FUNGAL INFECTIONS

• Medical mycology is the discipline that deals with the fungi that cause human disease.
• These fungal diseases, known as mycoses

DERMATOPHYTES
• Group of fungi that infect only superficial keratinized tissue (skin, hair & nails)
• They breakdown and utilize keratin
• They are incapable of penetrating subcutaneous tissue.
• They cause dermatophytoses also known as tinea or ringworm
• Dermatophytes are classified into three genera as follows
CANDIDIASIS
• Candidiasis is the mycosis caused by Candida albicans
• In healthy individuals they do not produce disease because growth is suppressed by other
microbiota and other host resistance mechanisms. However, if anything upsets the normal
microbiota and immune competency, Candida may multiply rapidly and produce
Candidiasis
• Because Candida can be transmitted sexually, it is also listed by the CDC as a sexually
transmitted disease
Napkin (diaper) candidiasis
• It is typically found in infants whose diapers are not changed frequently and therefore are
not kept dry.
Candidal vaginitis
• It can result as a complication of diabetes, antibiotic therapy, oral contraceptives,
pregnancy, or any other factor that compromises the female host .
• Candida can be transmitted to males during intercourse and lead to balanitis; thus it also
can be considered a sexually transmitted disease
Mortality is almost 50% when Candida invade the blood or disseminate to visceral organs, as
occasionally seen in immunocompromised patients
NORMAL MICROBIOTA OF HUMAN BODY
The term “normal microbial flora” denotes the population of microorganisms that inhabit the skin
and mucous membranes of healthy normal persons

Skin

…………………………………………………………………………………………………………..

Mouth

……………………………………………………………………………………
Intestine

…………,,,,,,,,,…………………………………………………………………………………………………………………………………….

Genitourinary tract
 VIRAL INFECTIONS

Disease caused by Herpesvirus

General Features
It got an icosahedral capsid
It contains double stranded DNA genome surrounded by a lipid envelope containing
peplomers.
Chickenpox (Varicella) and Shingles (Herpes Zoster)
Chickenpox (Varicella) and Shingles (Herpes Zoster) are caused by single virus, for which it
is named varicella-zoster virus (VZV).
Chickenpox can be prevented or the infection shortened with an attenuated varicella vaccine
(Varivax; or the drug acyclovir (Zovirax or Valtrex)

Cytomegalovirus]
• Largest virus of herpesvirus family
• The HCMV can infect any cell of the body, where it multiplies slowly and causes the
host cell to swell in size—hence the prefix cytomegalo, which means “an enlarged cell.”
• Drugs ganciclovir (Cytovene-IV) and cidofovir (Vistide), are used only for high-risk
patients.
Epstein-Barr virus (EBV)
• Because the Epstein-Barr virus occurs in oropharyngeal secretions, it can be spread by
mouth-to-mouth contact (hence the terminology infectious and kissing disease) or shared
drinking bottles and glasses. A person gets infected when the virus from someone else’s
saliva makes its way into epithelial cells lining the throat
• The peak incidence of mononucleosis occurs in people 15 to 25 years of age. The
Epstein-Barr virus may well be the most common virus in humans as it infects 80 to 90%
of all adults worldwide
HEPATITIS VIRUS
Viral hepatitis is a systemic disease with primary inflammation in the liver.
Till now there are six hepatitis viruses: hepatitis A, B, C, D, E and G.
Hepatitis B is a DNA virus while other contain RNA genome
POLIOMYELITIS
Poliomyelitis [Greek polios, gray, and myelos, marrow or spinal cord], polio, or infantile
paralysis is caused by the poliovirus, a member of the family Picornaviridae
The poliovirus is a naked, positive-strand RNA virus with three different serotypes—P1, P2, and
P3. The virus is very stable, especially at acidic pH, and can remain infectious for relatively long
periods in food and water—its main routes of transmission.
The average incubation period is 6 to 20 days
In the minority of cases (less than 1%), the viremia persists and the virus enters the central
nervous system and causes paralytic polio.
The virus has a high affinity for anterior horn motor nerve cells of the spinal cord. Once inside
these cells, it multiplies and destroys the cells; this results in motor and muscle paralysis
Clinical features
The earliest manifestation consists of fever, malaise, headache, drowsiness, sore throat,
vomiting, and loss of appetite lasting 1- 5 days.
Prophylaxis
Two types of vaccines are available
Killed polio vaccine (Salk) IPV
Live attenuated oral polio vaccine (Sabin) OPV
Killed vaccine induces only systemic antibody response but do not provide intestinal immunity
Live vaccine induces both local secretory IgA antibodies in the intestine and also humoral
antibodies (IgG and IgM)
HIV
•Spherical enveloped virus
•Contain two identical copies of SS positive sense RNA genome
•In association with viral RNA is the reverse transcriptase enzyme
•Virus core surrounded by nuclocapsid
•Virus contain lipoprotein envelope
•Envelope glycoprotein are projecting spikes
•These spikes bind to CD4 receptors on susceptible host cells.
The infection cause damage to T4 lymphocyte.
•T4 cells are depleted in number and T4:T8 ratio is reversed.
The normal CD4:CD8 T-cell ratio of 2:1, is reversed to 0.5:1 in cases of AIDS.
When CD4 cells falls below 200 per mm3, the titer of virus increases markedly and there is
irreversible breakdown of immune defence mechanisms
AIDS is the final stage of HIV infection
HIV: Modes of Transmission
•Sexual contact: most important mode of transmission. It occurs among both homosexual as
well as heterosexual individuals
•Parenteral transmission: may occur through blood after receiving infected blood transfusions,
blood products, sharing contaminated syringes and needles in an intravenous drug abusers or
accidental inoculation
Perinatal transmission: infection may be transmitted from an infected mother to her child either
transplacentally or perinatally.
PREVENTION
•Sexual contact: use of condoms can prevent transmission of virus
•Sharing needles: contaminated needles or syringes should not be shared.
•Blood: all blood and blood products are to be screened for HIV. This also applies to donation of
cornea, semen, marrow, kidney and other organs.
•Screening of individuals within risk groups helps to identify the HIV infected persons
RABIES
Rhabdovirus are bullet or rod shaped (rhabdos, meaning rod) enveloped virus with single
stranded RNA genome.
Rabies virus is an important rhabdovirus. It causes rabies
It is transmitted to humans or other animals
By the bite of an infected animal whose saliva contains the virus;
By aerosols of the virus that can be spread in caves where bats dwell; or
By contamination of scratches, abrasions, open wounds, and mucous membranes with saliva
from an infected animal.
Symptoms of rabies usually begin 2 to 16 weeks after viral exposure and
Include anxiety, irritability, depression, fatigue, loss of appetite, fever, and a sensitivity to
light and sound.
The disease quickly progresses to a stage of paralysis. In about 50% of all cases, intense and
painful spasms of the throat and chest muscles occur when the victim swallows liquids.
The mere sight, thought, or smell of water can set off spasms.
Consequently, rabies has been called hydrophobia (fear of water). Death results from
destruction of the regions of the brain that regulate breathing
Treatment
Safe and effective vaccines (human diploid-cell rabies vaccine HDCV [Imovax Rabies] or
rabies vaccine adsorbed [RVA]) against rabies are available; however, to be effective they must
be given soon after the person has been infected
Prevention and control involves
Pre-exposure vaccination of dogs and cats,
Post exposure vaccination of humans, and
Pre-exposure vaccination of humans at special risk
 BACTERIAL PATHOGENS
Staphylococcus aureus
MORPHOLOGY
• Gram positive cocci arranged in grape like cluster
• Non motile
• Non sporing
• Cluster formation is due to the sequential division of bacteria in three perpendicular
planes with daughter cells remaining in close proximity
CULTURE
On Nutrient agar,
• Most of the strains produce golden yellow pigment.
On Blood Agar
• beta type of haemolysis is seen
On Mannitol salt agar
• Yellow colored colonies are seen on this medium due to the fermentation of mannitol
PATHOGENESIS
•S. aureus is an important pyogenic organism and lesions are localized in nature
Staphylococcal disesases may be classified as
I. Cutaneous-boils, abscesses, wound, burn
II.Deep infection-meningitis, bacteriaemia, septicaemia
III.Food poisoning-may follow after 2-6 hours after the ingestion of contaminated food which
contains preformed
IV. Skin exofoliativediseases-produced by strains of S.aureus that produce exofoliative toxin.
Staphylococcal scalded skin syndrome (SSSS) is an example of exofoliative disease.
V. Toxin shock syndrome (TSS)–it is caused by toxin shock syndrome toxin (TSST-1)
TREATMENT
•Benzyl penicillin is most effective antibiotic in sensitive strains
•Cloxacillin are used against beta lactamase producing strains.
•Vancomycin is used in infection with MRSA
•For mild superficial lesions, topical applications of bacitracin or chlorohexidine may be
sufficient
Streptococcus pyogenes
• Individual cocci and are arranged in chains.
• Chain formation is due to successive cell divisions occurring in one plane and daughter
cells failing to separate completely
• Non-motile
• Non-sporing
B. CULTURE
• Aerobes and facultative anaerobes
• Growth occurs only in media containing blood, serum or sugars.
• On BLOOD AGAR, colonies are circular, pin point with a wide zone of haemolysis
around them
TOXINS
Streptococcus produce two types of haemolysins
streptolysin O and streptolysin S
Streptolysin O
It is so named because it is oxygen labile
Streptolysin S
It is oxygen stable
PATHOGENECITY
Suppurative diseases:
1. Respiratory infections
2. Skin and soft tissue infections
3. Genital infections
Non suppurative sequelae:
1. Acute rheumatic fever
2. Acute glomerulonephritis
TREATMENT
• Penicillin G is the drug of choice
• In patients allergic to penicillin, erythromycin is used.
• Antibiotics have no effect on established rheumatic fever and glomerulonephritis
Vibrio cholerae
MORPHOLOGY
• Gram negative bacilli
• Comma shaped
• Non sporing
• Non capsulated
• Actively motile with a single polar flagellum and movement is named as darting motility
PATHOGENESIS
• The human infection occurs by ingestion of contaminated food and drink.
• The ingested organism passes through the acid barrier of stomach and multiplies in the
alkaline medium of the small intestine.
• V. cholerae produces enterotoxin named cholera toxin
• As a result, choleragen stimulates hypersecretion of water and chloride ions while
inhibiting absorption of sodium
• Death may result from the elevated concentrations of blood proteins, caused by reduced
fluid levels, which leads to circulatory shock and collapse
SYMPTOMS
• profuse watery diarrhea, sometimes described as “rice-water stools,”, vomiting, rapid
heart rate, loss of skin elasticity, dry mucous membranes, low blood pressure, thirst,
muscle cramps, restlessness or irritability
TREATMENT
• Oral rehydration therapy with NaCl plus glucose to stimulate water uptake by the
intestine;
• The antibiotics of choice are tetracycline, trimethoprim-sulfamethoxazole, or
ciprofloxacin.
• Tetracycline is useful in reducing the number of stools and it also shortens the period of
excretion of vibrio
Treponema pallidum
MORPHOLOGY
• Thin, delicate spirochete (speira, meaning coil and chaite, meaning hair) with tapering
ends
• Actively motile
• Does not take ordinary bacterial stains and cannot be seen under the light microscope in
wet films
• Because of the thinness of the spirals this cannot be seen by light microscope. However,
it can be made out by negative staining with india pink
• Its morphology and motility can also be seen by dark ground microscopy or phase
contrast microscopy
• It can be stained with silver impregnation method. The treponemes reduce silver nitrate to
metallic silver that is deposited on the surface enlarging the diameter of organism
• T. pallidum is the causative agent of syphilis
TREATMENT
• Primary and secondary syphilis are easy to treat with a penicillin injection.
• Penicillin is one of the most widely used antibiotics and is usually effective in treating
syphilis.
• People who are allergic to penicillin will likely be treated with a different antibiotic, such
as:doxycycline, azithromycin and ceftriaxone
TUBERCULOSIS
MORPHOLOGY
• It is caused by Mycobacterium tuberculosis
• Acid fast
• Non-sporing
• Non-capsulated
• Non-motile
• Tubercle bacilli can grow on wide range of enriched culture media but Lowenstien-
Jenesen (LJ) medium is most commonly used.
• Cell wall contains mycolic acid
The SYMPTOMS of tuberculosis are
• Fever, fatigue and weight loss.
• A cough, which is characteristic of pulmonary involvement, may result in expectoration
of bloody sputum
TREATMENT
• The antitubercular drug include bacteriocidal agents such as rifampcin, isoniazid,
pyrazinamide and bacteriostatic agents include ethambutol, ethionamide, cycloserine
Salmonella typhi
Morphology
Gram negative bacilli
Motile due to presence of peritrichous flagella
Non-sporing
Non-capsulated
Pathogenesis
Salmonellae produce three types of diseases in human: Enteric fever, Gastroenteritis and
Septicaemia
Enteric fever: this term includes typhoid fever (S. typhi) and paratyphoid fever (S. paratyphi A,
B, C). Infections due to S. typhi and S. paratyphi A are prevalent in India
Symptoms
Typhoid fever and paratyphoid fever have similar symptoms̵. People usually have a sustained
fever (one that doesn’t come and go) that can be as high as 103–104°F (39–40°C)
Other symptoms of typhoid fever and paratyphoid fever include
Weakness
Stomach pain
Headache
Diarrhea or constipation
Cough
Loss of appetite

Widal test for the demonstration of antibodies.

It is an agglutination test for the detection of agglutins (H and O) in patient with enteric fever.
Salmonella antibodies start appearing in the serum at the end of first week and rise sharply
during the third week of enteric fever. Two specimens of sera at an interval of 7-10 days are
preferred to demonstrate a rising antibody titre
Treatment
Chloramphenicol has been the antibiotic of choice for enteric fever.
Amoxycillin, ampicillin, cotrimoxazole are also effective
Resistance to chloramphenicol has been reported. Fluoroquinolones (ciprofloxacin, ofloxacin)
and third generation cephalosporins (ceftazidime, cefotaxime, ceftriaxone, cefoperazone) are
useful in such multiresistant cases
Clostridium
The genus Clostridium consist of anaerobic, spore forming, Gram positive bacilli.
•The spore are wider than bacterial bodies, giving the bacillus a swollen appearance resembling a
spindle.
•The name Clostridium is derived from the word Kloster (Meaning a spindle)
•Genus contain bacteria that causes three major diseases are gas gangrene, tetanus and food
poisoning
Most species are motile except C. perfringens and C. tetani, which are non motile
•All clostridia are non-capsulated with exception of C. perfringens
COMPLEMENT
Complement was discovered many years ago as a heat-labile component of human blood plasma
that augments phagocytosis.
This activity was said to “complement” the antibacterial activity of antibody; hence, the name
complement.
It is now known that the complement system is composed of over 30 serum proteins that have a
complex (and somewhat confusing) nomenclature.
This system has three major physiological activities:
1. defending against bacterial infections by facilitating and enhancing phagocytosis
(through opsonization, chemotaxis, activation of leukocytes, and lysis of bacterial cell
walls);
2. bridging innate and adaptive immunity (augmentation of antibody responses,
enhancement of immunologic memory); and
3. disposing of wastes (immune complexes, the products of inflammatory injury, clearance
of dead host cells).
Complement Components
• The complement system comprises of about 30 serum proteins grouped into complement
components, the properdin system and the regulatory proteins.
• The complement components are named by numerals.
• There are nine components; C1 to C9. C1 has three subunits—C1q, C1r and C1s
• The properdin system and the regulatory proteins are named by letter symbols, e.g.
factor-B.
COMPLEMENT PATHWAYS
There are three pathways of complement activation:
1. Classical pathway: This is an antibody dependent pathway. Pathway is triggered by the
antigen–antibody complex formation
2. Alternative pathway: This is an antibody independent pathway, triggered by the antigen
directly
3. Lectin pathway: This is a recently described pathway. It resembles classical pathway, but it is
antibody independent.
Stages of complement activation
There are four main stages in the activation of any of the complement pathways.
1. Initiation of the pathway
2. Formation of C3 convertase
3. Formation of C5 convertase
4. Formation of membrane attack complex (MAC).
All the three pathways differ from each other in their initiation till formation of C3 convertase.
Then, the remaining stages are identical in all the pathways
 ANTIBODY: STRUCTURE, TYPES AND FUNCTIONS
Antibodies are not found at a place as such, but whenever our immune system encounters antigen
or a pathogen, B cells get activated immediately releasing antibodies into the bloodstream. These
immunoglobulins undergo mitosis resulting in cell division and continuously produce antibodies
as a result of producing more cells. These antibodies remain in the blood for some time but B
cells remember these antigens and repeat the same course of action whenever they reappear in
our body
What are Antibodies?
An antibody or immunoglobulin (Ig) is a glycoprotein that is made by activated B cells called
plasma cells. These are large, Y-shaped blood proteins produced by plasma cells. They bind to
foreign particles and invade them. These particles are foreign bodies that get attacked by
Antibody.
Antigens are foreign pathogens that invade the body and have the capability to give rise to a
response from our immunity system either by grouping up with a larger molecule or alone after
binding with antibodies for a particular immune response. Hence, antigens stimulate the
production of antibodies by the immune system
Antibody Structure

• An antibody has a Y-shaped structure, made up of four polypeptide subunits. Each

subunit has two identical light and heavy chains.
 • The N-terminus of each heavy chain forms an antigen-binding domain with a light chain.
There are two antigen-binding domains forming the arms of the “Y” shape. They are
known as ‘fragment antigen-binding’ (Fab) domains.
• The C-terminus of the heavy chains forms ‘fragment crystallization’ (Fc) domain, which
helps in the interaction with the effector cells.
• All four polypeptide subunits are held together by disulfide and non-covalent bonds.
• The heavy chains of the antibodies contain a variable region and three constant regions.
Each antibody has two identical antigen-binding sites and they differ in the antibodies.
Types Of Antibodies
Antibodies or immunoglobulins(Ig) are of five different isotypes. This classification is on the
basis of their H chains. Let’s look at the different types of immunoglobulins and their functions.
IgG
• Most abundant isotype in the plasma, and comprises 80% of the total antibody content in
the serum. It detoxifies substances that are harmful and recognizes the antibody-antigen
complex.
• It is transferred to the placenta through the foetus and protects the infant until its birth.
• It facilitates the process of phagocytosis and provides immunity to the developing foetus.
• It neutralizes the toxins and pathogens and offers protection to the body.
• IgG is divided into four subclasses- IgG1, IgG2, IgG3, and IgG4. Among these, only
IgG3 and IgG4 possess the ability to cross the placenta.
IgM
• IgM is the first antibody produced in response to a microbial attack by B cells.
• It is the largest antibody and is found in a pentameric form.
• It circulates in the blood and lymph and constitutes 6% of the total antibody content in
the serum.
• It is involved in agglutination and opsonization.
• It has a large number of antigenic sites on its surface and therefore facilitates efficient
activation of the immune system.
IgA
• Usually found in liquids such as breast milk, serum, saliva, fluids of the intestine. IgA in
breast milk protects an infant’s gastrointestinal tract from microbial activity.
 • It constitutes 13% of the total antibody content in the serum and is divided into 2 sub-
classes- IgA1 and IgA2. Among these, IgA1 is highly found in the secretions and is also
called the secretory immunoglobulin.
• It provides the first line of defence against the pathogens and limits inflammation. It also
activates the complement pathway and participates in the immune response.
IgD
• It is involved in the production of the antibody by B cells.
• It is present as a monomer and weighs around 1,80,000 dalton.
• It comprises less than 1% of the total antibody content in serum.
• It acts as a receptor on B cell surface and participates in B cell activation and
differentiation
IgE
• IgE is present in the least amounts, around 0.02% of the antibody content in the serum.
• These are present in the linings of the respiratory and intestinal tracts and respond to
allergic reactions.
Functions of Antibody
Following are some of the key functions of antibody:
• Binds to pathogens
• Activates the immune system in case of bacterial pathogens
• Directly attacks viral pathogens
• Assists in phagocytosis
• Antibody provides long-term protection against pathogens because it persists for years
after the presence of the antigen.
• It neutralizes the bacterial toxins and binds the antigen to enhance its efficiency.
• They also act as the first line of defence for mucosal surfaces.
• They ingest cells by phagocytosis.
• Few antibodies bind the antigen present on the pathogens. These aggregates the pathogen
and they remain in secretions. When the secretion is expelled out, the antigen is also
expelled.
 ANTIGENS
“An antigen is a molecule that initiates the production of an antibody and causes an immune
response.”
Antigens are large molecules of proteins, present on the surface of the pathogen- such as
bacteria, fungi viruses, and other foreign particles. When these harmful agents enter the body, it
induces an immune response in the body for the production of antibodies.
For example: When a common cold virus enters the body, it causes the body to produce
antibodies to prevent from getting sick.
The properties of antigens are as follows:
1. The antigen should be a foreign substance to induce an immune response.
2. The antigens have a molecular mass of 14,000 to 6,00,000 Da.
3. They are mainly proteins and polysaccharides.
4. The more chemically complex they are, the more immunogenic they will be.
5. Antigens are species-specific.
6. The age influences the immunogenicity. Very young and very old people exhibit very
low immunogenicity
Types of Antigens
On the basis of Origin
There are different types of antigens on the basis of origin:
Exogenous Antigens
Exogenous antigens are the external antigens that enter the body from outside, e.g. inhalation,
injection, etc. These include food allergen, pollen, aerosols, etc. and are the most common type
of antigens.
Endogenous Antigens
Endogenous antigens are generated inside the body due to viral or bacterial infections or cellular
metabolism.
Autoantigens
Autoantigens are the ‘self’ proteins or nucleic acids that due to some genetic or environmental
alterations get attacked by their own immune system causing autoimmune diseases.
 Tumour Antigens
It is an antigenic substance present on the surface of tumour cells that induces an immune
response in the host, e.g. MHC-I and MHC-II. Many tumours develop a mechanism to evade the
immune system of the body.
Native Antigens
An antigen that is not yet processed by an antigen-presenting cell is known as native antigens.
On the Basis of Immune Response
On the basis of the immune response, antigens can be classified as:
Immunogen
These may be proteins or polysaccharides and can generate an immune response on their own.
Hapten
These are non-protein, foreign substances that require a carrier molecule to induce an immune
response
Structure of Antigens
 The structure of antigens might be different depending on the nature of the antigen, their size,
and immunogenicity.
 All immunogenic antigens have a specific structural component called epitope or antigenic
determinant.
 The number of epitopes differs in different antigens and determines the number of antibodies a
single antigen can bound to.
 The region on antibodies that interacts with antigens is called a paratope. It has been
established that the structure of epitope and paratope can be defined with a lock and key
metaphor as the structures are specific and fit with one another.
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

IMMUNE RESPONSE AND DURATION OF IMMUNITY

An immune response is a reaction which occurs within an organism for the purpose of
defending against foreign invaders. These invaders include a wide variety of different
microorganisms including viruses, bacteria, parasites, and fungi which could cause serious
problems to the health of the host organism if not cleared from the body.
There are two fundamentally different types of immune responses to an invading microorganism
and/or foreign material.
The nonspecific immune response is
 Also known as nonspecific resistance and innate or natural immunity; it offers
resistance to any microorganism or foreign material encountered by the vertebrate host.
 It includes general mechanisms inherited as part of the innate structure and function of
each animal (such as skin, mucus, and constitutively produced antimicrobial mediators
like lysozyme), and acts as a first line of defense.
 The nonspecific immune response defends against foreign particles equally and lacks
immunological memory—that is, nonspecific responses occur to the same extent each
time a microorganism or foreign body is encountered.
Specific immune responses
 Also known as acquired, adaptive, or specific immunity, resist a particular foreign
agent. Moreover, the effectiveness of specific immune responses increases on repeated
exposure to foreign agents such as viruses, bacteria, or toxins; that is to say, specific
responses have “memory.” Substances that are recognized as foreign and provoke
immune responses are called antigens
 The antigens cause specific cells to replicate and manufacture a variety of proteins that
function to protect the host. One such cell, the B cell, produces and secretes glycoproteins
called antibodies.
 Antibodies bind to specific antigens and inactivate them or contribute to their
elimination. Other immune cells become activated to destroy cells harboring intracellular
pathogens
 The first contact that an organism has with a particular antigen will result in the
production of effector T and B cells which are activated cells that defend against the
pathogen. The production of these effector cells as a result of the first-time exposure is
called a primary immune response.
 Memory T and memory B cells are also produced in the case that the same pathogen
enters the organism again. If the organism does happen to become re-exposed to the same
pathogen, a secondary immune response will kick in and the immune system will be
able to respond in both a fast and strong manner because of the memory cells from the
first exposure
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Innate immunity is initiated within hours and provides a rapid array of defenses, whereas the
antigen-specific adaptive immune responses are induced during the first weeks after infection.
While the innate immune response is immediate, the adaptive immune response is not. However,
the effect of the adaptive immune response is long-lasting, highly specific, and is sustained long-
term by memory T cells.

Line of Timeline Cells Antigen Examples

Defense Dependency

Innate First Immediate Natural killer Independent Skin, hair,

(non specific) response (0 -96 cells, cough,
hours) macrophages, mucous
neutrophils, membranes,
dendritic phagocytes,
cells, mast granulocytes
cells,
basophils,
eosinophils

Adaptive Second Long term (>96 T and B Dependent Pus, swelling,

(specific) hours) lymphocytes redness, pain,
T and B
lymphocyte
response
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

STERILIZATION AND DISINFECTION

The ability to control microbial populations on inanimate objects, like eating utensils and
surgical instruments, is of considerable practical importance. Sometimes it is necessary to
eliminate all microorganisms from an object, whereas only partial destruction of the
microbial population may be required in other situations.
Sterilization [Latin sterilis, unable to produce offspring or barren]
• It is the process by which all living cells, spores, and acellular entities (e.g.,
viruses, viroids, and prions) are either destroyed or removed from an object or
habitat.
• A sterile object is totally free of viable microorganisms, spores, and other
infectious agents. When sterilization is achieved by a chemical agent, the chemical
is called a sterilant.
In contrast, disinfection
• It is the killing, inhibition, or removal of microorganisms that may cause disease.
• The primary goal is to destroy potential pathogens, but disinfection also
substantially reduces the total microbial population.
• Disinfectants are agents, usually chemical, used to carry out disinfection and are
normally used only on inanimate objects. A disinfectant does not necessarily
sterilize an object because viable spores and a few microorganisms may remain.
Sanitization
• It is closely related to disinfection.
• In sanitization, the microbial population is reduced to levels that are considered
safe by public health standards.
• The inanimate object is usually cleaned as well as partially disinfected. For
example, sanitizers are used to clean eating utensils in restaurants
• It also is frequently necessary to control microorganisms on or in living tissue with
chemical agents.
Antisepsis [Greek anti, against, and sepsis, putrefaction]
• It is the prevention of infection or sepsis and is accomplished with antiseptics.
These are chemical agents applied to tissue to prevent infection by killing or
inhibiting pathogen growth; they also reduce the total microbial population.
• Because they must not destroy too much host tissue, antiseptics are generally not
as toxic as disinfectants
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Chemotherapy
It is the use of chemical agents to kill or inhibit the growth of microorganisms within
host tissue.
A suffix can be employed to denote the type of antimicrobial agent.
• Substances that kill organisms often have the suffix –cide [Latin cida, to kill]; a
germicide kills pathogens (and many nonpathogens) but not necessarily
endospores.
• A disinfectant or antiseptic can be particularly effective against a specific group,
in which case it may be called a bactericide, fungicide, algicide, or viricide.
• Other chemicals do not kill, but they do prevent growth.
• If these agents are removed, growth will resume. Their names end in -static [Greek
statikos, causing to stand or stopping]—for example, bacteriostatic and
fungistatic.
Topic: Modes of Transmission/spread of pathogens
To maintain an active infectious disease in a human population, the pathogen must be
transmitted from one host or source to another. Transmission is the third link in the
infectious disease cycle and occurs by four main routes: airborne, contact, vehicle, and
vector-borne

Airborne Transmission

Because air is not a suitable medium for the growth of pathogens, any pathogen that is
airborne must have originated from a source such as humans, other animals, plants, soil,
food, or water.

In airborne transmission the pathogen is truly suspended in the air and travels over a
meter or more from the source to the host. The pathogen can be contained within droplet
nuclei or dust.

 Droplet nuclei can be small particles, 1 to 4 µm in diameter, that result from the
evaporation of larger particles (10 µm or more in diameter) called droplets. Droplet
nuclei can remain airborne for hours or days and travel long distances. Chicken pox
and measles are examples of droplet-spread diseases.
 When animals or humans are the source of the airborne pathogen, it usually is
propelled from the respiratory tract into the air by an individual’s coughing,
sneezing, or vocalization. For example, enormous numbers of moisture droplets are
aerosolized during a typical sneeze. Each droplet is about 10 µm in diameter and
initially moves about 100 m/second or more than 200 mi/hour!
 Dust also is an important route of airborne transmission. At times a pathogen
adheres to dust particles and contributes to the number of airborne pathogens when
the dust is resuspended by some disturbance. A pathogen that can survive for
 relatively long periods in or on dust creates an epidemiological problem, particularly
in hospitals, where dust can be the source of hospital acquired infections

Contact Transmission

Contact transmission implies the coming together or touching of the source or reservoir
of the pathogen and the host. Contact can be direct or indirect. Direct contact implies an
actual physical interaction with the infectious source. This route is frequently called
person-to-person contact.

 Person-to-person transmission occurs primarily by touching, kissing, or sexual

contact (sexually transmitted diseases); by contact with oral secretions or body
lesions (e.g., herpes and boils); by nursing mothers (e.g., staphylococcal infections);
and through the placenta (e.g., AIDS, syphilis). Some infectious pathogens also can
be transmitted by direct contact with animals or animal products (e.g., Salmonella
and Campylobacter).
 Indirect contact refers to the transmission of the pathogen from the source to the
host through an intermediary—most often an inanimate object. The intermediary is
usually contaminated by an animate source. Common examples of intermediary
inanimate objects include thermometers, eating utensils, drinking cups,
stethoscopes, and neckties. Pseudomonas bacteria are easily transmitted by this
route. This mode of transmission is often also considered a form of vehicle
transmission.

In droplet spread the pathogen is carried on particles smaller than 5 µm. The route is
through the air but only for a very short distance—usually less than a meter. As a result
droplet transmission of a pathogen depends on the proximity of the source and the host.
Contact with oral secretions may also result when droplet nuclei contaminate body surfaces
that touch mucous membranes (e.g., respiratory secretions on hands that contact eyes).
Vehicle Transmission

Inanimate materials or objects involved in pathogen transmission are called vehicles.

 In common vehicle transmission a single inanimate vehicle or source serves to

spread the pathogen to multiple hosts but does not support its reproduction.
Examples include surgical instruments, bedding, and eating utensils. In
epidemiology these common vehicles are called fomites [s., fomes or fomite]. A
single source containing pathogens (e.g., blood, drugs, IV fluids) can contaminate a
common vehicle that causes multiple infections. Food and water are important
common vehicles for many human diseases

Vector-Borne Transmission

Living transmitters of a pathogen are called vectors. Most vectors are arthropods (e.g.,
insects, ticks, mites, fleas) or vertebrates (e.g., dogs, cats, skunks, and bats).

Vector-borne transmission can be either external or internal.

In external (mechanical) transmission the pathogen is carried on the body surface of a

vector. Carriage is passive, with no growth of the pathogen during transmission. An
example would be flies carrying Shigella organisms on their feet from a fecal source to a
plate of food that a person is eating.

In internal transmission the pathogen is carried within the vector. Here it can go into either
a harborage or biologic transmission phase.

 In harborage transmission the pathogen does not undergo morphological or

physiological changes within the vector. An example would be the transmission of
Yersinia pestis (the etiologic agent of plague) by the rat flea from rat to human.
 Biologic transmission implies that the pathogen does go through a morphological
or physiological change within the vector. An example would be the developmental
sequence of the malarial parasite inside its mosquito vector
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

CULTIVATION OF BACTERIA

Bacteria cultivation is a biological activity wherein microorganisms multiply

themselves in a predetermined culture media under laboratory conditions.

There are various procedures of cultivating bacteria

 Isolation of bacteria

 To estimate viable counts

 Testing for antibiotic sensitivity

 Maintenance of stock culture

 To separate different types of bacteria with the help of microbial culture media

 Certain manipulation of cells and genetic studies of the cell also need that bacterium to be
cultured in vitro.

There are various types of microbial culture media present and they are classified into
six different groups as follows:

 Basal media: This type of media is used for the culture of bacteria, which do not need
enrichment of media. For example, Peptone water, nutrient agar, Nutrient broth are
notable aspects.

 Enriched media: This media is enriched by adding serum, eggs, or blood. For example,
Lowenstein-Jensen media is the most known.

 Selective media: This type of culture is used for the cultivation of a particular type of
bacteria by preventing the growth of undesired bacteria and allowing the growth of
desired bacteria. The example of selective media includes MacConkey agar. It contains
bile salts and crystal violet, which interferes with the growth of gram-positive bacteria
and favours the growth of gram-negative bacteria.

 Storage media: This type of media is used for the storage of bacteria for a longer period.
For example, chalk cooked meat broth and Egg saline medium are notable.
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

 Indicator media: An indicator is included in the media wherein a particular bacterium

causes changes in the indicator such as tellurite. For example, Blood agar and
MacConkey agar are evident examples of indicator media.

There are mainly three methods of cultivation of anaerobic bacteria such as an

atmosphere free of oxygen, an anaerobic indicator, and an anaerobic jar with a catalyst.

 McIntosh–Fildes anaerobic jar: This jar is used to generate an anaerobic condition for the
cultivation of anaerobic bacteria in a laboratory. The principle of this jar is evacuation
and replacement, wherein the mixture of gas replaces inner gas with oxygen. This
consists of 85% nitrogen, 10% hydrogen, and 5% carbon dioxide.

 An anaerobic indicator: This is a sachet-containing test, which contains test strips

saturated with resazurin solution. It checks the atmosphere in a shielded container
whether it can be used for incubation or not
 Dr. Naresh Khanduri, Ph.D (Faculty of Medicine)

Morphology of Bacterial Cell

 Dr. Naresh Khanduri, Ph.D (Faculty of Medicine)

VIRUS

1. They do not possess any cellular organization and hence they are acellular
2. This means they lack most of the cell components like organelles, plasma membrane,
ribosomes, etc.
3. Hence they may usage of the host machinery in order to replicate.
4. Virions range in size from about 10 to 400 nm in diameter
5. The virion contains a nucleic acid core and an outer protein coating called- capsid.
6. The capsid is composed of a large number of protein subunits called capsomeres.
7. within a protein coat held there is nucleocapsid ( composed of a nucleic acid, usually
either DNA or RNA)
8. Some viruses also contain an outer envelope made of proteins and phospholipids.
9. Those virions having an envelope are called enveloped viruses; whereas those lacking an
envelope are called naked viruses
10. The various morphological types of viruses primarily result from the combination of a
particular type of capsid symmetry. There are three types of capsid symmetry: helical,
icosahedral, and complex
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Bacterial Reproduction
Just like any other organism, bacteria also reproduce to continue their species.
Since they are unicellular and do not have a well-organized cell, bacteria have been
grouped under prokaryotes.
Asexual Reproduction in Bacteria
Binary Fission
Bacteria are one of the world's most rapidly proliferating microorganisms, multiplying
every 4−20 minutes. Bacteria can proliferate endlessly and at a very fast rate under ideal
conditions. The phenomenon through which bacteria reproduce is known as binary
fission
The process of binary fission is usually rapid, and its speed varies among species. The
time required by bacteria to double the number of cells it has is called doubling time
 In binary fission, a single bacterial cell divides into two daughter cells.
 At first, the bacterial cell reaches critical mass in its form and cell components.
The circular double-stranded DNA of the bacteria undergoes replication and new
complementary strands are formed.
 These two strands of DNA are then moved to the different poles of the cell and a
transverse septum then takes place and develops in the middle region of the cell
which separates the two new daughter cells and thus binary fission I completed.
Budding
 In this method of reproduction, the bacterial cell develops a small swelling at one
side which continuously increases in size.
 At the same time, the nucleus also undergoes division where one part with some
cytoplasm enters the swelling and the other part remains with the mother cell.
 The outgrowth is called the bud and it eventually gets separated from the mother
cell by a partition wall.
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Sexual Reproduction in Bacteria

Transformation
 In transformation, a bacterium takes up DNA from its environment and often
DNA that’s been shed by another bacteria
 In this process, the DNA of capsulated bacteria is transferred into non-capsulated
bacteria. If the DNA is circular it is called a plasmid.
Transduction
 In this type of sexual reproduction of bacteria, foreign genes are transferred into a
bacterial cell with the help of a virus. These viruses are called bacteriophages and
they are not virulent. The virus acts as a carrier vehicle and passes over genes from
one host to another
Conjugation
 The form of gene transfer and recombination in prokaryotes that requires direct
cell-to-cell contact. 2. A complex form of sexual reproduction commonly
employed by protists.
 STAINING METHODS
The chemical substances commonly used to stain bacteria are known as dyes. Dyes are classified
as natural or synthetic. The former is used mainly for histological purposes while the latter are
used mainly for bacterial stain preparation.

Chemically, a dye (stain) is defined as organic compound containing a benzene ring plus
chromophore and auxochrome group

………………………………………………………………………………………………………
SIMPLE STAINING

The aim of simple staining is to study the morphology and arrangement of bacterial cells. The
most commonly dyes used in simple staining are methylene blue, crystal violet and carbolfuchsin

………………………………………………………………………………………………………
.

GRAM STAINING
Result Interpretation

 Purple color represents Gram Positive bacteria

 Red/Pink color represents Gram Negative bacteria
ACID FAST STAINING
Result Interpretation

 Red Cells: Acid Fast

 Blue Cells: Non Acid Fast
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

VARIOUS TYPES OF INFECTION

 MULTIPLICATION/REPLICATION OF VIRUS
Viruses multiply only in living cells. The host cell must provide the energy and synthetic
machinery and the low- molecular-weight precursors for the synthesis of viral proteins and
nucleic acids
The virus replication occurs in seven stages, namely;
1. Attachment
2. Entry,
3. Uncoating,
4. Transcription / mRNA production,
5. Synthesis of virus components,
6. Virion assembly and
7. Release (Liberation Stage)
Attachment
• It is the first step of viral replication. The virus attaches to the cell membrane of the
host cell. It then injects its DNA or RNA into the host to initiate infection.
• In animal cells these viruses get into the cell through the process of endocytosis which
works through fusing of the virus and fusing of the viral envelope with the cell membrane
of the animal cell and in plant cells it enters through the process of pinocytosis which
works on pinching of the viruses
Entry
• The cell membrane of the host cell invaginates the virus particle, enclosing it in
a pinocytotic vacuole. This protects the cell from antibodies like in the case of
the HIV virus
Uncoating
• Cell enzymes (from lysosomes) strip off the virus protein coat. This releases or renders
accessible the virus nucleic acid or genome
Transcription / mRNA production
• For some RNA viruses, the infecting RNA produces messenger RNA (mRNA), which
can translate the genome into protein products. For viruses with negative stranded RNA,
or DNA, viruses are produced by transcription then translation.
• The mRNA is used to instruct the host cell to make virus components. The virus takes
advantage of the existing cell structures to replicate itself.
Synthesis of virus components
The components are manufactured by the virus using the host's existing organelles:
• Viral proteins: Viral mRNA is translated on cellular ribosomes into two types of viral
protein
• Viral nucleic acid (genome replication): New viral genomes are synthesized; templates
are either the parental genome or newly formed complementary strands, in the case of
single-stranded genomes. These genomes are made by either a viral polymerase or (in
some DNA viruses) a cellular enzyme, particularly in rapidly dividing cells
Virion assembly
• A virion is simply an active or intact virus particle. In this stage, newly synthesized
genome (nucleic acid), and proteins are assembled to form new virus particles.
• This may take place in the cell's nucleus, cytoplasm, or at plasma membrane for most
developed viruses.
Release (liberation stage)
• The viruses, now being matured are released by either sudden rupture of the cell, or
gradual extrusion (force out) of enveloped viruses through the cell membrane.
• The new viruses may invade or attack other cells, or remain dormant in the cell. In the
case of bacterial viruses, the release of progeny virions takes place by lysis of the infected
bacterium. However, in the case of animal viruses, release usually occurs without cell
lysis.
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

CONTRIBUTIONS OF DIFFERENT SCIENTISTS

Anton von Leeuwenhoek: Already discussed
Louis Pasteur
1. In 1861, he resolved the controversy of spontaneous generation versus biogenesis
and proved that microorganism are not spontaneously generated from inanimate
matter but arise from other microorganism
2. He was also responsible for saving a principal industry in France. I.e. manufacture
of wine and beer. He found that fermentation of fruits and grains, resulting in
alcohol was brought about by microbes and also determined that bacteria were
responsible for the spoilage of wine during fermentation.
3. Pasteur also suggested that mild heating at 62.80C for 30 minutes rather than
boiling was enough to destroy the undesirable organism without ruining the taste
of the product, the process is called pasteurization.
4. Pasteur work appeared to demonstrate that microbes could be cause of disease for
if they could spoil the wine; perhaps they could also make the body sick. This led
to the development of germ theory of diseases
5. Pasteur while working on chicken cholera developed the technique of attenuating
cultures. This attenuated culture was called vaccine, in honor of Edward Jenner,
who had used cowpox virus to protect humans from smallpox disease. Using this
method, Pasteur developed anthrax vaccine. 5 years later he was successful in
preparing vaccine against rabies
Robert Koch
The first direct demonstration of role of bacteria in causing disease was provided by
Robert Koch, a German physician who first of all isolated anthrax bacillus
1. He perfected the technique of isolating bacteria in pure culture
2. He also introduced the use of solid culture media in 1881 by using gelatin as a
solidifying agent
3. In 1882, he discovered Mycobacterium tuberculosis.
The most notable contribution of Koch was the establishment of the casual relationship
between a microorganism and specific disease by applying a set of criteria referred to as
Koch Postulates. The postulates are
1. The microorganism must be present in every case of the disease but absent from
healthy organisms
2. The suspected microorganisms must be isolated and grown in a pure culture
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

3. The same disease must result when the isolated microorganism is inoculated into a
healthy host
4. The same microorganism must be isolated again from the diseased host.
Robert Koch will be remembered for both discovery of important disease producing
microorganism and his fundamental contribution to bacteriological techniques
During Koch’s studies on bacterial diseases, it became necessary to isolate suspected
bacterial pathogens in pure culture—a culture containing only one type of
microorganism.
At first Koch cultured bacteria on the sterile surfaces of cut, boiled potatoes, but this was
unsatisfactory because the bacteria would not always grow well. Eventually he developed
culture media using meat extracts and protein digests because of their similarity to body
fluids. He first tried to solidify the media by adding gelatin.
 Separate bacterial colonies developed after the surface of the solidified medium
 When the gelatin medium hardened, individual bacteria produced separate
colonies.
Despite its advantages, gelatin was not an ideal solidifying agent because
 it can be digested by many bacteria and
 Melts at temperatures above 28°C.
A better alternative was provided by Fannie Eilshemius Hesse, the wife of Walther
Hesse, one of Koch’s assistants She suggested the use of agar as a solidifying agent—she
had been using it successfully to make jellies for some time.
 Agar was not attacked by most bacteria
 Did not melt until reaching a temperature of 100°C.
 Once melted, it did not solidify until it reached a temperature of 50°C,
Eliminating the need to handle boiling liquid and providing time for manipulation of the
medium.
Another important tool developed in Koch’s laboratory was a container for holding
solidified media—the petri dish (plate), named after Richard Petri, who devised it. These
developments directly stimulated progress in all areas of bacteriology
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Joseph Lister
A famous English surgeon is known for his notable contributions to the antiseptic
treatment for the prevention and cure of wound infections
1. Lister concluded that wound infections too were due to microorganism.
2. In 1867, he developed a system of antiseptic surgery designed to prevent
microorganism from entering wounds by the application of phenol on surgical
dressing and at times it was sprayed over the surgical areas.
3. He also devised a method to destroy microorganism in the operation theatre by
spraying a fine mist of carbolic acid into the air thus producing antiseptic
environment
4. He also heat sterilized the instruments to be used during surgery
5. Thus Joseph Lister was the first to introduce aseptic techniques for control of
microbes by the use of physical and chemical agents. Because of his notable
contributions, he is known as father of antiseptic surgery
Virus Discovery
 Viral pathogens were also studied during this time. The discovery of viruses and
their role in disease was made possible when Charles Chamberland (1851–1908),
one of Pasteur’s associates, constructed a porcelain bacterial filter in 1884.
 Dimitri Ivanowski and Martinus Beijerinck (pronounced “by-a-rink”) used the
filter to study tobacco mosaic disease. They found that plant extracts and sap from
diseased plants were infectious, even after being filtered with Chamberland’s
filter.
 Because the infectious infectious agent passed through a filter that was designed to
trap bacterial cells, the agent must be something smaller than a bacterium.
Beijerinck proposed that the agent was a “filterable virus.”
 Eventually viruses were shown to be tiny, acellular infectious Agents
Elie Metchnikoff
 He (1845–1916) discovered that some blood leukocytes could engulf disease-
causing bacteria. He called these cells phagocytes and the process phagocytosis
[Greek phagein, eating].
As soon as the relationship between microorganism and disease was established, many
scientists initiated work in search of substances that would kill pathogens without
harming the patient
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Paul Ehrlich
 While experimenting with dyes for controlling pathogen he in 1904, found that the
dye trypan red was active against the trypanosome that causes sleeping sickness
and could used therapeutically. This dye with antimicrobial activity was referred
to as magic bullet.
 Subsequently, Ehrlich in collaboration with Sakahiro, introduced the drug
salvarsan as a treatment for syphilis caused by Treponema pallidum.
 Use of salvarsan marked the beginning of the era of chemotherapy
Alexender Fleming
 Credited for the discovery of first wonder drug penicillin
 Discovery of penicillin is a fascinating and fortunate incident. One day in
September, 1928, he observed that the plate of Staphylococcus aureus had been
contaminated with a green mold Penicillium notatum which had accidently fallen
in the plate. Observing his plate, Fleming noted that the colonies of
Staphylococcus aureus were evidently destroyed by nearby penicillium colonies.
He isolated and subcultured the mold for further study. He extracted from the
fungus a compound which he called penicillin that could destroy several
pathogenic bacteria
The discovery of penicillin stimulated the search for other antibiotics
Selman Waksman
 He announced in 1944 that he and his associates had found a new antibiotic,
streptomycin, produced by the actinomycete Streptomyces griseus.
 This discovery arose from the careful screening of about 10,000 strains of soil
bacteria and fungi.
 The importance of streptomycin cannot be understated, as it was the first drug that
could successfully treat tuberculosis
 Waksman received the Nobel Prize in 1952, and his success led to a worldwide
search for other antibiotic-producing soil microorganisms
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

Edward Jenner
 He observed that countryside milkmaids who contracted cowpox while milking
were subsequently immune to smallpox. On may 14, 1796, he proved that
inoculating people with pus from cowpox lesions provided protection against
smallpox. Eventually the process was termed as vaccination based on latin word
vacca meaning cow.
Sergei Winogradsky
 The Russian microbiologist Sergei Winogradsky (1856–1953) made many
contributions to soil microbiology.
 He discovered that soil bacteria could oxidize iron, sulfur, and ammonia to obtain
energy, and that
 Many bacteria could incorporate CO2 into organic matter much like
photosynthetic organisms do.
 Also isolated anaerobic nitrogen-fixing soil bacteria
 Studied the decomposition of cellulose
Martinus Beijerinck
 He isolated the aerobic nitrogen-fixing bacterium Azotobacter, a root nodule
bacterium also capable of fixing nitrogen (later named Rhizobium), and sulfate-
reducing bacteria
Beijerinck and Winogradsky also developed the
 Enrichment culture technique and the
 Use of selective media,
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

THE DISCOVERY OF MICROORGANISMS

Even before microorganisms were seen, some investigators suspected their existence and
responsibility for disease.

 Among others, the Roman philosopher Lucretius (about 98–55 B.C.) and the
physician Girolamo Fracastoro (1478–1553) suggested that disease was caused by
invisible living creatures.
 The earliest microscopic observations appear to have been made between 1625
and 1630 on bees and weevils by the Italian Francesco Stelluti, using a microscope
probably supplied by Galileo
 In 1665, the first drawing of a microorganism was published in Robert Hooke’s
Micrographia.

However, the first person to publish extensive, accurate observations of microorganisms

was the amateur microscopist Antony van Leeuwenhoek (1632–1723) of Delft, The
Netherlands

 Leeuwenhoek earned his living as a draper and haberdasher (a dealer in men’s

clothing and accessories), but spent much of his spare time constructing simple
microscopes composed of double convex glass lenses held between two silver
plates
 His microscopes could magnify around 50 to 300 times, and he may have
illuminated his liquid specimens by placing them between two pieces of glass and
shining light on them at a 45° angle to the specimen plane. This would have
provided a form of dark-field illumination in which the organisms appeared as
bright objects against a dark background and made bacteria clearly visible
 Beginning in 1673, Leeuwenhoek sent detailed letters describing his discoveries to
the Royal Society of London. It is clear from his descriptions that he saw both
bacteria and protozoa
 Dr. Naresh Khanduri, Ph. D (Faculty of Medicine)

As important as Leeuwenhoek’s observations were the development of microbiology

essentially languished for the next 200 years.

 Little progress was made primarily because microscopic observations of

microorganisms do not provide sufficient information to understand their biology.
 For the discipline to develop, techniques for isolating and culturing microbes in
the laboratory were needed. Many of these techniques began to be developed as
scientists grappled with the conflict over the Theory of Spontaneous Generation.
This conflict and the subsequent studies on the role played by microorganisms in
causing disease ultimately led to what is now called the Golden Age of
Microbiology