Module 1: Introduction to Immunology & Serology

Immunology

Study of a host’s reactions when foreign substances (IMMUNOGENS) are introduced into the body

Serology

Study of the noncellular portion of the blood known as serum

1718

When did Lady Mary Wortley Monatgu introduced variolation?

Lady Mary Wortley Montagu

• Introduced Variolation (smallpox inoculation) to the West

• Immunity to smallpox was conferred by inserting the dried exudate of smallpox pustules into the nose

Variolation

• practice of deliberately exposing an individual to material from smallpox lesions

• This technique however aroused severe opposition as physicians felt it was far too risky

1798

When did Edward Jenner introduced first vaccination?

Vaccination

• deliberately introducing a potentially harmful microbe into a patient (form of artificial actively-acquired immunity)

Edward Jenner

• Postulated that inoculation with cowpox could confer immunity to smallpox, and thus the concept of vaccination was initiated.

• first made him a medical and social pariah, as they were in opposition to both the church and popular beliefs.

• Because his method was much safer then variolation, the use of vaccinations gradually became widely accepted

1857 - 1870

When did the confirmation of the role of microbes happen?

Louis Pasteur

• Although his original interests were in fermentation of wine and beer, he was the first to isolate the organisms that caused the fermentation process, and his work eventually led him to the development of Pasteurization as means of halting fermentation.

1. Role of Microbes in Fermentation

2. Germ Theory of Disease

3. Attenuation

4. Therapeutic vaccination

What are the contributions of Louis Pasteur?

1878

The year of confirmation and popularization of the germ theory of disease

Germ theory of disease

• The theory states that “Diseases are caused by microorganisms. Their growth and reproduction within their hosts can cause a disease.

• This proved that microorganisms, known as pathogens, can lead to disease which disproved the ancient theory of spontaneous generation which stated that “Living organisms could originate from non living matter”.

Germ

may refer to a virus, bacterium, protist, fungus, or prion

Attenuation

• Theory that bacterial virulence could be attenuated by culture in vitro, and used as vaccine

TRUE

TRUE OR FALSE: Pasteur’s study of chicken cholera showed that it was possible to prepare weakened strains of various microbes in the laboratory and use them as protective vaccines’

1885

The year when therapeutic vaccination was introduced

Attenuated vaccine

a vaccine created by reducing the virulence of a pathogen but still keeping it viable.

Pasteur Institute

The rabies vaccine brought Pasteur international fame and led to the establishment of the?

Robert Koch

• His work with anthrax was the first to link a specific microorganism with a specific disease, rejecting the idea of spontaneous generation and supporting the germ theory of disease.

• demonstrated the bacterial etiology of anthrax

• His rigorous analysis of the complex life cycle of Bacillus anthracis explained many aspects of the disease’s transmission.

• established his postulates which sets standards for pathological microbiology and epidemiology.

1. The bacteria must be present in every case of the disease.

2. The bacteria must be isolated from the host with the disease and grown in pure culture.

3. The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host

4. The bacteria must be recoverable from the experimentally infected host.

Koch’s four postulates

Hypersensitivity

a normal but exaggerated/uncontrolled immune response to an antigen that can produce either inflammation, cell destruction, or tissue injury.

Tuberculin Skin Test (TST)

• a type IV cutaneous (delayed) hypersensitivity

• Makes use of soluble antigens from the cell wall of Mycobacterium tuberculosis to induce a reaction in people who have or have had tuberculosis.

Purified Protein Derivative (PPD) Test or Mantoux Skin Test

TST is also known as?

1. Mast cells

2. Side chain theory

What are the contributions of Paul Ehrlich?

Mast cells

are large tissue cells found in connective tissue that have basophilic granules containing vasoactive amines, such as histamine and heparin

Side chain theory

• Paul Ehrlich postulated the antibody formation through this

• States that certain cells had specific surface receptors for antigens that were present before contact with antigen occurred

• Once antigen was introduced, it would select the cell with the proper receptors, combination would take place, and then receptors would break off and enter the circulation as antibody molecules

• New receptors would form in place of those broken off, and this process could be repeated

Elie Metchnikoff

• Introduced the concept of Phagocytosis ( CELLULAR THEORY OF IMMUNITY via phagocytosis by macrophages and polymorphonuclear leukocytes)

Phagocytosis

a form of endocytosis in which specialized cells (phagocytes) engulf and destroy foreign particles, such as microorganisms or damaged cells

Cellular theory of immunity

Concept states that cells, not antibodies, were responsible for the immune response of an organism

1. Neutrophils

2. Monocytes

3. Eosinophils

Three kinds of Phagocytes

Emil Von Behring and Shibasaburo Kitasato

• Demonstrated Antibody Activity against diphtheria & tetanus Toxins

• Injected diphtheria and tetanus toxins into guinea pigs, goats, and horses, and when these animals developed immunity, they derived antitoxins from their serum.

Humoral theory of immunity

• Concept states that immunity is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides.

• is so named because it involves substances found in the humors or body fluids.

• It attempted to cure tetanus with passive immunotherapy.

Hans Ernst August Buchner

• is so named because it involves substances found in the humors or body fluids.

• It attempted to cure tetanus with passive immunotherapy.

Jules Bordet

Demonstrated that this factor has two components:

1. Maintains its effect after being heated (specific heat stable factor à antibodies)

2. Loses its effect after being heated (nonspecific heat labile factor; initially called alexin à refers to complement)

Complement

group of soluble blood proteins consisting of C1- C9. It results to the release of anaphylatoxins toxins that has inflammatory effects and compliment mediated opsonization and cell lysis

Karl Landsteiner

• Father of Blood grouping

• Discovery of ABO BLOOD GROUP is his major contribution in the field of blood banking

• His discovery led to transfusion of ABO compatible blood and greatly decreased transfusion reactions

Haptens

are a simple chemical group that can bind to antibody once it is formed but cannot stimulate antibody formation unless tied to a larger carrier molecule

hapten-carrier conjugate

can act as an immunogen, and is capable of stimulating antibody production by the B-cells.

Paul Portier and Charles Richet

Who discovered anaphylaxis?

Anaphylaxis

is an immediate type I hypersensitivity reaction characterized by local reactions such as urticaria (hives), and angioedema (swelling), or systemic reactions in the respiratory tract, cardiovascular system, GIT, and skin

Maurice Arthus

Who discovered Arthus reaction?

Arthus reaction

• an immediate type III hypersensitivity reaction that occurs when an animal has a large amount of circulating antibody and is exposed to the antigen intradermally, resulting in a localized inflammatory response due to deposition of immune complexes

• The response, characterized by local erythema, induration, hemorrhage, and necrosis became known as this

Almroth Wright and Stewart Douglas

Who discovered opsonization?

Opsonins

literally means to prepare for eating. These are serum proteins that attach to a foreign substance and help prepare it for phagocytosis.

• Antibodies

• Complement proteins

Opsonins can be any of the following:

Clemens Von Priquet and Bela Schick

• Described serum sickness

• Described the strange, non-disease related symptoms that some diphtheria patients developed when treated with a horse serum antitoxin

• Type III hypersensitivity reaction that results from the buildup of antibodies to animal serum used in passive immunization

• Symptoms include fever, rash, and polyarthritis (when 5 or more joints are affected with joint pain)

Alexander Fleming

• He demonstrated that his own nasal mucus had the ability to inhibit the growth of a certain strain of bacteria in culture

• He realized that this was largely due to the action of a protein within the mucus that caused the bacterial cells to lyse/break apart hence the name.

Lysozyme

• Are naturally occurring enzymes that damage bacterial cell walls

• Abundant in a number of secretions such as tears, saliva, human milk, and mucus and are also present in cytoplasmic granules of the polymorphonuclear neutrophils (PMNs)

Karl Albert Luwdig Aschoff

• German pathologist

• He grouped the cells based on their phagocytic activity.

• Reticuloendothelial system

Reticulo

refers to the propensity of these large phagocytic cells in various organs to form a network or a reticulum.

Endothelial

refers to their proximity to the vascular endothelium from which they were sometimes believed to arise.

Mononuclear phagocyte system

is the body’s defense system and is composed of macrophages and a network of specialized cells of the spleen, thymus, and other lymphoid tissues

Tiselius and E.A. Kabat

Identified Gamma Globulin

Karl Landsteiner and Alexander Weiner

• Identification of the Rh antigens

• They transfused guinea pigs and rabbits with Rhesus monkey red cells.

Philip Levine

Discovered hemolytic disease of the newborn

Jules Freund and Katherine McDermott

• Introduced adjuvants

• They published a paper on their experiments on immunization of guinea pigs with horse serum containing killed tubercle bacilli and adjuvants.

Adjuvants

• are substances administered with an immunogen that increases the immune response.

• May be added to a vaccine to boost the immune response to produce more antibodies and longer-lasting immunity thus minimizing the dose of antigen needed.

Freund’s Complete adjvuvants

is composed of inactivated and dried Mycobacteria (usually M. tuberculosis) while the Incomplete Form (FIA or IFA) lacks the Mycobacteria component and is just water in oil emulsion.

Astrid Fagraeus

• Demonstrated that plasma B cells are specifically involved in antibody production.

• Plasma cells are transformed B cells that actively secretes antibody.

Morton Simonsen and W.J. Dempster

• Noted the appearance of plasmacytoid cells in the renal cortex of grafted kidneys in dogs within a week after transplantation, and they thought that the cells of the graft were reacting to antigens of their newly found host.

• The transfused cells regard the recipient’s body as foreign and attack the tissues of the recipient within the first 100 days posttransplant.

Graft-versus-host disease

is a condition that results from transplantation of immunocompetent cells into an immunodeficient host.

Tissue typing

before a stem cell transplant or bone marrow transplant, the recipient and donor have to be checked how closely their Human Leukocyte Antigens (HLA) match.

Major histocompatibility complex (MHC)

Human Leukocyte Antigens are now known as?

Niels Jerne, David Talmage, Macfarlane Burnet

Postulated Clonal Selection theory

Theory Selection theory

Theory postulated to explain the specificity of antibody formation, based on the premise that each lymphocyte is genetically programmed to produce a specific type of antibody and is selected by contact with antigen

Alick Isaacs and Jean Lindermann

Introduced interferons

Interferons

are cytokines produced by T cells and other cell lines that inhibit viral synthesis or act as immune regulators.

Cytokines

are chemical messengers produced by stimulated cells that affect the function or activity of other cells.

Secretory immunoglobulins (IgA)

• are the main immunoglobulin found in mucous secretions, such as tears, saliva, sweat, colostrum, and secretions from the genitourinary tract, gastrointestinal tract, prostate, and respiratory epithelium.

• It is also found in small amounts in blood

• secretory component protects the immunoglobulin from being degraded by proteolytic enzymes.

Henry N. Claman

Identified T and B cells

Otto Prausnitz and Heinz Küstner

Developed Prausnitz-Küstner (PK) Test

Kimishige and Teruko Ishizaka

• published several articles describing an antiserum that could block the PK test, indicating that it reacted with a key factor in allergic inflammation, perhaps the reagin. They called this factor γE antibody.

• they never succeeded at isolating and characterizing the γE antibody because considering its very low concentration in serum.

IgE/Homocytotropic antibody/Prausnitz Küstner antibody

mediates allergic reaction by binding to allergen and interacts with its high affinity receptor on mast cells causing the cells to degranulate and release histamine.

Rolf Zinkernagel and Peter Doherty

introduced major histocompatibility complex

Major Histocompatibility Complex (MHC)

• they determine whether transplanted tissue is histocompatible.

• the requirement that APC or target cells express MHC molecules that the T cell recognizes in order for T cell to respond to the antigen presented by that APC or target cell Different T cells are restricted to either Class I or Class II MHC antigens

Georges Kohler and Cesar Milstein

Introduced/discovered monoclonal antibodies

monoclonal antibodies

are very specific antibody derived from a single antibody producing cell that has been cloned or duplicated produced through hybridoma technology.

• Highly specific recognition of only one epitope of an antigen

• High consistency among experiments

• Minimal cross-reactivity

Advantages of monoclonal antibodies:

Rolf Kiessling, et al.

introduced natural killer cells

Natural Killer (NK) Cells

• are lymphocytes that are unique as they have the ability to recognize stressed cells in the absence of antibodies and MHC allowing for a much faster immune reaction.

• Ability to mediate cytolytic reactions and kill target antigens without prior exposure to them.

• Their target are virally infected cells and tumor cells/cancer cells

Kendala A. Smith

Discovered and characterized first interleukins

Interleukins

• these proteins are produced by leukocytes and act on leukocytes

• regulate cell growth, differentiation, and motility.

• Important in stimulating immune responses such as inflammation.

• may contribute to the severe damage to lung tissue caused by cytokine release in patients with serious COVID-19 infections

Luc Montagnier and Robert Gallo

Discovered HIV as cause of AIDS

Hepatitis B vaccine

produced by genetic engineering

1986

When was Hepatitis B vaccine produced?

1992

When was Hepatitis A vaccine developed?

Ian Frazer

Developed the Human Papillomavirus (HPV) vaccine

Human Papilloma Virus

• infection is the most common sexually transmitted infection

• Caused by a virus that causes skin or mucous membrane growths (warts) and can lead to cervical cancer

Bruce A. Beutler Et al.

Discovered Toll-like receptors

Toll-like receptors

• are usually expressed in macrophages and dendritic cells.

• are gatekeepers of innate immunity

• Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses.