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Introduction
Immunology is the study of physiological mechanisms that
are used to defend the body from invasion by foreign or
infectious agents
In response to diseases caused by infectious agents, the
body develops cells dedicated to defense these form the
immune system
Protective/adaptive immunity takes time to develop, while
microorganisms can rapidly multiply and cause disease
Immunity involves two responses:
1. Flexible but specific defenses of the adaptive immune response
2. Fixed defenses of the innate immune response
Historical Perspective
430 BC- Thucydides recognized that only those who had
recovered from the plague could nurse the sick without
becoming sick again.
Fifteenth century- Chinese and Turks used dried crusts from
smallpox pustules (inhaled or inserted into small cuts in the
skin variolation) to induce immunity.
1796- Jenner realized milkmaids who had contracted cowpox
(mild disease symptoms compared to smallpox) were not
susceptible to smallpox.
He theorized that using fluid from a cowpox pustule would induce
immunity to smallpox
Tested theory on 8 yr old boy- inoculated boy with fluid from cowpox
pustule then later injected the boy with smallpox. The boy didnt
contract smallpox.
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Historical Perspective
Origins of immunology attributed
to Edward Jenner
Discovered in 1796 that cowpox
vaccinia protected from human
smallpox
Procedure called vaccination
Prevents severe disease by
exposing the immune system to
the infectious agent in a
weakened or killed state.
Provides long term protection
against the real pathogen with
very little risk of becoming sick.
Examples
of the types
of
pathogen
are listed,
along with
the
diseases
they cause
Pseudohyphae
Mycobacterium
tuberculosiscauses
tuberculosis
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Commensal Bacteria
-Over 1000 microbial
species in the human gut
(normal flora).
-These bacteria typically
cause no harm to the host.
-Commensal = eat at the
same table. Not harmful
-When a round of antibiotics
is taken, there is no
specificity for the pathogen
so a large percentage the
bacteria (good and bad) are
killed.
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Strong barriers to
infection provided by the
skin, hair, and nails are
colored blue
More vulnerable mucosal
membranes are colored
red
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Complement (Innate)
- Series of proteins that act to tag an invader for uptake
(phagocytosis) by other immune cells or by poking holes in the
microbe by completing the complement cascade.
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Inflammation
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It works rapidly
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Many of the cells of the innate immune system are the same
cells used by the adaptive immune system
Vaccinations require that the innate immune system is
engaged in order to provide memory.
Innate immune system activates and aids in the adaptive immune
response.
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Principle Characteristics of
Innate and Adaptive Immunity, Figure 1.8
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2. Mononuclear phagocytes
Neutrophils
Eosinophils
Basophils
based on morphology and cytoplasmic staining characteristics
4. Dendritic cells
Hematopoiesis
The generation of the cellular elements of blood, including:
Red blood cells (RBC)
White blood cells (WBC) or leukocytes
Megakaryocyte - Platelets
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The
pluripotent
stem cell
divides and
differentiates
into more
specialized
progenitor cells
that give rise to
the
lymphoid
lineage
myeloid
lineage
erythroid
25
Most
abundant
leukocytes
are the
neutrophils
Followed by
lymphocytes
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Lymphocytes
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Lymphoid Cells
Lymphocytes are divided into three classes
1. B cells (Igs receptor)
2. T cells (TCR)
3. NK cells (Natural killer cells)
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Neutrophils
Effectors of innate immunity specialized in the capture,
engulfment and killing of microbes
Work in the anaerobic conditions found in damaged tissue
Are short-lived and die at site of the infection one the major reasons
for pus formation at the site of injury
Pus former = pyogenic
Are phagocytic cells that contain toxic substances in intracellular
granules (primary and secondary granules)
Employ oxygen-dependent and oxygen-independent pathways to
destroy pathogens
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Mononuclear Phagocytes
Monocyte progenitors in the bone marrow differentiate into
pro-monocytes, which enter the blood, where these
differentiate into monocytes
Monocytes circulate in the blood for about 8 hours, then
mature and migrate into tissues, they are then referred to as
macrophages.
Both monocytes and macrophages are phagocytic
Monocytes in the peripheral blood
Macrophages in the tissues
34
Mononuclear Phagocytes
Differentiation of monocyte into macrophage requires
changes
Monocyte cells enlarge 5-10 times
Increased intracellular organelles
Increased phagocytic ability
Production of hydrolytic enzymes
Secretion of soluble factors
35
36
Dendritic Cells
Dendritic cells are so called because of their many surface
membrane folds, similar in appearance to dendrites of the
nervous system
These folds allow maximum interaction with other cells of
the immune system
What is the dendritic cells main job?
37
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Mast Cells
Mast cells are found in the skin, connective tissue and
mucosal epithelial tissue of the respiratory and digestive
tracts
The origin of mast cells is uncertain but precursors
differentiate in the bone marrow and mature in tissues
When activated mast cells degranulate, they release
pharmacological mediators (e.g. histamine) which cause
Vasodilation
Increase vascular permeability
Attract leukocytes to the site of degranulation
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Eosinophils
Eosinophils are granular leukocytes which stain with eosin
(red)
They are present at low levels in the circulation (1-6% of blood
leukocytes
Eosinophils have some phagocytic activity but are primarily
responsible for extracellular killing of large parasites such as worms
They usually bind to an antibody-coated parasite and release the
contents of their granules (degranulate) onto the parasite surface
One of the three granulocytes
41
Basophils
Basophils are granulocytes which stain with basic dyes (blue)
and are present in very low numbers in the circulation (<0.2%
of the granular leukocytes)
Basophils and mast cells are very similar in morphology
Both contain and release large characteristic electron-dense granules
in their cytoplasm during allergic reactions (e.g. histamine)
Like all the granulocytes, basophils are produced from stem cells in
the bone marrow
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Megakaryocyte
Megakaryocyte is a bone marrow cells responsible for the
production of blood platelets when its cytoplasm becomes
fragmented
These fragments are blood platelets
Megakaryocytes account for less than 1% of bone marrow cells but
can be 10 to 15 times larger than a typical red blood cell
The nucleus of the megakaryocyte is very large and lobulated, which,
under a light microscope, can give the false impression that there are
several nuclei
Erythrocytes
Erythrocytes bind to immune complexes composed of antigen
and antibody and carry these complexes to the liver where
these are cleared by Kupffer cells
Erythrocytes have an important immunological role in clearing
immune complexes from the circulation in persistent
infections and in some autoimmune diseases
Kupffer cells = phagocytic cells of the liver that line the
hepatic sinusoids
46
Hematopoiesis is active
throughout life because blood
cells are both vital and short-lived
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48
49
Process of Phagocytosis
Macrophage (pink)
E. Coli (green)
50
Phagocytic process
Several stages
1. Phagocyte attraction to the site of infection
2. Phagocyte contact with the microbe
3. Ingestion (endocytosis)
4. Killing of the ingested microbe by means of oxygen and oxygenindependent mechanisms
Opsonization
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Mechanisms of Protection
Antigens- Any molecule or molecular fragment that can be bound to by an
antibody or be bound by an MHC molecule and presented to a T-cell.
Can be proteins, lipids, or sugars
Can be found on the surface or secreted by microorganisms
Antibodies (immunoglobulins)- Proteins molecules synthesized by cells of
immune system part of the humoral immunity
Humors = bodily fluids
That recognize antigens
55
Adaptive Immunity
Occasionally the infection outruns the innate immune
response
Innate immunity has a restricted number of receptors to recognize
pathogens
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Lymphatic System
60
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Circulating Lymphocytes
Encounter Lymph-borne Pathogens in
Draining Lymph Nodes
Lymphocytes leave blood and
enter lymph nodes where they are
activated by pathogens
Pathogens drain from site of
infection (example: foot) to lymph
nodes via afferent lymphatic
vessels
Activated lymphocytes stay in
lymph nodes and divide and
differentiate into effector cells,
while non-activated cells leave
through efferent lymphatics
Lymphocytes recirculate at a rate
of 5 X 106 cells/min
62
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2.
Cytotoxic T cells
3.
Helper T cells
5.
1.
4.
B cells
6.
7.
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The Spleen
Filter for blood that removes old or damaged cells = Red pulp
Site where blood-borne pathogens encounter lymphocytes (a secondary lymphoid
organ) = White pulp.
Blood is the only way in and out for lymphocytes as well as pathogens.
Spleenic macrophages and dendritic cells in the spleen take-up antigen and
stimulate T an B-cells.
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The Spleen
White pulp of
spleen consists of
sheath of
lymphocytes called
the periarteriolar
lymphoid sheath
(PALS)
surrounding a
central arteriole
(CA)
T cells are closest
to the CA, while B
cells are more
peripheral, forming
a B cell corona
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A Region of GALT
Peyers
patch
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Immunological Memory
Lymphocytes that expand persist, providing long term
memory
First time infection results in a primary response which leads to
memory (T and B cells) of the pathogen.
Subsequent infections with the same pathogen, having the same
antigens, will elicit a secondary response which is much faster and
stronger than the original primary immune response.
This is the basis of vaccination
71
Comparison of a Primary
and Secondary Immune Response
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