Structure of Immune

System
JULY MARY JOHNSON
Structure of Immune System
Central lymphoid organ - Bone
marrow
• All the cells in blood are originated from pluripotent
hematopoietic stem cells of bone marrow and the
process is called a hematopoiesis.

• In early fetal life, hematopoiesis occurs in liver;

gradually the stem cells migrate to bone marrow.

• By birth, the stem cells occupy most of the bone

marrow space of large bones.
Central lymphoid organ - Bone
marrow
• As the individual ages, hematopoietic activity in large bones
decreases and after puberty hematopoiesis is mostly confined to axial
bones such as pelvis, vertebrae, sternum, skull & ribs.

• Progenitor T and B cells originate in bone marrow.

• Further development of B cells occurs in bone marrow itself.

• Progenitor T cells migrate to thymus for further proliferation.

 Central lymphoid organ - Thymus
• Site of proliferation and maturation of T cells.

Development:
 Developed in the embryonic life (third month)
from third/fourth pharyngeal pouch.
Highly active at birth, continues to grow for
many years, reaches its peak size at puberty, and
then it degenerates.
Central lymphoid organ - Thymus
Structure:
• Thymus has two lobes surrounded by a fibrous
capsule
• Septa arising from capsule divide thymus into
lobules, and each lobule is differentiated into
an outer cortex & an inner medulla
Thymus -Cortex

Densely populated and contains:

• Thymocytes- Immature T lymphocyte (many in

number).

• Cortical epithelial cells and

• Nurse cells (specialized epithelial cells with

long membrane extensions that surround
many thymocytes)
Thymus -Medulla

• Sparsely populated and contains:

Thymocytes which are relatively more
mature and fewer in number
Medullary epithelial cells

Interdigitating dendritic cells

Hassall’s corpuscles (concentric layers

of degenerating epithelial cells)
 Thymus
• Only 2-5% of the developing T cells become mature and released out
from thymus.
• Remaining T cells are destroyed as they are either not capable of
recognizing MHC or are believed to be self-reacting in nature.
• The released T cells mediates cell mediated immunity
• Defect in maturation of T lymphocytes results in severe life-
threatening cell mediated immunodeficiency disorders.
E.g.,
• DiGeorge syndrome (immunodeficiency disorder) - congenital aplasia
of thymus.
• Nude mice- Mice with congenital absence of thymus.
PERIPHERAL LYMPHOID ORGAN -
Lymph Node
• Small bean shaped organs.

• Occur in clusters or in chains, distributed along the

length of lymphatic vessels.

• Lymph nodes act as physiological barriers - filter the

microbial antigens carried to lymph node by
activating the T and B cells.
Lymph Node - Structure

Lymph node is divided into three parts:

Cortex

Medulla (both are B cell areas)

Paracortex (T cell area).

• Bears the lymphatic vessels (efferent

and afferent) and blood vessels.
Lymph Node - Cortex
Contains lymphoid follicles that
are composed of:
• B cells
• Few special type of dendritic cells
(called follicular dendritic cells)
• Occasional T cells.
Lymphoid follicles are mainly of
two types:
• Primary lymphoid follicles
• Secondary lymphoid follicles
Primary lymphoid follicles

• Found before the antigenic stimulus.

• Smaller

• Contain resting B cells.

Secondary lymphoid follicles

• Following contact with an antigen -

resting B cells starts dividing and become
activated.

• Activated B cells differentiate rapidly into

plasma cells and memory B cells.

• Follicles become larger called secondary

lymphoid follicles.
Secondary lymphoid follicles

• Has two areas:

o Central area - germinal center
o Peripheral zone - contains activated B
cells.
Lymph Node – Paracortical area and
Medulla
Paracortical are:

o Present in between cortex and medulla.

o T cell area of lymph node (rich in naive T cells).

o Contains macrophages and interdigitating dendritic cells, which trap the

antigens and present to T cells.

Medulla:

o Innermost area of lymph node.

o Rich in B-lymphocytes (mainly plasma cells).

Spleen

• Largest secondary lymphoid organ.

• Acts as physiological barrier similar

to lymph node in clearing the
microbial antigens through the
antigenic stimulation of T and B
cells.
Spleen - Structure

• Situated below the diaphragm on left side of the

abdomen.

• Adult spleen measures about 5-inch in length &

weighs around 150gm.

• Divided into two compartments: central white

pulp and outer red pulp, surrounded by capsule
and intervened by trabeculae.
Spleen - Structure

• White pulp:
o Central densely populated area.

o Contains T cells and B cells.

o It has two parts:

 Periarteriolar lymphoid sheath (PALS), which is T

cell area
 Marginal zone is located peripheral to the PALS

and is populated by B cell lymphoid follicles

Spleen - Structure

• Red pulp:
o Area that surrounds the sinusoids.

o Filled with red blood cells (RBCs).

o Older and defective RBCs are destroyed

here.
Mucosa Associated Lymphoid Tissue
(MALT)
• Defense mechanisms in the mucosal sites to prevent
the microbial entry.

• Group of lymphoid tissues lining these mucosal sites

are collectively known as mucosa associated
lymphoid tissue (MALT).

• Examples of MALT are:

o lamina propria of intestinal villi, tonsils, appendix
and Peyer’s patches)
LYMPHOID CELLS
• Lymphocytes are the major components of cells of immune system.

• Based on function and cell membrane structure:

o T lymphocytes

o B lymphocytes

o NK (natural killer) cells.

• Lymphocytes can also be classified into:

o Naive lymphocytes

o Lymphoblasts.
Naive lymphocytes

• Resting B and T lymphocytes that have not interacted with antigen

(unprimed lymphocytes).

• Also known as small lymphocytes (6µm); having thin rim of cytoplasm,

larger nucleus with dense chromatin; fewer mitochondria, ribosomes,
and lysosomes.

• Short life span (1-3 months).

Lymphoblasts
Naive cells interact with antigen
in the presence of cytokines

Activated and transform into lymphoblasts

Effector cells Memory cells.

Effector cells

• Function in various ways to eliminate antigen.

• Short life span (few days to few weeks)

• Large lymphocytes (15 µm in size), having wider rim of cytoplasm with

more organelles.
o Effector B cells - Antibody producing plasma cells

o Effector T cells - Helper T cells and cytotoxic T cells.

Memory cells

• Remain dormant like naive cells.

• Capable of transforming into effector cells rapidly on subsequent

antigenic challenge.

• Longer life span; providing long term immunity to may pathogens.

Differences between naive, effector
and memory cells
T LYMPHOCYTES

• T cells constitute 70–80% of blood

lymphocytes.

• Unlike B cells, they do not have

microvilli on their surface.

• Bear specialized surface receptors called

T cell receptors (TCR).
T cell receptor

• Main function - antigen recognition.

• Unlike B cell receptor which binds to antigen

directly, TCR does not recognize antigen by itself.

• Can only respond to an antigen which is

processed and presented by the antigen
presenting cells (APC) such as macrophages.
T Cell Development
• Major events of T cell maturation take
place in thymus.
• Progenitor T cells are originated from
the fetal liver or in adults from the
bone marrow and send to the thymus
through blood stream.
• Two types of effector T cells:
o CD4+ helper T cells
o CD8+ cytotoxic T cell.
B Lymphocytes

• Mediators of humoral immunity; constitutes 10-15% of blood

lymphocytes.

• Named after their site of maturation (bursa of Fabricius in birds and

bone marrow in human and other mammals).
B Lymphocyte

• Development in peripheral lymphoid organs:

o Immature B cells migrate from bone marrow to peripheral lymphoid
organs (lymph node and spleen).
o Transform into mature B cells following contact with appropriate antigen.
Mature or naive B cells

• Most mature B cells (95%) belong to the follicular B cell type and produce
surface receptor IgD in addition to IgM.

• Play an important role in humoral immune response.

• Following antigenic stimulus, the mature B cells transform into activated B

cells (lymphoblasts).

• Which further differentiate into either effector B cells i.e. plasma cells
(majority) or memory B cells.
Mature or naive B cells

• Plasma cells (antibody secreting cells):

o Oval, large (15µm size), with an eccentrically oval
nucleus containing large blocks of peripheral
chromatin (cartwheel appearance)
o Cytoplasm contains abundant organelles.
o Short life span of two or three days.
Differences between T cell and B
cell
Natural killer (NK) cells

• Large granular lymphocytes.

• Constitute 10-15% of peripheral blood

lymphocytes.

• Derived from a separate lymphoid lineage.

• Similar to cytotoxic T cells, NK cells also are

involved in destruction of virus infected cells
and tumor cells.
Macrophage

• Monocytes/macrophages originate from bone marrow, from a

separate lineage; i.e. from the granulocyte-monocyte progenitor cells.

• Macrophages are motile, travel by amoeboid movement throughout

the tissues and are called as free or wandering macrophages.

• While, some reside in particular tissue, become non-motile and are

called fixed macrophages.
Macrophage
• Monocytes:
o Present in blood.
o Largest blood cells measuring 12-20µm size.
o Do not divide.
o Average transit time -8 hours in blood; then they migrate to tissues
Macrophage
• Macrophages:
o When monocytes migrate to tissues, they
transform into macrophages
o Macrophages differ from monocytes in the
following:
 5-10 folds larger than monocytes
 Contain more lysozymes and cell organelles
 Produce more lytic enzymes and cytokines
 Possess greater phagocytic activity
 Have a longer life in tissues (months to years)
Types of Macrophages
 Functions of Macrophages
• Phagocytosis:
o Macrophages are the principle
cells involved in phagocytosis.
o Steps:
Functions of Macrophages
• Antigen presentation:
o Promote adaptive immunity, by acting as APCs.
Macrophages capture the antigen

Process into smaller antigenic peptides

Present the antigenic peptides along with the MHC class II molecules to
the helper T cells

Facilitates helper T cell activation.

Functions of Macrophages
• Activated macrophages:
o On exposure to cytokines such as interferon-γ, macrophages become
activated  greater phagocytic ability  produce many cytokines  act
against intracellular bacteria, virus infected cells and tumor cells.
o Also express higher level of MHC class II, hence can act as efficient
APCs.
Functions of Macrophages
• Secretory products of macrophages have various biological functions-
o Interleukin 1 (IL-1):Promotes inflammatory responses, fever and activate
helper T cells.
o IL-6 & TNF-α:Promote innate immunity, (inflammation & fever) and eliminate
the pathogens.
o Interferon α & β -have antiviral activity.
o TNF-α: Lyse the tumor cells (anti-tumor activity)
o Growth factors such as CSF (colony stimulating factor): promote
hematopoiesis.
o Following tissue injury, various mediators are secreted from macrophage;
which help in tissue repair and scar formation.
Dendritic cells
• Possess long membranous cytoplasmic
extensions resembling dendrites of neurons
- hence named as dendritic cells.
• Originate from bone marrow, but the
pathway is uncertain.
• Develop as a separate lineage from stem
cells or may originate from the macrophage
lineage.
Types of Dendritic cells
Functions of Dendritic cells
• Non-phagocytic in nature.
• Most efficient APCs.
• Main function is to capture, process and present the antigenic
peptides on their cell surface to the helper T cells.
• Carry high level of MHC class II and co-stimulatory B7 molecules.
• Act as messengers between the innate and the adaptive immune
systems.
Granulocytic cells
• Granulocytes are a category of white blood cells characterized by the
presence of granules in their cytoplasm.
• E.g. neutrophils, eosinophils and basophils.
• Differ from each other by cell morphology and cytoplasmic staining
and function.
Neutrophils
• Possess multilobed nucleus and a granulated cytoplasm that stains
with both acid and basic dyes.
• Cytoplasm - heavily granular; contains several granules such as
myeloperoxidase, lysozyme, defensins, elastase, gelatinase, etc.
• Constitute 50%–70% of the circulating WBCs.
Neutrophils
• Level is greatly increased in presence of infection under the influence of
certain cytokines such as IL-8.
• Principal phagocytes of innate immunity.
• Mechanism of microbial killing:
o Both by oxygen dependent and independent mechanisms.
Eosinophils
• Bilobed nucleus and a granular cytoplasm that stains red with the acid
dye eosin.
• Phagocytic.
• Constitute only 1-3% of total leukocytes.
• Number is greatly increased in certain allergic conditions and
helminthic infections.
• Interleukin-5 is believed to be the eosinophil chemotactic factor.
Basophils
• Non-phagocytic granulocytes.
• Function – secretes contents of granules.
• Lobed nucleus and heavily granulated cytoplasm that stains with the
basic dye methylene blue.
• Resemble mast cells in their function.
• Granules are rich in histamine & other mediators that play a major
role in certain allergic responses.
Mast cells
• Present in various body sites such as skin, connective tissues of
various organs, and mucosa (respiratory and intestinal).
• Contain cytoplasmic granules rich in histamine and other active
substances.
• Play an important role in the development of certain allergic (type I
hypersensitivity) reactions.
MAJOR HISTOCOMPATIBILITY COMPLEX
(MHC)
• Complex is a group of genes.
• Coding for a set of host cell surface molecules that bind to peptide
fragments derived from pathogens
• Display them on the host cell surface for recognition by the
appropriate T-cells.
• Present in almost all the human cells, but first discovered on the
surface of leukocytes; hence in humans, the MHC coded proteins are
also called as human leukocyte antigens (HLA).
Major Histocompatibility Complex
(MHC)
• Serve as a unique identification marker for every individual.
• Following transplantation of a graft, the recipient mounts an immune
response against the graft’s MHC molecule and vice versa.
• The acceptance or rejection of the graft is directly dependent on the
MHC molecules of the graft and the recipient.
• As the MHC molecules determine the compatibility between the graft
and host tissues, they are named as histocompatibility antigens.
 Structure & Role of MHC Class I
molecule
• Association of β2 microglobulin with α chain is
necessary for the expression of MHC I
molecules on to the cell surface.
• Antigen peptide groove of class I MHC molecule
(i.e. the site, where the antigen peptide binds)
is formed by the cleft between α1 and α2
domains.
• α3 domain binds to CD8 molecule present on
cytotoxic T cells during antigen presentation.
Structure of MHC Class II molecules
Differences between MHC class I
and MHC class II molecules
Cytokines
• Definition - Cytokines are chemical substances which serve as messengers,
mediating interaction and communication between the various cells of
immune system.

• Major classes of Cytokines

o Lymphokines- produced by lymphocytes

o Monokines- produced by monocytes & macrophages

o Interleukins- produced by WBCs and acting on the same or different WBCs

o Chemokines- involved in chemotaxis and other leukocyte behavior