Download BIO SEMINAR PPT FINAL

Chapter 18: Natural
Defenses Against Diseases
1.
2.
3.
4.
5.
Animal Defense System – Arthur Wong
The Human Immune System: An Overview – Victoria Ting
B Cells: The Humoral Immune Response – Heather Yeom
T Cells: The Cellular Immune Response – Philip Peng
Disorders of the Immune System (focus on HIV) – Vivien So
• Defend animals against pathogens
• Distinguish between self and nonself
– Non-specific defense
• General protection
– Specific defense
• Specific target
Lymphatic System
• Lymphoid tissues
• eg. Bone marrow,
spleen, lymph nodes
– Removal of tissue
fluids
– Produce immune cells
White Blood Cells
• Phagocytes
– engulf, digest nonself substances
• Lymphocytes
– Specific defences against
We’re All In This Together
• Immune system works as a team
– Antibodies
– T cell receptors
– Major Histocompatibility complex (MHC)
– Cytokines
Non-specific Barriers
• Skin
• prevent entry
• Normal flora
• competition
• Mucous
• block & trap
• Digestive tract
• destroy
Cellular Defenses
• Complement proteins
– Sequence of destruction
• Phagocytes
– Monocytes  Macrophages
• Natural killer cells
Under Attack
• Body’s response to
infection
• Mast cells release
histamine
– capillaries dilated &
leaky
• Enter the phagocytes
– engulf & produce
cytokines
• Healing & pus
The Human Immune System:
An Overview
Textbook Pages: 370-374
Presented by: Victoria Ting
The Main Features of the Immune
System
1. Specificity
2. Ability to respond to a diversity of foreign
molecules and organisms
3. Ability to distinguish self from nonself
4. Immunological memory
The Main Features of the Immune
System: Specificity
• Lymphocytes (B cells & T cells) are involved in specific
defence mechanisms
– T cell receptors, and antibodies made by B cells bind
to specific foreign substances (antigens)
• Antigens have specific sites that the immune
system recognizes, called antigenic
determinants
• Host animal responds to an antigen by producing T
cells or B cells’ antibodies that match the antigenic
determinants of that antigen
– Each T cell and antibody is specific to ONE
antigenic determinant
The Main Features of the Immune
System: Diversity
• Humans can respond to an estimated 10
million different antigenic determinants
– Why? Remember, potential pathogens like
foreign molecules, viruses and bacteria can
have many species, and each species can
have slightly different features on its cell
surface
– Immune system recognizes an antigenic
determinant and activates the appropriate
lymphocytes (B cells and T cells)
The Main Features of the Immune
System: Distinguishing Foreign
Substances
• The human body has MANY different
proteins, each with its own 3D structure
that is able to generate an immune
response
– Every cell in body has a LOT of antigenic
determinants
• Therefore, the immune system must be able to
recognize the body’s own antigenic determinants
and not attack them
The Main Features of the Immune
System: Immunological Memory
• After responding to a certain pathogen
once, the immune system “remembers”
that pathogen, and another exposure to
that pathogen will have a more rapid and
powerful response
• Saves us from having the chicken pox
twice!
• Explains why vaccination and inoculation
work
Immune System’s Responses
Against Invaders
• Humoral immune response – B cells
– B cells create antibodies to react with
antigens
• Cellular immune response – T cells
– T cells recognize and bind to antigens
Clonal Selection
• Clonal selection explains: diversity of
immune response, ability to distinguish
foreign substances, and immunological
memory
• Each human has a diversity B and T cells;
this diversity is due to changes in DNA that
occur just after the cells are formed
– Example: clonal selection of B cells
Clonal Selection
Clonal Selection: Immunity and
Immunological Memory
• Results: immunity and immunological
memory
– Activated lymphocytes makes 2 types of cells:
effector cells (which attack antigens) and
memory cells (which can divide on short
notice to make more effector and memory
cells)
– When human body encounters an antigen...
1. Primary immune response is activated
2. Any subsequent encounters with that antigen
activate a secondary immune response
Clonal Selection: Immunity and
Immunological Memory
Primary Immune Response
• Lymphocytes recognize antigen, produce
clones of effector and memory cells
– Effector cells destroy antigens and die; one or
more memory cells are added to the immune
system (and provide immunological memory)
Clonal Selection: Immunity and
Immunological Memory
Secondary Immune Response
• Shorter lag time
• Greater rate of antibody production
• Larger production of total antibodies and T
cells than primary response
Amount of antibody or T cells
(arbitrary units)
Clonal Selection: Immunity and
Immunological Memory
An Application of Immunological
Memory: Vaccines
Immunization – inoculation with antigenic
proteins, pathogen fragments, or other
molecular antigens
Vaccination – inoculation with whole
pathogens that have been modified so that
they can’t cause disease
*both initiate primary immune response
(making memory cells) without causing
illness
Distinguishing Self from Non-self:
Self-tolerance
The human body has self-tolerance (the
body doesn’t attack its own molecules, but
those same molecules would spark an
immune response in another individual)
– Based on 2 mechanisms:
1. Clonal deletion – removing B and T cells from the
immune system if they are anti-self
2. Clonal anergy – immune response to self
antigens is supressed
B Cells: The
Humoral
Immune
Response
Heather Yeom
B Cell
• Survive clonal deletion
• Released from Bone Marrow (“B” CELL!)
• Humoral Immune Response
– Produce antibodies when fully activated
• 2 types:
– Plasma B Cells (Plasma Cell)
– Memory B Cells
Immunoglobulin
• A class of proteins
acts as receptors and
effectors in the
immune system.
• Structure:
– Variable Regions
• Heavy Chain
• Light Chain
– Constant Regions
• Heavy Chain
• Light Chain
Hybridoma
• A monoclonal antibodies producing cell.
• Monoclonal antibodies application:
– Immunoassays: method to detect molecules
in tissues and fluids. (eg. Pregnancy test)
– Immunotherapy: method of killing cancer cells.
– Passive immunization: inoculation with the
antibody immediately. (eg. Early rabies
infection, rattle snake bites, and babies born
with hepatitis B virus infection)
Humoral Immune Response
2 Phases:
• Activation Phase
• Effector Phase
The Cellular Immune Response
and T Cells
<killer T
cell
killing
cell
Presented by Philip Peng
What is a T cell?
- lymphocyte developed from stem cells
- processed in thymus gland
(thus the “T”)
- involved in both humoral immune
response (HIR) and cellular immune
response (CIR)
Two Main Types
Helper T cells:
- TH cells / CD4+ cells
- secretes cytokines in HIR & CIR
Cytotoxic T cells:
- TC cells / CD8+ cells / “killer T cells”
- “search and destroy” bad cells in CIR
It’s Visual Demo
Time!
The Good Guys vs. The Bad Guys
- MHC cells present everywhere
- How to tell good from bad?
- Test:
1) Recognize self MHC proteins?
2) React with own antigens?
Houston, we have a problem…
- TC cells kill off all that isn’t you
- Issue: results in organ
transplant rejections
- Workaround:
immunosuppresants + antibodies
(i.e. cyclosporin)
So Long, and Thanks for All the Fish
Cellular Immune Response:
- TC cells detect non-self antigets via MHC I proteins and
kills via lysing/apoptosis
- Thank the T cells for being
alive!
- Next up… Vivien!
Sources: Life – The Science of Biology Textbook,
http://www.karlloren.com/images/96500b.jpg,
http://www.surgery.usc.edu/divisions/hep/patientguide/graphics/medications2.gif
Disorders
Immune
System
Disordersof
of the
the Immune
System
Disorders of the Immune System
• 1) Overreaction (autoimmune disease,
hypersensitivity)
• 2) Function weakly or not at all (immune
deficiency disorder)
HIV/AIDS
• Immune deficiency disorder
• Human Immunodeficiency Virus (HIV)
targets the TH cell (helper T cell); it’s a
retrovirus that eventually leads to Acquired
Immune Deficiency Syndrome (AIDS)
Transmission of HIV
• Through blood (needle contaminated with virus
after being used to inject an infected individual)
• Through exposure to broken skin, open wound,
body fluids like blood, semen from an infected
individual
• Through blood of an infected mother to baby
through birth
HIV/AIDS
• HIV initially infects macrophages, TH cells
and dendritic cells in blood and tissue
• Infected cells carry virus to lymph nodes
and spleen where T cells mature and B
cells reside
• HIV preferentially infects activated TH cells
that are already responding to other
antigens, enabling it to reproduce
vigorously
• Up to 10 billion viruses are made every
day in this initial phase of infection
• TH cells quickly decrease, and infected patient
shows symptoms such as enlarged lymph nodes
and fever
• T cells recognize infected lymphocytes; immune
response mounted, antibodies specific to HIV
appear in blood and symptoms fade within three
weeks
• Over the next several months, patient
has a high level of circulating HIV
complexed with antibodies which
are gradually removed by dendritic
cells
• But before they are filtered out, antibodycomplexed viruses still infect TH cells that
come in contact with them
• The secondary infection process reaches a
low, steady-state level called the set point
- this point varies for individuals and is a
strong predictor of the rate of progression of
the disease
• During the dormant period, patients feel fine and their TH
cell levels are adequate to mount immune responses
• Eventually, the virus destroys TH cells and their numbers
fall to dangerous levels
- at this point, the patient has “full blown AIDS” and is
susceptible to infections that TH cells would normally
have eliminated
- these are called opportunistic infections because they
take advantage of the crippled immune system
The Virus
How HIV Attacks
• Attaches to TH cells via their surface
protein CD4 which acts as a receptor for
the viral envelope protein glycoprotein120
(gp120)
• After binding, virion enters cell by
membrane fusion
• Soon, a cDNA copy of the RNA genome
is made via reverse transcriptase
• Reverse transcriptase lacks the proofreading
property of many DNA polymerases so errors are
not corrected
• up to 10 incorrect bases out of 8000
• this is advantageous to HIV because genetic
mutations allow its proteins to escape the host’s
immune response
• they also challenge scientists who are trying to
design drugs and vaccines to bind to the changing
proteins
• Integrase catalyzes insertion of cDNA into
host chromosome
• cDNA becomes a permanent part of TH
DNA and is replicated (may remain part of
TH cell genome for more than 10 years)
- provides molecular camouflage against
defenses of host cell as well as therapy
• This latent period ends if HIV-infected TH
cell becomes activated as it responds
naturally to antigens
• When TH cell is activated, the entire integrated
cDNA viral genome is transcribed into RNA
which may stay as is or be spliced
- unspliced RNAs become genomes of new HIV
particles; spliced RNAs act as mRNAs to make
viral structural proteins
• Protease completes the formation of individual
viral proteins
• Viral membrane proteins are made and
transported by host cell organelles
• Cytoplasmic tails of the viral gp120 membrane
proteins bind to the core particles and viruses
bud from the infected cell
Treatment
• General therapeutic strategy is to try to
block stages in the viral life cycle without
damaging host cell
HAART
• Highly Active Antiretroviral Therapy (late 1990s)
• Combination of drugs acting at different parts of the viral
cycle
- uses a protease inhibitor and two reverse transcriptase
inhibitors
• Has achieved considerable success in delaying the
onset of AIDS symptoms in people infected by three
years or more
• May eliminate HIV entirely in some patients, especially
those treated within the first few days of infection, before
the virus has arrived in the lymph nodes
- most face a lifetime of anti-HIV treatment
• 80% of patients who take HAART develop mutant strains
of HIV that are resistant to the treatment
- never-ending race to modify HAART by adding new
and/or different drug combinations
- 140 different HAART treatments
• Hope to develop a vaccine against HIV, though the first
major clinical trial of such a vaccine was unsuccessful