Assoc. Prof. Ma. Jennifer R.

Tiburcio, MSMT

Immunology
Scope of Immunology
Molecular Mechanisms of Immune Response
Development of Testing for Disease States
Recognition of Self Antigen
Manipulation of the Immune System
Definitions
Cells, Organs, Molecules & Systems
Body components respond & interact
Desirable & undesirable interactions
Manipulation of the Immune System

Subdisciplines
Serology
Immunochemistry
Immunobiology
Immunopathology
Immunogenetics
Psycho-neuro immunology

Foreign Substances
Bacteria
Viruses
Fungi
Parasites

Immunity (Resistance)
Ability of the host to resist infections.

Susceptibility
Vulnerability or lack of resistance
Innate Immunity
Nonspecific
Activation of nonspecific cells and
molecules
First line of defense
External and Internal defenses
Innate or nonspecific immunity
External defenses
Natural barriers to infection
Skin, body secretions & mucous
membranes ex. T. pallidum & S.
mansoni
Innate or nonspecific immunity
External defenses
Skin
lactic acid & fatty acid bacteriostatic agents
Body secretions
Tears
washing action
lysozyme

Innate or nonspecific immunity
External defenses
If the pathogens are
Inhaled mucus & ciliated epithelium of the
RT as filters
Swallowed mucus of the DT prevents
adsorption & penetraton of pathogens
Innate or nonspecific immunity
External defenses
Low pH of the stomach
kills pathogens

Normal flora of the small intestines
inhibits attachment to host cells
Innate or nonspecific immunity
Internal defenses
1. Physiologic barriers
temperature
oxygen tension
complement proteins
interferons
Alpha
(leukocyte interferon)
Virus induced leukocyte
Null lymphocytes
Anti viral
Activates NK cell
Immunosuppresive agent
Beta
(fibro-epithelial, BCSF
ILK-6)
Double stranded RNA induced
fibroblast cultures
Epithelial, fibroblast, macro-
phages
Anti-viral
Induces secretion of Ig
Inducing acute phase
reaction
Gamma
(Immune)
Immunologically stimulated
lymphocyte cultures
T & B lymphocytes

Immunoregulator

Types of Interferon
Innate or nonspecific immunity
Internal defenses
2. Phagocytosis
involves engulfment & destruction of
pathogens & particulate matter by cells of
the mononuclear phagocytic system

Innate or nonspecific immunity
Internal defenses
Monocytes & macrophages
host defense (phagocytosis)
Differences
location in the tissues
role in host defense
Innate or nonspecific immunity
Internal defenses
Monocyte immature precursor of
macrophage
Arises from the bone marrow cells
Release in the circulation, enters the tissues &
become macrophage
Tissue Macrophages
No peroxidase
Specific names
Alveolar macrophages
Kupffer cells
Microglial cells
Histiocytes
lung
liver
brain
Connective tissue
Innate or nonspecific immunity
Internal defenses
Macrophage
biologically active molecules (cytokines)
Interferon (IFN) 1, 6
Tumor necrosis factor (TNF)
function as antigen presenting cell (APC)
Innate or nonspecific immunity
Internal defenses
PMNLs or neutrophils
filled w/ granules containing potent
digestive
chemicals
exerting nonspecific cytotoxic activity
against a wide range of normal &
malignant targets
Innate or nonspecific immunity
Internal defenses
Natural Killer (NK) cells
granule-filled cells
not phagocytic
contribute to nonspecific defense against
infected body cells & tumor cells
Innate or nonspecific immunity
Internal defenses
Phagocytosis occurs in 2 stages
1. Recognition & ingestion of antigen
(pathogen)
2. Actual degradation of antigen (pathogen)
Innate or nonspecific immunity
Internal defenses
Recognition & ingestion
Directly primitive patterns recognition
receptors
Indirectly - opsonins
Innate or nonspecific immunity
Internal defenses
Ingestion
occurs when the phagocyte extends a finger-
like projection pseudopodia

contained in a vacuole - phagosome


Innate or nonspecific immunity
Internal defenses
Degradation of the pathogen
Cytotoxic molecules are generated in 3 ways
1. formation of phagolysosome prodn of
defensin
lactoferrin
lysozyme
Innate or nonspecific immunity
Internal defenses
2. Activation of enzymatic complex
NADPH oxidase prodn of
reactive O
2
intermediates
superoxide anion
hydrogen peroxide
hydroxyl radicals

Consumption of O
2
& formation of these products
respiratory burst



Innate or nonspecific immunity
Internal defenses
3. Nitric oxide (phagosome membrane)

Defects in phagocytic function can occur at
any one of these steps
Innate or nonspecific immunity
Internal defenses
3. Inflammation
Inflammatory response
- initiated by chemical mediators
- symptoms (redness, swelling , pain, heat)
- collectively a series of vascular events
that serve as a defense mechanism
Innate or nonspecific immunity
External defenses
Events include
1. Clotting mechanism activation
2. Increased blood flow
3. Increased capillary permeability
4. Enhanced influx of phagocytic cells
Site of infection
clotting mechanism is activated
pathogens trapped in the clots
infection becomes localized
immune cells (phagocytic cells)
Neutrophils accumulate within 30-60 mins
Cause of inflammatory response persists (5-6
hrs)
macrophages & lymphocytes
infiltration
Inflammation continues
augmentation by the elements of acquired
immunity
(Abs & molecules - activated lymphocytes)
These cells attach to the adhesion molecules
on the surrounding blood vessel walls

Vasodilating substances (bradykinin &
histamine)
increase the flow of blood
also cause increase capillary permeability
(the blood vessel walls near the infection
site become permeable to the passage of
phagocytic cells into the tissue spaces)
In the tissue spaces,
the phagocytic cells can engulf the
pathogens
mediate repair
produce molecules that control further
cellular interactions

Multiple mediator systems regulate
inflammation
soluble blood plasma proteins of the clotting system
the kinin system
complement system
molecules that induce the systems
invading microorganisms
injured tissues
products from participating WBCs
Serum acute phase proteins
characterized groups of molecules
produced during tissue-damaging
infections

C-reactive protein
produced by the liver
in response to macrophage-derived IL-6
binds to the C-polysaccharide cell wall
component of many bacteria & fungi
activates the C system the surface
associated C increases phagocytosis &
promotes C mediated lysis of the
organism

Innate or nonspecific immunity
Components of Innate
immunity
preformed
standardized
without memory
nonspecific
Innate or nonspecific immunity
An organisms innate immunity depends on

race
species
sex
Genetic Factors
Genes
Ex. Duffy receptors on the red cell membrane
Acquired or specific Immunity
recognize & respond to a specific invader even w/o prior
exposure & marked by an enhanced response on
repeated exposures to the invader
specificity
diversity
memory
Distinguish self from nonself
self-limiting
inducibility
Acquired or specific Immunity
Specific Immune Responses
1. Humoral immunity
antibodies (produced by B cells)
extracellular antigens (bacteria, microbial
exotoxins, viruses in their extracellular phase)
acute bacterial infections
Acquired or specific Immunity
Specific Immune Responses
2. Cellular immunity
antigen specific cells (T-cells)
intracellular parasites (viruses)
rejection of organ transplants & tumor cells
chronic bacterial infection, viral, fungal &
parasitic infections
Acquired or specific Immunity
Active
acquired gradually after antigen exposure
lasts for years & is highly protective
Passive
immediate & has low to moderate protective
effectiveness
does not develop memory in the recipient

Acquired or specific Immunity
Naturally acquired
during convalescence from an infection
placental passage of antibody from mother to
fetus

Acquired or specific Immunity
Artificially acquired
vaccination
injection of gamma
globulin


Natural
1
st
line of defense
Acquired
Reinforcement of the ultimate means
of resistance
Mechanism of action
Very general
Mechanism of action
Highly specific
Cells involved
PMN, macrophages of the RES, NK
cells
Cells involved
T & B lymphocytes
Soluble mediators
Lysozyme, interferon, complement,
etc
Lacks memory component
Resistance not improved by repeated
infections
Soluble mediators
Lymphokines & antibodies

w/ memory component
Resistance improved by repeated
infections
Immune System
(Computerized war machine)
Virus enters the body,
Comes out of its protein
coat
Releases its DNA or RNA
and
Begins to replicate
Cells respond by releasing
chemicals
T & B cells are alerted
Danger is in the area
Low grade fever results
Note the surface markers
Cells challenge &
demand password from
the invader
Report to the nearest
lymph node head quarters

Localized lymph node
swelling
Increased WBC count
T cells kill on contact if
possible
Report to the thymus
Instruct the lymph node
to release more T cells
B cells release antibody
Complement components
increased in serum
Change antibody shape
Activates complement
cascade molecules
Neutralizing & destroying
the invaders
Lack of appetite
Weakness
Inflammation
General aches and pains
Antigens pour into the
bloodstream
Attach themselves to the
invaders
Causing clumping
Diarrhea
Vomiting
Nausea
Inflammation

Release of histamine &
other chemicals
Stimulate macrophages
Improved appetite
Decreased fatigue
Decreased
inflammation
Lowered WBC count
Macrophages ingest dead
tissues & injured cells
Return to the lymph tissue
Provide future rapid
response
IMMUNITY
Which one of the following is a cell
classed with adaptive immunity?
A. phagocyte
B. neutrophil
C. antigen presenting cell
D. B cell
E. natural killer cell
Which one of the following cells plays an
important role in host immunity to
helminths?
A. natural killer cells
B. mast cells
C. eosinophils
D. macrophages
E. neutrophils
The main role of cytotoxic T cells and
natural killer cells is to destroy
A. extracellular bacteria
B. intracellular bacteria
C. virally infected cells
D. helminths
E. all of the above
Humoral innate immunity includes all
of the following except
A. lysozyme
B. lactoferrin
C. pepsin
D. complement
E. resident flora
Megan, an active three year old girl, was chasing
her puppy when she slipped on loose gravel. She
tried to break her fall and as a result scraped both
her hands.
1. What anatomical barrier was breached as a result
of scraping her hands?


2. Breaching anatomical barriers permits entry of
microorganisms & other antigens. Which category
of the immune system would be activated
immediately following entry of foreign particles?
skin
Innate
3. What class of cells would initially target
the antigen?
phagocytes
Which of the following is(are) characte-
ristic(s) of acute phase reactants?
A. Nonspecific indicators of inflammation
B. Rapid increase following infection
C. Enhancement of phagocytosis
D. All of the above