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Immunology

The document provides an overview of immunology, detailing the immune response, types of immunity, and the roles of various immune cells and antibodies. It distinguishes between innate and acquired immunity, explains the functions of B and T lymphocytes, and discusses the mechanisms of phagocytosis and antibody production. Additionally, it covers the structure and function of antibodies, including their role in diagnosing and treating diseases.

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0% found this document useful (0 votes)
18 views125 pages

Immunology

The document provides an overview of immunology, detailing the immune response, types of immunity, and the roles of various immune cells and antibodies. It distinguishes between innate and acquired immunity, explains the functions of B and T lymphocytes, and discusses the mechanisms of phagocytosis and antibody production. Additionally, it covers the structure and function of antibodies, including their role in diagnosing and treating diseases.

Uploaded by

takeshaw2023
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Immunology

Antonia Stanisclaus
Karlene Gibbs
Objectives
2.1. define the term, “immune response”;
2.2. distinguish between the humoral and the cell mediated
immune responses; Include the sequence of events involved in
each response.
2.3. explain the role of memory cells in long-term immunity; T-
and B- memory cells.
2.4. compare the origin and maturation of B- and T-
lymphocytes; Include the types of T-cells and their function
(refer to HIV); B-cells and their function.
2.5. describe the mode of action of phagocytes; Revision of
phagocytosis; include role of mast cells and histamine
production; complement; phagocytes as antigen presenting cells.
Objectives cont’d
2.6. relate the molecular structure of a typical antibody
molecule to its function; Use of labelled diagram of typical
antibody showing its ‘Y- shaped’ structure; include the function
of the various parts; specificity of antibody to antigen.
2.7. state what is meant by a monoclonal antibody;
2.8. describe the use of monoclonal antibodies in diagnosis and
treatment; The anticancer drug, MabThera; details required of
the use of monoclonal antibodies in pregnancy testing
2.9. distinguish between active and passive immunity, natural
and artificial immunity; and, Include examples for each type.
2.10. explain the role of vaccination in providing immunity.
Mention the successes and challenges of the use of vaccines to
reduce the incidence of diseases.
Immunology: Introduction
Immunology: A branch of medicine and Biology that
deals with the study of the immune system and
immunity.
“Immunity: Is the ability to recognize self from non-
self “
Immunity: “the capacity to recognize the intrusion
of material foreign to the body and to mobilise
cells and cell products to help remove that
particular sort of foreign body with greater speed
and effectiveness.” – Sir Macfarlane Burnet
Immunology: Introduction
The immune response:
- The body’s reaction to foreign antigen i.e. a foreign
body or anything that is non-self.
- the production of antibodies in response to antigens
Antibody:
- A molecule that is synthesized by an animal in
response to the presence of foreign bodies known as
antigens. Each antibody is a protein molecule called an
immunoglobulin.
Immunology: Introduction
Antigen:
- A molecule which can cause antibody formation.
All cells possess antigens on their surface
membranes which act as markers, enabling cells t
‘recognize’ each other. Are usually proteins or
glycoproteins
Our leukocytes are able to tell self from non-self
Immunology: Introduction
The Immune System protects the body from infection by
pathogens
Pathogen: any organism that causes illness. Tend to be
microorganisms e.g viruses, bacteria, fungi
Parasites: organisms living on or inside another organism
called a host.
Tend to refer to tapeworm, round worms, fleas
Innate & Acquired Immunity
Innate Immunity or Non-Specific Immunity
-First line of defense against invading organisms
-The response is same for all pathogens and is
activated immediately on infection
-No memory or lasting protective immunity
Acquired Immunity or Specific Immunity
-Second line of defense against invading
organisms
- The response is Antigen-specific involving
humoral and cell mediated immunity
-There is lasting protective immunity
Innate Immunity
The Body’s Primary Defense
The Skin and mucus membranes are the body’s Primary
Defense Mechanism
– Skin
• Physical barrier: blocks pathogens
– Mucus membranes protect openings to the
environment e.g mouth, eyes , ears, nostril, anus,
genitals. By providing
• Physical barrier: Secreting mucus to trap pathogens.
This is made by goblet cells which are part of the
epithelium lining the digestive, respiratory and Urinary
tracts.
Innate Immunity
The Body’s Primary Defense
The Skin and mucus membranes are the body’s Primary
Defense Mechanism (cont’d)
– Chemicals Barrier: antimicrobial substance which
lower pH inhibiting pathogen growth.
• e.g lysozymes in tears, HCL in stomach acid,
Bactericidal enzymes (Spermine) in semen,
Innate Immunity
The Body’s Primary Defense
Internally, the body’s Primary defense also consist of
− Phagocytic cells like neutrophils, monocytes and
macrophages
− Natural killer cells (NK cells)
− Cells that release inflammatory compounds e.g.
basophils, mast cells and eosinophils
− Complement proteins found in blood
The Acquired Immune System
The Secondary Defense Mechanism is the Acquired
/Specific Immune System.
An Immune response is the way the body deals with a
foreign body or anything that is non self.
It involves:
1. Action of White blood cells (WBC’s)or Leukocytes
2. Antigens:
• Protein or glycoprotein molecules that help the body
distinguish self from non-self( foreign markers are seen
as non self and antibodies are made against it)
• On Foreign bodies e.g. pathogens, they stimulate the
production of antibodies
Type Of White Blood Cells % By Volume Of WBC Description Function

Neutrophils 60 – 70 % Nucleus has many Phagocytize and destory


interconnected lobes; blue bacteria; most numerous
granules WBC

Eosinophils 2–4% Nucleus has bilobed nuclei; red Play a role in ending allergic
or yellow granules containing reactions
digestive enzymes

Basophils <1% Bilobed nuclei hidden by large Function in inflammation


purple granules full of chemical medication; similar in function to
mediators of inflammation mast cells

Lymphocytes (B Cells and 20 – 25 % Dense, purple staining, round the most important cells of
T Cells) nucleus; little cytoplasm the immune system; effective
in fighting infectious
organisms; act against a
specific foreign molecule
(antigen)
Monocytes 4–8% Largest leukocyte; kidney Transform into macrophages;
shaped nucleus phagocytic cells
Three Types of Leukocytes
Neutrophils:
– Multi-lobed nucleus
– Destroy bacteria by phagocytosis
– Short life span hours – few days
– First responders of the innate immune system

Monocytes:
– Kidney shaped nucleus
– Life span: months
– Involved in Phagocytosis
– Migrates out of the blood
– Differentiate (develop into macrophages when in tissue)e.g alvelolar
macrophage in alveolar of lungs, Kuffer cells in Liver
Three types of Leukocytes
Lymphocytes:
– Dark oval nucleus with thin blue/purple cytoplasmic rim
– Lifespan: variable ( hours – years)
– Mount the cell immune response
• B cells:
– Remain in bone marrow
– Become Plasma cells (produce antibodies)
– Destroy bacteria and toxins
• T Cells:
– Migrate to Thymus where they differentiate (mature)
– Cell mediated immunity
– Attack viruses fungi some bacteria , transplant organs , Cancer cells
• Natural Killer cells NK
– Attack many microbes
– Direct Attack on cells
– Part of the innate immune system
The Thymus
A lymphoid organ located in the neck region of vertebrates
responsible for maturation of T cells. (Only mature T-cells
can identify foreign cells)
In humans it becomes much smaller during puberty.
Associated Disorder: Severe combined
immunodeficiency, SCID. A rare disease affecting
children’s Immune system due to abnormal
T cells. Patient is kept in a sterile
Environment.
Processes involved in the Immune
Response
Processes involved in the Immune Response

Phagocytosis: a non specific response


– Amoeboid movement: crawling by flowing of their cytoplasm
– Phagocytes engulf invading bacteria and clean up debris
– Phagocytotic vesicles are formed. Lysosomes with hydrolytic
enzymes and acids fuse and digest the pathogen.
– Phagocytes are the first line of defense against microbes E.g
Neutrophils and monocytes

Use of Complements(non-specific response) proteins which


are always present in the blood that help phagocytes fight
bacterial infections.
• attract phagocytes to the site of infection by chemotaxis (Cell
movement towards a chemical stimulus)
• Destroy foreign cells: punch holes in cell surface membrane of
bacteria (lysis)
• Coating/tagging bacteria with opsonins (protein) which make
pathogens easily recognized by phagocytes (Opsonisation)
Processes involved in the Immune Response
Antigen presentation: a specific response
– Involve the action of lymphocytes
– The body identifies antigens on a microorganism as a foreign
antigen and makes antibodies against it .
– Macrophages called Antigen Presenting Cells(APC), engulf and digest
the antigen.
– The APC display some of the bacteria (antigen) on their cell
membrane .
– Lymphocytes ( B cells) with a complementary antibody for that specific
bacterial antigen bind to the antigen.
– This antigen -antibody complex stimulates: more B cells to produce
more antibody; and t cells (T8-Natural killer and T4-helper cells )to
destroy the pathogen

Antibody production: A specific response to a specific antigen)


– Antibodies are glycoprotein ( consist of amino acid and sugar
units)
– Made by the plasma cell ( B -lymphocytes)
The Immune Response:
The Characters
– The Bacteria or pathogen with its foreign antigen
– Phagocytes: Neutrophils and Macrophages(non-specific/
innate)

– Lymphocytes (specific/adaptive)
• B cells: differentiate to plasma cells which release
antibodies and memory cells
• T Cells
– T4 Helper cells(effector cells & memory cells)
– T8 cells (effector killer cells, memory cells, suppressor cells)
• Natural Killer cell( innate immunity)
Summary
Innate Nonspecific
Immunity
Specific and Non-Specific Defenses

Durant, 2013, p.274


Innate Non Specific Immunity
Innate immune system consists of cells and
proteins that are always present and ready to
mobilize and fight microbes at the site of
infection. 1) physical epithelial barriers, 2)
phagocytic leukocytes, 3) dendritic cells, 4) a
special type of lymphocyte called a natural killer
(NK) cell, and 5) circulating plasma proteins.
Adaptive(Acquired Immunity)
Adaptive immune system, /learnt Specific Response
which becomes activated by intrusion of a pathogen
the resultant effect is to cause proliferation and
potent mechanisms for neutralizing or eliminating
the microbes involving the:
– humoral immunity, mediated by antibodies produced by B
lymphocytes,
– cell-mediated immunity, mediated by T lymphocytes.
Summary

Crash course video :Immunology and Innate


Immunity
https://www.youtube.com/watch?v=GIJK3dwC
WCw
Quiz
• Which of the following is NOT a function of phagocytes in the human body?
– Secretion of Antibodies
– Removal of dead cell
– Cleaning of debris in the plasma
– Engulfing invading microorganisms

• In some cases the body’s immune response is very specific and targeted; in other situations it
is not. Which of the following is not part of the body’s nonspecific response system?
– Neutrophils
– Macrophages
– Inflammation
– Antibodies

• T cells mature in the


– Bone marrow
– Lymph nodes
– Spleen
– Thymus
Quiz
• Which of the following does not protect body surfaces?
– Skin
– Mucus
– Gastric Acid
– Salivary amylase
• Polymorphonuclear neutrophils attack bacteria:
– By Oxygen Dependent mechanisms
– By Oxygen independent mechanisms
– By phagocytosis
– By endocytosis
• An Immune response is BEST defined as:
– A defensive reaction by the immune system
– A bodily defense reaction which recognizes invading substances and produces a range of
cellular and chemical agents directed at the substance.
– A reaction which recognizes an invading substance
– The body’s reaction to infection
Two systems of the Specific
Immune Response
Humoral Immune Response (fluid)
• B-Lymphocytes
– Become plasma cells which produce antibodies against
pathogens while they are in the blood, lymph, or between cell
(interstitial fluid).

Cell mediated Immune Response


• T-Lymphocytes:
– T cell made in the bone marrow but differentiated in the Thymus
(in the thorax above he heart ). Importance:
» Early removal – death due to deficiency of lymphocytes
» Graft from older thymus to baby mouse – no antigen
recognition
» Removal from an older mouse – no adverse effects
Definition
Antigen :
-An Antigen is a molecule which can cause antibody
formation. All cells possess antigens in their cell surface
membranes which act as markers, enabling cells to
“recognize” each other.
-Antigens are glycoproteins (proteins with a carbohydrate
tail).

The body distinguishes its own antigens (“self”) from


foreign Antigens(“non-self”) and makes only specific
antibodies against those non self antigens.
Maturation of B cells

• Naive B cells are stimulated by T helper cells


to mature into plasma cells to produce
antibodies against a specific antigen.
Humoral Response
• Each B lymphocyte recognizes and responds to a particular antigen
• B cell produce a specific antibody (a glycoprotein) against each specific antigen
• The antibodies are placed on the cell membrane of the B cell and act as receptors for
foreign antigens
• If a B lymphocyte meets a bacterial antigen specifically matching the antibodies on
its cell membrane, (found either in the blood or displayed on a APC) it binds to it.
(Clonal selection)
• This antibody- antigen complex trigger an immune response:
– B lymphocyte divides by mitosis making clones of itself and memory cells
(Clonal
proliferation/clonal expansion)
– Some of the new B lymphocytes differentiate into
• Plasma cells/ effector cells: rapidly produce and release antibodies at a rate
(2000 per sec.)
• Memory cells: don’t secrete antibodies but remain in blood to quickly
mount a second response if the pathogen re: enters the body.
B Lymphocyte Response to antigen

(Ramesar,2011)
The Structure of an Antibody
The Structure of an Antibody
– Glycoproteins: Their polypeptide chains are held by disulphide bridges
– Variable region:
• Antigen binding site
• The shape is complementary to a particular antigen(even those
the body may have not yet been exposed to as yet)
– Hinge region: allows flexibility for binding to antigen
– Constant region: is the same for all antibodies

– The body can produce many different kind of antibodies made by


shuffling different parts of the gene for the variable region.
Collectively they are known as Immunoglobulins and are represented
as IgG, IgA etc.
Antibodies
Types of Antibodies
– IgA: bacterial infection
– IgE: activate mast cells to release histamine
(allergic reactions)
– IgG: helps macrophage engulf pathogens,
neutralize toxins
– IgM: agglutination of bacteria activate
complements
Antibodies
Antibodies function by causing:
• Agglutination: pathogen clump together at the
variable end ( This hold them together to make
bigger targets for phagocytes)
• Neutralize toxins: bind to and neutralize toxins
• Prevent pathogen binding to host
• Immobilize pathogen e.g immobilize some bacteria
by binding to their flagella
• Opsonisation: coat the pathogen to facilitate
phagocytosis.
• Activate complements
Green, Stout,Taylor, 1997,p.486
Summary
Crash Course : Adaptive Immunity –The Humoral
Response
https://www.youtube.com/watch?v=2DFN4IBZ3rI
Quiz
• The monomers that make up heavy and light chain of an antibody are held together by
– Peptide bonds
– Hydrogen bonds
– Glyosidic bonds
– Disulfide bonds
• Which of the following BEST describes the term “Immune Response”?
– Formation of blood clot to limit the entry of foreign organisms
– Production of cells and substances which protect the body from foreign organisms
– Secretion of mucus to trap foreign organisms at the skin
– Recognition and protection of self -cells.
• What type of cells produce antibodies?
– Macrophages
– T lymphocytes
– Natural Killer cells
– Plasma cells
. Activation of B cell receptor by binding of an epitope results in the formation of:
A. Plasma cells and T Cytotoxic cells
B. Memory cells and T Cytotoxic cells
C. Plasma cells for antibody production and Memory cells for Primary response
D. Plasma cells for antibody production and Memory cells for Secondary response
Two systems of Immune Responses
Humoral Immune Response (fluid)
• B-Lymphocytes
– Become plasma cells which produce antibodies against
pathogens while they are in the blood, lymph, or between cell
(interstitial fluid).

Cell mediated Immune Response


• T-Lymphocytes:
– T cell made in the bone marrow but differentiated in the Thymus
(in the thorax above he heart ). Importance:
» Early removal – death due to deficiency of lymphocytes
» Graft from older thymus to baby mouse – no antigen
recognition
» Removal from an older mouse – no adverse effects
Maturation of T lymphocytes
• Initially all T cells produce glycoprotein CD4 and CD8
but as thy mature in the thymus they differentiate.
Each cell produces only one type of glycoprotein and
so become either:
– a CD4 cell producing CD4 receptors (T Helper cells)
– Or CD8 cells producing CD8 receptors (T – Killer &
Suppressor cells)
• In the thymus T lymphocytes are tested only those
with receptors that recognize the body’s own cells
without without attacking it ( autoimmune reaction)
i.e about 2% t cells.
Cell Mediated Response
T-Lymphocytes
T Cells attack:
-Body cell infected with microbes e.g viruses
-Transplant organs and tissue
-Cancer causing cells

The whole cell is involved in the attack hence


the name cell mediated
Cell Mediated Response
T-Lymphocytes
Cell membrane of T cells have specific receptors
with particular shapes like antibodies.

These receptors do not recognize the whole


antigen but only fragments presented to them

T-lymphocytes produce Lymphokines : peptide


molecules involved in the immune response .
They are also called cytokines or interleukins
Cell Mediated Response
• T Lymphocytes are stimulated when they come in
contact with an antigen either free floating in the
blood, from invading virus / bacteria, on the cell
membrane of a APC Macrophage, or on membrane
of an infected viral cell)
• Antigen binds to receptors on the cell membrane of
the T lymphocyte and begins to divide by mitosis(
clonal proliferation)
• Each T lymphocyte recognizes a specific antigen (
specific response) and reacts to the foreign antigen
differently
Cell Mediated Response
T 4cell or helper cells work with APC Macrophages
(NB HIV infects and destroying T4 Helper cells)
• The T4 helper cell produces substances called
cytokines/lymphokines / interleukins which: are protein
mediators to direct/stimulate the immune system response
by causing signaling between its cells
• Stimulate clonal proliferation in T -cells
» cytotoxic killer cells which destroy infected cells marked
with viral particles, cancer cells containing mutant protein
By producing chemicals that punch holes in their cells.
• Promote inflamation
• Stimulate and activates B cells specific to the antigen to
differentiate into plasma cells producing antibodies
• Stimulate APC Macrophages to carry out phagocytosis
Cell Mediated Response
There are two types of T8 cell ( suppressor cells ,& killer/ cytotoxic
cells)
• T killer cells produce small amounts of lymphokines but destroy
the cells to which it binds once connected with foreign antigens
specific to its receptors.
• T killer cells attack virus infected cells and cancer causing cells
by secreting chemicals e.g peroxides( they are our main
defenses against viral diseases.
• They are also involved in rejection of transplanted organs

T memory cells remain in the body to help mound a faster second


response if the pathogen reenters the cell again
T-Lymphocytes Response to antigen

(Ramesar,2011)

Quiz
Which of the following is correct about cell mediated and humoral immunity?
Cell Mediated Humoral
A. Involves T-killer cells Involves B-Cell
B. Involves B cells Involves T- Killer cells
C. Produces antibodies Produces antibodies
D. Does not involve cell to cell interaction Involves cell to cell interaction

• Clonal selection occurs when antigen is encountered by:


A. Neutrophils
B. Mast Cells
C. T Cells
D. Basophils

• Protection against microorganisms inside cells is provided by:


A. T- cells
B. Antibodies
C. CB3
D. The membrane attack complex

• Which of the following is not true about antibodies.


A. neutralize toxins
B. bind to specific antigens
C. activate the complement system
D. are effective only when attached to T-cells
Cell Mediated & Humoral Responses

(Taylor et al ,2012)
Humoral Responses

Ramser, 20
Cell Mediated Response
http://highered.mheducation.com/sites/007249
5855/student_view0/chapter24/animation__the
_immune_response.html
AIDS and the Specific Immunity
• Humoral
• Cell meditated

https://www.youtube.com/watch?v=ng22Ucr33
aw
Summary

• Although the Immune system response is


presented as two separate mechanisms,
In reality, there are constant interactions
between cells- in the Cell mediated response
and chemicals in the Humoral response.
Question
a. Define the mode of action of phagocytes
b. Define the term “ Immune Response”
c. i)Describe the origin and maturation of T-
Lymphocytes.
ii)Describe the changes that occur to T-
lymphocytes during an immune response
d. i)Describe how B- Lymphocytes are involved in
the immune response
ii) Describe the importance of B Memory cells in
immunity
Answer to Question
a • Amoeboid cells that circulate in the blood • Squeeze
through the gaps in capillary walls • Move rapidly to the site of
infection • By chemotaxis • Engulf antigen <250 nm in a vesicle
• Lysosomes fuse to vesicles • Kills and digest pathogens •
Enzymes/hydrolases/hydrogen peroxide digest pathogens •
Some form a network of cells which are concentrated in organs
such as liver, lung, spleen, kidney

• b • Defence reaction which recognises the intrusion of


foreign material/antigen/non-self [1] • Mobilises cells and cell
products to remove the foreign material with great speed and
effectiveness [1]
Answer to Question
• c i • Form in bone marrow from stem cells by mitosis • Migrate to thymus
to develop • Variant genes code for specific surface receptor • Each T-cell
has specific receptor/wide range of T-cells • T-cells are presented to
body’s own antigen in MHC proteins • If they bind to the MHC-antigen
complex, they are killed • Those that survive can have CD4 or CD8
receptors ii • APC presents antigen/epitope to T-helper cells • Epitope
and specific T-cell receptor are complementary • Clonal selection •
Followed clonal expansion/mitosis of specific T-cell • T-cells secrete
cytokines

• d i • APC cells present antigen to B-cells • Clonal selection • Clonal


expansion • T-helper cells secrete cytokines • B-cells stimulated to divide
by mitosis and differentiate into plasma and memory cells • Antibodies
secreted into blood • Memory cells remain and circulate in blood
Answer to Question
• Produced during first exposure to antigen • Remain
in circulation for a long time/long-term protection •
During second exposure to antigen, differentiate
quickly to form plasma cells and more memory cells •
Cause faster production and greater concentration of
antibodies

Complements
Complements: group of about 20 proteins which are always present in the
blood.
• They help phagocytes fight bacterial infections.
• Precurser of enzymes ( Zymogen or un reactive form of an enzyme.
• Upon activation , it causes a cascade effect involving large number of
protein molecules. This activation and cascade rxn occurs due to :
• Complement binding to an Antigen -antibody complex
• Complements binding directly to a pathogen
• Complements help destroy pathogens by:
• attract phagocytes e.g macrophage to the site of infection by chemotaxis :
Cell movement towards a chemical stimulus e.g in the inflammatory
response
• Destroy foreign cells: punch holes in cell surface membrane of bacteria
• Opsonisation : proteins produced in the cascade (opsonin) , coats/tagging
bacteria making them easily recognized
by phagocytes
Complements

(Ramesar,2011)
Phagocytosis
Mode of action:
Phagocytosis: a non specific response
– Amoeboid movement : crawling by flowing of
their cytoplasm
– Phagocytes engulf invading bacteria and clean up
debris
– Phagocytotic vesicles are formed. Lysosomes with
hydrolytic enzymes and acids fuse and digest the
pathogen.
– Phagocytes are the first line of defense against
microbes E.g Neutrophils and monocytes
Phagocytosis
The Inflammatory Response
Changes triggered by chemical released from damaged cells at the site of an
injury or infection. E.g. Bradykinins and prostaglandins
That signaling lymphocytes and Macrophages to the damaged area to
destroy any pathogen that would have entered.
The Result:
Redness, Pain, Increased Temperature, Swelling
Mast cells activated by the injury or by binding to IgE antibodies, or to
complements release Histamine. This causes:

-Blood capillaries to dilate and become permeable.


-Increased blood flow to the infection site bringing complement proteins and
Macrophages and Neutrophils to the infection site by chemotaxix.
-Capillaries leak fluids into surrounding tissue leading to edema
Inflammation

(Ramesar,2011)
The Inflammatory Response
Over time pus accumulates (a fluid mixture of white blood cells,
dead microbes and cell debris) at the infection site.

• They result in dilation of blood vessels, contraction of smooth


muscles eg in air ways, appearance of skin rashes ,tissue fluid
accumulation.
• Mast cell are also involved in auto immune diseases e.g
rheumatoid arthritis, Multiple sclerosis

• Systemic inflammation (response throughout the entire body


due to a serve injury or inflamtion appendicitis ,tonsillitis.
Body temp rises eg in a fever pyrugens
Allergic Reactions
Allergy is a hypersensitivity to an antigen from the
environment. In this case it is called an Allergen and
results in an increased activity of the immune system
involving IgE antibodies.

These antibodies work together with mast cells and


basophils. Histamine and other chemicals are released
causing an inflammatory response (leaky capillaries,
rashes, swelling)

Antihistamine drugs are used to relieve some of the


symptoms.
Crash course Videos
Part 1
https://www.youtube.com/watch?v=GIJK3dwC
WCw
Part 2
https://www.youtube.com/watch?v=2DFN4IBZ3
rI
Part 3
https://www.youtube.com/watch?v=rd2cf5hVal
M
Words to note
• Innate
• Acquired
• Active
• Passive
• Artificial
• Natural
• Primary response
• Secondary response
Definitions
• Active Immunity : ability for the body’s defense cells to
produce specific antibodies etc against a specific pathogen to
produce specific antibodies
• Passive immunity: Immunity due to antibodies produced by
another organism.
• Natural Immunity : immunity acquired naturally .eg due to an
infection or through antibodies gained by breast feeding.
• Artificial immunity: Immunity acquired through vaccination
using a weakened form of the pathogen.
Innate vs Adaptive (Acquired)
Innate immune system consists of cells and
proteins that are always present and ready to
mobilize and fight microbes at the site of
infection. 1) physical epithelial barriers, 2)
phagocytic leukocytes, 3) dendritic cells, 4) a
special type of lymphocyte called a natural killer
(NK) cell, and 5) circulating plasma proteins.
Adaptive(Acquired Immunity)
Adaptive immune system, /learnt becomes activated by intrusion
of a pathogen the resultant effect is to cause proliferation and
potent mechanisms for neutralizing or
eliminating the microbes involving the:
– humoral immunity, mediated by antibodies produced by B
lymphocytes,
– cell-mediated immunity, mediated by T lymphocytes.
Immunity
Active Immunity
– Immunity developed when the body makes its
own antibodies after being stimulated by an
antigen.
• Natural: Becoming immune after catching the disease
• Artificial: after being given a vaccine contains a
weakened attenuated form of the antigen
– Herd immunity: immunity to a disease in a
population over time by vaccinating most persons
thus reducing the likelihood of contracting the
disease. At least 80% of the population must be
vaccinated for it to work.
Immunity
Passive Immunity
– Immunity developed from being given antibodies
made by a different organism. Not long lasting as
no lymphocytes have been activated.
• Natural: Baby becomes immune due to antibodies
received from its mother through the placenta and
breast milk
• Artificial: immunity after being injected with antibodies
from someone else e.g Urgent passive immunity using
antitoxins against Tetanus toxin from the bacterium
Clostridium tetani if too late for vaccination.
The Immune System
Primary response Slow…
This occurs when a pathogen enters the body for first time. There are not
many B cell differentiated into plasma cells with antibodies for the
antigen.
The body takes time to produce the right antibodies against the pathogen .
Until then, the pathogen multiplies and the person shows symptoms of the
disease.

The Secondary response is faster…


Memory cells are produced which remember the specific antigen
(Memory B cells divide into plasma cells producing specific antibodies to
the antigen. Memory T cells with specific receptors divide they attach to
and kill the cell carrying the antigen.)
So a stronger quicker immune response is made upon re: infection. The
person is now immune as the pathogen id removed before adverse
symptoms develop.
Primary and Secondary Response
Primary and secondary Response
The role of vaccination in
providing immunity.

The successes and challenges of the use of


vaccines to reduce the incidence of diseases.
Vaccines
Work on the basis of Active immunity.
Contain antigens that cause your body to
produce memory cells against a particular
pathogen without the pathogen causing disease.
Thus making you immune.
Booster vaccines are given after several years to
ensure memory cells are produced ( keep
protection level up)
Vaccination
Vaccination
Vaccination
Types of vaccines:
Toxoids: toxins produced by tetanus and diphtheria are detoxified but their
antigenic properties remain to stimulate antibody production.
Killed organisms: involve use of dead bacteria and viruses for immunization
e.g flu vaccine.
Live vaccines: is attenuated or weakened organism but still containing the
antigens to stimulate immunizations e.g for Tuberculosis, Measels, Mumps
,Rubella, Polio. For small Pox , an un attenuated virus was used. This was a
different strain which was harmless.
New vaccines are developed using only the proteins coded for the antigen for
the pathogen in question. Large amounts of antigens can be prepared in
this way. E.g cholera, thyphoid, hepatitist B vaccines
Vaccination Success and Challenges
-Edward Jenner Father of Immunology Small Pox
https://www.youtube.com/watch?v=yqUFy-t4MlQ
-Why Vaccines Work:
https://www.youtube.com/watch?v=3aNhzLUL2ys
The Polio Story
https://www.youtube.com/watch?v=gE4ef0yQZRU
Vaccine Hesitancy
https://www.youtube.com/watch?v=qO5QOIIL_ZE
https://www.youtube.com/watch?v=2h55LrgNVZ4
Questions

• Name two Primary defenses against pathogens and parasites


• Define the term immune response
• What are antigens?
• What are structures found on the surface of T lymphocytes?
• Draw and label the structure of a B Lymphocyte
• Draw and label the structure of an antibody
• Give two differences between the primary and secondary
response
Questions
• Describe how a phagocyte responds to an
invading pathogen.
• Describe the function of Antibodies
• Emily had chickenpox as a child. She was
exposed to the virus that causes it as a
teenager but did not experience any
symptoms. Explain why.
Questions
• What is the difference between active and passive
immunity?
• Explain the difference natural passive and artificial
passive immunity.
• Give two advantages of vaccinations
• Why is protecting biodiversity important for the
development of new medicine?
• Influenza is caused by a virus that constantly changes it
antigens.
– Why a New influenza vaccine is made every year?
– How are new influenza vaccines chosen every year?
Monoclonal Antibodies
In 1970 Scientists developed a way to select a type of B lymphocytes to
produce large amounts of its antibodies . Monoclonal Antibodies.
Problem:
B lymphocytes that made clones of plasma cells did not produce antibodies
Plasma cells that made antibodies did survive for long in a culture medium

To solve this, B lymphocytes are fused with cancer cells to form hybridoma
cell. These Hybridoma cells continuously form clones of cells secreting
the same type of antibody (Monoclonal antibodies.)
Monoclonal Antibodies
How to make monoclonal antibodies
Steps
Mouse is immunized against an antigen
Mouse antibodies are produced and tested
Mouse cell are mixed with rapidly cloning cells to form a hybrid.
Only Hybrid cells are allowed to grow and are tested to ensure production of
the right antibodies
Hybrid cells are modified to be used( humanized)

https://www.youtube.com/watch?v=M3zllm8QbCM
Monoclonal Antibodies in
Diagnosis
Monoclonal Antibodies in
Diagnosis
Used to locate where blood clots occur in a body suspected of a blood thrombosis( dislodged clot)
– Mouse injected with human fibrin ( a protein found in blood clot)
– Fibrin acts as the antigen in the mouse
– Mouse B lymphocytes proliferate producing antibodies for human fibrin especially in spleen
(The spleen is responsible for production and removal of blood cells and forms
part of the immune system)
B plasma cells releasing fibrin antibodies are mixed with cancer cells.
This hybridoma cells are cultured producing large amounts of antibodies
Antibodies are labeled using a radioactive chemical that produces gamma
radiation
Labeled antibodies used in a patients blood bind to fibrin molecules and show
up on a gamma film to indicate the areas where the blood clot releasing
fibrin is located
Monoclonal Antibodies in
Diagnosis of Pregnancy
Used to test pregnancy to detect the presence of a hormone HCG- Human
Chorionic Gonadotrophin in the urine. (Only secreted in Pregnancy)
– In the pregnancy kit, Monoclonal antibodies are made using mouse
lymphocytes specific to HCG in the urine.
– Urine added to the sample window saturates the absorbent pad and begins
to moves up the test strip.
– HCG antibodies bind to coloured latex particles forming an antibody-particle
complex . If HCG is present in the urine it bind to the mobile antibody-particle
complex.
– A fixed monoclonal antibody for HCG is found in the Results window. As the
HCG- antibody-latex complex passes this region ,a coloured line is seen. This is
region called the Test Results Region.
– There is yet another region containing another monoclonal antibody ( an anti-
mouse antibody) .This react against the antibody – latex complex whether or
not it has HCG bound to it. This is called the Control Region and confirms that
the test has worked properly.
How Pregnancy Kits work
• https://www.youtube.com/watch?v=l9Ob2hH
fXGE
• https://www.youtube.com/watch?v=aOfWTsc
U8YM
Monoclonal Antibodies in
Diagnosis of Disease
Differentiate between diseases with similar symptoms.E.g:
-STDs Chlamydia &Gonorrhoea: both caused by a bacterium that causes
pelvic inflammation and possibly infertillity. Monoconal antibodies
make diagnosis faster and more reliable
-Herpes 1 ( Cold sores) and Herpes 2 ( genital infection)
-Leukemia and Lymphomas ( Cancers of WBC’S)
Early Diagnosis of other cancers Lung, breast ,colon rectal
-Testing body fluid samples
-By directly locating tumors : using monoclonal antibodies attached to
radioactive tracer e.g Iodine -131 specific to a cancer antigen. The
antibody would find the location of the antigen which would be
identified due to the radioactive tracer used.
Diagnosis of streptococcal infections
Monoclonal Antibodies in
Treatment of diseases
Treatment of Disease (Magic bullet) Paul Ehrlich
Ehrlich reasoned that since a compound could selectively target a disease-causing
organism, then a toxin for that organism could be delivered along with the
selective agent . "magic bullet" – referred to an ideal therapeutic agent created to
kill only the organism targeted. This lead to the development of antibody-drug
conjugates(a monoclonal antibody linked to a cytotoxic biologically active drug),
selectively delivered to their designated targets (e.g. cancer cells).
This mechanism of action of Monoclonal antibodies can be an effective in
treating disease e.g If attached to a isotope or a toxic drug the antibody
would be able to destroy the target cell
limitations
-Normal cells may also be destroyed since similar markers on cancer cells
are present on normal cells
-Antibody attach to the surface of the cell but does not enter it to deliver
the toxin
Monoclonal Antibodies for
Treatment (MabThera drug)
MabThera : (rituximab)an anticancer drug is a
monoclonal antibody for a protein(CD20)
found on the membrane of B lymphocytes
• In the cancer no-Hodgkin Lymphoma , B Lymphocytes
are the cancerous cells
• Binding of rituximab kills the B lymphocyte as well as
normal ones since they have the same CD20 receptor
• Rituximab is also used in treating other autoimmune
diseases involving over active B lymphocytes e.g
rheumatoid arthritis.
Monoclonal Antibodies in
Diagnosis

https://www.youtube.com/watch?v=XLSQ7bInY
bE

https://www.youtube.com/watch?v=B0y811xI2
mk
Monoclonals in HIV Infection
The extraordinary antigenic diversity of HIV-1 also presents
formidable challenges to defining NAbs that could provide broad
protection against diverse circulating HIV-1 strains. Several new
potent monoclonal antibodies (MAbs) have been identified, and
are beginning to yield important clues into the epitopes common
to diverse HIV-1 strains. In addition, antibodies can also act in
concert with effector cells to kill HIV-infected cells; this could
provide another mechanism for antibody-mediated control of
HIV-1 replication. Understanding the impact of antibodies on
HIV-1 transmission and pathogenesis is critical to helping move
forward with rational HIV-1 vaccine design.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253031/
Monoclonal Antibodies in organ
transplants
Prevent rejection of transplants:
– Monoclonal antibodies are used to suppress T cells which normally
destroy transplanted organs
– This is more effective than drugs used to suppress the entire immune
system since only the Tcells are suppressed .

Tissue Typing to reduce the risk of rejection before carrying out


a transplant
– Find a compatible donor whose antigens is a close match to the
recipient
– Monoclonal antibodies are cultivated to find out the types of antigens
present in the donor to increase the accuracy of the match
Additional Information
Blood Groups
• In order to give or receive blood, both donor and recipient must be
compatible with each other.
• If this does not occur then agglutination occurs.
• Agglutination (or clumping of cells) is one process by which antibodies
function to destroy pathogens. In this case, the immune response occurs
due to reaction between glycoproteins on the cell membrane of the
donors red blood cells called agglutinogens (these act as antigens) and
antibodies (agglutinins) in the recipients plasma

• AB,O are alleles of one gene. A and B alleles make A and B antigens
respectively . The protein produced by the O is non functional
Blood Group
Fact1: The two antigens that exist are A and B. The two complementary
plasma antibodies in the plasma are a and b
Fact 2:A person with a specific antigen does not have the corresponding
antibody in their plasma. E.g A person with antigen A on their RBC cell
membrane does not have a antibodies in their plasma . That individuals is
said to have blood group A. Similarly, a person with B antigens on their
cell membrane is said to have blood group B and so does not have b
antibodies in their plasma.
Fact 3: If there are no Specific antigens on the Rbcs cell membrane, then the
individual has blood group O and has antibody a and b
Fact 4: If both specific antigens are on the RBC the individual has blood group
AB. There are no antibodies in the plasma
Blood Groups
Mixing two blood groups together may result in
different consequences.
Figure 14.6 Blood groups
Blood Group O A B AB
% Population 46 42 9 3
Antigen - A B A+B
Antibody a+b b a -

Blood group O is called the Universal donor no antigens to cause


agglutination by the recipients antibodies. Little agglutination – donor
blood diluted by recipients.

Blood group AB is called the Universal Recipient no antibodies to cause


agglutination. They can only donate to AB.Why?
Blood groups
Figure 14.43 Interactions between human blood groups. In major
transfusion blood groups are matched more accurately.
Recipient O A B AB
----------- a+b b a ---
Donor
O ---- ---- ---- -----
a +b

A Clump ---- Clump -----


b

B Clump Clump ------ ------


a

AB Clump Clump Clump ------


---
Blood Groups
Recipient O A B AB
----------- a+b b a ---
Donor
O
a +b
A
b
B
a
AB
---

ttps://www.youtube.com/watch?v=HQWlcS
p9Sls
Blood Groups Summary
Donate Receive

Blood group O: O,A,B,&AB O


Blood group A: A, AB O,A
Blood Group B: B,AB O,B
Blood group AB AB O,A,B,AB
Major Histocompatibility Complex
Marker (MHC)
Major Histocompatibility Complex (MHC)are :
– special markers found on all cells ( except red blood cells) and are used
by the immune system to recognize self.
– coded for by genes on chromosome 6
– glycoproteins and are attached to the cell membrane with the
carbohydrate tail extended as a flag.
– act as antigens and are attacked by T –cells if they are foreign(e.g
rejection of transplanted organs)
There are three classes:
MHCI- are recognized by CD 8 receptors on T 8cells,
MHC II- are recognized by CD 4 receptors on T4cells
MHCIII
The rhesus Factor
A special antigen found on red blood cells of 85% of the population. These
persons are rhesus positive: RhD positive (Dominant)
The 15% lacking this rhesus antigen are called rhesus negative RhD negative (
Recessive)
– rhesus negative blood does not usually have antibodies angainst rhesus positive blood
– If rhesus negative individual is given rhesus positive blood antibodies for the antigen are
produce. This can be problematic.

Eight blood groups:


– A RhD positive (A+)
– A RhD negative (A-)
– B RhD positive (B+)
– B RhD negative (B-)
– O RhD positive (O+)
– O RhD negative (O-)
– AB RhD positive (AB+)
– AB RhD negative (AB-)

NHS,2015
The rhesus Factor
E.g in pregnancy if a rhesus negative mother has a rhesus
positive baby .
– rhesus positive blood gets into the mother during ate pregnancy .
– Antibodies are produced against the red blood cells of the fetus which
may not be in sufficient quantities to affect the first child but may
cause haemolytic disease of other rhesus positive babies.

In UK 85% of the population is RhD positive , (36% of the


population has O+, the most common type).
– As aresult in cases of uncertainty or emergency, O RhD negative blood
(O-) can safely be given to anyone because it doesn't have any A, B or
RhD antigens on the surface of the cells, and is compatible with every
other ABO and RhD blood group.
Q&A
Q&A
ai • First line of defence against invading organisms to
eliminate them and prevent infection
• Antigen-nonspecific defence mechanisms that a host
uses immediately on exposure to antigen/response is
same for all pathogens
• There is no memory or lasting protective
immunity/resistance to disease is unchanged after
infection 2–3 points [1)

ii • Physical barriers – epidermis of skin, mucous


membranes
• Chemical factors – lysozyme, complement proteins,
histamines
• Phagocytic cells – neutrophils, monocytes and
macrophages
• Cells that release inflammatory compounds – basophils,
mast cells and eosinophils
• Any valid point
b.i Histamine [1]
ii • Causes cells of capillary wall to pull away from each
other/capillaries become ‘leaky’/diapedesis [1]
• Relaxes the smooth muscles of arterioles causing
increased blood flow to area [1]

iii Cell 1 – neutrophil


Cell 2 – monocyte
Cell 3 – macrophage

iv • Attract the phagocytes (neutrophil, monocyte,


macrophage) to the site of infection by a process called
chemotaxis
• Destroys bacteria by making holes in them/lysis
• Coat/tags the bacteria so phagocytosis can take
place/opsonisation
• Causes local vasodilation
v • Second line of defence against invading organisms to
eliminate them and prevent infection
• Antigen-specific defence mechanism which involves
humoral and cell mediated immunity
• Involves the formation of antibodies and cytokines
secreted by B- and T-lymphocytes
• There is lasting protective immunity/resistance to
disease improves after infection

vi • Ingests pathogen and digests it


• Pieces of antigen are displayed on the cell surface of
macrophage in grooves within MHC proteins
• Acts as antigen presenting cells (APC)
• The displayed antigens on the APCs are shown to Thelper
cells
• Appropriate T-helper cells selected
• T-helper activates appropriate B-cells – clone selected
which produce antibodies
• 12 a Plasma/effector cells [1]
• b See Figure 11.9 in Biology Unit 2 for CAPE® Examinations
• c • Hinge region: gives molecule flexibility/allows molecule to
• bind to more than one epitope/antigen/pathogen [1]
• • Disulphide bonds: hold two heavy chains together/hold
• heavy and light chains together/maintain the quaternary
• structure of the molecule/maintain the shape of the
• molecule [1]
• d • To bind to different antigens
• • Specific to antigen/complementary shape/lock and key Well explained [1]
• e i • Any substance that when introduced into the blood or
• tissue induces the production of antibodies
• • Foreign substance which stimulates an immune
• response/production of antibodies
• ii Living:
• • Antibody response/primary response would be greater
• • More memory cells produced/lifelong protection [1]
• Attenuated:
• • Would not cause disease/no harm/lack of symptoms of
• disease
• f i • No memory cells to detect antigen
• • Time taken for degradation and presentation of antigen
• by APC to T- and B-cells
• • Time taken for specific clone to be selected
• • Time taken for clonal expansion
• • Time taken for the plasma cells to differentiate
• • And produce antibodies
• ii • Primary response is slower than secondary response
• • Primary response is smaller than secondary response
• • Secondary response remains higher after 40 days Any 2 points [2]
• iii • Secondary response is faster because of many memory
• cells present
• • Memory cells have to go through fewer differentiations
• to form plasma cells
• • More antibodies produced because many memory cells
• were present to stimulate many plasma cells production
• 13 a i • Natural: acquired through disease/illness [1]
• • Artificial: achieved through injections/given
• intentionally [1]
• ii With active immunity, the antigen enters body and
• antibody production is stimulated. In passive immunity,
• antibodies are supplied directly to the body. [2]
• b
• Example Type of immunity
• Baby feeding on breast milk Natural passive
• Child exposed to a friend with chicken pox Natural active
• Receiving the MMR vaccine as a child Artificial active
• Receiving the H1N1 vaccine as an adult Artificial active
• Getting an emergency tetanus injection after
• stepping on a rusty nail Artificial passive
• c • Vaccine contains antigen
• • Antigen activates the immune response
• • Memory cells (both T and B) would be made, which
• remain in circulation in body
• • When infected again, secondary response would be
faster
• d • Given an anti-venom/specific antibodies to toxin
• • Through injection
• • Provides immediate protection
Resources
National Health ServicesUK.2015. Retrieved from
http://www.nhs.uk/conditions/Bloodgroups/pages/intro
duction.aspx

Ramesar, M. J. (2011). Biology Unit 2 for CAPE Examinations.


Cambridge University Press.

Taylor, D. G. (2012). Biological Science Third edition. Cambridge


University Press.

Tylor,N., Dodds,J., Dodds,J.,Bradfield,P.(2002).A2 Level Biology.


Pearson Limited Edition.

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