Transcript Introductory Immunology

Introductory Immunology
Dr Lindsay Marshall
MB451, ext. 4017
e-mail: [email protected]
Lecture timetable
All lectures Tuesday morning, 9am, Sumpner lecture theatre
Week
Date
Lecture topic
14
Jan 27th
Subject overview
15
Feb 3rd
The innate immune system
16
Feb 10th
B cells and antibodies
17
Feb 17th
Antigen presentation
18
Feb 24th
T cells and cytokines
19
March 3rd
20
March 10th
Lymphocyte recirculation
21
March 17th
Immunopathology
Anatomy of the lymphoid organs
Some useful text books:
Sompayrac. How the immune system works, 4th ed., 2012.
Library class mark: 616.079 SOM
35 copies (+ 16 copies of 3rd ed.)
Parham. The Immune System, 3rd ed., 2009; 4th ed. 2014
Library class mark: 616.097 PAR
29 copies in library
Todd & Spickett ‘Immunology’, 2010.
Library class mark: 576.80973 TOD
18 copies in library
Course assessment –BY1IM1
Good news…
 No coursework
Bad news…
 Continuous assessment: 5 multi-choice questions EVERY WEEK
Questions are available via Blackboard for 24 hours after the lectures (until 10 am
Wednesday morning)
These make up 40% of the module (you can PASS this module just by doing well
on the continuous assessment…)
MORE good news…
 Tests start next week!
 A (very small) bit of bad news…
 Final exam in May-June.
 Closed book, 30 MCQ in 1 hour.
Quizzes on Blackboard
 Log on to Blackboard as usual and select BY1IM1
 Click on the “Quizzes” button
 You can have up to 10 attempts at each quiz in the
24 hours that it is available
 Only your BEST score will be counted
Aston Replay
 All these lectures will be recorded via Panopto and available via
Aston Replay
 So you can listen again as often as you like
 You might still want to print out lecture slides before the lecture and
add notes to them during the lecture, then you can recap areas that
you didn’t understand first time round by listening to the recordings.
 You SHOULD be able to pass the exam without loads of extra
reading- but the only way you’ll get top marks (in anything) is if you
are reading the text books in addition to making good lecture notes.
Immunology
 Immunity: from immunis (Greek) meaning ‘exempt’
 Immunity provides exemption (protection) from
infectious disease
Why’s it so difficult?
(it isn’t really!)
 Details…
 Immunology is full of details and terminology and sometimes these get in the
way of understanding
 The purpose of this course is to…
 1) introduce you to all of the cells, mediators and jargon associated with immunology
and
 2) to give you a basic understanding of how your immune system works so that we
can build on this in future courses
 Feel free to ask questions- there’s no such thing as a “silly” question, if you
have a question, chances are someone else is wondering the same thing!
 You can… ask me during the lecture
ask me after the lecture, l don’t mind
e-mail me any time
use the discussion board on BY1IM1, that way you can answer
each other’s questions
The immune system and the Premier league
The immune response is a network of events, like a football match
In football, watching one player doesn’t give you the full picture of
the match
For immunology, learning about one cell type doesn’t let you
understand the entire immune response
This lecture is the overview or a quick tour of the whole immune
system
Future lectures will look at each player in more detail – at the end
of this module, we can put all the details together and we’ll
understand exactly how and where the immune response works
The immune system has 3 components
 1. Physical barriers
 2. Innate immune response
 3. Adaptive immune response
1. Physical barriers
 First line of defence
 Stop anything (pathogens) getting in
 Skin
 Mucous membranes (respiratory tract, GI tract)
2. Innate immune response
 Second line of defence after physical barriers
 Innate means ‘existing at the time of birth’
The case of the infected splinter
(or how your innate immune system works)
 You step on a large splinter
 This splinter is covered in bacteria (possibly pathogenic), which
have now been given a free pass through the physical barriers (i.e.
straight past the first line of defence) into the body
 In a couple of hours you can see where the splinter went in – your
skin is red and swollen and it hurts!
 The redness, the swelling and the pain are all good - these are the
signs of inflammation that show that your innate immune response
(second line of defence) is working
Macrophages to the rescue
 Cells aren’t fixed, they can move around within your body, the
macrophages are the first cell type to defend against attack
Macro means BIG
Phage means EAT,
so the macrophages are big,
hungry cells that will devour the
bacteria from the splinter in a
process called “phagocytosis”
(cell-eating)
Macrophages eat anything
 Macrophages eat invaders
 Macrophages eat rubbish (cell debris)
 Macrophages eat dead cells
 Macrophages even eat iron filings…
Where do macrophages come from?
 Haematopoiesis occurs in fetal liver and then the bone marrow
B lymphocyte
T lymphocyte
Natural killer (NK) cell
Bi-potential
cell
Self-renewing
stem cell
Macrophage
Neutrophil
Eosinophil
Mast cell
Megakaryocyte
Red blood cell (erythrocyte)
What do macrophages get up to?
 Monocytes – “baby” macrophages
 Two billion in circulation
 Remain in the blood for about 3 days
 Then they travel to the capillaries
 They leave the blood, get into the tissues turn into macrophages and
hang out, eating rubbish and watching out for bacterial invaders
 Remember- monocytes in blood, macrophages in tissue
What happens when the macrophages find an
invader?
1.
Phagocytosis
What happens when the macrophages find an
invader?
1.
2.
Phagocytosis
Call for back-up
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Increased blood flow to area (redness)
Increased tissue fluid leakage (swelling)
Increased nerve activity (pain)
Inflammation
What happens when the macrophages find an
invader?
1.
2.
Phagocytosis
Call for back-up
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3.
Increased blood flow to area (redness)
Increased tissue fluid leakage (swelling)
Increased nerve activity (pain)
Produce alarm signals (cytokines)
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Alert other macrophages to come and help
Alert other cells to come and help (neutrophils)
What happens when the macrophages find an
invader?
1.
2.
Phagocytosis
Call for back-up
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3.
Increased blood flow to area (redness)
Increased tissue fluid leakage (swelling)
Increased nerve activity (pain)
Cytokine production
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Alerts other macrophages to come and help
Alerts other cells to come and help (neutrophils)
All this adds up to…
THE ACUTE INFLAMMATORY RESPONSE
(This explains the redness, swelling and pain that
we felt around that splinter)
Macrophages are really useful…
 Macrophages act as lookouts
 They are the first to encounter the enemy
 They send out signals to recruit more defenders
 They hold off the invaders until back-up arrives
 This battle is usually over in a few days
 Innate immunity acts to LIMIT infection
The adaptive immune system
 The third level of defence
 Edward Jenner - small pox vaccine
 1790s - small pox major health problem
 Milkmaids often got cowpox
 Cowpox symptoms are like small pox
 Milkmaids didn’t get small pox
 So Edward Jenner injected cow pox pus into a boy
o (vacca - vaccine)
 Then Jenner infected the boy with small pox…
 The boy didn’t get small pox!
 His adaptive immune response protected him
 But he was only protected against the pox virus - adaptive immunity is SPECIFIC to
the invader
Antibodies
Antibodies are the molecules of adaptive immunity
- Identified as proteins in the blood of immune people
Antigen binding regions (Fab)
IgG - prototypic antibody molecule
IgG is the most common antibody
Light chain
In people, there are also IgM, IgA,
IgE and IgD
All have specialised functions and
distributions
Heavy chain
Effector function region (Fc)
What do antibodies do?
 Antibodies are multi-functional molecules:
 Agglutinate invaders
 Precipitate invaders
 Neutralise invaders
 Eliminate infected cells
 Opsonise invaders (tagged for destruction)
 In bacterial invasion- antibody Fab regions bind to the invaders and
antibody Fc regions bind macrophages - antibodies act as bridges
Antibody
Y
Hungry
macrophage
FcR
Bacterium
Where do antibodies come from?
 B lymphocytes (or B cells)
 Made in the bone marrow
 (haematopoiesis)
 Educated in the bone marrow
 (tolerance or self-recognition)
 Set free to find their antigen and once they have found it, they
will be activated (clonal selection), they’ll differentiate into
plasma cells and concentrate on making soluble antibodies
 Remember: one plasma cell makes one specificity
of antibody
The other lymphocytes (T cells)
 Look like B cells
 Have cell surface receptors (TCR) that look like antibodies
 TCR production is similar to antibody production (modular
design)
 T cells also undergo clonal selection
 TCR binds specific antigen
 T cell selected as special
 Proliferation: builds up a clone of identical T cells
 Slow, specific response
3 kinds of T cell (for now):
 Killer, TC cells
search and destroy infected cells
 Helper, TH cells
produce signals to instigate and maintain an
appropriate adaptive immune response
 Regulatory, Treg cells
put the brakes on once the danger is past
prevent self-reactivity
Antigen presentation to T cells
 T cells need help to recognise antigens
 T cells cannot “see” native, soluble, intact proteins
 Special proteins (MHC) present antigens to T cells
(Major histocompatibility complex)
 Two types of MHC: Class I and Class II
 Class I MHC – expressed on every cell
o Only seen by Killer T cells
o Tell the Killer T cells what’s going on inside the cell
 Class II MHC – expressed by specialised cells – the antigen presenting
cells (APC)
o Only seen by the Helper T cells

Activation of adaptive immunity
 B cells and T cells need to regulated, so they must be activated before they
can function
 For many aspects of adaptive immunity, a two signal system is adopted
 For T cells, these 2 signals are:
 1. antigen-specific: T cell recognises antigen presented in MHC class II on APC
 2. non-specific: protein on APC binds receptor on T cell
 Like opening a safe deposit box with two keys
 Both signals are the keys for activation
 Either key alone - no joy
 Both keys together - ACTIVATION
Secondary lymphoid organs
 For adaptive immunity to be activated, the T cell specific for the
invader needs to see the APC that has previously encountered the
same invader… unlikely over the whole body area
 Secondary lymphoid organs make these encounters more likely
The lymphatic system
 Mammals have two plumbing systems:
 Cardiovascular system
o pressurised
o pumps blood round the body
 Lymphatic system
o not pressurised
o drains tissue fluid that leaks out of capillaries
 Lymph collects in lymphatic vessels and is transported back to the blood,
via the lymph nodes
 Lymph collects proteins, cells etc from the tissue on its route
The lymphatic system
 Invaders (bacteria, viruses) get carried to
lymph nodes in the lymph
 APC travel through lymph nodes
 T cells and B cells circulate via lymph
nodes
 Lymph nodes are the place to be!
 Increases the probability that the
lymphocyte will encounter antigen/APC
and be activated
Immunological memory
 B cells and T cells are activated, proliferate, get rid of the
invaders and then most will die

This stops our system being filled up with old T cells and B cells
once the infection is cleared
 BUT… some of these ‘experienced’ T cells and B cells will hang around
in case we are infected a second time
 Memory cells are key to adaptive immunity
o They are easier to activate than ‘naïve’ cells
o There are more of them than the naïve cells
o They provide more effective protection to subsequent infections
Tolerance to ‘self’
 Adaptive immunity is RANDOM
 BCR (antibodies) and TCR are randomly generated by modular
design
 So there is a chance that the BCR and TCR might NOT
recognise an invader
 This can become problematic if the BCR/TCR do recognise
host or self - autoimmune diseases may result
 This risk is minimised because B cells and T cells are ‘taught’ to
tolerate self
 Not yet fully understood how this happens
 But autoimmune diseases are pretty rare
Why do we need both innate and adaptive
immune systems?
 Innate - fast, effective but not specific
 Adaptive - slower but tailored to fit
 Innate immune system informs the adaptive immune
system
 Innate immunity integrates the response  It tells either B cells or T cells to react depending on the invader and
where they should go to find the invader
Today’s lecture in a nutshell
 3 lines of defence- physical barriers, innate immunity, adaptive
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immunity
Macrophages are the cells of innate immunity
T and B cells are the cells of adaptive immunity
Antibodies, made by B cells, are the molecules of adaptive
immunity
T cells need the help of MHC to “see” antigen
Cell encounters occur in specialised lymphoid tissue
Lymph percolates through the tissues, collecting cells and antigens
Adaptive immunity has specific memory to protect us against
subsequent infections
Mistakes can be made in immune responses- these are rare but
devastating