Leona Melodia T.

Matheus, MD, FPCS, FPSGS

IMMUNE SYSTEM
}  Provides defense or
immunity against infectious
agents, from viruses to
muticellular parasites

}  Two types of immunity:

1. Innate immunity
2. Adaptive immunity
}  Present from birth
}  Involves WBCs (mainly granulocytes) and anti-
microbial chemicals e.g. HCl & other organic acids,
defensins, lysozyme, complement, and interferon
}  Immediate and nonspecific acations, including physical
barriers like the skin & mucous membranes of the GIT,
respiratory and GUT
–  Prevent infections or penetration of the host body
–  Microorganisms that penetrated the barriers are quickly
removed by neutrophils and other WBCs in adjacent
conn. tiss.
}  Acquired gradually by exposure to microorganisms,
is more specific, slower to respond, and is a more
recent development evolutionarily

}  Aimed at specific microbial invaders: involves production

of memory lymphocytes so that a rapid response can
be mounted if the same invader appears again

}  Two types:
1. Cell-mediated immunity correspond to two
2. Humoral immunity types of lymphocytes
}  Responsible for cell-mediated immunity

}  Functional subsets:
1. T helper cells – assist immune responses by
secreting cytokines (chemicals used by immune
system cells to communicate with each other and
coordinate defensive measures)

2. Cytotoxic (Killer T) cells – destroys virus-infected

and malignant cells
- Attach to the cell sources of antigens and remove
them by releasing substances that trigger apoptosis
3. Regulatory or Suppressor T cells – switch off
the immune response when the initiating
stimulus is removed
- suppress immune responsiveness to self-antigens

4. γδ T cells – small subpopulation that migrate

to the epidermis and mucosal epithelia, become
intraepithelial, and do not re-circulate to 2o
lymphoid organs
- similar in function to cells of innate immunity
}  Responsible for antibody production and mediate
humoral response
}  B cells have the ability to mature into plasma cells
which synthesize antibodies (immunoglobulins)
}  Antibodies neutralise or destroy invading
microorganisms by binding to one or more antigens
associated with the organism
}  5 Structural classes of immunoglobulins:
1. IgG 4. IgM
2. IgA 5. IgE
3. IgD
}  Reticular connective tissue

}  Parenchyma: Lymphocytes

}  Stroma: Reticular cells and fibers

}  Other cells: plasma cells & antigen-presenting cells

(APCs) = part of the mononuclear phagocyte system

}  Function: protection from invasion and damage by

foreign substances, cells or microorganisms =
“Immune System”
}  A small spherical or oval cell with a large rounded
(or slightly indented on one side) nucleus,
surrounded by a narrow, non-granular cytoplasm

}  Sizes:
1. Small (6-9 um) – 20-50%
of white cells in circulation
2. Large (9-20 um) – 3% of
circulating WBC; also called
“Lymphoblast”
}  Lymphocytes are formed initially in two
1o or central lymphoid organs:
a. Bone marrow for B lymphocytes
b. Thymus for T lymphocytes

}  Most lymphocyte activation and proliferation

occur in 2o or peripheral lymphoid organs:
a. Spleen
b. Lymph nodes
c. Tonsils
d. MALT (Mucosa-associated lymphoid tissue)
 LOOSE (DIFFUSE)
LYMPHATIC TISSUE

- few, irregularly scattered

lymphocytes

- stroma predominate:
spongelike

- (+) lamina propria of URT & UDT and internodular

regions of spleen, tonsils, and Peyer’s patches
DENSE LYMPHATIC
TISSUE

- abundant, closely
packed lymphocytes

- (+) in lamina propria

of LRT and LDT
(e.g. ileum, colon,
vermiform appendix)
NODULAR LYMPHATIC
TISSUE

-  compact, circumscribed
aggregates of lymphocytes
= follicles or nodules

- found singly (lamina propria

of GIT, respiratory, GUT) or
in aggregates (walls of the
ileum [Peyer’s patches] and
vermiform appendix)
-  Lymphatic nodule (follicle) primarily contains
B lymphocytes

-  Lymphatic nodule or follicle may have:

a. Germinal center (of Fleming):
central pale staining portion
= made of large lymphoblasts
= temporary structures
= “ secondary lymphoid nodule”

b. Mantle/Corona: peripheral
dark staining portion
= made of small lymphocytes
}  Location: superior anterior mediastinum

}  Fully formed and functional at birth: produces T cells

}  Has 2 lobes and weighs about 30-40 gms at puberty

}  At puberty, undergoes involution and is rapidly

replaced by adipose tissue = “Organ of childhood”
}  Capsule: Loose conn. tiss.
- forms coarse septae or trabeculae
that subdivides it into lobules

}  Each lobule has:

1. Thymic cortex –
outer darkly basophilic zone of
dense lymphatic tissue

2. Thymic medulla –
pale-staining central zone of
loose lymphatic tissue
}  Packed with T lymphoblasts
or thymocytes, numerous
macrophages as well as
thymic epithelial cells
(TECs) which have features
of both epithelial and reticular
cells
◦  TECs have large euchromatic
nuclei that are morphologically
and functionally diverse
◦  Has 3 major types in the cortex
}  Types of TECs:
1. Squamous TECs:
- forms a blood-thymus barrier that prevents
unregulated exposure of thymocytes to antigens

2. Stellate TECs: (+) processes that contain

keratin tonofilaments
- form a cytoreticulum to which macrophages
and developing lymphocytes attach

3. Other squamous TECs:

- form a corticomedullary barrier
}  Light stained; (+) fewer
and larger, more mature
lymphocytes

}  3 types of medullary TECs:

1. Forms a 2nd layer of corticomedullary barrier
2. Forms a cytoreticulum that
a. supports less densely packed T lymphocytes,
dendritic cells, and macrophages
b. expresses specialized proteins specific to cells
of other organs
3. Large aggregates of TEC called
Hassall’s bodies or
Thymic corpuscles
–  Characteristic feature of
the thymus

–  Cells secrete several cytokines

that control activity of local
dendritic cells, including
factors that promote
development of regulatory
T cells
}  Main function: induction of central tolerance,
and along with regulatory T cells prevent
autoimmunity

}  Other functions = development of lymphocytes

responsible for Cellular/Cell-mediated immunity:
1. Homograft rejection
2. Delayed hypersensitivity
3. Graft vs. Host reaction
4. Immune response to fungi, bacteria and virus
}  Spheroid or bean-shaped organs, 10 mm X 2.5 cm
in size, found along the course of lymphatic vessels

}  Convex surface: entry point

of afferent lymphatics
Concave surface (hilum):
where efferent lymphatics
leave and where artery,
vein, and nerve penetrate
the organ
}  Capsule: Dense conn. Tiss. =
forms septae/trabeculae through
which blood vessels branch

}  Stroma: Reticular tissue

}  Parenchyma: 3 major regions

1. Cortex – outer, dense stain
2. Medulla – central, pale stain
3. Paracortex – smaller area
between these two
}  Components:
1. Subcapsular/Marginal
sinus – immediately inside
the capsule; receive lymph
from afferent lymphatics
- Gives rise to Cortical or
Trabecular sinuses
between lymphoid nodules

2. Lymphoid nodules, (+) or (-) germinal centers

- Formed largely of Helper T cells and
proliferating B lymphoblasts
}  No precise boundaries

}  Recognized from outer cortex by

its lack of B cell lymphoid nodules
◦  Rich in T helper cells

}  Most lymphocytes enter a lymph

node through the paracortex via
high endothelial venules
(HEVs) = endothelial lining is made
of cuboidal cells; located mostly here)
}  Two components:
1. Medullary cords [A]=
branched cordlike masses of
lymphoid tissue extending
from paracortex
- (+) T & B cells, plasma cells

2. Medullary sinuses [B] =

dilated spaces lined by
discontinuous endothelium
- continuous with cortical sinuses and converge at the
efferent lymphatics
}  Afferent lymph vessels (convex border) subcapsular
sinus cortical sinus medullary sinus efferent
lymph vessels leave LN

}  Functions of Lymph Nodes:

1. Filters lymph – prevent spread of
microorganisms and tumor cells

2. Site for B-cell activation and

differentiation to antibody-
secreting plasma cells
}  Location: (L) upper quadrant of the abdomen beneath
the diaphragm

}  Capsule: Dense conn. tiss.

◦  Large trabeculae originate at the hilum (medial surface)
that carry BV, nerves, and
lymphatics to the splenic pulp

}  Parenchyma (Splenic pulp):

a) White pulp (20%)
b) Red pulp
}  Consists of:
1. Lymphoid nodules: made of B
cells, (+)/(-) germinal centers

2. Periarteriolar lymphoid
sheaths (PALS)
–  cylindrical sheath of T cells
around a central arteriole
–  Central arteriole is pushed to the
periphery by a developing nodule
}  Consists of splenic cords
(of Billroth) and splenic
sinusoids (lined by Stave cells)

}  Stave cells: elongated endothelial

cells lining the sinusoids, oriented
parallel to the blood flow, with
open slits between the cells
◦  Allow separation of healthy
RBCs from effete cells in the
splenic cords
}  From the hilum, Trabecular arteries leave the
trabeculae and enter the parenchyma as Central
arterioles
◦  If germinal centers (+), arteriole is displaced to one side

}  Central arteriole eventually pass into the red pulp

where it gives off Penicillar arterioles (arteries
of the red pulp)

}  Each Penicillar arteriole branches into 2 0r 3

Sheathed capillaries
}  Blood flow in the red pulp can take either of 2 routes:
a. Closed circulation – sheathed capillaries
connect directly to the sinusoids; blood is
always enclosed by endothelium

b. Open circulation – open-ended capillaries from

penicillar arterioles dump blood into the stroma
of the splenic cords
o  Plasma and all formed
elements re-enter sinusoids
in between Stave cells
o  Stiff or effete, swollen RBCs
are blocked and undergo
selective removal by macrophages
}  From the sinusoids blood proceeds to small red
pulp veins that converge as trabecular veins,
which in turn form the splenic vein
Functions of the Spleen:

(1)  Only lymphoid organ involved in filtration of

blood = defense against blood-borne antigens
(2) Production site of antibodies and activated
lymphocytes
(3) Store normal red blood cells within the splenic
sinuses
(4) Main site of old erythrocyte destruction
(5) Conserve and temporarily store iron
}  Large, irregular masses
of lymphoid tissue in the
mucosa of the posterior
oral cavity & nasopharynx

}  3 Locations:
1. Palatine tonsils
2. Lingual tonsils
3. Pharyngeal tonsil
}  Paired, oval-shaped bodies

}  Location: posterior lateral walls

of oral cavity

}  Covering:
◦  Free surface = SSNKE
◦  Attached surface = capsule of DCT
(partly encapsulated)

}  Surface area: deep invaginations

= Tonsillar crypts
}  Location: along the }  Location: posterior
base of the tongue wall of nasopharynx

}  LE: SSNKE with crypts }  LE: PCCE with a thin

underlying capsule
}  Same features as
palatine tonsils but }  Mucosa with diffuse
lack distinct capsules lymphoid tissue and
nodules has shallow
infoldings but lack
crypts
}  The retrovirus that produces acquired immuno-deficiency
syndrome (AIDS) infects and rapidly kills helper T cells
◦  Reduction of this lymphocyte group cripples the patient’s immune
system, rendering then susceptible to opportunistic bacterial,
fungal, protozoan and other infections

}  Neoplastic proliferation of lymphocytes producing a

malignant lymphoma is often located in one or more
lymph nodes
◦  This may obliterate the normal architecture of the node and convert
it to an enlarged, encapsulated structure filled with lymphocytes, a
condition called lymphadenopathy
}  Splenomegaly (enlargement of the spleen) can be
due to a variety of causes e.g. lymphoma, malignant
growth, and sickle cell disease
◦  The splenic capsule is relatively thin, and an enlarged spleen
is susceptible to traumatic rupture, a potentially life-
threatening event due to blood loss in the abdominal cavity

◦  This may necessitate surgical removal of the spleen,

splenectomy

◦  Functions of the organ are carried out by the other lymphoid

organs, with erythrocyte removal occurring in the liver and
bone marrow