PRELIM LEC: INTRODUCTION TO IMMNUNOLOGY AND SEROLOGY AND ITS HISTORICAL BACKGROUND Flashcards
Study of a host’s reactions when foreign substances are introduced into the body
IMMUNOLOGY
How the body fights infection, irritants (allergen, UV), carcinogens and toxins.
IMMUNOLOGY
Host’s reaction when foreign substances (antigens) are introduced to the body.
IMMUNOLOGY
Best defined as the study of components of the immune system and how the body defends itself against dse.
IMMUNOLOGY
How the body components respond and interact to provide immunity.
IMMUNOLOGY
IMMUNOLOGY
HOW?
Recognition, Interaction, Disposal, Regulation
IMMUNOLOGY
WHO?
Cells, Molecules, Tissues
It is also the study of the medically related consequences that arise when these mechanisms
IMMUNOLOGY
IMMUNOLOGY It is also the study of the medically related consequences that arise when these mechanisms either:
- fail
- respond in an exaggerated way
fail can lead to:
- autoimmune disorder
- immunodeficiencies
respond in an exaggerated way can lead to:
hypersentivity disorders
*
Consequences of immune interactions:
a. Elimination of pathogen (desirable)
b. Overexertion (Undesirable); may lead to autoimmune dse
own immune system attacking own body (ex. arthritis, Graves, Cushing, Lupus); failure to identify own cells
Autoimmune disorder
immune system does not perform well, low immune system.
Immunodeficiency
Study the px background before concluding status of immunity. Developed from prior exposure.
IMMUNITY
Condition of being resistant to infection
IMMUNITY
It is from which the study of immunology is rooted from.
IMMUNITY
Principle: Antigen gains entrance to an appropriate lymphoid area of the body.
IMMUNITY
Immune system can be advantageously manipulated to protect or treate dse
IMMUNITY
EXAMPLE OF Immune system can be advantageously manipulated to protect or treate dse
Vaccination & Anti-inflammatory drugs
Composed of wide array of cells, soluble molecule (humoral factors), and tissues
IMMUNE SYSTEM
Composed of wide array of cells, soluble molecule (humoral factors), and tissues with the following characteristics:
- Specificity
- Memory
- Mobility
- Replicability
- Cooperation between different cells or cellular products
Primary role – recognize self from non-self, and defend against non-self
IMMUNE SYSTEM
IMMUNE SYSTEM PRIMARY ROLE 2 TYPES:
➔ Natural and Acquired Resistance
➔ Recovery
IMMUNE SYSTEM Divided into two categories:
- Innate/Natural Immune System
- Adaptive/Acquired/Specific Immune System
do not possess immunologic memory
Innate/Natural Immune System
possess immunologic memory
Adaptive/Acquired/Specific Immune System
TYPES OF IMMUNITY:
- INNATE IMMUNITY
- ADAPTIVE IMMUNITY
Present at birth “natural”
INNATE IMMUNITY
No prior exposure to pathogen required
INNATE IMMUNITY
Little or no memory of prior exposure
INNATE IMMUNITY
Non-specific
INNATE IMMUNITY
Immediate response
INNATE IMMUNITY
Same response upon reexposure
INNATE IMMUNITY
Acquired; develops overtime
ADAPTIVE IMMUNITY
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Exposure to pathogen required
ADAPTIVE IMMUNITY
Has memory of prior exposure
ADAPTIVE IMMUNITY
Specific
ADAPTIVE IMMUNITY
Slow response
ADAPTIVE IMMUNITY
Faster and increased response upon reexposure
ADAPTIVE IMMUNITY
Both systems are essential to maintain good health; in fact, they operate in concert and are dependent upon one another for maximal effectiveness.
- INNATE IMMUNITY
- ADAPTIVE IMMUNITY
A foreign substance that may or may not induces an immune response
ANTIGEN
ANTIGEN 2 TYPES:
- Non-self
- Self-antigen
may or may not elicit immune response (e.g., carbs, proteins, amino acids, blood donated, food we ate)
Non-self
- from our body; Immunogens – always cause disease (ex. D. latum); Pathogen – immunogen that in living form (ex. fungi, bacteria, viruses)
Self-antigen
always cause disease (ex. D. latum)
Immunogens
immunogen that in living form (ex. fungi, bacteria, viruses)
Pathogen
2 TYPES OF TOLERANCE:
- Immunological tolerance
- Self-tolerance
the failure to mount an immune response to an antigen → bad thing; can’t recognize immunogen
Immunological tolerance
failure to attack the body’s own proteins
and other antigens a → good thing [immune system tolerates self-antigen; if body will not able to tolerate antigen an autoimmune response will happen]
➔ Eliminate non-self-components such as
infectious agents
Self-tolerance
During a plague in Athens, described a phenomenon where individuals who recovered from a certain disease rarely contracted the same disease again.
THUCYDIDES (430 B.C.)
Started the concept of immunity
THUCYDIDES (430 B.C.)
He recognized their “immune status”
THUCYDIDES (430 B.C.)
The term “smallpox” was first used in Europe in the 15th century to distinguish it from “great pox” (syphilis).
SMALLPOX
One of the deadliest known dse known to human and the only dse eradicated worldwide (most significant milestone in medicine)
SMALLPOX
Only infects humans.
SMALLPOX
Symptoms: High fever, vomiting, mouth sores, and characteristic of pustular (fluid-filled) lesions, which can lead to death.
SMALLPOX
1st discovered in 1350 BCE from Egyptian mummies.
SMALLPOX
Infected Mozart and Abraham Lincoln
SMALLPOX
Infected individuals are called “Speckled monster”
SMALLPOX
“Corkscrew-shaped” under Phase Contrast Microscope
SMALLPOX
SMALLPOX It is an infectious disease caused by two virus variants:
- Variola major
- Variola minor
mild form of smallpox (Alastrim, Cuban itch, cotton pox, milkpox, white pox); may be due to prior exposure/re-exposure to the virus of the same strain.
Variola minor
serious form of smallpox (manifestation of severe symptoms)
Variola major
Ancient practice of presenting smallpox to the patient, inducing immune response.
VARIOLATION
It was first done in Asia and some parts of Africa.
VARIOLATION
Further refinements did not occur until the late 1700s
VARIOLATION
Precursor of vaccination
VARIOLATION
It involves exposing healthy people to a material comingfrom an manifested material of infection/disease (e.g. “smallpox” lesion).
VARIOLATION
Farmers such as ________ infected his
family with cowpox during 1774 when he
observed that exposure of milkmaids to
cowpox conferred immunity to smallpox
Benjamin Jesty
This has been revealed successful when
attempts to infect his son by physicians during
1805 indicated that his son was immune to
smallpox.
Benjamin Jesty
He observed cross-reactivity without knowing it was hence called the “Unsung hero of
vaccination.”
Benjamin Jesty
animal disease, smallpox- human disease if ever contracted it well led to fever, cough but it will not show a symptom of other disease. It is an orthopoxvirus from the family of poxviridae (Group 5)
Cowpox
Developed a custom of inhaling dried powdered crust from smallpox lesions blown into the nostrils using a pipe; INSUFFLATION
CHINESE (1500s)
*
Mary Montagu
LADY MARY WORTLEY MONTAGU (1720s)
Wife of the British Ambassador of Turkey
LADY MARY WORTLEY MONTAGU (1720s)
Introduced variolation to Europe in 1921
LADY MARY WORTLEY MONTAGU (1720s)
Practiced variolation through INOCULATION
LADY MARY WORTLEY MONTAGU (1720s)
She observed a practice from the Ottoman Empire (where his husband is assigned), a form of variolation where smallpox is planted or inoculated on the skin using needle or lancet.
LADY MARY WORTLEY MONTAGU (1720s)
This did not always work because some died or were disfigured. (lack of standard, which led to osteomyelitis/disfigured in bone)
LADY MARY WORTLEY MONTAGU (1720s)
Test subjects: Prisoners and abandoned children
LADY MARY WORTLEY MONTAGU (1720s)
After countless tries, it was found to be effective. She then performed inoculation to the royal family, including her son
LADY MARY WORTLEY MONTAGU (1720s)
Inoculation became fashionable in Europe amongst royal families
LADY MARY WORTLEY MONTAGU (1720s)
Founder of cross-immunity
EDWARD JENNER (1796)
Heard that rural communities practiced inoculation of cowpox to protect themselves against smallpox
EDWARD JENNER (1796)
He then tested this hypothesis through his experiment which demonstrated the world’s first vaccine.
EDWARD JENNER (1796)
– phenomenon in which exposure to one agent provides protection against another agent
Cross-immunity
antigenic similarity of the different
viruses
Cross-reactivity
Agents of smallpox & cowpox have cross
reactivity somehow the same antigenic
property but different viruses, after the infection of cowpox you will have the immunity against smallpox
EXAMPLE OF Cross-reactivity
WHAT DATE Edward Jenner took fluid from “cowpox” lesion of Sarah Nelmes (Milkmaid), and inoculated it to an 8 year old boy, James
Phipps
May 14,1796
WHAT DATE Jenner inoculated the boy with matter from fresh smallpox lesion.
July 1, 1796
*
Injection of cellular material to induce immunity. From the latin word ‘vacca’ means cow. It is the act of introducing vaccine into the body to provide protection from a specific dse; much safer and effective than variolation. Six millennia (600 years) before the vaccine for smallpox was created.
Vaccination
100 years later after smallpox, led advancement to vaccination (attenuated vaccines)
LOUIS PASTEUR (1880-1881)
Patented vaccination, hence the “Father of Immunology”
LOUIS PASTEUR (1880-1881)
Basis: Older bacterial cultures of Pasteurella multocida would not cause disease in chickens (broth culture inoculated chicken shows not so potent toward chicken)
LOUIS PASTEUR (1880-1881)
to CHANGE; to MAKE A PATHOGEN LESS VIRULENT. Compose of heating, drying, and chemical means.
Attenuation
He developed vaccines against:
1. Chicken cholera
2. Anthrax
3. Rabies (1885)
LOUIS PASTEUR (1880-1881)
These two procedures were successful in decreasing smallpox mortality
VARIOLATION & VACCINATION
WHO declared the total eradication of smallpox in 1979
VARIOLATION & VACCINATION
Observed white blood cells ingesting dye
HAECKEL (1862)
Note: Cells engulfs, antibodies neutraliizes/tags microorganisms
HAECKEL (1862)
Discovered cellular immunity and observed pahogocytosis
ELIE METCHNIKOFF (1880 -1900)
When rose thorn is introduced to starfish larvae, motile cells migrate and clustered around the thorn.
ELIE METCHNIKOFF (1880 -1900)
He then posited that phagocytosis served as a natural immune mechanism.
ELIE METCHNIKOFF (1880 -1900)
a process by which a cell is capable of engulfing or “eating” other cells.
Phagocytosis
Concept of Cellular Immunity was born (how cells phagocytize, how monocyte move to become macrophage)
ELIE METCHNIKOFF (1880 -1900)
Discovered humoral immunity
EMIL VON BEHRING and SHIBASABURO KITASATO (1890)
Animals immunized with diphtheria and tetanus toxins produced non-cellular ‘antitoxins’ which neutralize or destroy the toxin.
EMIL VON BEHRING and SHIBASABURO KITASATO (1890)
These antitoxins would then be later known as ‘antibodies’ who dicovered
Paul Ehrlich
protective factors in the blood and other body fluids
Antibodies
Concept of Humoral Immunity was born (Humoral – part of fluid,
soluble]
EMIL VON BEHRING and SHIBASABURO KITASATO (1890)
Wrote the book entitled “THE SPECIFICITY OF SEROLOGICAL REACTIONS”
KARL LANDSTEINER
Human immune system is specific in protecting its own antigen (memory)
KARL LANDSTEINER
Typhoid Mary
MARY MALLON
A cook who spread a febrile disease that killed almost 50 persons.
MARY MALLON
Based on Columbian theory, it suggests that syphilis was endemic in Haiti and was subsequently contracted and carried to Europe by the crew of Christopher Columbus.
CRISTOPHER COLUMBUS
WHO DISCOVERED Side-chain theory
EHRLICH (1900s)
Antibodies have receptors which act only on specific antigen (if antibody made from S.aureus specific only for S.aureus type)
Side-chain theory
Discovered opsonins which coat pathogens to make them more susceptible to ingestion by phagocytic cells.
ALMROTH WRIGHT (1903)
An APR that envelops microorganisms, which
will then be tagged by antibodies → envelop → phagocytosis. It basically enhances phagocytosis
Opsonin
are not too different; it happens simultaneously in the body.
➔ Both are significant in successful immune
responses.
➔ Both are dependent upon each other, and
operate in combination.
➔ Ex. bacteria free floating in the blood when
macrophage see it can eat easily but sometimes macrophage is confused now the humoral immunity will help by releasing opsonins (opsonins coat non-self-antigen making macrophage eat in few seconds)
➔ Both are dependent upon each other, and operate in combination.
Cellular immunity & humoral immunity
Discovered Koch’s bacillus (MTB)
ROBERT KOCH
Delayed type hypersensitivity
ROBERT KOCH
Passive administration of antitoxin
EMIL VON BEHRING
Non-disease casuing bland substances can cause anaphylactic shock (uncontrolled hypersensitivity; T1)
PORTIER, RICHET
Discovered type 2 hypersensitivity
MAURICE ARTHUS
Discovered polio vaccine
SALK & SABIN
Cutaneous vaccine
Salk
Oral vaccine
Sabin
Smallpox vaccination
EDWARD JENNER (1796)
Observed phagocytosis
HAECKEL (1862)
First live attenuated vaccine
LOUIS PASTEUR (1880-1881)
Cellular theory of immunity via phagocytosis
ELIE METCHNIKOFF (1888)
Humoral theory of immunity proposed
VON BEHRING, KITASATO (1890)
Cutaneous (Delayed-type) Hypersensitivity
ROBERT KOCH (1891)
Discovered precipitins
ROBERT KAUS (1897)
Antibody formation theory (Side-chain theory)
EHRLICH (1900)
Discovered serum therapy; serum
antitoxin
EMIL VON BEHRING (1901)
Immediatehypersensitivity /
anaphylaxis
PORTIER, RICHET (1902)
Arthus reaction of intermediate
hypersensitivity
MAURICE ARTHUS (1903)
Discovered opsonization
ALMOTH WRIGHT (1903)
Complement
JULES JEAN BAPTISTE VINCENT BORDET (1919)
Discovered ABO Blood group
KARL LANDSTEINER (1930)
Development of polio vaccine
SALK AND SABIN (1949)
Development of vaccine against
yellow fever
REED (1951)
Identification of basic antibody structure
GERALYN EDELMAN, RODNEY PORTER (1972)
First monoclonal antibodies
KOHLER (1975)
Discovered Major Histocompatibility Complex (MHC)
GEORGE SNELL, JEAN DAUSET, BARUJ BENACERRAF (1980)
Radioimmunoassay
ROSALYN YALLOW (1977)
Nobel prize winner for antibody diversity
SUSUMU TONEGAWA (1987)
Performed first transplantation
EDWARD DONALL THOMAS, JOSEPH MURRAY (1991)
FOXP3, the gene directly regulatory T cell development
2001
Development of human papillomavirus vaccine.
FRAZER (2005)