
where they act as Ag-presenting cells.
(T Cell Progenitors)
Effect of Thymectomy?
Site of T Cell Maturation
Effect of Thymectomy in
Adult
Circulation of Naïve and Activated/Memory
T Lymphocytes
Activated/Memory
Lymphocyte Circulation in pig?