UNIT 3 – MICROORGANISMS AND INFECTION

HISTORY OF MICROBIOLOGY

Robert Hooke (1665):

• The word cell was coined by the Englishman, Robert Hooke (1635-1703).
• In his descriptions (1665) of the fine structure of cork and other plant materials,
he observed honeycomb like structure in a thin slice of cork was due to the dead
cell walls of plant cells in microscope
• Hooke’s description was published in the Book ‘Micrographia’ by Royal
Society of London
The concept of Cell theory was proposed by two German Scientists Schleiden and
Schwann
• All living things are made up of cells.
• The cell is basic structural & functional unit of living things.
• All cells come from pre-existing cells by division.
Anton van Leeuwenhoek (1680s):
• Microorganisms are invisible to naked eye and it was seen only after the
development of Microscope.
• Antony van Leeuwenhoek, who lived in Delft, Holland, from 1632 to 1723, was
the first to report his observations with accurate descriptions and drawings
• Leeuwenhoek was an amateur scientist who spent much of his spare time
grinding glass lenses. During his lifetime he made more than 250 microscopes
consisting of home-ground lenses mounted in brass and silver, the most
powerful of which would magnify about 200 to 300 times These microscopes
bear little resemblance to the compound light microscope of today, which is
capable of magnifications of 1,000 to 3,000 times.
• However, the lenses of Leeuwenhoek's microscopes were well made and his
descriptions of protozoa were so accurate that many of the forms he described
are easily recognized today. Leeuwenhoek carefully recorded his observations
in a series of letters to the British Royal Society.
 • Leeuwenhoek named the microorganisms as ‘animalcules’.

Spontaneous Generation vs Biogenesis

• Spontaneous generation is defined as the living things arising from non-living

matter
• Biogenesis is defined as the living things arising from other living things

Francisco Redi (1626-1697):

• Italian Scientist Francesco Redi showed that the larvae found on putrefying
meat arose from eggs deposited by flies, and not spontaneously as a result of the
decay process
He did some experiment to prove his idea. i) He took jar with meat and left
open. The files were attracted by the meat and it laid eggs on the meat. Thus,
contaminating the meat and maggots developed inside the jar. ii) He took jar
with meat and closed with lid so that the files are not attracted iii) He took jar
with meat and covered with gauze so that the flies were attracted by the meat
and laid eggs on the gauze.

Figure represents,
Jar A→ Open Jar with meat attracted by flies
Jar B→ Closed Jar with meat, no flies
 Jar C→ Jar covered with gauze and flies attracted by the odor of the meat and
laid eggs on the covering
Thus, he proved that it was biogenesis not spontaneous generation.
John Needham (1713-1781)
• Needham observed the appearance of organisms not present at the start of the
experiment and concluded that the bacteria originated from the meat. About the
same time,
Lazaro Spallanzani (1729-1799)
• Spallanzani boiled beef broth for an hour and then sealed the flasks. No
microbes appeared following incubation. But his results, confirmed in repeated
experiments failed to convince Needham, who insisted that air was essential to
the spontaneous production of microscopic beings and that it had been excluded
from the flasks by sealing them.
Franz Schulze (1815-1873)
• Schulze passed air through strong acid solutions into boiled infusions
Theodor Schwann (1810-1882)
• Schwann passed air into his flasks through red-hot tubes
Golden Era of Microbiology
Louis Pasteur
• Louis Pasteur’s swan neck flask experiment disproved spontaneous generation
theory.
• He is also called “Father of Microbiology”.
• He prepared a flask with a long, narrow gooseneck opening (Fig. 5). The
nutrient solutions were heated in the flask, and air untreated and unfiltered could
pass in or out but the germs settled in the gooseneck, and no microbes appeared
in the solution. Also observed that heat could kill the microbes. This led to the
development of ‘Pasteurization’.
 Figure 1: Swan neck flask experiment
Robert Koch (1843-1910):
• The first proof of the involvement of bacteria in disease and the definitive proof
of the germ theory of disease came from the German Robert Koch. In 1876
Koch showed the relationship between the cattle disease anthrax and a bacillus
which we now know as Bacillus anthracis.
Koch's postulates are:
(1) A specific organism can always be found in association with a given disease.
(2) The organism can be isolated and grown in pure culture in the laboratory.
(3) The pure culture will produce the disease when inoculated into a susceptible
animal.
(4) It is possible to recover the organism in pure culture from the experimentally
infected animal.

John Tyndall:
• Discovered highly resistant bacterial structure called Endospore
• Prolonged boiling and intermittent heating were necessary to kill the spores to
make the infusion completely sterilized and this process is known as
Tyndallisation
Joseph Lister:
• He is the Father of antiseptic surgery
• He concluded that wound infections were due to microorganisms ans also
devised a method to destroy microorganisms in the operation theatre by
spraying a fine mist of carbolic acid into the air
Fanne Hesse:
• She proposed the use of agar in culture media which is not attacked by bacteria
and which is better that gelatin due to its higher melting points and solidifying
points.
Richard Petri:
• Developed the Petri dish, a container used for solid culture media.
Edward Jenner:
• First person to prevent small pox.
• Discovered the technique of vaccination.
Alexander Fleming:
• Discovered the Penicillin from Penicillium notatum that destroy several
pathogenic bacteria.
Paul Ehrlich:
• Discovered the treatment of syphilis by using arsenic compound

MAJOR CLASSIFICATION OF MICROBES

• Taxonomy is the science of the classifying organisms

✓ Taxonomy includes: (a) Identification. (b) Nomenclature. (c) Classification.
• Identification – is the process of studying and recording the identical and
distinguishing features Nomenclature – is the process of assigning names to the
various taxonomic ranking of each living organism.
Classification – is the orderly arrangement of organisms into groups, preferably in
a format, that shows evolutionary relationships.
Hierarchy of Taxonomy
• To classify each species eight successive taxa are used. They are Domain,
Kingdom, Phylum, Class, Order, Family, Genus and Species

Examples of Taxonomy

The scientific classification of humans is as follows:

• Domain: Eukaryota
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Primates
• Family: Hominidae
• Genus: Homo
• Species: sapiens
Two Kingdom Classification:
• Introduced by Carolus Linnaeus in 1758
• Kingdom Plantae and Animalia
Three Kingdom Classification:
• In 1866 by a German zoologist, E. H. Haeckel suggested third kingdom.
• Three kingdom classification system includes Bacteria, Archaea, Eukaryota.
Whittaker 5 Kingdom classification:
• Kingdom Monera
• Kingdom Protista.
• Kingdom Myceteae or Fungi.
• Kingdom Plantae
• Kingdom Animalia
Six Kingdom classification:
▪ Six kingdom was introduced by Carl Woese et al. (1977).
▪ Archaebacteria and Eubacteria under Prokaryotes and rest of the four
kingdoms Protista, Fungi, Plantae and Animalia under Eukaryotes.
 MICROSCOPY
Introduction
• Microscopy is the technical field of using microscopes to view samples and
objects that cannot be seen with the unaided eye (objects that are not within the
resolution range of the normal eye).
• Used to study fine structure of cells and sub-cellular components.
• PRINCIPLE: Microscopy is to get a magnifies image, in which structures may
be resolved which could not be resolved with the help of an unaided eye.
Magnification - ability to enlarge images
⚫ Increase in size of the object.
⚫ Magnification beyond the resolving power is of no value. It is because the larger
image will be less distinct in detail and fuzzy in appearance
Resolution
• The ability to see two close objects as two distinct objects called resolution.
• The resolving power of human eye is 0.25 mm
• The resolution can be calculated as
Maximum resolution: R = (0.061λ)/ N.A
Where, 0.61 is a geometrical term, based on the average 20-20 eye,
λ= wavelength of illumination, N.A. = Numerical Aperture
Numerical aperture
• Ratio of the diameter of the lens to its focal length
• NA of a lens is an index of the resolving power
• NA can be decreases by decreasing the amount of light that passes through a
lens
NA can be calculated as N.A. = n sin α
Where, n = index of refraction of medium, α= < subtended by the lens
MICROSCOPY CATEGORIES

Figure 2: Types of Microscopes

LIGHT (OPTICAL) MICROSCOPE
• Light microscopy involves use of optical lenses and light radiations
• Light travels as wave in crests & troughs.
• The amplitude of the crests & troughs determine the brightness of the light.
• The number of time complete wave occur per unit time is called as frequency
and the distance between two consecutive crests is called wavelength (λ) of the
light.
• Light microscope wavelength in the range 400-700 nm make up visible
spectrum.
• While the UV region consists of wavelengths ranging from 100-385 nm.
• Visualizing any object directly by human eye involves incidence & reflection of
light
in the visual range.
• Microscopes use day light or light emitted by incandescent bulb.
• Fluorescent & UV microscope employ UV radiations
 Figure 2: Compound Microscope
PARTS OF A MICROSCOPE
Mainly three parts
⚫ Magnifying parts –objective and eyepiece lens
⚫ Mechanical parts – Base, pillars, curved arm, body tube, Coarse adjustment, Fine
adjustment, Mechanical stage, Revolving nose piece
⚫ Illuminating parts- Condenser, Diaphragm, Illuminator (Light source)
Eyepiece or Ocular is what you look through at the top of the microscope. Typically,
standard eyepieces have a magnifying power of 10x. Optional eyepieces of varying
powers are available, typically from 5x-30x.
Eyepiece Tube holds the eyepieces in place above the objective lens.

Objective Lenses are the primary optical lenses on a microscope. They range from
4x-100x and typically, include, three, four or five on lens on most microscopes.
Objectives can be forward or rear-facing.
Nosepiece houses the objectives. Standard objectives include 4x, 10x, 40x and 100x
although different power objectives are available.
Coarse and Fine Focus knobs are used to focus the microscope. Coaxial focus knobs
are more convenient since the viewer does not have to grope for a different knob.
Stage is where the specimen to be viewed is placed. A mechanical stage is used when
working at higher magnifications where delicate movements of the specimen slide are
required.
Stage Clips are used when there is no mechanical stage. The viewer is required to
move the slide manually to view different sections of the specimen.
Aperture is the hole in the stage through which the base (transmitted) light reaches
the stage.
Illuminator is the light source for a microscope, typically located in the base of the
microscope.
Condenser is used to collect and focus the light from the illuminator on to the
specimen.
Iris Diaphragm controls the amount of light reaching the specimen.
Condenser Focus Knob moves the condenser up or down to control the lighting focus
on the specimen.
DARK FIELD MICROSCOPE
• An illumination technique used to enhance the contrast illuminates the sample
with light that will not be collected by the objective lens, and thus will not form
part of the image. This produces the classic appearance of a dark, almost black,
background with bright objects on it.
• A bright-field microscope can be adapted as a dark-field microscope by adding
a special disc called a stop to the condenser.
• The stop blocks all light from entering the objective lens except peripheral light
that is reflected off the sides of the specimen itself. The resulting image is a
brightly illuminated specimens surrounded by a dark (black) field.
Uses:
• This microscope is used to study spirochetes in the exudates form leptospiral or
syphilitic Infections.
 Figure 3: Bright vs Dark field microscope

Figure 4: Organisms under Microscope

PHASE CONTRAST MICROSCOPE

• In 1935 F.Zernike produced the phase contrast microscope. Phase-contrast
microscope is also called as Zernike microscope.
 • Phase-contrast microscope uses a special condenser and objective lenses. This
condenser lens on the light microscope splits a light beam and throws the light
rays slightly out of phase. The separated beams of light then pass through and
around the specimen, and small differences in the refractive index within the
specimen show up as different degrees of brightness and contrast.
Uses:
✓ Phase-contrast microscopy is especially useful for studying microbial motility,
studying eukaryotic Cells, determining the shape of living cells, and detecting
bacterial components such as endospores and Inclusion bodies that contain poly-
-hydroxyalkanoates (e.g., poly-hydroxybutyrate), polymetaphosphate, sulfur, or
other substances

Figure 5: Phase contrast Microscope

FLUORESCENCE MICROSCOPE:
✓ It was developed by Haitinger and coons
✓ A fluorescence microscope differs from an ordinary brightfield microscope in
several
 respects. It utilizes a powerful mercury vapor arc lamp for its light source.
✓ A darkfield condenser is usually used in place of the conventional Abbé
brightfield
condenser.It employs three sets of filters to alter the light that passes up through
the instrument to the eye.
✓ Microbiological speciemen that is to be studied must be coated with special
compounds that possess the quality of fluorescence. Such compounds are
calledfluorochromes. AuramineO, acridine orange, and fluorescein are well-
known fluorochromes
USES:
✓ It is used to study the substance like chlorophylls, riboflavin, vitamin A,
collagen which have the property of auto fluorescence. Some cellular
components like cellulose, starch, glycogen, protein and Y chromosome can be
made visible under this microscope by staining them with fluorochromes.
✓ It used to identify Y chromosome to determine sex, determination of microbial
cells in the infected tissue and to
✓ study the structure of proteins

Figure 5: Fluorescent Microscope

ELECTRON MICROSCOPE
✓ In 1932 Knoll and Ruska invented first electron microscope. The electron
microscope uses a beam of electrons rather than visible light. The magnified
 image is visible on a fluorescent screen and can be recorded on a photographic
film.
✓ The drawback of the electron microscope is specimen are killed in order to
view the cells or organisms. Images produced by electrons lack color, electron
micrographs are always shades of black, gray, and white.
✓ Two general forms of EM are the transmission electron microscope (TEM) and
the scanning electron microscope (SEM).
✓ Transmission electron microscopes are the method of choice for viewing the
detailed structure of cells and viruses. This microscope produces its image by
transmitting electrons through the specimen.
✓ Because electrons cannot readily penetrate thick preparations, the specimen
must be sectioned into extremely thin slices (20–100 nm thick) and stained or
coated with metals that will increase image contrast.
✓ The darkest areas of TEM micrographs represent the thicker (denser) parts, and
the lighter areas indicate the more transparent and less dense parts.

Figure 6: TEM

Scanning Electron microscope

✓ The specimen is placed in the vacuum chamber and covered with a thin coat of
gold.
✓ The electron beam then scans across the specimen and knocks loose showers of
electrons that are captured by a detector. An image builds line by line, as in a
television receiver.
✓ Electrons that strike a sloping surface yield fewer electrons, thereby producing a
darker contrasting spot and a sense of three dimensions.
✓ The resolving power of the conventional SEM is about 10 nm and
magnifications with the SEM are limited to about 20,000x.

Figure 6: SEM
 Microbes as infectious agents: Typhoid, Tuberculosis, Malaria, Hepatitis, Polio, Dengue, AIDS, SARS

Sl.No. Disease Causative Mode of Pathogenesis Symptoms Prevention Treatment

organism transmission
1 Typhoid Salmonella typhi Direct contact S. typhi enters through the mouth and spends 1 Fever and Live Antibiotics -
with the feces to 3 weeks in the intestine and makes its way rash attenuated ciprofloxacin (for non-
of an infected through the intestinal wall and into the vaccine pregnant adults) and
person bloodstream. ceftriaxone

From the bloodstream, it spreads into other

tissues and organs.
SL.NO DISEASE Causative Mode of Pathogenesis Symptoms Prevention Treatment
organism transmission
2 Tuberculosis Mycobacterium TB spreads The bacteria usually attack the Cough that lasts 3 weeks or BCG Vaccine isoniazid (INH), rifampin
tuberculosis through the air lung and other parts of the longer, Coughing up blood (RIF), ethambutol
when a person body. or mucus (EMB), pyrazinamide
with TB coughs Weight loss (PZA)
or sneezes Loss of appetite
Weakness or fatigue
Fever
Night sweats
Sl.No. Disease Causative organism Mode of transmission Pathogenesis Symptoms Prevention Treatment
3 Malaria Plasmodium It’s typically transmitted Once the parasites are inside body, Shaking chills, Sleeping under Atovaquone/Prog
vivax, P. ovale, P. through the bite of an they travel to the liver, where they high fever, a mosquito uanil (Malarone),
malariae, and P. infected Anopheles mosqui mature and later enter the profuse sweati net may help Chloroquine,
falciparum to. Infected mosquitoes bloodstream and begin to ng, headache, prevent being Doxycycline,
carry infect red blood cells. nausea, bitten by an Mefloquine,
the Plasmodium parasite. vomiting, infected Primaquine,
abdominal mosquito. Tafenoquine
pain, diarrhea, Covering your
anemia, skin or
muscle pain, using bug sprays
convulsions, containing
coma, bloody DEET] may also
stools help prevent
infection.
Sl.No. Disease Causative Mode of transmission Pathogenesis Symptoms Prevention Treatment
organism
4 Dengue Dengue virus Dengue viruses are Range from subclinical infection to Belly pain Sleeping Fluid replacement, Can
spread to people dengue fever, dengue hemorrhagic fever tenderness under be self-healing, Oral
through the bite of an (DHF), and eventually dengue shock Vomiting (at a mosquito rehydration therapy and
infected Aedes species syndrome (DSS) least 3 times net, IV fluids
(Ae. aegypti or Ae. in 24 hours) Covering
albopictus) mosquito. Bleeding skin or
from the using bug
nose or sprays
gums containing
Vomiting DEET help
blood, or prevent
blood in the infection.
stool
Sl.No. Disease Causative Mode of Pathogenesis Symptoms Prevention Treatment
organism transmission
5 Hepatitis Hepatitis Transmitted Hepatitis virus is acquired by mouth (through fatigue, flu- Vaccines entecavir ,
A, B, C, through contact fecal-oral transmission) and replicates in the like for hepatitis A tenofovir ,
D, and E with infectious liver. symptoms, and hepatitis B, lamivudine,
Virus body fluids, After 10-12 days, virus is present in blood and is dark urine, Safe sex adefovir and
such as blood, excreted via the biliary system into the feces. pale stool, practices, Practice telbivudine
vaginal abdominal good personal
secretions, or pain, loss of hygiene such as
semen, appetite, thorough hand-
containing the unexplained washing with
hepatitis B virus weight loss soap and water.
(HBV).
Injection
drug use,
having sex
with an
infected
partner, or
sharing
razors with
an infected
person.
Sl.No. Disease Causative Mode of transmission Pathogenesis Symptoms Prevention Treatment
organism
6 AIDS Human HIV is a sexually CD4 T-cell depletion and Rapid weight loss, Abstinence, No cure exists for
Immunodeficiency transmitted infection chronic inflammation are Recurring fever or never AIDS, but strict
Virus (STI). the two signature events profuse night sweats, sharing adherence to
It can also be spread that drive HIV Extreme and needles, and antiretroviral
by contact with pathogenesis and unexplained tiredness, using regimens (ARVs) can
infected blood progression to AIDS. Prolonged swelling of condoms dramatically slow the
From mother to child the lymph glands in disease's progress as
during pregnancy, the armpits, groin, or well as prevent
childbirth or breast- neck, Diarrhea that secondary infections
feeding lasts for more than a and complications.
week, Sores of the
mouth, anus, or
genitals. Pneumonia.
Sl. Disease Causative Mode of Symptoms Prevention Treatment
No organism transmission
.
7 SARS SARS- SARS is an ⮚ The first symptom of the illness is generally fever (>38°C), • washing hands No drugs,
associated airborne virus which is often high, and sometimes associated with chills and frequently or including antibi
coronavirus and can spread rigors. cleaning with an otics, appeared
through small ⮚ It may also be accompanied by other symptoms including alcohol-based to be effective
droplets of saliva headache, malaise, and muscle pain. detergent against SARS.
in a similar way ⮚ At the onset of illness, some cases have mild respiratory • avoiding touching Instead,
to the cold and symptoms. the eyes, mouth, healthcare
influenza. and nose with providers
⮚ Typically, rash and neurologic or gastrointestinal findings are
unclean hands offered
absent, although a few patients have reported diarrhoea
• covering the supportive care,
during the early febrile stage.
mouth and nose including the
⮚ After 3-7 days, a lower respiratory phase begins with the
with a tissue when use of
onset of a dry, non-productive cough or dyspnoea (shortness
coughing or medications to
of breath) that may be accompanied by, or progress to,
sneezing relieve
hypoxemia (low blood oxygen levels).
• avoiding sharing symptoms, such
⮚ In 10–20% of cases, the respiratory illness is severe enough to food, drinks, and as fever and a
require intubation and mechanical ventilation. utensils cough. In the
⮚ The white blood cell count is often decreased early in the • staying at least 3 hospital, some
disease, and many people have low platelet counts at the feet away from people needed
peak of the disease. other people a ventilator to
• regularly cleaning help them
surfaces with breathe.
disinfectant
Sl.No. Disease Causative Mode of Pathogenesis Symptoms Prevention Treatment
organism transmission
8 Polio Polio virus It enters the The virus invades local lymphoid tissue, enters Sore throat, Vaccination Treatment includes
body through the bloodstream, and then replication Fever, (OPV) bed rest, pain
the mouth and of poliovirus in motor neurons of the brain stem Tiredness, relievers and
spreads results in cell destruction. Nausea, portable ventilators.
through: Headache,
Contact with Stomach
the feces of an pain.
infected person.
Droplets
from a
sneeze
or
cough
of an
infected
person
(less
commo
n).
 Unit-3
Immune System

Introduction
Study of immune system and its functions
A defense system that has evolved to protect animals from invading foreign molecules and
pathogens

Hematopoiesis
Hematopoiesis is defined as the generation of blood- and immune cells from the hematopoietic
stem cells (HSCs). HSCs differentiate into common myeloid progenitor (CMP), and common
lymphoid progenitor (CLP). CMP becomes blood and innate immune cells and CLP develop into
adaptive immune cells.

Types of Immunity

Innate Immunity
Immunity, the state of protection from infectious disease. Consists of both less specific and more
specific components. The less specific component, innate immunity. It provides the first line of
defense against infection. Most components of innate immunity are present before the onset of
infection. It comprises a set of disease-resistance mechanisms that are not specific to a particular

1
pathogen, instead recognizing various classes of molecules, specifically, to frequently
encountered pathogens.

Acquired or Adaptive Immunity

Adaptive immunity responds with a high degree of specificity as well as the remarkable property
of memory. The immune response to the second challenge occurs more quickly than the immune
response first, E.g. lymphocytes and antibodies.

Adaptive immunity displays four characteristic attributes:

 Diversity- enhanced responses to recurrent or persistent microbes

 Immunologic memory- responses to distinct microbes are optimized for defense against
these microbes
 Self/non-self recognition- prevents injurious immune responses against host cells and
tissues
 The antigenic specificity of the immune system permits it to distinguish subtle differences
among antigens. The immune system has potential diversity in recognizing the antigenic
molecules. Once it recognize and respond to the antigen and exhibits immunologic
memory. So when the second encounter happen with the same antigen, enhanced
immune response will occur. Also, it has the capacity to distinguish between self and non-
self recognition and respond only to non-self molecules.

 The phagocytic cells are intimately involved in activating the specific immune response..
As an inflammatory response develops, for example, soluble mediators are produced that
attract cells of the immune system. The immune response will serve to regulate the
intensity of the inflammatory response. Through the carefully regulated interplay of
adaptive and innate immunity, the two systems work together to eliminate a foreign
invader.

2
Barriers of Immune System

Anatomic Barriers Skin Mechanical barrier retards entry of microbes.

Acidic environment (pH 3 5) retards growth of microbes.
Mucous membranes Normal flora compete with microbes for
attachment sites and nutrients.
Mucus entraps foreign microorganisms.
Cilia propel microorganisms out of the body.

Physiologic barriers

Temperature Normal body temperature inhibits growth of some pathogens.

Fever response inhibits growth of some pathogens.

Low pH Acidity of stomach contents kills most ingested microorganisms.

Chemical mediators Lysozyme cleaves bacterial cell wall.

Interferon induces antiviral state in uninfected cells.
Complement lyses microorganisms or facilitates phagocytosis.
Toll-like receptors recognize microbial molecules, signal cell to
secrete immunostimulatory cytokines.
Collectins disrupt cell wall of pathogen

Phagocytic/ endocytic Various cells internalize (endocytose) and break down foreign

3
 barriers macromolecules.
Specialized cells (blood monocytes, neutrophils, tissue
macrophages) internalize (phagocytose), kill, and digest whole
microorganisms

Inflammatory barriers Tissue damage and infection induce leakage of vascular fluid,
containing serum proteins with antibacterial activity, and influx of
phagocytic cells into the affected area.

Bone Marrow
In humans and mice, bone marrow is the site of B-cell origin and development. Arising from
lymphoid progenitors, immature B cells proliferate and differentiate within the bone marrow, and
stromal cells within the bone marrow interact directly with the B cells and secrete various cytokines
that are required for development. Like thymic selection during T cell maturation, a selection
process within the bone marrow eliminates B cells with self-reactive antibody receptors. Bone
marrow is not the site of B-cell development in all species. In birds, a lymphoid organ called the
bursa of Fabricius, a lymphoid. The lymph nodes, spleen, and various mucosal associated
lymphoid tissues (MALT) such as gut-associated lymphoid tissue (GALT) are the secondary (or
peripheral) lymphoid organs.

Thymus
The thymus is the site of T-cell development and maturation. It is a flat, bilobed organ situated
above the heart. Each lobe is surrounded by a capsule and is divided into lobules, which are
separated from each other by strands of connective tissue called trabeculae. Each lobule is
organized into two compartments: the outer compartment, or cortex, is densely packed with
immature T cells, called thymocytes, whereas the inner compartment, or medulla, is sparsely
populated with thymocytes.

B Cells
B lymphocytes mature within the bone marrow; when they leave it, each expresses a unique
antigen-binding receptor on its membrane. This antigen-binding or B-cell receptor is a membrane-
bound antibody molecule. When a naive B cell (one that has not previously encountered antigen)
first encounters the antigen that matches its membrane bound antibody, the binding of the antigen
to the antibody causes the cell to divide rapidly; its progeny differentiate into memory B cells and
effector B cells called plasma cells. Memory B cells have a longer lifespan than naive cells, and
they express the same membrane-bound antibodies as their parent B cell. Plasma cells produce
the antibody in a form that can be secreted and have little or no membrane-bound antibody.
Although plasma cells live for only a few days, they secrete enormous amounts of antibody during
this time. It has been estimated that a single plasma cell can secrete more than 2000 molecules
of antibody per second. Secreted antibodies are the major effector molecules of humoral
immunity.

4
T Cells

These cells arise in the bone marrow. Unlike B cells, which mature within the bone marrow, T
cells migrate to the thymus gland to mature. During its maturation within the thymus, the T cell
comes to express a unique antigen-binding molecule, called the T-cell receptor, on its membrane.
T-cell receptors can recognize only antigen that is bound to cell-membrane proteins called major
histocompatibility complex (MHC) molecules. There are two major types of MHC molecules: Class
I MHC molecules, which are expressed by nearly all nucleated cells of vertebrate species, consist
of a heavy chain linked to a small invariant protein called -microglobulin. Class II MHC molecules,
which consist of an alpha and a beta glycoprotein chain, are expressed only by antigen-presenting
cells. There are two well-defined subpopulations of T cells: T helper (TH) and T cytotoxic (TC)
cells. T helper and T cytotoxic cells can be
distinguished from one another by the presence
of either CD4 or CD8 membrane glycoproteins on
their surfaces. T cells displaying CD4 generally
function as TH cells, whereas those displaying
CD8 generally function as TC cells.