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Elements of innate and
acquired immunity
E. coli bacteria adhering to the surface
of epithelial cells of the urinary tract
Figure 2.1
The developmental
pathway of various
cell types from
pluripotential bone
marrow stem cells.
Neutrophil
This granulocyte has very tiny light staining granules (the granules
are very difficult to see). The nucleus is frequently multi-lobed with
lobes connected by thin strands of nuclear material. These cells are
capable of phagocytizing foreign cells, toxins, and viruses.
When taking a Differential WBC Count of normal blood, this type
of cell would be the most numerous. Normally, neutrophils account
for 50-70% of all leukocytes. If the count exceeds this amount, the
cause is usually due to an acute infection such as appendicitis,
smallpox or rheumatic fever. If the count is considerably less, it
may be due to a viral infection such as influenza, hepatitis, or
rubella.
Eosinophil
This granulocyte has large granules (A) which are acidophilic and appear pink
(or red) in a stained preparation. This micrograph was color enhanced to
illustrate this feature. The nucleus often has two lobes connected by a band of
nuclear material. (Does it looks like a telephone receiver?) The granules contain
digestive enzymes that are particularly effective against parasitic worms in their
larval form. These cells also phagocytize antigen - antibody complexes.
These cells account for less than 5% of the WBC's. Increases beyond this
amount may be due to parasitic diseases, bronchial asthma or hay fever.
Eosinopenia may occur when the body is severely stressed.
Basophil
The basophilic granules in this cell are large, stain deep blue to purple, and are often
so numerous they mask the nucleus. These granules contain histamines (cause
vasodilation) and heparin (anticoagulant).
In a Differential WBC Count we rarely see these as they represent less than 1% of all
leukocytes. If the count showed an abnormally high number of these cells, hemolytic
anemia or chicken pox may be the cause.
Lymphocyte
The lymphocyte is an agranular cell with very clear cytoplasm which stains
pale blue. Its nucleus is very large for the size of the cell and stains dark
purple. This cell is much smaller than the three granulocytes (which are all
about the same size). These cells play an important role in our immune
response. The T-lymphocytes act against virus infected cells and tumor cells.
The B-lymphocytes produce antibodies.
This is the second most numerous leukocyte, accounting for 25-35% of the
cells counted in a Differential WBC Count. When the number of these cells
exceeds the normal amount, one would suspect infectious mononucleosis or a
chronic infection. Patients with AIDS keep a careful watch on their T-cell
level, an indicator of the AIDS virus' activity.
Distinctive membrane molecules on lymphocytes
Monocyte
This cell is the largest of the leukocytes and is agranular. The nucleus is
most often "U" or kidney bean shaped; the cytoplasm is abundant and light
blue (more blue than this micrograph illustrates). These cells leave the blood
stream (diapedesis) to become macrophages. As a monocyte or macrophage,
these cells are phagocytic and defend the body against viruses and bacteria.
These cells account for 3-9% of all leukocytes. In people with malaria,
endocarditis, typhoid fever, and Rocky Mountain spotted fever, monocytes
increase in number.
Development of dendritic cells & macrophages
Macrophages are 5 - 10 fold larger
than monocytes, and contain more
organelles, especially lysosomes.
Alveolar macrophages in the lung
Histiocytes in connective tissues
Kupffer cells in the liver
Mesengial cells in the kidney
Microglial cells in the brain
Osteoclasts in bone
- Langerhans cells
- Interstitial dendritic cells
- Interdigitating dendritic cells
- Circulating dendritic cells
(veiled cells)
SEM micrograph of follicular dendritic
cells showing long, beaded dendrites
Phagocytosis and processing of exogenous
antigen by macrophages
Erythrocyte
The background cells in this micrograph are erythrocytes (red blood
cells). These cells are non-nucleated, biconcave discs that are filled
with hemoglobin. The primary function of these cells is to carry
oxygen from the lungs to the body cells.
Woman usually have 4-5 million erythrocytes per cubic millimeter of
blood, men have 5-6 million. If this number is considerably higher,
polycythemia may be the cause. If the number is considerably less,
the person has anemia.
Sickle cell anemia is an inherited condition which results in some
erythrocytes being malformed. The gene for this condition causes the
hemoglobin to be incorrectly formed, which in turn causes some
erythrocytes to take on a crescent shape. These cells are not able to
carry adequate amounts of oxygen to cells.
Phagocytic defenses
Phagocytes : - class of cells capable of ingestion (engulfment)
& destruction of microorganisms
- recruited to site of inflammation
- two cell types
1) neutrophil (PMN) - 1st to accumulate around invaders
& initiate phagocytosis
2) tissue & blood borne macrophages (mononuclear
phagocytes - migrate to site & initiate phagocytosis
Figure 2.2
Endocytosis and phagocytosis by macrophages.
Figure 2.3
A polymorphonuclear leukocyte (surrounded by erythrocytes
in a blood smear) with a trilobed nucleus and cytoplasmic granules.
(Photograph courtesy of Dr. A. C. Enders, School of Medicine,
University of California, Davis).
Figure 2.4
A scanning electron micrograph of a macrophage
with ruffled membranes and a surface covered with microvilli.
(Photograph courtesy of Dr. K. L. Erickson, School of Medicine,
University of California, Davis)
Figure 2.5
Schematic representation of NK cell inhibitory receptors and killing.
Inflammation
- Def: Tissue reaction to infection or injury, characterized
by erythema, swelling, heat, pain & loss of normal
tissue function
- Necessary for proper functioning of host defenses
Erythema : due to increased blood flow
Swelling : due to increased extravascular fluid &
phagocytic infiltration
Heat : due to increased blood flow & pyrogens
Pain : due to tissue distruction & irritation of sensory
nerve receptors
Major events in the inflammatory response
Tissue bactericides
Substance
Source
Composition
Activity
Serum, saliva,
sweat, tears
Serum, tissues,
secretions
Saliva, tissues
(neutrophils)
protein
bacteriolysis
glycoprotein
Iron binding
protein
oxidation
Fibronectin
Serum, mucosa
glycoprotein
Opsonization,
clearance
Interferons
Virus inf. cells
protein
Virus resistance
Interleukins
Macrophages,
lymphocytes
protein
Complement
serum
proteins
Lysozyme
Lactoferrin &
transferrin
Peroxidase
Activation of
immune system
Lysis,
inflammation
Figure 2.6
The distribution of lymphoid tissues in the body.
Roles of various lymphoid tissues
in immune system function
Generating
stem cells
bone marrow
source of lymphocytes
Regulating
production
thymus, BM
bursa
sites of regulation of
lymphocyte development
Providing
environment
for cell-Ag
interaction
spleen, BM
lymph nodes
tonsils
Peyer’s patch
site of lymphocyte-Ag
interactions
Primary lymphoid organs
- maturation of lymphocytes
- removal of self-reactive lymphocytes
• Thymus
– differentiation of T cell lymphocytes
• Bone Marrow (bursa of Fabricus in birds)
– differentiation of B lymphocytes
Rat thymus
Thymus
1. Lymphoepithelial organ
2. Differentiation of T lymphocytes
3. Only 5 - 10% of maturing T cells survive
4. Size
1) relative size greatest in newborn
2) absolute size greatest in puberty
3) atrophy after puberty
5. Maturation of T cells - mainly during fetal
development and for a short time after birth
Figure 2.7
The cellular organization of the thymus.
Thymus & tolerance
- Tolerance results if host lacks T cells with receptors
specific for Ag
- Range of T cell receptors (TCR) determined in thymus
BM stem cells
React w/ self MHC
Positive selection
Thymocyte proliferation
React w/ “self” thymocytes
Negative selection
Apoptosis
Secondary lymphoid organs
- angen-induced activation of lymphocytes
• Spleen (filters blood)
• Lymph nodes (filter lymph)
• Mucosa-associated lymphoid tissue (MALT)
– Gut-associated lymphoid tissue (GALT)
• Peyer’s patches, tonsils, appendix, …….
– Bronchus -associated lymphoid tissue (BALT)
• diffused aggregates of lymphocytes
Spleen
- Removes Ag & aged blood cells
- Stores RBC & platelets
- Site for Ab production & effector T cells
- Consists of
red pulp - storage of RBC & Ag trapping
white pulp - immune response
Erythrocytes &
macrophages
Rich in
lymphocytes
Figure 2.8
Schematic views and light micrograph of a section of spleen.
B cells
Macrophages
T cells
Derived from follicles after Ag stimulation
Response of spleen to antigen
Ag trapped in spleed
macrophages in marginal zone, red pulp
primary follicles in white pulp
Ab producing cells in primary follicles
germinal center in primary follicles
Figure 2.9
(A) A diagrammatic
representation of a section
of a lymph node.
(B) A section through a
lymph node showing the
capsule, the subcapsular
sinus, the medulla (upper
left), and the cortex with
secondary follicles
containing
germinal centers. Also
shown
(upper right) is a follicle
without a germinal center.
Lymphatic vessels
Structure of M cells and production of IgA at inductive sites
Figure 2.10
Circulation of lymph and fate of antigen following
penetration through (1) the bloodstream, (2) the skin, and
(3) the gastrointestinal or respiratory track.
Figure 2.11
The interrelationship between innate and acquired immunity.