The Immune System & Lymphoi

Organs

Bulseco, Carino,
Dinglasan, Salanguit
The Immune System
Provides defense or immunity against
infectious agents like
-proteins
- viruses
-bacteria
-parasites
-fungi
Kinds of Immunity: Innate (nonspecific)
and Adaptive (specific)
Innate Immunity
Nonspecific
Protect against foreign cells or matter
without recognizing the invaders specific
identity
Does not require prior exposure to invaders
Physical barriers:
-skin
-mucous membranes (gastrointestinal,
respiratory, urogenital tracts)
 Innate Immunity
Neutrophils and leukocytes
- remove bacteria, fungi and parasites
that manage to penetrate the barrier
Toll-like receptors (TLRs)
present on leukocytes
- allow the recognition and binding of
surface components of invaders
Natural killer (NK) cells
- destroy various unhealthy host cells like
those infected with virus or bacteria, and
as well as potentially tumorigenic cells
Innate Immunity: Antimicrobial
chemicals produced by leukocytes and
other cells of the tissue barriers
Hydrochloric acid (HCl) and organic
acids
-in regions with low pH
-kills entering microorganisms directly
-inhibit growth
Defensins
- short cationic polypeptides produced by
neutrophils and other epithelial cells
-kills bacteria by disrupting cell walls
Innate Immunity: Antimicrobial
chemicals produced by leukocytes and
other cells of the tissue barriers
Lysozyme
-made by neutrophils and cells of epithelial
barriers
-kills by hydrolyzing bacterial cell wall
components
Complement
-system of proteins in blood plasma, mucus and
macrophages
-react with bacterial surface components to aid
removal of bacteria
Interferons
- paracrine factors from leukocytes and virus-
Adaptive Immunity
Specific, slower to respond and
evolutionarily more recent
development
Requires exposure to foreign
substances
Involves B and T lymphocytes
Immune responses are aimed at a
specific microbial invader
Involve production of memory
 Cytokines
A diverse group of peptides and
glycoproteins
Provide a chemical communication
network that synchronizes the component
of immune response
Involved in both innate and adaptive
immunity
Chemical mediators that induce and
regulate the events leading to
inflammation
 Cytokines
Major responses induced in target cells:
Chemotaxis, or directed cell movements
toward and cell accumulation at sites of
inflammation. Cytokines producing this effect
are called chemokines.
Increased mitotic activity in certain
leukocytes, both locally and in the bone
marrow.
Stimulation or suppression of lymphocyte
activities in adaptive immunity. The group of
cytokines involved in such activity are called
 Antigens
-any molecule that the host does not
recognize as self
-either proteins or large polysaccharides
Epitope or antigenic determinant
- small molecular domains of antigens
which immune cells recognize and
react to
Immune response of antigen may be:
cellular, humoral or both
 Antibodies
- a glycoprotein for the immunoglobulin family that
interacts specifically with an antigenic
determinant
- secreted by plasma cells that arise by terminal
differentiation of clonally proliferating B
lymphocytes whose receptors recognize and bind
to specific epitopes
-can either accumulate in the blood plasma and
interstitial fluid of tissues or
-transported across epithelia into the secretion of
glands
-some are membrane proteins on the surface of B
lymphocytes or other leukocytes
 Antibodies
Immunoglobulins
- have two identical light chains and two
identical heavy chains bound by disulfide
bonds
Fc region isolated carboxyl-terminal
portion of the heavy-chain molecules
Variable region first 110 amino acids
near the amino-terminal ends of the light
and heavy chains that varies
Antigen-binding site variable portions
of one heavy and one light chain; usually 2
 Classes of Antibodies

o IgG
-most abundant (75%-85%)
-highly soluble, stable (half-
life>3weeks), crosses the placental
barrier into the fetal circulation
- passive immunity
o IgA
-present in almost all exocrine secretions
- dimeric
- J chain
-produced by plasma cells in mucosae of
the digestive, respiratory and
reproductive tracts
-binds to the secretory component,
which is released by the epithelial cells
during IgA transcytosis
-relatively resistant to proteolysis
Classes of Antibodies
o IgM
- constitutes 5%-10% of blood
immunoglobulin
-pentameric form united by a J chain
- produced in an initial response to an
antigen
-when bound to an antigen, it is the
most effective antibody class in
activating the complement system
Classes of Antibodies
o IgE
- usually a monomer
-much less abundant in the
circulation
- when it encounters the antigen
that elicited its production, the
antigen-antibody complex
triggers the liberation of
substances like histamine,
heparin and leukotrienes
o IgD
-least abundant immunoglobulin
on plasma
- monomers of IgD are bound to
the surface of B lymphocytes
-act as antigen receptors in
triggering B-cell activation
Actions of Antibodies
3 actions of innate immunity:
Complement activation:
antigen-antibody complexes with IgG or
IgM bind polypeptides of the complement
system
after activation, specific complements
bind and rupture membranes of invading
cells, clump antigen-bearing bacteria or
cells, and elicit arrival of relevant
leukocytes
Actions of Antibodies
Opsonization:
refers to the ability of receptors on
macrophages, neutrophils, and
eosinophils to recognize and bind
the Fc portions of antibodies
It increases efficiency of
phagocytosis by leukocytes at site
of infection
Actions of Antibodies
NK cells activation:
antibodies bound to antigens on
virus-infected cells of the body are
recognized by the primitive
lymphocytes called NK cells
Activated NK cells kill infected cell
by releasing perforin and various
granzymes
Antigen Presentation
Major Histocompatibility Complex (MHC)
- cellular identity tags that are genetic markers of
self
- no two individuals have the same sets of MHC genes
Two classes:
o MHC class I found on all body cells except
erythrocytes
- CD8 on cytotoxic T cells bind to Class I
o MHC class II found only on the surface of APCs like
macrophages, B cells and dendritic cells
- CD4 on helper T cells bind to Class II
 THYMUS
Bilobed organ in the mediastinum

Most active and prominent before puberty

Main function: induction of central tolerance, which

prevents autoimmunity.

Origin: Embryos third pair of pharyngeal pouches

(endoderm), with precursor lymphoblasts circulating
from the bone marrow to invade and proliferate in this
unique thymic epithelium during its development.

Site of T-lymphocyte differentiation and the selective

removal of T cells reactive against self-antigens
 THYMUS

THYMUS

Figure 14-8 Copyright McGraw-Hill Companies

 THYMUS

Thymic cortex
contains an extensive population of T
lymphoblasts (or thymocytes)

Associated with the unique thymic

epithelial cells (TECs)
 CORTEX OF THE THYMUS

The cortical
zone of an
Figure 14-9 active thymus
Copyright McGraw-Hill Companies
 CORTEX OF THE THYMUS

The epithelial
reticular cells
Figure 14-9
Copyright McGraw-Hill Companies
 Three major types of TECs in the
cortex of the thymus:
Blood-thymus barrier:
Squamous TECs layer
Prevents unregulated exposure of thymocytes to
antigens.
Cytoreticulum:
Stellate TECs
Where macrophages and developing
lymphocytes attach instead of to reticulin fibers
Secrete numerous cytokines for T-cell
development
 Corticomedullary barrier:
Squamous cortical TECs
Express MHC class II molecules but form a sheetlike
structure

Three related types of medullary TECs

form the following:
A second layer of the boundary between cortex
and medulla.
A cytoreticulum
Large aggregates of TECs, sometimes
concentrically arranged, called Hassall
corpuscles
 THYMIC MEDULLA

Medulla of the thymus

with Hassall
corpuscles.
Figure 14-10 Copyright McGraw-Hill Companies
Role of the Thymus
in T-Cell Maturation
& Selection
T lymphoblasts populate the cortex and
begin to proliferate
Recombine regions of the TCR and chain
genes
Express these TCR proteins as well as both CD4
and CD8.

Thymocytes two-stage selection process

of quality control
Ensures that mature T cells have TCRs that are
fully functional but do not recognize and strongly
bind MHC with self-antigens.
Role of the Thymus in T-Cell Maturation &
Selection

Positive selection:
cells survival depends on
whether its TCRs can recognize
and bind antigens on the MHC
molecules properly

X Cells that failed the test undergo apoptosis

and are removed by the macrophages.

Positively selected move to the medullary

compartment.
Figure 14-11 Copyright McGraw-Hill Companies
 Negative selection:
survival depends on a
cell not binding to MHC
molecules with such
peptides

T cells that strongly bind

MHCs containing these
selfpeptides undergo
apoptosis.
Most of these lymphocytes will
have stopped expressing either
CD8 or CD4, and become either
helper T cells or cytotoxic T
cells
MUCOSA-ASSOCIATED LYMPHOID
TISSUE
Secondary lymphoid structures

Where most lymphocytes are activated

by antigen presentation.

Lymphocytes, IgA-secreting plasma cells,

APCs, and lymphoid nodules

One of the largest lymphoid organs,

containing up to 70% of all the bodys
immune cells.
 TONSILS
Tonsils
Large, irregular masses of lymphoid tissue
in the mucosa of the posterior oral cavity
and nasopharynx

Three types:
Palatine tonsils
Covered by stratified squamous epithelium
Tonsillar crypts: invaginations
This tissue is underlain by dense connective
tissue that acts as a partial capsule.
 TONSILS
Lingual tonsils
situated along the base of the tongue
With crypts
Lack distinct capsules

Pharyngeal tonsil
Situated in the posterior wall of the nasopharynx
Covered by pseudostratified ciliated columnar
epithelium
Thin underlying capsule
Lacks crypts
TONSILS
TONSILS

Lymphoid
TONSILS

Epithelium
MUCOSA-ASSOCIATED LYMPHOID
TISSUE

Here large aggregates of lymphoid nodules

comprise the Peyer patches

The simple columnar epithelium that covers

the lymphoid nodules of Peyer patches includes
large epithelial M cells with apical microfolds
rather than the brush border
PEYERS PATCH
PEYERS PATCH
SEM

Figure 14-13 Copyright McGraw-Hill Companies

M CELL
PEYERS PATCH AND M
CELLS

Transcytosis
APPENDIX
 Lymphocytes
Regulate and carry out adaptive immunity
Bone marrow where cells destined to
become B Lymphocytes remain
Thymus location of progenitors of T
lymphocytes
Secondary lymphoid organs
B and T cells circulate
Includes the MALT, the lymph nodes and the
spleen
 Lymphocytes
continuously recirculate through the body in
connective tissues, blood, and lymph.
CD markers (cluster of differentiation)
allow lymphocytes to be distinguished as B
cells and subcategories of T cells
by immunocytochemical methods.

Lymphocytes of a new born not yet exposed to

antigens are immunocompetent.
Lymphoid organs and main paths of lymphatic
vessels
Various specific and nonspecific functions of antibodies
Lymphoid tissue
Reticular connective tissue filled with large
number of lymphocytes.
Diffuse within areas of loose connective tissue
or surrounded by capsules.
Dark blue in H&E stained sections due
basophilic nuclei and very little cytoplasm of
lymphocytes.
Lymphoid tissue
In all secondary lymphoid tissue the
lymphocytes are supported by a rich reticulin
fiber network of type III collagen.
Reticular cells produce the fibers

Typically contains various APCs and plasma

cells
Reticular fibers and cells of
lymphoid tissue

Reticular fibers Cells of typical lymphoid tissue

 T Lymphocytes
Long lived lymphocytes

75% of the circulating lymphocytes

Recognize antigenic epitopes via surface

proteins complexes, T-cell receptors or
TCRs.
TCRs include two glycoproteins called and
chains

MHC restricted
 T Lymphocytes:
Types
Helper T cells
CD4
Assist immune responses by producing cytokines.
CTLs are CD8+
Bind specific antigens on foreign cells or virus-infected
cells displayed by MHC class I molecules
Also called killer T cells
Attach to the cell sources of the antigens and remove
them by releasing perforins and granzymes
Triggers apoptosis
This represents cell-mediated immunity
T Lymphocytes:
Types
Regulatory T cells
Also called Tregs or suppressor T cells
Are CD4+ and CD25+ and serve to inhibit specific immune
responses
Identified by the presence of Foxp3 transcription factor
Produce peripheral tolerance, which acts to supplement
the central tolerance that develops in the thymus
T lymphocytes
Migrate to the epidermis and mucosal epithelia, becoming
largely intraepithelial, and do not recirculate to secondary
lymphoid organs
Activation of
lymphocytes
Activation of
lymphocytes
 B Lymphocytes
The surface receptors for antigens are monomers
of IgM or IgD with each B cell covered by about
150,000 such B-cell receptors (BCRs).
BCRs bind an antigen on an exposed part of the
infectious agent and the surface complexes then
undergo endocytosis

In all secondary lymphoid tissues they interact

with scattered follicular dendritic cells
(FDCs).
 Lymph Nodes
Bean-shaped
Encapsulated structures
Generally only 10 mm by 2.5 cm in
size
400 to 450 lymph nodes in our
body
 Lymph node
Primary function:
production of lymphocytes
filters lymph
provides a site for B-cell activation
differentiation to antibody-secreting
plasma cells.
 Lymph node
3 separate functional
compartments:
1. an outer cortex
2. a central medulla
3. and a smaller area between these
two called the paracortex
FIGURE 14-15 Copyright McGraw-Hill Companies
FIGURE 14-16 Copyright McGraw-Hill Companies
 Lymph nodes
Cortex
Components:
Subcapsular sinus
Cortical sinuses
Lymphoid nodules
FIGURE 14-17 Copyright McGraw-Hill Companies
 Lymph node

Paracortex
lack of B-cell lymphoid nodules
lymphoid tissue rich T cells
high endothelial venules (HEVs)
FIGURE 14-18 Copyright McGraw-Hill Companies
 Lymph nodes

Medulla
Components
Medullary cords
Medullary sinuses
FIGURE 14-20 Copyright McGraw-Hill Companies
Diseases of Lymph Nodes

Lymphadenopathy
Neoplastic proliferation of
lymphocytes producing a malignant
lymphoma

Metastatic cancer cells

From a primary tumor that goes to
the lymph nodes.
 Spleen
Large lymphoid organ without a
cortex/medulla structure
Functionally different regions:
white pulp and red pulp.
FIGURE 14-21 Copyright McGraw-Hill Companies
 Spleen
White pulp
only 20% of the spleen
secondary lymphoid tissue
associated with small central
arterioles that are also enclosed by
periarteriolar lymphoid sheaths
(PALS) of T cells.
FIGURE 14-23 Copyright McGraw-Hill Companies
 Spleen
Red pulp
filters blood
Function
removes defective erythrocytes
recycles hemoglobin iron
- Parts:
splenic cords
splenic sinusoids.
stave cells.
FIGURE 14-25 Copyright McGraw-Hill Companies
 Spleen

Blood flow in red pulp in two ways:

Closed Circulation
Open Circulation
FIGURE 14-22 Copyright McGraw-Hill Companies
 Spleen
Blood filtration
interaction with splenic cord
macrophages
 Disease
Splenomegaly
enlargement of the spleen
Disease