Immunology and Serology Reviewer Summary PDF

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IMMUNOLOGY AND SEROLOGY INTRODUCTION TO IMMUNOLOGY •

Study of the reaction of a host when foreign substances are introduced into the body

•

Study of all aspects of body defenses, such as antigens and antibodies, allergy and hypersensitivity

•

Role of Immune System

a. Defending the body against infections b. Recognizing and responding to foreign antigens c. •

Defending the body against the development of tumors

The function of the immune system is to recognize self from non-self and to defend the body against non-self. Such a system is necessary for survival

HISTORY

NOTE! ☺ ✓

The first written records of immunological experimentation date back to the 1500s, when the Chinese developed a practice of inhaling powder made from smallpox scabs in order to produce protection against this dreaded disease. This practice of deliberately exposing an individual to material from smallpox lesions was known as variolation

✓

Variolation(inoculation)- method of scratching the skin and applying pulverized powder from a smallpox scab

✓

Variolation -fresh material taken from a skin lesion of a person recovering from smallpox was subcutaneously injected with a lancet in to the arm or leg of a nonimmune person

✓

Vaccination, from vacca , the Latin word for “cow.”

✓

Live attenuated vaccine was discovered by Louis Pasteur.

✓

Attenuation involves the use of bacteria or viruses that have been weakened through exposure to modifying conditions such as chemical treatment, hot or cold temperatures, aging, or repeated in vitro passage in cell culture.

✓

A vaccine is an antigen suspension derived from a pathogen. Vaccines are routinely administered to healthy individuals to stimulate an immune response to an infectious disease. Vaccination therefore is a form of immunoprophylaxis, or the prevention of disease through immunization.

✓

Vaccinia pertains to cowpox

✓ Variola major pertains to Smallpox ✓ Variola minor pertains to Alastrim ✓ A vaccine is an antigen suspension derived from a pathogen. It is a form of immunoprophylaxis, or the prevention of disease through immunization.

✓ Nonparenteral routes of antigen delivery such as oral, intranasal, aerosol, transcutaneous, intradermal, and rectal are also being studied

✓ Oral vaccines have an additional advantage in that they can potentially stimulate mucosal immunity as well as humoral antibody production and cell-mediated responses

It is thought that Pasteur discovered the effect of attenuation by accident during his studies of chicken cholera. After returning from a summer vacation in 1881, he noticed that he had left a culture of the bacteria that cause chicken cholera, now known as Pasteurella multocida, on his laboratory bench. Instead of disposing of the aged culture, he decided to use it to inoculate chickens. The chickens did not develop the disease; furthermore, when Pasteur later inoculated them with a fresh culture of the bacteria, they proved to be resistant to cholera.

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CHARACTERISTICS OF CONVENTIONAL VACCINES Composition Attenuated

Inactivated

Toxoids

Purified components

Induce both humoral and cellmediated immunity.

Killed microorganisms

Can safely be given to immunocompromised individuals

Intramascularpolio(salk),Hepatitis A,

Bacterial toxins that have been chemically inactivated so that they are not

Induces an immune response to the Pathogenic component(s) of a microorganism

Diphtheria

pathogenic

Safer than administration of an intact organism

Biochemically purified

Similar with toxoids.

components of

Produces fewer side effects than whole bacteria

Biochemically purified polysaccharide from bacterial

Effective in inducing immunity after a single dose.

Same with toxoids

BCG, TYPHOID FEVER, ORAL POLIO, MEASLES, MUMPS, GERMAN MEASLES, CHICKEN POX, ROTAVIRUS, YELLOW FEVER

Influenza (Intramuscular or intradermal), rabies

Tetanus

Pertussis (whooping cough)

Streptococcal pneumonia, Haemophilus influenza type b Neisserial meningitis

capsule Recombinant antigen

Examples

Live pathogens that have been weakened by growth under modified culture conditions

a microorganism Polysaccharides

Advantages

Protein produced by genetically modified nonpathogenic bacteria, yeast, or other cells

Highly purified protein that is safer

Hepatitis B

than administration of intact organism

Human papilloma virus (cervical, anal, genital cancers)

FACTORS AFFECTING IMMUNOGENICITY There are many factors that affect the quality of the immune response to a vaccine antigen. Important factors include the age of the recipient, the individual’s immune status, and the nature of the vaccine

In general, it is recommended that vaccines be administered to the youngest individuals at risk for the vaccine’s targeted disease, as long as effectiveness and safety of the vaccine have been demonstrated in that age group Some vaccines, such as the live, attenuated vaccine for measles, mumps, and rubella, are not started until 12 to 15 months of age because administration before that age does not result in an effective immune response Other vaccines, such as those for meningococcal meningitis and HPV, are not administered until 11 to 12 years of age because the risk for contracting these infections is greater during adolescence In general, the most immunogenic vaccines consist of live, attenuated organisms that are able to replicate in the host; the least immunogenic vaccines consist of purified components (subunits) derived from the pathogen

Because of the broad immunity induced by live, attenuated vaccines, they generally induce an effective immune response after just a single dose

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SIGNIFICANT MILESTONES IN IMMUNOLOGY (TURGEON) 1798

Jenner

Smallpox vaccination

1953

1862

Haeckel

Phagocytosis

1957

18801881

Pasteur

Live, attenuated chicken cholera and anthrax vaccines

1957

Interferon

18831905

Metchnikoff

Cellular theory of immunity through phagocytosis

19581962

HLA’s

1890

Von Behring, Kitasata

Humoral theory of immunity proposed

19641968

T cell and B cell cooperation in immune response

1891

Koch

Demonstration of cutaneous (delayed-type) hypersensitivity

1972

Identification of antibody molecule

1900

Ehrlich

Antibody formation theory

1975

1902

Portier, Richet

Immediate-hypersensitivity anaphylaxis

19851987

Identification of genes for T cell receptor

1903

Arthus

Arthus reaction of intermediate hypersensitivity

1986

Monoclonal hepatitis B vaccine

1938

Marrack

Hypothesis of antigen-antibody binding

1986

Hypothesis of allograft rejection

19961998

Identificationof toll like receptors

FOXP3, the gene directing regulatory T cell development

1944

Graft versus host reaction Burnet

Kohler

Mosmann

Clonal selection theory

First monoclonal antibodies

Th1 versus Th2 model of T helper cell function

1949

Salk, Sabin

Development of polio vaccine

2001

1951

Reed

Vaccine against yellow fever

2005

1798

Edward Jenner, an English countryside physician demonstrated that protectqion from cowxpox could be generated by the transfer of postural material from a cowpox lesion instead of the more hazardous smallpox lesion

1880

Louis Pasteur demonstrated that injection of killed microbes provided protection upon subsequent exposure to live counterpart

1888

Ellie Metchnikoff demonstrated that certain blood cells ingest foreign material

1894

Jules Bordet discovered complement

1897

Robert Kaus discovered precipitins

1901

Emil Von Behring had the distinction of being awarded as the first immunology related Nobel Prize for his works on serum therapy

1984

Discovery of the T cell receptor gene

1987

Susumu Tonegawa was awarded the Nobel Prize for his 1978 discovery of the genetic principles underlying the generation of antibodies with different specificities

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Frazer

Development of human papillomavirus

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YEAR

SCIENTIST

RESEARCH

1901

Emil Von Behring

Serum antitoxins

1905

Robert Koch

Cellular immunity in TB

1908

Elie Metchnikoff, Paul Ehrlich

Phagocytosis Immunity

1913

Charles Richet

Anaphylaxis

1919

Jules Bordet

Complement

1930

Karl Landsteiner

Human blood group antigens

1960

MacFarlane Burnet, Peter Medawar

Discovery of immunologic tolerance

1972

Gerald Edelman, Rodney Porter

Structure of antibodies

1977

Rosalyn Yalow

Radioimmunoassay

1980

George Snell, Jean Dausset, BarujBenaceraf

Major Histocompatibility complex

1984

Niels Jerne

Immunoregulation

Georges Koehler, Cesar Milstein

Monoclonal antibody

1987

Susumu Tonegawa

Antibody Diversity/Specificity

1991

Edward Donnall Thomas, Joseph Murray

Transplantation

1996

Peter Doherty, Rolf Zinkernagel

Cytotoxic T cell recognition of virally infected cells

2008

Francoise Barre- Sinoussi, Luc Montagnier

Human immunodeficiency virus

An English country doctor by the name of Edward Jenner discovered a remarkable relationship between exposure to cowpox and immunity to smallpox. After observing the fact that milkmaids who were exposed to cowpox had apparent immunity to smallpox, he deliberately injected individuals with material from a cowpox lesion and then exposed them to smallpox. He thus proved that immunity to cowpox, a very mild disease, provided protection against smallpox. The phenomenon in which exposure to one agent produces protection against another agent is known as cross-immunity

OVERVIEW OF NATURAL VS ADAPTIVE IMMUNITY Innate, or natural immunity, is the individual’s ability to resist infection by means of normally present body functions. These are considered nonadaptive or nonspecific and are the same for all pathogens or foreign substances to which one is exposed. No prior exposure is required and the response lacks memory and specificity. Many of these mechanisms are subject to influence by such factors as nutrition, age, fatigue, stress, and genetic determinants Acquired immunity, in contrast, is a type of resistance that is characterized by specificity for each individual pathogen, or microbial agent, and the ability to remember a prior exposure, which results in an increased response upon repeated exposure. Both systems are essential to maintain good health; in fact, they operate in concert and are dependent upon one another for maximal effectiveness. Natural immunity is responsible for both first and second line of defense, while adaptive immunity is responsible for the third line of defense

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NATURAL/

▪

Present at birth

INNATE IMMUNITY

▪

Standardized response for all Antigen

▪

Lacks memory

▪

Responsible for the first and second line of defense in the body

▪

Pathogen recognized by receptors encoded in the germline

▪

Receptors have broad specificity

▪

Immediate response

▪

Not present at birth

▪

Diverse response for each antigen

▪

Capable of recalling previous antigen thus with memory

▪

Secondary immune response is greater than primary immune response

▪

Responsible for the Third line of defense in the body

▪

Pathogen recognized by receptors generated randomly

▪

Receptors have very narrow specificity; i.e., recognize a specific epitope

▪

Slow (3-5 days) response

ADAPTIVE/ ACQUIRED IMMUNITY

THREE LINE OF DEFENSE IN THE HUMAN BODY First Line of Defense (innate immunity)

The external defense system which is composed of structural barriers that prevent most infectious agents from entering the body. COMPOSITION ✓

Unbroken skin (pH of 5.5 to 5.6) and the mucosal membrane surfaces, Lactic acid in sweat, and the acidity in GIT and Vagina (pH about 5), Cilia lining in respiratory tract, The flushing action of urine

✓

Lactic acid in sweat, for instance, and sebum/fatty acids from sebaceous glands maintain the skin at a pH of approximately 5.6. This acid pH keeps most microorganisms from growing.

✓

Lysozyme, an enzyme found in many secretions such as tears and saliva, and it attacks the cell walls of microorganisms, especially those that are gram-positive.

✓

The production of earwax (cerumen) protects the auditory canals from infectious disease.

✓

Normal microbial flora in the body. Many locations of the body, there is normal flora that often keeps pathogens from establishing themselves in these areas. This phenomenon is known as competitive exclusion

Types of Barriers Mechanical barriers Chemical barrier

Biological barriers

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Skin, mucous membrane, cilia, mucus -enzymes like lysozyme found in secretions (tears, saliva, sweat) lactic acid in sweat -HCL in the GI tract -acid in urine -skin and mucous membrane (Steven's 4th edition) -normal flora

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Second Line of Defense

The internal defense system, in which both cells and soluble factors play essential parts. The internal defense system is designed to recognize molecules that are unique to infectious organisms.

(innate immunity)

COMPOSITION: ✓

Phagocytosis, Inflammation, Acute phase reactants, Antimicrobial substances such as complement, Properdin, Interferon alpha and beta, TNF, and Betalysin. CELLULAR COMPONENT

Mast cells, Basophils, Eosinophil, Neutrophils, Macrophages, Dendritic cell, and NK cells Third Line of Defense

HUMORAL COMPONENT Complement, Lysozyme, Interferon alpha and beta

If a microorganism overwhelms the body’s natural resistance, a third line of defensive resistance exists. Acquired, or adaptive, immunity is a more recently evolved mechanism that allows the body to recognize, remember, and respond to a specific stimulus, an antigen. Adaptive immunity can result in the elimination of microorganisms and recovery from disease and the host often acquires a specific immunologic memory. This condition of memory or recall (acquired resistance) allows the host to respond more effectively if reinfection with the same microorganism occurs.

(acquired immunity)

CELLULAR COMPONENT

HUMORAL COMPONENT

T lymphocytes, B lymphocytes, Plasma cells

Antibodies, and cytokines

THE NATURAL IMMUNITY

I.ACUTE PHASE REACTANTS normal serum constituents that increase rapidly by at least 25 percent due to infection, injury, or trauma to the tissues They are produced primarily by hepatocytes (liver parenchymal cells) within 12 to 24 hours in response to an increase in certain intercellular signaling polypeptides called cytokines (e.g IL-6, IL1, and TNF-alpha) They are indicator of inflammation PROTEIN

RESPONSE TIME (HR)

NORMAL CONCENTRATION (mg/dL)

INCREASE

FUNCTION

6-10

0.5

1000x

Opsonization, complement activation

Serum amyloid A

24

3.0

1000x

Removal of cholesterol

Alpha1- antitrypsin

24

200-400

2-5x

Protease inhibitor

Fibrinogen

24

110-400

2-5x

Clot formation

Haptoglobin

24

40-200

2-10x

Binds hemoglobin

Ceruloplasmin

48-72

20-40

2x

Binds copper, oxidizes iron

C3

48-72

60-140

2x

Opsonization, lysis

?

0.15-1.0

?

Complement activation

CRP

Mannose-binding protein

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C-REACTIVE PROTEIN

✓

CRP is a trace constituent of serum originally thought to be an antibody to the c-polysacharide of the pneumococci

✓

Elevated levels are found in conditions such as bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis and after a heart attack

✓

CRP acts somewhat like an antibody because it is capable of opsonization (the coating of foreign particles), agglutination, precipitation, and activation of complement by the classical pathway

✓

The main substrate is phosphocholine, a common constituent of microbial membranes. It also binds to small ribonuclear proteins; phospholipids; peptidoglycan; and other constituents of bacteria, fungi, and parasites

✓

In addition, CRP binds to specific receptors found on monocytes, macrophages, and neutrophils, which promotes phagocytosis.

✓

the most widely monitored of the acute-phase reactants and is the best indicator of acute inflammation

✓

Hs- CRP is a significant risk factor for myocardial infarction and ischemic stroke

✓

Test: Reverse passive agglutination, Precipitation, RIA, Complement fixation

✓

Serum half-life: 19 hours CDC criteria for CRP value associated with Heart disease Low risk 3mg/dl

SERUM AMYLOID A

MANNOSE-BINDING PROTEIN

ALPHA1ANTITRYPSIN

CERULOPLASMIN

HAPTOGLOBIN

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✓

It is associated with HDL cholesterol, and it is thought to play a role in metabolism of cholesterol (remov...