IMMUNITY Flashcards
Immunity
Protection against disease
immune system
The body’s defense system
Lines of Defences Against Diseases
To prevent infectious diseases from entering and spreading
1) First line of defence
External, non-specific
2) Second line of defence
- Internal, non-specific immune
response - Involves phagocytes
3) Third line of defence
- Internal, specific immune response
- Involves lymphocytes
Both non-specific and specific defences work
together to protect the
body against diseases
Antigens
In general, antigens are macromolecules on cell surfaces
* E.g. protein, glycoprotein, glycolipid, polysaccharides etc.
2 TYPES OF ANTIGENS
Self and Non-self
Non-self antigens =
macromolecules that activates an immune response
Macromolecules are found on…
– foreign materials’ surface (e.g. pathogen, allergen)
– surface membrane of infected host cells
→Stimulates production of antibodies
non self antigen
self antigens AKA
cell marker
self antigens
- Macromolecules on cell surface membranes of host cells
- Cell surface antigens do NOT trigger body’s immune system
- No antibodies are produced
when we say antigen in general
we are usually
referring to NON-self antigen though
Immune response =
the body’s immune reaction towards
non-self antigens
Involves WBCs that made in bone marrow
2 types of WBS
phagocytes and lymphocytes
phagocytes in _ defence
non specific
lymphocytes in _ defence
specific
2 types of phagocytes
Neutrophils
* Monocytes
→ which mature into macrophages
2 types of Lymphocytes
B-lymphocytes
* T-lymphocytes
phagocytes passed throughout
life
phagocytes function
- Patrol in blood, tissues and organs
- Remove dead cells and pathogens
→By phagocytosis
phagocytes involved in
non-specific defense
→responds to many different non-self antigens
phagocytes appearance
Lobed nuclei
* Granular cytoplasm – due to many vesicles
Neutrophils
Multi-lobed nucleus
* Have receptor proteins on its membrane
→ To identify pathogens as non-self
* When there is an infection, large numbers
are released from bone marrow
→ Accumulate at site of infection
neutrophils lifespan
Short-lived (few hours-days)
→Dies after digesting pathogens
→Dead neutrophils form pus
Monocyte → Macrophage
Lobed nucleus / kidney-bean shaped
* Larger than neutrophils
* Have receptor proteins on its membrane
→ To identify pathogens as non-self
Monocytes circulate in
blood
→Mature into macrophages when it leaves
blood and enter organs
monocyte lifespan
Long-lived cells
Macrophages found in
organs such as
liver, lungs, spleen, kidney, lymph nodes
Role of Macrophages
Initiates / starts the immune response
macrophages mechanism
1) Has various receptor proteins of cell surface
* Can detect non-self antigens
* Non-specific
2) Engulf pathogen / foreign material via
phagocytosis (Chap 4)
* Fusion of phagocytic vacuole with lysosome
3+4) Cuts up pathogens using lysozymes
5) Antigens presented on its cell surface
→Macrophages act as
antigen-presenting cells (APC)
6) Some cell fragments released by exocytosis
* APCs can activate/stimulate lymphocytes
other APCs can include
B cells and other types of
phagocytes too!
Lymphocytes produced in
bone marrow before birth
lymphocytes function
- Involved in specific immune responses
→responds to only specific non-self antigens - Mature lymphocytes circulate in the blood
and lymph
→Accumulate at sites of infection
Appearance of lymphocytes
Smaller than phagocytes
* Large round nucleus
* Little cytoplasm
2 main types of lymphocytes
Both made in bone marrow, but mature in different places and
have different functions
1. B-lymphocytes (B cells)
* Mature in bone marrow
* Produces antibodies
2. T-lymphocytes (T cells)
* Mature in thymus
* Does NOT produce antibodies
both B cells and T cells
work together to defend the immune system
Millions of different types of B and T-lymphocytes with
receptors of different shapes
lymphocytes are
SPECIFIC = each type of lymphocyte responds to 1 type of
antigen only
E.g. Each type of B cell produce 1 type of antibody receptor
→which responds to 1 type of antigen only
So the body can respond to almost any type of pathogen
LymphocytesOnly mature lymphocytes
can circulate in the blood & lymph and
carry out immune responses
lymphocytes have
telomerase to divide continuously
Maturation of B-Lymphocytes
Maturation of B-Lymphocytes
1) All B cells are formed in the bone marrow before birth
→ Genes in B cells that code for antibodies code for diff types of
antibodies for diff types of B cells
2) Forms a specific antibody that acts as glycoprotein receptor on
surface membrane of B cells
→Binds to specific antigen that is complementary in shape
3) B lymphocytes divides and mature in bone marrow
→ Mature B lymphocytes circulate in blood and concentrate in liver,
spleen & lymph nodes
Antibodies
* Aka
immunoglobulins
antibodies are
Globular glycoproteins
antibodies are made up of
4 polypeptide chains:
* 2 heavy chains
* 2 light chains
antibodies have
Quaternary structure
Held together by disulfide bonds
→ gives stability
antibodies have 3 regions
1) Variable region (Fab)
2) Constant region (Fc)
3) Hinge region
) Variable region (Fab)
- Every chain has a variable region = 4 in total
- Provide 2 identical antigen-binding sites
- Specific for binding antigen
→ Complementary shape to antigen
→ Shape determined by primary structure
= specific seq of amino acids - R groups at antigen-binding site forms H
bonds and ionic bonds with specific antigen
Sequence of amino acids at the variable region is
different for each type of antibod
Each type of antibody binds
different antigens
Constant region (Fc)
- Formed by light and heavy chains
- When circulating in blood: binds to receptors on phagocytes
- When antibody acts as B cell receptor:
attach to cell surface membrane of B cell - Gives antibody class
3) Hinge region
- Held by disulfide bridges
- Gives flexibility when binding to antigen
Action of Antibodies
Prevent entry into cell
Attach to flagella
Agglutination
Lysis of pathogen
Opsonisation
Neutralise toxins
Prevent entry into cell
Attach to flagella
Agglutination
Lysis of pathogen
Opsonisation
Neutralise toxins
Action of B-Lymphocytes
- Pathogens invade
- Antigen presentation cell formation
- Only specific B lymphocytes has receptors with the
complementary shape to antigen will be activated
→ Clonal selection - B cell divides by mitosis
→ Clonal expansion - Activated B cells develop into plasma cells and memory cells
Plasma Cells
- Short lived (few weeks)
- Do not divide and do not have telomerase
- Produce and secrete antibodies rapidly
→ by exocytosis
→ into blood plasma, lymph, lungs and stomach lining - Antibodies are glycoproteins
→ So plasma cells have extensive network of RER
and Golgi
Memory Cells
- Long-lived, remain in circulation
- Has telomerase
- Provides long term immunity
- Last for many years/lifetime
memory cells during second invasion of same pathogen
- Enable faster response during
2
nd invasion of same antigen,
as many memory cells are circulating - During 2nd invasion, it divides rapidly (clonal expansion)
→Form more plasma cells → more antibodies
→Infection is destroyed before symptoms develop
→ Body immune to pathogen
Memory cells during Secondary response
- Faster response
- Many memory cells circulating
- More cells specific for pathogen, higher
chance of encountering pathogens quickly - More plasma cells formed
- More antibodies produced
- No symptoms developed
Memory cells during primary response
- Slower response
- Only a few B cells specific
to the antigen is present - Individual becomes ill
Maturation of T-Lymphocy
1) All T cells produced in bone marrow before birth
2) Maturation in thymus gland
→ thymus shrinks after puberty
* Produce specific T cell receptors on cell
surface membrane
→Binds to specific antigen that is complementary in shape
→T cell receptor’s structure similar to antibodies
3) Mature T cells circulate in blood and lymph
Action of T-Lymphocytes
- Pathogens invade
- Antigen presentation cell formation
- Only specific T lymphocytes has
receptors with the complementary shape
to antigen will be activated
→ Clonal selection - T cell divides by mitosis
→ Clonal expansion - Activated T cells develop into
T helper cells and T killer cells
T helper cells function
1) Secrete cytokines / interleukins which
a) Stimulate specific B cells
* To divide and develop into plasma cells & memory B cells
* Increased antibody levels
b) Stimulate macrophages
* To carry out phagocytosis more
vigorously
c) Stimulate killer T cells
* To divide and produce more toxins
T Helper Cells Functions
Form T helper memory cells
* Secondary response
* Long term immunity
Cytotoxic T Killer Cells
1) Seeks out infected host cells (including APC, cancer cells)
and pathogens and destroys them
a) Attach to surface of cells
b) ‘Punch’ holes into cells
c) Secrete toxins into cells
* E.g. hydrogen peroxide,
perforin
Cytotoxic T Killer Cells
Functions:
Forms killer T memory cells
* Secondary responses
* Long term immunity as it is long-lived
2 types of immunity
active and passive
active immunity
Own immune response is activated
– Own lymphocytes are activated by antigens
– Own antibodies are made
– Takes time, not immediate
– Memory cells formed → results in long-term immunity
passive immunity
Immune response is NOT activated
– Own lymphocytes cells not activated
– NO plasma cells to produce antibodies
– Protection is immediate
– NO memory cells formed → only short-term immunity
Active Natural
Immunity
E.g. Catching a cold
Natural: Antigens
from the
environment
Active Artificial
Immunity
E.g. Vaccination
Artificial: Antigens are introduced via injection into vein or muscle / consumed
→ activate the immune response artificially
Antigens can be attenuated / made harmless (e.g. heat-treated, cut up,
inactivated toxins)
Antigen used could be dead or alive
Passive Natural
Immunity
E.g. Maternal antibodies
Natural:
1) Antibodies pass from mother infant through placenta
→ remain for months
2) Breast milk that is colostrum-rich has antibody (IgA) that prevents growth of bacteria/viruses in the stomach of infant
Passive Artificial
Immunity
E.g. Antibodies or antitoxins
Artificial: Antigens are introduced via injection
Antibodies are collected from blood of donor / animals who are vaccinated or suffer from the same disease
→ Contains the specific antibodies against the specific antigen
Vaccination
activates the immune system
→ producing memory cells that result in
long term immunity
Effective Vaccines
Provide sufficient antigens
→ To mimic or copy natural infections
→ To form sufficient plasma and memory cells for long-term protection Give lifetime protection against pathogen
→ Pathogen unable to developed in immunised person
E.g. vaccines using live pathogens, smallpox vaccine
Ineffective Vaccines
Do not mimic natural infections
→ No plasma and memory cells formed Do not give lifetime protection
→ Require booster injections
→ To stimulate secondary response in order to give protection Do not provide sufficient protection against pathogen
→ Maybe due to pathogen’s high mutation rate or ability to hide from immune system
E.g. vaccines using dead pathogens, cholera vaccine
2 modes of vaccination
mass vacination
ring vaccination
mass vacination
Vaccinate a large number of people at the same time
Ring vaccination
- Perform contact tracing with infected person
- Vaccinate the area of community the person is in / people who was in contact with the person
ring vaccination aim
Vaccinate a high proportion of the population
→ To achieve herd immunity
Mass vaccination results in
herd immunity
herd immunity advantages
- Less chance of transmission of disease
→Reduce pool of infected people in the community
→Fewer people can catch the disease and be source of infection - Protection of those unvaccinated / immunocompromised as disease does not spread
Common Barriers to Vaccinatio
1) Poor response to vaccines
* People that are immunocompromised
* People who lack protein (malnutrition)
* Less antibodies made
2) Pathogens can mutate rapidly (antigenic variation)
* Form diff strain with diff antigens
* Memory cells are unable to recognise pathogen that has major
changes in antigen structure
3) Pathogens can escape from immune system (antigenic concealment)
* By living inside cells / covering bodies with host proteins /
suppressing immune system
How was smallpox eradicted?
An effective vaccine was developed!
* Same vaccine used everywhere
→ Variola virus – stable, low mutation rate
* Use live virus so strong immune response
→ similar Vaccinia virus
* One dose enough to give life-long immunity,
no boosters needed
* Vaccine is heat stable
* Easy to administer
→ Use bifurcated needle
→ Needle can be sterilized and reused
Mass vaccination for smallpox was very successful!
This is due to:
- High percentage of population immunized
→ Low cost needed to for mass production
of vaccine
→ Many volunteers became vaccinators
→ Result in herd immunity - Infected people were easy to identify
→ Few symptomless carriers
→ Can perform contact tracing and
ring vaccination
→ Can isolate cases to prevent spread
Why isn’t TB eradicated already?
BCG vaccine is available!
* It is not eradicated even though there is a high coverage of
vaccination!
why is TB not eradicated even though there is high coverage of vaccine
- Vaccination does not work in adults >35yo
- High percentage cover (above 90%) needed to achieve herd
immunity
→ Not yet done in every country - Difficult for surveillance / to ensure vaccination
→ Due to high birth rates and high migration rates
→ Latent TB is symptomless and found in 1 in 4 people
Why can’t we vaccinate against malaria?
No effective vaccines against malaria
why is there no effective vaccine against malaria
Protoctists are eukaryotes
→ Many more genes than bacteria & viruses
* Display diff antigens on its cell surface for:
→ Diff species / strains
→ Different stages of its life cycle
* Parasite changes antigens during infection
→ Diff genes coding for antigens switch on during infection
* Plasmodium parasite hides in liver and RBCs
Why can’t we vaccinate against cholera?
No effective vaccines against cholera
* Oral vaccination only gave limited protection as it was excreted
why is there no effective vaccine against cholera
- Many different strains of cholera
→ Bacterium mutates - Vibrio cholerae lives in the host’s intestines
→ Beyond reach of antibodies
Monoclonal =
only 1 type of antibody, specific for 1 antigen
problem with monoclonal antibodies
- B cells that divide by mitosis DO NOT produce antibodies
- Plasma cells that secrete antibodies DO NOT divide
solution for monoclonal antibodies
Fuse plasma cells + cancer/myeloma cells
→ hybridoma cells that CAN divide and CAN produce antibodies
how to produce monoclonal antibdoies
1) Inject foreign antigen (e.g. pathogen) into mice
2)Allow time for immune response tooccur
3) Collect plasma cells from spleen
3) Fuse plasma cells with cancer cells to produce hybridoma cells
→ Use fusogen for fusion
4) Clone hybridoma cells
→ Use HAT medium for hybridoma growth
5) Screen for cell secreting desired antibody
→ By separating cells and culture in individual wells
→ Select only one type
6) Grow hybridoma cells in large scale culture
diagnosis of using monoclonal antibodies
- Monoclonal antibodies have same specificity and detects only
one antigen
→ Can distinguish between diff pathogens / strains
→ Fast diagnosis than having to culture pathogen
→Less labour intensive
→Quicker diagnosis = quicker treatment - Can be tagged with a fluorescent label/dye
→Can detect location of tissues expressing antigen
→E.g. cancer cells, blood clots - Cheap, safe, fast results, easy to use, accurate
(Also used in blood typing, pregnancy tests etc.)
treatment using monoclonal antibodies
- Used to target specific diseased cell by binding to receptors on
its cell surface
→ Can kill cell by stimulating the immune system
→ Can attach radioactive substance / drug to Mabs to kill cell - Can bind to antigens on pathogens
→ Result in artificial passive immunity
problems of using monoclonal antbodies in treatment
- Causes some side effects
- Antibodies made in animals recognised as non-self
- Trigger immune response in humans
→ Allergic reaction - Remains in the body for short period of time as it is destroyed
- Need to be administered more than once in small amounts
solutions for the problems in using monoclonal antibodies in treatment
Humanise Mabs
1) Alter genes that code for heavy and light chains of antibodies
→ Code for human antibodies instead of mice and rabbit’s
2) Changing type and position of sugar groups attached to heavy chains
→ Arrangement of sugar groups same as human antibodies
