Cells, Tissues, & Organs of

The Immune System

 Key concepts about immune cells

1. The principle cells of the immune system:

Antigen-presenting cells Lymphocytes => Effector cells

2. All immune cells are derived from Hematopoietic stem cells

in Bone Marrow (BM) (& Fetal liver during fetus).

3. Immune cells are divided into two major lineages:

=> Lymphoid & Myeloid
=> Multiple cell types => express distinct Surface molecules
(markers) => Classification

4. Development and differentiation of different cell types

depend on Cell Interactions and Cytokines.
Cells of the Immune System
All cells in the immune
system are derived from
stem cells and either
myeloid or lymphoid
precursors under the
control of cytokines
 Cells of innate immunity-I

1. Innate immune cells are derived from Bone Marrow.

2. Their primary function is to identify and kill microbes.

Antigen-presenting cells (APCs) additionally function
to present Ag to and activate lymphocytes.

3. Innate immune cells recognize the common microbial

structures PAMPs through Pattern-Recognition
Receptors (PRRs) -limited diversity.
Classes of innate
immune cells
Innate immune cells are
classified as following:
- Monocyte/Macrophage
- Dendritic cell (DC)

- Polymorphonuclear
granulocyte (PMN;
Neutrophil, Eosinophil,
Basophil)
- Mast cell
- NK cells (lymphocyte)
=> Killing virus-infected
cells & tumors
 Antigen presenting cells (APC)
1. Dendritic cells (DC): powerful in antigen processing
and presentation.
2. Macrophage: powerful in antigen processing and
destruction, but low in antigen presentation.
 Key concepts of Dendritic
Cells (DCs)
1. Most effective Ag-presenting cells linking innate and
adaptive immunity

2. High MHC-II expression on DCs

3. Several types of DCs:

(1) Myeloid DCs (also known as conventional DCs)
(2) Lymphoid DCs => Plasmacytoid DCs
(3) Lymphoid organ-specific DCs:
Follicular DCs in Lymph nodes (lacking MHC-II)
Interdigitating Dcs in Lymph nodes & Thymus
Dendritic cells (DCs) as Ag-presenting
cells (APCs)

FDC:Follicular DC
 Key concepts of
Monocytes/Macrophages
1. Relatively long-lived and distributed throughout the
whole body.

2. Engulf and kill pathogens by phagocytosis.

3. Express various receptors to recognize different

pathogens, e.g. PRR, Scavenger receptor,.etc.

4. Trigger inflammation and Antigen presentation

Maturation of Macrophages

Activated Macro
Monocytes are quiescent precursors
to macrophages and are found in all
tissues in the body. On activation by
invading pathogens, cytokines etc.,
monocytes differentiate into
macrophages (an angry monocyte)
that can phagocytose pathogens and
present antigen to T cells to engage
the adaptive immune response
 NEUTROPHILS (PMNs)
60% of leukocytes (white blood cells)
Have receptor for Fc region of IgG & C3b
Release Matrix Metalloproteinase (MMP)
First to arrive in acute inflammation, actively
killing bacteria, by generation of Hydrogen
peroxide & Oxygen free radicals releasing LPS.
Cytoplasm contain Lysosomal Peroxidase + Acid
Hydrolases
Cytoplasmic granules contain digestive enzyme
(Myeloperoxidase) & Lactoferrin (binds Fe)
 GRANULOCYTES
NEUTROPHIL SUMMARY
Kill microbes by:
Toxic Oxygen molecule

Digestive Enzymes stored within Lysosomal

granules
EOSIONPHILS (1 3% of leukocytes)
Have receptors for Complement
Bi-lobed nucleus + red granules (Giemsa stain)
Chemotactic factors for Eosinopkils:
Histamine C5a LTB4 PAF
ECF-A (anaphylaxis)
Mostly in parasitic(*MBP)& allergic conditions
Contents & Functions: Histaminase
Pyrogen (fever) Peroxidase (kill bacteria)
Aryl sulfatase (degrade LT) *Major Basic Protein
 EOSIONPHILS

CLINICAL CORRELATION
Classically seen with:
Atopic allergies
Worm infections
Collagen Vascualr diseases
Neoplastic disorders
Skin rash
Granules (histaminase, arylsulfatase) help control
allergic reactions
Neutrophils, mast cells
basophils and eosinophils
are important
granulocytic cells involved
in phagocytosis or release
of innate immune
inflammatory mediators
Neutrophils, normally found in
circulation, migrate out of blood
vessels to sites of infection in effort to
phagocytose invading bacteria
 BASOPHILS (1% of
leukocytes) (smallest)
Contain much granules with:
RNA Mucopolysaccharide
Histamine
(hypersensitivity
madiator)
Have receptors for Fc portion
of IgE
IgE binding degranulation
Histamine
allergic reactions
Mast cells release histamine,
cytokines and other
inflammatory mediators when
IgE bound to the surface of the
cell is crosslinked by an allergen
 Cells of Adaptive immunity
1. Lymphocytes are the key players of the adaptive
immunity.

2. Lymphocytes are able to specifically recognize and

respond to diverse antigens.
=> Antigen (Ag) receptors on lymphocytes
=> Specificity (Clone), Diversity (Repertoire: total number of
Ag-specific lymphocytes in an individual; 107-9), & Memory

3. Lymphocytes are classified into three major groups:

- B cells => Antibodies => Humoral immunity
- T cells => Multiple subtypes => Cell-mediated immunity &
Regulate other immune cells
- NK cells => Innate immunity
Classes of
Lymphocytes
1. B cells => Plasma cells
=> Abs
2. T cells:
- T helper cells
- T cytotoxic cells
- T regulatory cells
=> suppress immune
responses
3. NK cells
4. Subtypes in each class
 LYMPHOCYTES (30% of circulating WBC)
B Lymphocytes:

Differentiate into Plasma cells Antibodies

CDb5-positive IgM
CDb5-negative IgG, IgA, IgE
Memory B cells:generated after exposure to Ag
Mature B cell: have surface IgM & IgD that
bind Ag cause B cell Ab
B cell respond to:
T-cell-independent Ag Ig without CD4 cells
T-cell dependent Ag regulate T-cells B cell Ab
 T LYMPHOCYTES
Helper T cells (CD4 positive)
Stimulate B-Lymphocytes Plasma cell Ab
Promote cytotoxic T- cell (CD8) response
Activation due to recognition of Class 11
MHC on Antigen-presenting cells
Produce Lymphokines, Differentiation
Factors, Inflammatory Cytokines (IL-2)
Cytotoxic T cell (CD 8 +)
Recognize Foreign Ag & Class 1 MHC
Lyse virus infected cells & tumor cells
 Natural killer (NK) cells
Also known as large granular lymphocytes (LGL) (10 -15%
of Lymphocytes)
Kill Tumor cells, Defend against Viral infections
Identified by the CD56+/CD16+/CD3-
Recognize Foreign Ag independent of MHC
Mediate Ab-dependent cellular toxicity (ADCC)
Kill Opsonized or Ab-coated cells
Activated by IL-2 and IFN- to become LAK cells
 Anatomy & Functions of Lymphoid Tissues
& Organs
 Organs Of Immune System
Primary Lymphoid Organs
Bone Marrow and Thymus
Maturation Site
Secondary Lymphoid Organs
Spleen, lymph nodes,
MALT (mucosal associated lymph tissue)
Waldeyers Ring: Lingual Tonsil + Soft Palate
LNS + Tonsils + Adenoids
GALT (gut associated lymph tissue)
Peyers patch
Trap antigen, APC, Lymphocyte Proliferation
Primary lymphoid organs:
BM & Thymus
=> Lymphocyte
development, selection,
& maturation.

2nd lymphoid organs:

Lymphoid nodes & Spleen
=> Lymphocyte
activation & effector
functions

BM
Other immune cells
Eg. DCs, Macrophages,
PMNs
The Lymphatic
System

Link to the blood

circulation system
 Thymus

Bilobed Organ on Top of Heart

Reaches Max. Size During Puberty
70g infants, 3 g in adults
95-99% Of T Cells Die in Thymus
self reactivity or no reactivity to Ag
Consists of Cortex and Medulla
Rat Thymocytes Sensitive to Glucorticoids
 Organization:
Stroma:
Connective tissue capsule invaginates into
Parenchyma as Septa divides into Lobules
Cortex:
Differentiating Thmocytes surrounded by
meshwork of Epithelial Reticular cell +
Macrophages
Medulla:
Epithelial Reticular cells + Mature T cells
Hassall corpuscles = concentrically arranged
dead / dying Reticular cells +
Macrophages + Neutrophils + Nuclear
material ?origin
LYMPHORETICULAR SYSTEM
THYMUS (cont)
THYMECTOMY result in:
Poor development of other Lymphoid tissue
Absence of cell-mediated immunity
DeGeorge syndrome (congenital absence)
Decrease B and T cells increase
infections death
Also Hypoparathyroidism Tetanus
 Thymus-I
1. The site of T cell maturation =>
Thymus-dependent (T)
lymphocytes or T cells =>
Thymocytes: developing T cells in
thymus

2. Upper anterior thorax (above

the heart).

3. Multiple lobules => Each has

Outer Cortex => Dense T cells
Inner Medulla => Sparse T cells
Other cells: thymic epithelial
cells (TECs), DCs, Macrophages
=> Cell-cell interactions and
Cytokines
Thymus
 Function
Takes in immature T cells and puts out mature
(immunocompetent) T cells
Increased diversity of T cells
T cell selection
T cell selection
Based on MHC/Ag complex recognition
Recognize MHC/Non self AG complexes
Recognize MHC/Self Ag complexes
Do not recognize MHC/Ag complexes
Athymic condition
Natural
Other
T cell
differentiation
in the Thymus
 BONE MARROW STRUCTURE
Structure
Microscopic
Less well defined than thymus
Role of stromal cells
Very large tissue (3 5% body mass)
In Long bones + Cranium + Ribs + Iliac crest

Two Functional Parts:

Vascular + Adipose
Hematopoietic
Blood cells from single Stem cell
 BONE MARROW
A primary organ
Site for Hematopoiesis + B cell maturation
Site of origin of Stem cell T-cell production
A secondary organ: site for Plasma cell Ab
Contains activated T cells
Function
Hematopoiesis
B cell maturation
B cell selection
Puts out mature, naive B cells
 HEMATOPOIETIC CELL DIFFERENTIATION
Pluripotent Stem cell Myeloid + Lymphoid
progenitor cells
Myeloid Stem cell give rise to:
Monocyte Macrophage
Eosinophil
Basophil
Megakaryocyte Platelet
Erythroblast Erythrocyte
 Lymphoid Stem cell give rise to:
Pre-B cell Late pre-B cell Immature B
cell Mature B cell Plasma cell Abs

Pre-T cell (enters Thymus) Helper T cell

+ Cytotoxic T cell + TDTH cell
NK cell
Stimuli for Differentiation:
Colony-stimulating Factors Erythropoietin
Thymosin Ags (self or foreign)
After maturation in Thymus or Bone marrow,
Lymphocytes migrate to Spleen + LNs +
MALT
 Bone Marrow
1. The site of generation of
all immune and blood cells
<= Hematopoietic Stem Cell

2. Provides Cell-cell
interactions and Cytokines
for the development of
all immune cells.
<= Stromal reticular cells
& other cells
B cell development in the
Bone Marrow
Lymphatic vessels:
Drain the entire body to regional lymph
nodes is a secondary circulatory system
moving antigen to lymph nodes where B
and T cells can respond
 LYMPH NODES
Neck, axillae, groin, mediastinum and abdominal cavity
Most common site for adaptive immune response
Filters Lymph of Foreign bodies
Encapsulated, kidney shaped, concave side with Hilum (entry &
exit of Blood vessels + Nerves)
Each lymph node is surrounded by a fibrous /colagenous capsule,
it penetrates in to node and form septa/trabeculae.
The lymph flows through the afferent lymphatics and leaves
through efferent lymphatics. (Ag enters).
Lymph nodes:
Encapsulated organ
found throughout the
body. Ag from the
periphery is moved
here through
lymphatics by antigen
presenting cells.
Lymphoid follicles
(collection of T and B
cells) in the node on
encountering their
specific Ag will
proliferate generating a
germinal center that
leads to the formation
of fully mature,
effector T and B cells.
 2nd Lymphoid Organ-Lymph Node (LN)
LNs => Small nodular
organ => Body
=> Lymphocyte activation

Lymphocytes =>
Segregated in the
distinct regions of LN

The outer cortex

=> B cell zone (follicle)
=> Germinal Center (2nd
follicle)=>B cell activation

The inner region

=> T cell zone
Lymph Node (LN) Section
 Each lymph node is divided into
a. outer cortex - B cell area (consist B cells)
b. intervening paracortical region - T lymphocytes, dendritic
cells and mononuclear phagocytes. T cells (70%) located
there are CD4+ helper cells
c. inner medulla - mixture of B cells, T cells, plasma cells and
macrophages
Cortex:
Composed of Lymphatic nodules
(B cells)/primary follicles .
Diffuse Lymphatic tissue (T cells)
Mixes with Supcapsular & Peritubular sinuses
(Macrophages)
Germinal centers:
Will present inside Nodules/primary follicles of Cortex
Mainly B cells Plasma cells Abs
Where Ags are processed increase in number +
development of Germinal centers
Medulla:
In center of LN
Contain medullary cords of Lymphoid tissue extend into
Cortex
Medullary Sinuses transmit Lymph to Hilium, that will exists
thru Efferent Lymphatics.
 SPLEEN
Peripheral (Upper Left Quadrant of Abdomin)
Filters Blood of old + defective RBCs
Protects against Blood-borne pathogns
Stroma:
Dense CT capsule containing Smooth muscle
Trabeculae branches off Capsule
partition parenchyma of Splenic Pulp
Delicate meshwork of Reticular CT filters
Blood
 Spleen
1. The site of immune
responses to blood Ags
=> A filter of blood

2. White pulp => T cell & B

cell zones
Marginal zone (MZ)
Red pulp (RP)

3. T cells => periarteriolar

lymphoid sheaths
B cells => follicle
=> marginal zone
Spleen:
Encapsulated organ found
under the liver. Highly
vascular organ that filters
blood. Is responsible for
eliminating blood-borne
pathogens (filter blood).
RBCs carrying immune
complexes are processed
here to remove Ag. Also
has follicles that on
encountering their specific
Ag will proliferate
generating a germinal
center that leads to the
formation of fully mature,
effector T and B cells
 Splenic Parenchyma (White & Red Pulp)
White Pulp:
Lymphatic tissue arranged in Sheaths/malpighi
follicle.
Increases with Antigenic stimulation
Periarteriolar Lymphocyte Sheath (PALS)
Rich in T cells
Marginal zone mostly B cells form Primary
follicles + Ag Secondary follicles with Germinal
centers (B cells)
White Pulp In Marginal Zone, Dendritic cells trap
& process Ag, and migrate to PALS to present Ag
to Antigen-specific cells
 SPLEEN
Splenic Parenchyma
Red Pulp
Mostly RBC-filled sinusoids + Macrophage in
Reticular fiber network
Most of Filtration occur here
Sinuses of various sizes separated by Pulp
(Billroth) cords
RBCs + Platelets exposed to Macrophages in Pulp
cords, which phagocytize worn-out or damaged cells
Sinusoids lined by endothelial cells with
numerous fenestrations filtration
 Phagocytosis mainly by Macrophages
outside the sinusoids, by extending finger-
like projections into the sinusoids, that push
thru the fenestrations between the
endothelial cells
 GUT-ASSOCIATED-LYMPHOID TISSUE
Non-encapsulated
Located in the Submucosa + Lamina propria
Site of immune responses to ingested Microbs + Food
antigens
Structure:
Large follicular aggregates
Peyer patches (Small Intestine villi)
Intraepithelial Lymphocytes
Peyers Patches:
Lymphoid tissue in the small intestine composed of T and B cells
and Ag-presenting cells not encapsulated. Part of the Mucosal
Associated Lymphoid Tissue: MALT Pathogens move through
M cells where they encounter collections of lymphocytes that
can generate a germinal center on encountering their specific Ag.
Responses here usually generate IgA producing B cells.
 Function:
Ag-presenting cells (M cell) in the Mucous
Membranes endocytose Microbes + Ags which
are presented to T Lymphocytes between the
Lymphoid follicles
B cell become activated form Germinal
Centers become Plasma cells IgA
IgA react with receptor on Intestinal Epithelial cells
crosses cytosol of epithelial cell cleaved
excreted into lumen of intestine as secretory IgA
(sIgA) protected against hydrolysis by intestinal
fluids destroy Microbes.
sIgA also found in Saliva
BRONCHUS-ASSOCIATED LYMPHOID
TISSUE (BALT)

Lymphoid tissue beneath Respiratory mucosa

Tonsils
Organization:
Aggregates of B cells Plasma cells Abs
Humoral immune response
Mucosa-Associated Lymphoid Organs
(MALT)
 Types of Tonsils
Palatine Tonsils:
Bilateral in the Oropharynx
Dense Lymphoid tissue with Germinal centers
Numerous Epithelial invaginations (crypts)
Lingual Tonsils:
Base and Posterior Lateral Tongue
With an Inflamed Lingual Tonsil, Squamous
cell carcinoma MUST be R/O
 Pharyngael Tonsils (Adenoids)
Unpaired aggregate of Lymphoid tissue in
the Posterior Wall of the Nasopharynx
Surfaced by Pseudostratified Columnar
Epithelium with Cilia + Goblet cells

Waldeyers Ring = Ring of Lymphoid tissue located

on Soft Palate + Floor of Mouth +
Palatine Tonsil + Lingual Tonsil
 SUMMARY
1. Immune cells are derived from Bone Marrow (BM).
T-lineage progenitor cells are first derived from BM and move to
Thymus for maturation.

2. Key cells in innate immune responses include

- Macrophage & DCs => Ag presentation
- Granulocytes (PMNs)
- NK cells

3. Key cells in Adaptive immune responses include

- B lymphocytes => Ab => Extracellular bacteria
- Several T cell types => Fight intracellular microbes &
Regulate the program of an immune response

4. Primary lymphoid organs (BM & Thymus)=> Immune cell development

2nd lyphoid organs (LN & Spleen)=> Concentrate Ag from tissues
or blood for lymphocyte activation.
Overview of
Lymphocyte
Generation &
Activation-I
Overview of
Lymphocyte
Generation &
Activation-II
 Activation of Lymphocytes
In general, lymphocyte
activation requires Two
Signals (from Antigen
presenting cells (APCs))

Signal 1:
Ag Ag receptor on
lymphocytes (T & B)

Signal 2:
Molecules (innate
response)
Costimulatory receptors
on lymphocytes
Migration of
Lymphocytes-I
1. In LN, nave lymphocytes
HEVs
Rolling => Adhesion
=> Transmigration
Adhesion molecules for
cell-cell interactions

2. In peripheral infection
sites, effector
lymphocytes blood
vessels
Migration of Lymphocytes-II