Download Chapter 8

Document related concepts

Vaccination wikipedia , lookup

Complement system wikipedia , lookup

Anti-nuclear antibody wikipedia , lookup

T cell wikipedia , lookup

Hygiene hypothesis wikipedia , lookup

Lymphopoiesis wikipedia , lookup

Antibody wikipedia , lookup

DNA vaccination wikipedia , lookup

Phagocyte wikipedia , lookup

Immunocontraception wikipedia , lookup

Immune system wikipedia , lookup

Molecular mimicry wikipedia , lookup

Psychoneuroimmunology wikipedia , lookup

Adoptive cell transfer wikipedia , lookup

Adaptive immune system wikipedia , lookup

Monoclonal antibody wikipedia , lookup

Innate immune system wikipedia , lookup

Immunomics wikipedia , lookup

Cancer immunotherapy wikipedia , lookup

Polyclonal B cell response wikipedia , lookup

Immunosuppressive drug wikipedia , lookup

Transcript
TRANSMISSION OF
PATHOGENS
Infective agents can be transmitted from one host
to another by:
 A VECTOR







A carrying vector eg rats & fleas
An injecting vector eg mosquito – malaria
direct contact
Droplet infection in air breathed or sneezed out
Sexual contact
Contaminated food or water
Injecting with infected needle & syringe
Transmission of Disease
Diseases can be
transmitted in three
broadly different
ways:
Contact
transmission
Vehicle
transmission
Airborne droplet
transmission
Contact with
contaminated
blood
Insects
carrying
disease
Direct
contact
with skin
Vector
transmission
Contact with
contaminated
food
Vector Transmission
Many pathogens have more than one host. An intermediate host may
transmit the pathogen to its primary host.
Bites from a variety of animals can introduce pathogens.
Fleas
Rodents
Mosquitoes
Carried on many animals, they are
responsible for the spread of numerous
bacterial diseases, including bubonic
plague.
Hantaviruses are carried by rodents.
Infection occurs when humans come
in contact with rodent droppings.
Anopheles gambiae, a tropical
mosquito, is one of the vectors
for the malarial parasite.
Ticks
Fruit bat
Foxes
The deer tick transmits Lyme disease
from wild mammals to humans.
Hendra viruses are transmitted
in the droppings of fruit bats.
Rabies is transmitted in bites
from infected foxes and other
mammals (e.g. dogs).
Contact Transmission
Pathogens may be spread by contact with other infected humans or
animals.
Droplet Transmission
Indirect Contact
Direct Contact
Mucus droplets carrying disease
are discharged into the air.
Includes touching
contaminated objects.
Direct transmission of an agent
by physical contact between its
source and a potential host.
Examples:
coughing
Examples:
Examples:
sneezing
eating utensils
touching
laughing
drinking cups
kissing
talking
bedding
sexual intercourse
toys
money
used syringes
Vehicle Transmission
Disease may be transmitted through a medium such as blood, water, food,
or air.
Waterborne Diseases
Food-borne Diseases
Blood-borne Diseases
Usually associated with regions with
poor sanitation, especially where fecal
material enters the water supply.
Hepatitis B and meningococcal
disease can be spread by sharing
drinking bottles.
Occur when food is insufficiently
cooked, poorly stored, or prepared
in an unsanitary environment.
Blood-borne diseases are
transmitted when body fluids
from at least two animals (one of
them infected) are mixed.
Examples: Typhoid fever, cholera
and hepatitis B
Examples: Bacterial food
poisoning, e.g. salmonellosis and
hydatids
Examples: most viral pathogens
(including HIV, hepatitis)
Bacteria and Disease
Lactobacillus bacteria are part of the
normal flora found on healthy
humans
Of the many species of
bacteria that exist in the
world, relatively few are
Photo: CDC/Dr Mike Miller.
pathogenic.
Most bacteria form part
of the normal microflora
found on healthy humans.
Cell nucleus
Bacteria infect a host in
Human vaginal epithelial
cell
order to exploit the food
potential of the host’s body tissues. The fact that this exploitation
causes disease is not in the interest of the bacteria; a healthy host
is better than a sick one.
The Body’s Defenses
If microorganisms never encountered resistance from our defenses,
we would be constantly ill and would eventually die of various
diseases.
Nonspecific Defense Mechanisms
Specific Defense
Mechanisms
1st line of
defense
2nd line of
defense
3rd line of defense
Intact skin
Phagocytic white
blood cells
Specialized lymphocytes
(B-cells and T-cells)
Inflammation and
fever
Antibodies
Mucous
membranes
and their
secretions
Antimicrobial
substances
Non specific defences
These defences do not
differentiate between
any disease causing
agents. They stop all
things from entering the
body.
First line of Defence:
• Enzymes in mucus,
tears, gut
• Skin
• Sweat (contains acid)
• Ciliated epithelium
• Histamines
Eyes
Tears wash out pathogens
and also contain an enzyme
that can kill bacteria.
Nose
Mucus traps pathogens
which are then swallowed or
blown out in coughs and
sneezes.
Skin
The outer layer of skin is dead and
difficult for pathogens to grow on
or penetrate.
Cuts allow pathogens to gain entry
to the body.
Reproductive system
Slightly acid conditions in the
vagina and urethra help to stop the
growth of pathogens.
Mouth
Friendly bacteria help to
prevent the growth of
harmful pathogens.
Saliva cleans and removes
bacteria.
Lungs
Mucus in the lungs traps bacteria
and fungal spores. Tiny hairs,
called cilia, move the mucus to the
back of the throat where it is
swallowed.
Stomach
Acid helps to sterilise the
food.
Large intestine
Friendly bacteria help to
stop the growth of harmful
pathogens.
Faeces contains over 30%
live bacteria.
Second line
of Defence
THE NON-SPECIFIC
IMMUNE RESPONSE
Defence against disease

nd
(2
Line)
Cell-mediated defences
involving phagocytic
cells appear to have
been present early in
the evolution of
animals. Most
organisms are able to
distinguish self from not
self.
Recognising SELF
The bodies immune system has the ability to
recognise ‘self’ from ‘non-self’. This is
possible because all our cells have
specific protein markers on their surface
called ANTIGENS.
Genes on chromosome number 6, called the
Major Histocompatibility Complex (MHC),
code for the production of these self MHC
antigens
Distinguishing Self
The human immune system
achieves
self-recognition through the
major
histocompatibility complex
Location of
genes on
chromosome 6
for producing
the HLA
antigens
Class I HLA
Class II HLA
(MHC).
The MHC is a cluster of tightly
linked genes on chromosome
6 in humans.
These genes code for protein
molecules (MHC antigens)
which are attached to the
surface of body cells.
HLA surface proteins (antigens)
provide a chemical signature that
allows the immune system to
recognize the body’s own cells
MHC
The MHC antigens are used by the immune
system to recognize its own and foreign
material.
Class I MHC antigens are located on
the surface of virtually all human cells.
Class II MHC antigens are restricted to
macrophages and B-lymphocytes
Second Line of Defence:(Internal)
These include:

Once a foreign
material enters the
body the second line
of defense comes into
play.





‘Phagocytes’ &
‘Lymphocytes’ which are
White blood cells
Proteins called Antibodies
which destroy pathogens
‘Complement system’ which
is large blood proteins that
destroy bacteria
‘Interferon’ (proteins) which
are produced by virus
infected cells and interfere
with viral reproduction
Inflammation
Blood Cells
White Blood Cells
Phagocytes
*Neutrophil
*Macrophages
Lymphocytes
Phagocytes



Produced throughout life by the bone
marrow.
Scavengers – remove dead cells and
microorganisms.
Phagocytes are white blood cells that
ingest microbes and digest them by
phagocytosis.
The Action of Phagocytes
Detection
Phagocyte detects microbes by the
chemicals they give off
(chemotaxis), and the microbes stick
to its surface.
Microbes
Nucleus
Ingestion
The phagocyte wraps
around the microbe,
engulfing it and forming a
vesicle.
Phagosome
Lysosome
Phagosome forms
A phagosome (phagocytic vesicle)
is formed, enclosing the microbes
in a membrane.
Fusion with lysosome
Phagosome fuses with a
lysosome (containing
powerful enzymes that can
digest the microbe).
Digestion
The microbes are broken
down by enzymes into their
chemical constituents.
Discharge
Indigestible
material is
discharged from
the phagocyte.
Phagocytosis
Neutrophils





60% of WBCs
‘Patrol tissues’ as they squeeze out of the
capillaries.
Large numbers are released during infections
Short lived – die after digesting bacteria
Dead neutrophils make up a large proportion
of puss.
Monocytes
Monocytes and neutrophils share
the same stem cell. (Monocytes
are to macrophages what Bruce
Wayne is to Batman.) They are
produced by the marrow,
circulate for five to eight days,
and then enter the tissues where
they are mysteriously
transformed into macrophages.
Here they serve as the welcome
wagon for any outside invaders
and are capable of "processing"
foreign antigens and
"presenting" them to the
immunocompetent
lymphocytes. They are also
capable of the more brutal
activity of phagocytosis
Eosinophils

Eosinophils respond to
chemotaxis, substances released
by bacteria and components of
the complement system and can
perform phagocytosis. They are
often seen at the site of invasive
parasitic infestations and allergic
(immediate hypersensitivity)
responses. Individuals with
chronic allergic conditions (such
as atopic rhinitis or extrinsic
asthma) typically have elevated
circulating eosinophil count.
Lymphocytes

When activated by whatever
means, lymphocytes can
become very large. Although
such cells are classically
associated with viral
infection, they may also be
seen in bacterial and other
infections and in allergic
conditions.
Platelets

Platelets are small
fragments of cells
found in blood and
their main function is
involved in the blood
clotting process.
Macrophages





Larger than neutrophils.
Found in the organs, not the blood.
Made in bone marrow as monocytes, called
macrophages once they reach organs.
Long lived
Initiate immune responses as they display
antigens from the pathogens to the
lymphocytes.
Defensive molecules


Cytokines are an important group of
signalling molecules that coordinate many
aspects of our immune responses. They are
small glycoproteins released by body cells as a
means of communication with the immune
system.
Cytokines indicate the presence of damage or
a potentially dangerous invader.



Interferons are a class of cytokines. They are
produced by most virus-infected cells during
viral invasion and are also secreted by
activated T cells.
Their production and secretion is triggered by
the presence of double-stranded RNA, which
does not occur in uninfected cells.
Interferons are very active in interfering with
virus replication in cells.
Complement system


The complement system is a very complex group
of 20 serum proteins which is activated in a
cascade fashion.
Three different pathways involved in
complement activation.
 The first recognizes antigen-antibody
complexes,
 the second spontaneously activates on contact
with pathogenic cell surfaces,
 the third recognizes mannose sugars, which
tend to appear only on pathogenic cell
surfaces.

A cascade of protein activity follows
complement activation; this cascade can
result in a variety of effects including
phagocytosis of the pathogen, destruction
of the pathogen by formation and
activation of the membrane attack
complex, and inflammation.
The organs of your immune system are positioned
throughout your body.
They are called lymphoid organs because they are home
to lymphocytes--the white blood cells that are key
operatives of the immune system. Within these organs,
the lymphocytes grow, develop, and are deployed.
Bone marrow, the soft tissue in the hollow center of
bones, is the ultimate source of all blood cells, including
the immune cells.
The thymus is an organ that lies behind the breastbone;
lymphocytes known as T lymphocytes, or just T cells,
mature there.
The spleen is a flattened organ at the upper left of the
abdomen. Like the lymph nodes, the spleen contains
specialized compartments where immune cells gather and
confront antigens.
The Third Line of Defense
Specific resistance is a third
line of defense. It forms the
immune response and targets
The 2nd line of defense
specific pathogens.
The 3rd line of defense
Specialized cells of the immune
B cell:
Antibody
production
system, called lymphocytes
Lymphocytes
are:
T cell:
Cell-mediated
immunity
B-cells: produce specific
proteins called antibodies,
which are produced against
specific antigens.
T-cells: target pathogens
directly.
Lymphocyte (SEM)
Specific Immunity
This is the third line of
defense and has the
ability to remember a
previously encountered
organisms so as to
attack them.
This includes:



Immune responses
‘Specificity’: that is
they act on certain
foreign objects
‘Memory’: this is
where the system
remembers the foreign
object.
Plant immunity

To defend against
parasites plants use
encapsulation, a vast
array of chemical
defences including
antibiotics, enzymes
and hormones that
disrupt the function of
parasites. They also
allow rapid death of
tissue under attack.
Immune system of mammals
The immune response of
mammals involves:

Humoral immunity –
antibodies are released by
B cells

Cell mediated
immunity

- active destruction by T
cells
SPECIFIC IMMUNITY
Two main groups of LYMPHOCYTES are
involved in specific immunity. All lymphocytes
are made in the bone marrow. Some mature
in the bone marrow to become B cells others
leave early to mature in the Thymus, they
become T cells.
Specific Immunity
This is the third line of
defense and has the
ability to remember a
previously encountered
organisms so as to attack
them.
This includes:
• Immune responses
• ‘Specificity’: that is they
act on certain foreign
objects
• ‘Memory’: this is where
the system remembers
the foreign object.
White blood cells (leukocytes)
Are a diverse group of blood cells, all are Manufactured in the bone marrow
 Possess a nucleus
 Play a role in response to pathogens and/or foreign
material
 Capable of independent movement
Many have a role in non-specific defences.
Lymphocytes are important in specific defences.
Handout
Short lived and
broken down once
infection is resolved.
Live for many
years making
small amounts of
antibody.
Lymphocytes





Produce antibodies
B-cells mature in bone marrow then
concentrate in lymph nodes and spleen
T-cells mature in thymus
B and T cells mature then circulate in the
blood and lymph
Circulation ensures they come into contact
with pathogens and each other
Humoral immune response






Humoral means in the body fluids (blood and
extracellular)
B cells are lymphocytes that produce large quantities of
antibodies when stimulated by particular antigens. This
is the humoral immune response.
B cells are made in the bone marrow and spleen.
B cells have immunoglobulins (a protein that identify
antigens) on their surface.
Each B cell identifies one kind of antigen only.
When B cells identify an antigen, it replicates rapidly to
produce large numbers of special cells called PLASMA
cells.
Humoral Immunity
Other B-cells
recognize
different antigens
Surface antigen
The humoral response begins
when a foreign protein
(antigen) activates a particular
B-cell.
The particular B-cells multiply,
to form many plasma cells.
Plasma cells make antibodies
specifically designed to attack
and kill the identified pathogen.
Some B-cells differentiate into
long lived memory cells.
These memory cells will rapidly
produce antibodies if the same
pathogen enters the body
again.
Recognition
B-cell
Pathogen
Plasma cells
Second Exposure
Antibodies
Original
B-cell
B-cells (also called B-lymphocytes) originate
B–Cells
and mature in the bone marrow of the long
bones (e.g. the femur). They migrate from the
bone marrow to the lymphatic organs.
B-cells defend against:
Bacteria and viruses outside the cell
Toxins produced by bacteria (free antigens)
Each B-cell can produce antibodies against only
one specific antigen.
A mature B-cell may carry as many as 100 000
antibody molecules embedded in its surface
membrane.
B-cell
(B-lymphocyte)
B -Lymphocytes



There are approx 10 million different Blymphocytes, each of which make a different
antibody.
The huge variety is caused by genes coding
for antibodies changing slightly during
development.
There are a small group of clones of each
type of B-lymphocyte
B -Lymphocytes




At the clone stage antibodies do not leave the Bcells.
The antibodies are embedded in the plasma
membrane of the cell and are called antibody
receptors.
When the receptors in the membrane recognise an
antigen on the surface of the pathogen the B-cell
divides rapidly.
The antigens are presented to the B-cells by
macrophages
B–Cell Differentiation
B-cells differentiate into two kinds of cells:
Memory cells
Memory cell
When these cells encounter the same
antigen again (even years or decades
after the initial infection), they rapidly
differentiate into antibody-producing
plasma cells.
Plasma cells
These cells secrete antibodies against
antigens. Each plasma cell lives for only
Antibody
a
few days, but can produce about 2000
antibody molecules per second.
Plasma cell
B -Lymphocytes
B -Lymphocytes




Some activated B cells become PLASMA
CELLS these produce lots of antibodies, <
1000/sec
The antibodies travel to the blood, lymph,
lining of gut and lungs.
The number of plasma cells goes down after
a few weeks
Antibodies stay in the blood longer but
eventually their numbers go down too.
B -Lymphocytes




Some activated B cells become MEMORY
CELLS.
Memory cells divide rapidly as soon as the
antigen is reintroduced.
There are many more memory cells than
there were clone cells.
When the pathogen/infection infects again it
is destroyed before any symptoms show.
How B-cells work…
Pathogen (e.g. bacteria, virus)
Macrophage
B-cells
Each recognise
a different
antigen. The
correct one
develops into…
Macrophage
Phagocytoses pathogen
and displays antigens on
surface
Plasma cells
Clones of the
correct B-cell,
which produce
antibodies
1st meeting a pathogen, this
process takes 10-14 days
Memory B cell= subesquent
meetings, takes about 5 days
Antibodies






Also known as immunoglobulins
Globular glycoproteins
The heavy and light chains are
polypeptides
The chains are held together by
disulphide bridges
Each antibody has 2 identical
antigen binding sites – variable
regions.
The order of amino acids in the
variable region determines the
shape of the binding site
Antibodies



Antibodies are
specific proteins
produced by
lymphocytes that
react with particular
antigen molecules
Antigen – substance
capable of binding
with antibody
Antibody – specific
protein which binds
with antigen
How Antibodies work




Some act as labels to identify
antigens for phagocytes
Some work as antitoxins i.e. they block toxins
for e.g. those causing diphtheria and tetanus
Some attach to bacterial flagella making them
less active and easier for phagocytes to engulf
Some cause agglutination (clumping together) of
bacteria making them less likely to spread
Antigens and Antibodies
Molecular
model
Antibodies recognize
and bind to antigens.
Symboli
c model
Antibody
Antibodies are highly
specific and can help
destroy antigens.
Each antibody has at
least two sites that
can bind to an
One of the two
binding sites on the
antibody
antigen.
Antigen
Antibody Structure
Most of an antibody molecule is
made up of constant regions
which are the same for all
antibodies of the same class.
Hinge region connecting the
light and heavy chains. This
allows the two chains to
open and close (like a
clothes peg).
Heavy chain (long)
Light chain (short)
Variable regions form the
antigen-binding sites. Each
antibody can bind two antigen
molecules.
Antibody
The antigen-binding
sites between antibodies
of different types.
Antigen: Most antigens are
proteins or large polysaccharides and
are often parts of invading microbes.
Examples: cell walls, flagella,
bacterial toxins, viral proteins and
other microbial surfaces.
Type
Number of
antigen
binding sites
Site of action
Functions
IgG
2
Blood
Increase
Tissue
fluid
CAN CROSS
PLACENTA
macrophage activity
Antitoxins
Agglutination
Blood
Agglutination
IgM
10
Tissue
fluid
IgA
2 or 4
Secretions
(saliva,
tears, small intestine,
vaginal, prostate, nasal,
breast milk)
Stop
bacteria
adhering to host cells
Prevents bacteria
forming colonies on
mucous membranes
IgE
2
Tissues
Activate
mast cells
 HISTAMINE
Worm response
Blood group
Antigens present on the red blood cells
A
Contains anti-B antibodies,
but no antibodies that would
antigen A
B
Antibodies present in the plasma
antigen B
AB
antigens
A and B
O
Neither
antigen
A nor B
attack its own antigen A
Contains anti-A antibodies,
but no antibodies that would
attack its own antigen B
Contains neither anti-A
or anti-B antibodies
Contains both anti-A
and anti-B antibodies
Clonal Selection Theory

The clonal selection theory is the accepted
model for how the immune system responds to
infection and how certain types of B and T
lymphocytes are selected for specific antigens
invading the body.
There are 4 parts:




Each lymphocyte has a single type of receptor
with a unique specificity.
Receptor occupation is required for cell
activation.
The differentiated effector cells derived from
an activated lymphocyte has receptors of
identical specificity as the parental cell.
Those lymphocytes bearing receptors for self
molecules will be deleted early.
Cell mediated immune response


T cells are responsible for cell mediated
immune responses. They act against virus
infected cells, cancer cells and transplanted
tissue
T cells are formed in the thymus gland from
precursor cells made in bone marrow
T-cells originate from stem cells and mature
after passing through the thymus gland.
T-Cells
They respond only to antigenic fragments
that have been processed and presented
bound to the MHC by infected cells or
macrophages (phagocytic cells).
T-cells defend against:
Molecular Immunology Foundation, www.mifoundation.org
Intracellular bacteria and viruses.
Protozoa, fungi, flatworms, and
roundworms.
Cancerous cells and transplanted
foreign tissue.
T-cells attacking a cancer cell
T-Cells
T-cells can differentiate into four specialized types of cell:
Helper T-cell
Activates cytotoxic T cells and other helper T cells.
Necessary for B-cell activation.
Suppressor T-cell
Regulates immune response by turning it off when no more
antigen is present.
T-cell for delayed hypersensitivity
Causes inflammation in allergic reactions and rejection of
tissue transplants.
Cytotoxic (Killer) T-cell
Destroys target cells on contact.
Types of T cells

1.
2.
T helper cells –
acts with T cytotoxic cells (Killer T cells) to
destroy fungi, virus infected cells, cancer
cells and transplanted tissue
Work with B plasma cells to create
antibodies which inactive toxins bind to
bacteria, causing clumping and promoting
engulfment by phagocytes
Cell Mediated Immunity
Antigens, such as those
produced by abnormal
cells, are identified by
and activate specific
killer T-cells.
Killer T-cells
Antigen produced
by abnormal cell
Recognitio
n
Helper T-cell
Note: HIV (the AIDS virus) disrupts
the cellular immune system by
destroying helper T-cells.
The killer T-cells attach to and
destroy the abnormal cell.
Killer T-cells remain as memory
cells to quickly attack any
abnormal cells that reappear.
With the assistance of
helper T-cells the killer
T-cells begin to multiply.
T-Lymphocytes




After activation the cell divides to form:
T-helper cells – secrete CYTOKINES
 help B cells divide
 stimulate macrophages
Cytotoxic T cells (killer T cells)
 Kill body cells displaying antigen
Memory T cells
 remain in body
Abnormal cell e.g
cancer cell, infected cell
Killer T-cell
recognises antigen
How T-cells work…
X
Antigen
Clones of killer T-cell
attach to antigen
Normal cell
X
Killer T-cells release
perforin pores
X
Helper T-cell stimulates
correct killer T-cell to
multiply
Helper T-cell also
stimulates B-cells
to make antibodies
Suppressor T-cells
turn off immune
response
Abnormal cell gains
water, swells and
bursts
Memory Tcells stay in
circulation
FUNCTIONING OF THE IMMUNE SYSTEM
HUMORAL (ANTIBODY MEDIATED) IMMUNE RESPONSE
CELL MEDIATED IMMUNE RESPONSE
ANTIGEN (1ST EXPOSURE)
ENGULFED BY
MACROPHAGE
FREE
ANTIGENS
DIRECTLY
ACTIVATE
ANTIGENS
DISPLAYED
BY
INFECTED
CELLS
ACTIVATE
BECOMES
APC
STIMULATES
B CELLS
STIMULATES
STIMULATES
MEMORY
HELPER T
CELLS
GIVES RISE TO
STIMULATES
PLASMA
CELLS
HELPER
T CELLS
MEMORY
B CELLS
SECRETE ANTIBODIES
STIMULATES
ANTIGEN (2nd
EXPOSURE)
STIMULATES
CYTOTOXIC
T CELL
GIVES RISE TO
STIMULATES
MEMORY
T CELLS
ACTIVE
CYTOTOXIC T
CELL
Role of antigen receptors in the immune
response
• Both B cells and T cells carry customized receptor molecules that
allow them to recognize and respond to their specific targets.
• The B cell’s antigen-specific receptor that sits on its outer
surface is also a sample of the antibody it is prepared to
manufacture; this antibody-receptor recognizes antigen in
its natural state.
• The T cell’s receptor systems are more complex. T cells can
recognize an antigen only after the antigen is processed and
presented in combination with a special type of major
histocompatibility complex (MHC) marker.
• Killer T cells only recognize antigens in the grasp of Class I MHC
markers, while helper T cells only recognize antigens in the grasp
of Class II MHC markers. This complicated arrangement assures
that T cells act only on precise targets and at close range.
Role of cytokines in immune response
•
Cytokines are diverse and potent chemical messengers secreted by the
cells of your immune system. They are the chief communication signals of
your T cells. Cytokines include interleukins, growth factors, and interferons.
•
Lymphocytes, including both T cells and B cells, secrete cytokines.
Cytokines are also secreted by monocytes and macrophages. Interferons
are naturally occurring cytokines that may boost the immune system’s
ability to recognize cancer as a foreign invader.
•
Binding to specific receptors on target cells, cytokines recruit many other
cells and substances to the field of action. Cytokines encourage cell growth,
promote cell activation, direct cellular traffic, and destroy target cells-including cancer cells.
•
When cytokines attract specific cell types to an area, they are called
chemokines. These are released at the site of injury or infection and call
other immune cells to the region to help repair damage and defend against
infection.
Immunity to Infection

Immunity is the acquired ability to defend
against infection by disease-causing
organisms.

The adaptive immune system is responsible
for immunity.
Vaccines

The word vaccination comes from vacca, which is Latin for cow.

Edward Jenner could be considered the “father of vaccination”
as he developed a method of protecting people from smallpox.

He noticed that milkmaids who had previously been infected with
cowpox (similar disease but milder) did not catch smallpox.

In 1796, Jenner deliberately infected a small boy with material
from a cowpox pustule, then six weeks later infected the boy
with material from a smallpox pustule. The boy survived!

Our current understanding of pathogens indicates that Jenner
got lucky – not all dangerous diseases have a less pathogenic
equivalent as was the case with smallpox and cowpox.
Types of Vaccine

There are four main types of vaccinations:





Live attenuated vaccines
Killed vaccines
Toxoid vaccines
Component vaccines
Many vaccines contain adjuvants. This is a
general term given to any substance that when
mixed with an injected immunogen will
increase the immune response. Examples of
adjuvants include aluminium hydroxide and
aluminium phosphate.
Live attenuated vaccines

Contain bacteria or viruses that have been altered so they can't cause
disease.

Usually created from the naturally occurring germ itself. The germs used in
these vaccines still can infect people, but they rarely cause serious disease.

Viruses are weakened (or attenuated) by growing them over and over again in
a laboratory under nourishing conditions called cell culture. The process of
growing a virus repeatedly-also known as passing--serves to lessen the
disease-causing ability of the virus. Vaccines are made from viruses whose
disease-causing ability has deteriorated from multiple passages.

Examples of live attenuated vaccines include:

Measles vaccine (as found in the MMR vaccine)

Mumps vaccine (MMR vaccine)

Rubella (German measles) vaccine ( MMR vaccine)

Oral polio vaccine (OPV)

Varicella (chickenpox) vaccine
Killed vaccines

Contain killed bacteria or inactivated viruses.

Inactivated (killed) vaccines cannot cause an
infection, but they still can stimulate a protective
immune response. Viruses are inactivated with
chemicals such as formaldehyde.

Examples of inactivated (killed) vaccines:


Inactivated polio vaccine (IPV), which is the injected
form of the polio vaccine
Inactivated influenza vaccine
Toxoid vaccines

Contain toxins (or poisons) produced by the germ that
have been made harmless.

Toxoid vaccines are made by treating toxins (or poisons)
produced by germs with heat or chemicals, such as
formalin, to destroy their ability to cause illness. Even
though toxoids do not cause disease, they stimulate the
body to produce protective immunity just like the germs'
natural toxins.

Examples of toxoid vaccines:

Diphtheria toxoid vaccine (may be given alone or as one of the
components in the DTP, DTaP, or dT vaccines)

Tetanus toxoid vaccine (may be given alone or as part of DTP,
DTaP, or dT)
Component vaccines




Contain parts of the whole bacteria or viruses.
These vaccines cannot cause disease as they contain only parts of
the viruses or bacteria, but they can stimulate the body to produce
an immune response that protects against infection with the whole
germ.
Component vaccines have become more common with the advent
of gene technology, as the antigenic proteins can be identified and
cloned then expressed in a laboratory to provide material for
vaccination.
Examples of component vaccines:




Haemophilus influenzae type b (Hib) vaccine
Hepatitis B (Hep B) vaccine
Hepatitis A (Hep A) vaccine
Pneumoccocal conjugate vaccine
How do diseases evade the immune
response?

Pathogens that infect the human body have
evolved a number of different techniques for
avoiding the immune response.

These include:






Antigenic variation
Antigenic mimicry
Evading macrophage digestion
Hiding in cells
Immune suppression
Disarming antibodies
Avoiding the immune response


Antigenic variation

Some species of protozoan parasites evade immune response by shedding
their antigens upon entering the host.

Others (e.g. trypanosomes and malarial parasites) can change the surface
antigens that they express so that the specific immune system needs to
make a new antibody to respond to the infection. This is known as
antigenic variation.
Antigenic mimicry

This involves alteration of the pathogen’s surface so that the immune
system does not recognise the pathogen as “non-self”.

Blood flukes can hijack blood group antigens from host red blood cells and
incorporate them onto their outer surface so that the immune system does
not respond to the infection.
Avoiding the immune response

Evading macrophage digestion




Macrophages have an important role in the immune system as they
phagocytosis and destroy foreign material. Some microbes (e.g.
Leishmania) are able to avoid enzymatic breakdown by lysosomes and can
remain and grow inside the macrophage – this means they are able to avoid
the immune system.
Some bacteria can avoid phagocytosis by releasing an enzyme that
destroys the component of complement that attracts phagocytes.
Other bacteria can kill phagocytes by releasing a membrane-damaging
toxin
Hiding in cells

Bacteria such as heliobacter can invade the epithelial lining of the intestine
to multiply and divide, then transfer into neighbouring cells without entering
the extracellular space where they would be vulnerable to detection.
Avoiding the immune response

Immune suppression



Most parasites are able to disrupt the immune system of their host
to some extent.
HIV is an example of this. It selectively destroys T helper cells,
therefore disabling the host immune system.
Disarming antibodies


Bacteria such as Staphylococcus aureus have receptors on their
surface that disrupt the normal function of the host’s antibodies.
These receptors bind to the constant region (the stem) rather than
the normal antigen binding sites. This prevents normal signalling
between antibodies and other parts of the immune system such as
complement activation or initiating phagocytosis of a bound antigen.
Invader antigens are everywhere!
What does it need to get by?
Skin!
neutrophils
Monoctyes
(macrophages)
Invader
dies!
T - Helper
lymphs
B lymphs
Plasma B
cells
Memory B cells
Antibodies!!
Invader
dies!!
More
T - Helper
lymphs!
Cytotoxic T
lymphs
Invader
dies!!
Immunity
We have natural or innate resistance
to certain illnesses including most
diseases of other animal species.
Immunity involves a specific
defense
response by the host to invasion by
foreign organisms or substances:
Active immunity develops
Acquired immunity is the protection
after exposure to
that develops against specific
microorganisms or foreign
microbes or
substances
foreign substances.
Passive immunity is acquired
when antibodies are transferred
from one person to another.
Naturally Acquired Immunity
Naturally Acquired
Passive
Active
Antibodies pass from the mother
to the fetus via the placenta
during pregnancy or to her infant
through her milk.
The infant's body does not produce
any antibodies of its own.
Antigens enter the body
naturally, as when:
• Microbes cause the person
to catch the disease.
• There is a sub-clinical infection
(one that produces no evident
symptoms).
The body produces specialized
lymphocytes and antibodies.
Artificially Acquired Immunity
Artificially Acquired
Active
Passive
Antigens (weakened or dead
microbes or their fragments)
are introduced in vaccines.
Preformed antibodies in an
immune serum are
introduced into the body by
injection
(e.g. anti-venom used to
treat snake bites).
The body does not produce
any antibodies
The body produces specialized
lymphocytes and antibodies.
.
Induced Immunity
Active immunity
Production of a person’s own
antibodies. Long lasting
Natural Active
Artificial Active
When pathogen
Vaccination – usually
enters body in the contains a safe antigen
normal way, we
from the pathogen.
make antibodies
Person makes
antibodies without
becoming ill
Edward Jenner
Passive immunity
An individual is given antibodies by another
Short-term resistance (weeks- 6months)
Natural Passive
Baby in utero
(placenta)
Breast-fed babies
Artificial Passive
Gamma globulin
injection
Extremely fast, but
short lived (e.g. snake
venom)
Active and Passive Immunity
Active immunity
Lymphocytes are activated by antigens on
the surface of pathogens
Natural active immunity - acquired due to
infection
Artificial active immunity – vaccination
Takes time for enough B and T cells to be
produced to mount an effective response.
Active and Passive Immunity
Passive immunity
B and T cells are not activated and plasma
cells have not produced antibodies.
The antigen doesn’t have to be encountered for
the body to make the antibodies.
Antibodies appear immediately in blood but
protection is only temporary.
Active and Passive Immunity
Artificial passive immunity
Used when a very rapid immune response is
needed e.g. after infection with tetanus.
Human antibodies are injected. In the case
of tetanus these are antitoxin antibodies.
Antibodies come from blood donors who
have recently had the tetanus vaccination.
Only provides short term protection as abs
destroyed by phagocytes in spleen and liver.
Active and Passive Immunity
Natural passive immunity
A mother’s antibodies pass across the placenta
to the foetus and remain for several months.
Colostrum (the first breast milk) contains lots of
IgA which remain on surface of the baby’s gut
wall and pass into blood