Download Immune System

Lecture 13 – Ch. 43: Immune System
I.
II.
Overview
Innate Immunity
A. components
B. insect Toll receptor
C. human TLRs
IIII. Adaptive/acquired immunity
A. Lymphocytes
i. B-cells
ii. T-cells
B. humoral vs. cell-mediated
immunity
C. Antibodies
D. MHC molecules
IV. Immune memory
V. Immune System Problems
VI. Preparation for next lecture
Thought Question:
Why do we not get sick EVERY time someone near us sneezes?
Overview
cilia of tracheal cells
Pathogens
Viruses
Bacteria
Macroparasites
Irritants
Pollen
Dust
dust
For example…
Virus
Bacteria
Macroparasites
Influenza
Strep
Malaria
Ebola
Black Plague
Sleeping Sickness
Chicken Pox
Salmonella
River Blindness
West Nile Virus
E. Coli
Elephantiasis
pollen
Disease Defenses
A Way In?
Mucus membranes
Eyes
Nose
Mouth
Vagina
Urethra
Skin breeches (cuts,
punctures, scrapes)
Antigens = foreign molecules
specific to the invader
Immunity Overview
Which cells are exclusively part of
the adaptive immune system?
A.
B.
C.
D.
Dendritic cells
Macrophages
B cells
Natural killer cells
Innate Immunity
External Barriers
Skin
Dry dead cells
Constantly sloughed off
Secretions
Contain natural antibiotics
Mucus physically traps microbes
Internal Barriers
Dendritic cells – detect foreign particles alert innate and
adaptive immune systems
Mast cells – cause inflammation and alert of damaged tissues
Innate Immunity
Leukocytes
Phagocytes - ingest foreign
particles & cellular debris
Macrophages – consume
many cells
Neutrophils – die upon
consumption
Natural killer cells
Attack cancerous or infected body cells
Use proteins & enzymes to lyse cells
Inflammation
Innate Immunity
Initiated by damaged or infected cells
Histamine release by mast cells
Capillary flow and permeability increased
Phagocytes drawn to area
Cytokines –
recruit more
lymphocytes
 leads to
pus, swelling,
redness, heat
Innate Immunity
Inflammatory “Symptoms”
Warm, red, painful
Result of leaky capillaries
Increased fluid secretions
Removal of dead cells and waste
Pain
Swelling, chemical response
Alerts injured organism
Leukocytes
and fluid = pus
NSAIDs
Innate Immunity
Fever
Attacks large-scale infections
Macrophages release messenger protein
Hypothalamus raises body temperature
Increased metabolism
Constriction of skin blood vessels
Reduction of blood iron concentration
Immune cells reproduce more rapidly
Bacteria reproduce more slowly &
require more iron
Increases production of interferon to
increase viral resistance
GFP induced by Toll
Innate Immunity
Injected w pathogen
Stabbed, but no pathogen
Insects, like Drosophila, have hemocytes – cells that detect and
ingest pathogens, and secrete lysozyme from digestive tract.
Receptor proteins (Toll) signal from hemocytes to antimicrobial
peptides, specific to the type of pathogen
Innate Immunity
Vertebrates have Toll-like Receptors (TLRs) – recognize PAMPs
(pathogen-associated molecular patterns) that differ between
pathogens: lipopolysaccharide, flagellin, CpG DNA, ds RNA
Innate Immunity
Antimicrobial peptides in vertebrates:
the complement – family of proteins,
inactive and lyse infected cells
Interferon – cytokine made by host
cells, boosts immune response
One immune similarity between
insects and humans is…..
A.
B.
C.
D.
Both use B and T cells
Both have skin as a barrier
Both engage antimicrobial peptides
Both have adaptive immunity
Adaptive Immune System
Acquired/
adaptive
immunity –
consists of
lymphocytes
 B cells
and T cells
Responsible
for circulating
antibodies,
remembering
pathogens,
destroying
infected cells
Adaptive Immune System
B cells
Made and mature in bone marrow
Lymphocytes that make antibodies
– either secreted or embedded in
B cell membrane
Humoral immunity
B cells and antibodies attack
pathogens before they enter cells
After encounter pathogen, B cells
differentiate into memory B cells
and plasma cells
Adaptive Immune System
Clonal Selection:
Adaptive Immune System
B cell  Plasma cell
Plasma cells make and
secrete TONS of
antibodies, as opposed
to memory B cells
Which is NOT a function of B cells?
A.
B.
C.
D.
Produce memory cells
Secrete antibodies
Attack infected cells
Make clones of plasma cells
Adaptive Immune System
Antibody action
Defend against pathogens in blood or fluid
Can inactivate pathogens by binding to epitopes
Can stimulate phagocytosis
Can neutralize toxins or block adhesion
Can trigger complement system where
blood proteins destroy invaders
Adaptive Immune System
Antibodies
Secreted classes : IgM, IgG, IgA, IgE, IgD
Differ in tail region during production in B cells
Produced by B cells
Each composed of two
heavy chains and two
light chains
Constant region is same
Variable region is unique
to antibody
Bind antigens at each end
of “fork”
Genes are unique in that can
recombine into millions of
combinations in different B cells.
Transmembrane antigen
receptors inserted in B cells
Adaptive Immune System
Variable and joining regions – multiple DNA codes for each –
genes randomly (by recombinase) link variable region sequence
with joining sequence – spliced to constant region
Human B cells – 1.65 x 10^6 heavy and light chain combos
including variability of variable region
Adaptive Immune System
Immunospecificity
Antibodies are “pieced together” from many genes
Random combinations allow for millions of possibilities
Each B cell produces
unique antibodies
Over 100 million
different antibodies
in body  chances
of an antigen
encountering one
that fits are high
How does our body mount an immune attack to
a new pathogen (not previously encountered)?
A.
B.
C.
D.
E.
By using memory B cells
By chance encounter with a B-cell receptor
By attacking with macrophages
Both (b) and (c)
Both (a) and (c)
Adaptive Immune System
T cells
Made in bone marrow, mature
in thymus
Lymphocytes that cozy up to
infected cells – two types:
Helper T cells – recognize and
bind infected cells
Cytotoxic T cells – bind and
lyse infected cells
Cell-mediated immunity
T cells find and attack
pathogen-infected cells
Adaptive Immune System
Cell-mediated immunity
Cytotoxic T cells: Insert pores
in infected cells, enzymes break
down cells
Helper T cells stimulate
lymphocyte division
Some T cells develop into
memory cells – future protection
Adaptive Immune System
T cell receptors –
recognize pathogen
epitopes ‘presented’
on infected cells
Composed of one
alpha chain, one beta
chain
Have a variable and
constant region,
similar to Bantibodies
Adaptive Immune System
Self-tolerance
MHC = major histocompatibility complex
All cells have MHC molecules – most body cells have class I
(lymphocytes have class II)
MHC molecules displayed on cell surface – each binds a
specific peptide foreign fragment then “displays” it on surface.
Adaptive Immune System
Self-tolerance
T-cells (cytotoxic or helper T) bind to MHC presented antigens
Self-reactive lymphocytes with receptors to self epitopes are
eliminated before they leave bone marrow and mature
Adaptive Immune System
Helper T cells – CD4 protein that binds MHC molecules
Cytotoxic T cells – CD8 molecule that binds MHC
Helper T
Cytotoxic T
Which cells have MHC molecules displayed?
A.
B.
C.
D.
E.
Most body cells
Cancerous cells
Immune system cells
Transplanted cells
All white blood cells
Adaptive Immune System
Immune system must remember past victories...
• Memory cells “remember” specific antigens
• May survive for years
• Respond faster and larger to repeat invasion
Adaptive Immune System
Memory
Memory B and T cells are able to recognize pathogens and
fight off infections immediately
Then why do you keep
catching a cold?
Over 100 different known
rhinoviruses - it’s
possible to catch colds
(and flu) again and again
Cold viruses can mutate
quickly - thus antigens
are no longer
recognizable
Vaccines
Vaccinations take advantage of the immune response
Body is exposed to antigens to stimulate memory cells
Weakened or killed
pathogens retain surface
antigens, OR
Antigen molecules are
purified from the
pathogen, OR
Genetic engineering of
antigen into a harmless
microbe, OR
Related mild pathogen
shares antigen
molecules
Vaccines
Some vaccines are more effective than others
Small pox is the only infection
eradicated worldwide
Vaccines
The flu vaccine does
not cause influenza
You may get the
vaccine too late, or
catch a different virus
Vaccines are no less effective than a “natural” infection
Memory cells are still produced
Mild response to vaccine is less risky than a full-blown infection
The proposed link between vaccines and autism was disproved
Antibiotics
Antibiotics aid disease fight
Reduce growth and reproduction of living pathogens (not viruses)
Give immune system time to
fight infection
Humans have misused
antibiotics  “superbugs”
Overuse of antibacterial
products
Failure to complete full
course of antibiotics
Non-medicinal use of
antibiotics
Immune System Problems
Allergies
Immune overreaction
to harmless antigens
Histamine triggers
inflammation
Extreme response can
trigger anaphylaxis
Autoimmune Disorders
Immune system attacks healthy
body cells
Lupus, Rheumatoid Arthritis,
Multiple Sclerosis, Type 1
Diabetes, Celiac disease,
Crohn’s disease
Immune System Problems
Immune rejection
When tissue without “self” MHC
molecules (aka HLA) contact immune
system, response mounted
Can be countered by
immunosuppressive drugs
Immune Deficiency Syndromes
Severe Combined Immune
Deficiency (SCID): Few/no immune
cells produced  genetic
Acquired Immune Deficiency
Syndrome (AIDS): Due to Human
Immunodeficiency Virus (HIV)
Destroys helper T cells
Immune System Problems
Cancer
Cytotoxic T cells can recognize
and kill some cancer cells
Leukemia disables the
immune system
Other cancers are too fast
By the time cells appear
abnormal, the cancer has
grown and spread
Thought Question:
What can you do to fortify your immune system?
Things To Do After Lecture 13…
Reading and Preparation:
1.
Re-read today’s lecture, highlight all vocabulary you do not
understand, and look up terms.
2.
Ch. 43 Self-Quiz: #1 – 7 (correct answers in back of book)
3.
Read chapter 43, focus on material covered in lecture (terms,
concepts, and figures!)
4.
Skim next lecture.
“HOMEWORK” (NOT COLLECTED – but things to think about for studying):
1. Compare and contrast: T cells and B cells, the humoral response
compared to the cell-mediated immune response.
2. Explain the function and parts of the human innate immune system.
3. Describe the problem with each of the following: allergies, autoimmune
disorders, immune deficiency syndromes.
4. Why are people concerned about over-use or misuse of antibiotics?