Definition of terms and re-inoculated same boy with infectious

Immunology pus from patient in the active small pox.

 The study of immune system or immunity  No disease state followed these inoculations,
 the study of all aspects of host defense and experiment was repeated several times
against infection and of adverse with great success!
consequences of immune responses.
 The study of the physiological mechanisms Louis Pasteur- demonstrating that it was
which enable the body to recognize possible to attenuate, or weaken, a pathogen and
materials as foreign and to neutralize, administer the attenuated strain as a vaccine. In
metabolize or eliminate them without injury 1885, Pasteur administered his first vaccine to a
to the host tissue. human, a young boy who had been bitten
Immunity repeatedly by a rabid dog
State of protection from infectious diseases
Immune system Jenner's provided first clear evidence that active
A remarkably versatile defense system that has immunization could be used safely to prevent an
evolved to protect animals from invading infectious disease.
pathogenic microorganisms and cancer.
It is able to generate an enormous variety of Almost 70 Years later, Pasteur - introduced
cells and molecules capable of specifically pasteurization also. Recognized and exploited
recognizing and eliminating an apparently the general principle underlying vaccination
limitless variety of foreign invaders.
1.2. History of immunology At about 1900,
Its principles among the earliest written  Role of phagocytes and cellular immunity
observations; were elucidated
 Individuals recovering from certain disease  Killed vaccines were introduced
rarely contracted that same disease again.  Complement was described
 observation promoted deliberate attempts to In 20th century,
induce immunity  Acquired immunity resulted from both
 Athens plague as of Thucydides in 430BC cellular and humoral elements were
(recovered) people only nurse sick one demonstrated.
 Chinese(1500A.D) custom of inhaling crusts  Opsonization was described
from smallpox lesions to prevent  The term antigen came in to regular use
development of small pox in later life. Noble prize winners for immunologic
 Injecting materials from crusts or fluid from research
smallpox blisters ("variolation"), used  1901 Emil von Behring, Serum antitoxins
throughout the eastern world, in 1718 was  1905 Robert Koch, Cellular immunity to
introduced into western medicine by tuberculosis
 British ambassador's wife, to Turkey, had  1908 Elie Metchnikoff, Role of
her children so treated. phagocytosis
 Note- The virus used could be transmitted  1908 Paul Ehrlich, antitoxins in immunity
protection by variolation was hazardous to  1913 Charles Richet, Anaphylaxis
the community at large  1919 Jules Border, Complement-mediated
 In 1798, Jenner's work on vaccination, bacteriolysis
describing а related, yet safe procedure.  1930 Karl Landsteiner, Discovery of human
 Noted people, who had cow pox, were blood groups
spared in small pox epidemics, inoculated  1951 Max Theiler, Development of yellow
boy with pus from milk maid with cow poх, fever vaccine
 1957 Daniel Bovet,Antihistamines
 1960 F. Macfarlane Burnet and Peter
Medawar,
 Discovery of acquired immunological
tolerance
 1972 Rodney R. Porter and Gerald M.
Edelman,
 Chemical structure of antibodies
 1977 Rosalyn R. Yalow, Development of
 radioimmunoassay
 1980 George Snell, Jean Daussct and Baruj
Benacerraf
 Major histocompatibility complex 1.4 The Innate immunity
 1984 Cesar Milstein and Georges E. Köhler, Natural immune system (Innate Immunity)
Monoclonal antibody  Non - specific
 1984 Niels K. Jerne, Immune regulatory  First line of defense
theories  Repeated exposure - no augmentation
 1987 Susumu Tonegawa, Gene Components
rearrangement in antibody production a. Biochemical enzymes, C', etc.
 1991 E. Donnall Thomas and Joseph Murray secretions pH
 Transplantation immunology b. Physical
 1996 Peter C. Doherty, Role of major skin, cilia
histocompatibility complex c. Cells
 1996 Rolf M. Zinkernagel, in antigen Phagocytes, NK
recognition by by T cells Example
a. Burn response

Overall non-specific reaction of body to injury

or invasion starts immediately with infection or
trauma
 Reactants may initiate, expand, or sustain
the response
 Can be acute (short duration) or become
chronic (prolonged duration)
Has 4 cardinal signs: heat, pain, redness, loss invaders and contain antibacterial or
of function resulting from: antiviral substances.
Increased blood and plasma flow to the area  acidity (pH 5.6) of sweat, sebaceous
Increased capillary permeability by glands, vagina (pH 5) and stomach
retraction of endothelial cells (pH 1) - unfriendly to many
mediated by vaso active agents such as microorganisms
histamine and prostaglandins.  enzymes present in the skin and
 derived from injured cells and later stomach, tears
from cells that infiltrate the area.
Migration of leucocytes, particularly  Normal flora - out compete pathogens
Neutrophils and macrophages, from the for attachment sites on the epithelial cell
capillaries to the site of injury is due to a surface and for necessary nutrients.
process called chemotaxis.
Migration of white cells, especially early 1.4.2 INTERNAL INNATE DEFENSE
migration of neutraphils then macrophages SYSTEM
to the area To prevent expansion of penetration
Increased release of mediators such as
histamine from damaged mast cells -  Recognize carbohydrates not normally
furthering capillary dilation present on cells such as mannose
Increased concentration of acute phase  May cause nonspecific activation of
reactants that can amplify and/or control the white cells
response  Phagocytosis - by neutraphils,
eosinophils, basophils, or
COMPLEMENT macrophages, mast cells, and
a series of enzymes normally circulating in an dendritic cells
inactive form may be activated resulting in lysis  Clotting mechanism which entraps
or enhanced phagocytosis of cell organisms in fibrin clots
 Complement System can lye cells or
enhance phagocytosis
1.4.1 EXTERNAL INNATE DEFENSE Physiologic Barriers
SYSTEMS a. Soluble factors contribute to innate
Prevent entrance: immunity; they are collectively known
 Structural barriers - effective with most as acute phase reactants.
microorganisms b. Normal serum components, non-specific
 Skin - epidermis = layers of tightly responders to inflammation
packed c. Increase because of infection, injury,
 epithelial cells. Outer layer is dead cells trauma
and keratin, waterproofing protein d. Produced mostly by liver in response to
 Inner layer skin - dermis = blood inflammation and cytokine stimulation
vessels, hair follicles, sweat glands, and  Cytokines: IL-1, IL-6 and TNF alpha
sebaceous glands that produce an oily which are produced by macrophages and
secretion called sebum monocytes at inflammatory site are
 Cilia and cough reflex - helps expel activators
microbe ncontaining mucous;Sneeze Acute phase reactants are chemically varied
 Mucus - conjunctivae, alimentary, and include:
respiratory, and urogenital tracts saliva,  C-reactive protein,
tears, and mucous secretions wash away  serum amyloid A,
  mannose binding protein,  Formation of phagolysosome
 alpha-1 anti-trypsin,  Digestion
 haptoglobulin,  Release of debris
 fibrinogen, Phagocytosis
 ceruloplasmin, a. Is a form of endocytosis.
 alpha-1 acid glycoprotein b. Important body defense mechanism is
 Complement process in which specialized cells engulf and
destroy foreign particles such as
COMPLEMENT - a series of enzymes microorganisms or damaged cells.
normally circulating in an inactive form c. Macrophages and segmented Neutrophiils
 May be activated by the classical or alternate are the most important phagocytic cells.
pathways
 Can result in lysis or enhanced phagocytosis Can be divided in to several stages:
of cells
LYSOZYME, a hydrolytic enzyme in mucous Chemotaxis - attraction of leukocytes or
secretions and in tears, can cleave the other cells by chemicals
peptidoglycan layer of bacterial cell wall. Movement of neutraphils is influenced by
chemotaxins chemical messangers
INTERFERON, proteins produced by virus-  Complement, proteins from coagulation,
infected cells. Has many functions including  Products from bacteria and viruses,
ability to bind to nearby cells and induce a  Secretions from mast cells,
generalized antiviral state. lymphocytes,
 macrophages, and other neutraphils
C-REACTIVE PROTEIN
a. Normally trace levels in serum Adherence - binding of organism to the
b. Early acute inflammation indicator: surface of phagocytic cell.
 increases within 4-6 hrs of infection or Engulfment:- is the injestion of m/os and
trauma formation of phagosomes.
 100 to 1000 fold increase serum Digestion - after the foreign particle or m/os
concentration is ingested, cytoplasm lysosome fuse with
 concentration drops rapidly in serum phagosome. The enzymes of lysosome then
when stimulus removed contribute to microbial killing and lysis.
c. Enhances opsonization, agglutination,
precipitation, and classical pathway
complement activation - enhances removal
of irritant
PHAGOCYTOSIS
Phagocytic cells Chemotaxins such as
 Complement components
 Coagulation cascade proteins
 Bacterial and viral products
Attract phagocytic cells including:
 Mast cell, lymphocyte, macrophage,
neutrophil products
Physical contact between phagocytic cell
and foreign object results in
 Formation of phagosome
 1.5. THE ADAPTIVE IMMUNE SYSTEM Diversity- total number of antigenic specificities
1.5. Adaptive Immunity of the lymphocytes in an individual, called the
Specific lymphocyte repertoire, is extremely large.
Second line of defense
Repeated exposure - augmented - memory  estimated mammalian immune system can
Faster response discriminate 10^9 to 10^11 distinct antigenic
More vigorous response date ruminants.
Longer lasting response  This property of the lymphocyte repertoire is
Anamnestic called diversity. It is the result of variability
in the structures of antigen- binding sites of
COMPONENTS lymphocyte receptors for antigens.
Classic Immune System
Cells (Cell mediated) =CMI Memory- Exposure of the immune system to
Soluble Factors (Humoral immunity) = HI foreign antigen:
1.5. The adaptive immune system  enhances its ability to respond again to that
a. Capable of recognizing and selectively antigen.
eliminating specific foreign microorganisms  Responses to second and subsequent
and molecules(i.e., foreign antigens). exposure to the same antigen, called
b. Unlike innate immune responses, adaptive secondary immune responses, are usually
immune responses are reactions to specific more rapid and larger than the first or
antigenic challenges primary immune response.
c. Different populations of lymphocytes and
their products are the major actors together
with accessory cells - Antigen presenting
cells (APCs)
d. Cardinal features are:
 Specificity 1.5. The adaptive immune system
 Diversity, Memory, An effective immune response involves three
major groups of cells: Cellular Immunity (T
Cardinal Features of adaptive Immune lymphocytes), Humoral Immunity (B cells),
Responses and Accessory cells (antigen-presenting cells).

Specificity- The two major populations of lymphocytes-

specific for distinct antigen, and B-lymphocytes (B cells) of Humoral immunity
for different structural components of a and T-lymphocytes (T cells) of Cellular
single complex protein, polysaccharide, or Immunity provide us with our specific adaptive
other macromolecules. immunity
Portions of such antigens recognized by
individual lymphocytes are called Specialization -the immune system responds in
determinants or epitopes. distinct and special ways to different microbes,
This fine specificity exists because maximizing the efficiency of antimicrobial
individual lymphocyte express membrane defense mechanisms. Thus, humoral immunity
receptors able to distinguish subtle (slight) and cell mediated immunity are elicited by
differences in structure between distinct different classes of microbes or by the same
antigens. microbe at different stages of infection (extra
cellular & intra cellular)
Self -limitation- All normal immune responses B. Hypersensitivity reactions to usually
returning the immune system to its resting or harmless substances are often called
basal state with time after antigen stimulations, allergies or allergic reactions
process called homeostasis.  allergens - antigens that cause allergic
reactions
C. Most allergic reactions fall into one of four
major types:
1. Type I: Immediate IgE-mediated
2. Type II: Cytotoxic
3. Type III: Immune complex-mediated
4. Type IV: Delayed cell-mediated

TYPE I HYPERSENSITIVITY
A. Also called IgE Mediated Hypersensitivity
B. Mechanism

1.First exposure to antigen induces an IgE

antibody response leading to sensitization

i. Antigen is taken up by dendritic cells

(APC-antigen presenting cell
(macrophage) and merged with
MHC(major histocompatibility
complex-series of genes located on
chromosome-6 that code for antigens)
molecules
ii. APC presents the antigen to T-cells
iii. Activated T-cells release cytokines that
stimulate B-cells to produce plasma
1.Define the term immunity and immunology? cells which secrete large amounts of IgE
2. Describe the historical events of immunology iv. IgE antibodies bind to mast cell
and its development. receptors and the individual is now
3. What is the difference between innate and "sensitized"
adaptive immunity in terms of components and
type of immune response. 2. During the subsequent exposures, antigens
4. Explain major defense mechanism of innate activate IgE antibodies on the mast cell
immunity and adaptive immune system causing it to degranulate
i. Histamines, leukotrienes,
prostaglandins, and/or cytokines are
released
IMMUNOLOGICAL DISORDERS ii. These chemicals are the cause of hives,
Introduction hay fever, asthma and anaphylactic
A. There are three types of immunological shock
disorders 3. Reactions generally occur within 30 minutes
1. Hypersensitivity of exposure
2. Autoimmune disease
3. Immunodeficiency
C. Localized Anaphylaxis A. Also called Cytotoxic Hypersensitivity
1. Hives - an allergic skin condition because it utilizes antibodies that can
characterized by the formation of a wheal destroy normal cells by complement lysis or
and flare pattern by antibody-dependent cellular cytotoxicity
i. Frequently the result of seafood allergies (ADCC)
ii. These reactions are due to the release of B. Generally occur within hours after exposure
histamine which causes dilation of tiny
blood vessels and the leaking of plasma C. Transfusion Reactions - the ABO blood
into the area groups are the major cause of hemolytic
anemia in blood transfusion patients
2. Hay fever - itchy, teary eyes, sneezing, and
runny nose; occurs when allergic person 1.Recall that persons with A type blood
inhales an antigen rather than ingests it possess the A antigen and the natural
 also mediated by histamine antibody anti-B
3. Asthma - inhaled allergen causes chemical
mediators from IgE to stimulate increased 2. Persons with B type blood possess the B
mucus secretions and spasms of the bronchi antigen and the natural antibody anti-A
 leukotrienes and prostaglandins are
3. Persons with O type blood lack both the
responsible
A and B antigens but possess both the
natural antibodies anti-A and anti-B
D. Generalized Anaphylaxis
1. Antigen enters the bloodstream and 4. Persons with AB type blood possess both the
becomes widespread and the reaction A and B antigens but posses no natural
affects almost the entire body (systemic) antibodies
2. Loss of fluid from the blood vessels into
tissues causes swelling and possibly shock 5. In the case of ABO incompatibility, the
3. Reactions may be fatal within minutes antibodies cause reactions that include fever,
4. Bee sting, peanut, and penicillin allergies low blood pressure, pain, nausea, and vomiting
account for most cases
5. Can usually be controlled by 6. Cross-matching the bloods and other
techniques are used to ensure compatibility of
epinephrine injections
donor and recipient
E. Immunotherapy
1. Desensitization or immunotherapy is
often effective in decreasing the Type I D. Hemolytic Disease of the Newborn
hypersensitivity state 1. Also called Erythroblastosis fetalis
2. Results when mother is Rh - and baby
i. Repeated injections of very small is Rh+
amounts of antigen are given over 3. Upon delivery, Rh+ antigens are
several months transferred to the mother's
ii. This regimen leads to the formation of bloodstream which causes her to
specific IgG antibodies produce anti-Rh antibodies
iii. The IgG reacts with antigen before it 4. If the mother becomes pregnant again with
can bind to IgE and therefore it blocks Rht child, the antibodies cross the placenta,
the IgE reaction that might result in enter the circulation of the fetus, and cause
allergic reactions extensive fetal erythrocyte damage
TYPE II HYPERSENSITIVITY an
5. RhoGAM may be administered to prevent this
reaction
A) contains Rh antibodies and prevents the
mother's natural production of them
B) widely used at 28 weeks and after delivery
during all susceptible pregnancies

TYPE III HYPERSENSITIVITY

A. Also called Immune Complex-Mediated
Hypersensitivity
B. Occurs within hours or days after exposure
C. When there is a slight excess of antigen,
the antigen-antibody complexes activate
complements and stimulate neutrophil and
basophil degranulation
 Results in vasodilation, increased
vascular permeability, and inflammation
D. Small antigen-antibody complexes are
often deposited in the walls of small blood
vessels in skin, joints and kidneys where
they continue to cause inflammation and
eventually tissue damage
E. The complexes can also precipitate causing
clots to form in the small blood vessels leading
to failure or death of the organ
1. Known as Disseminated Intravascular
Coagulation: a condition resulting from
overstimulation of the blood clotting mechanism
in response to disease /injury such as severe
infection, acute leukemia, burns, trauma,
abruptio placenta or intrauterine fetal death.

a. While there's no cure for lupus, current

treatments focus on improving quality of life
through controlling symptoms and
b. minimizing flare-ups. This begins with
lifestyle modifications, including sun
protection and diet. Further disease
management includes medication such as
anti-inflammatory and steroids.