Dr Lindsay Marshall
MB451, ext. 4017 e-mail: l.marshall@aston.ac.uk

Lecture timetable
All lectures Tuesday morning, 9am, Sumpner lecture theatre
Week Date Lecture topic
14 Jan 27 th Subject overview
15
16
17
Feb 3 rd The innate immune system
Feb 10 th B cells and antibodies
Feb 17 th Antigen presentation
18 Feb 24 th T cells and cytokines
19
20
21
March 3 rd Anatomy of the lymphoid organs
March 10 th Lymphocyte recirculation
March 17 th Immunopathology

Some useful text books:
Sompayrac. How the immune system works, 4 th ed., 2012.
Library class mark: 616.079 SOM
35 copies (+ 16 copies of 3 rd ed.)
Parham. The Immune System, 3 rd ed., 2009; 4 th 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

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.

 Log on to Blackboard as usual and select BY1IM1
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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

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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 readingbut 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.

 Immunity: from immunis ( Greek) meaning ‘exempt’
 Immunity provides exemption (protection) from infectious disease

(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…
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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
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Feel free to ask questionsthere’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 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

 1. Physical barriers
 2. Innate immune response
 3. Adaptive immune response

 First line of defence
 Stop anything (pathogens) getting in
 Skin
 Mucous membranes (respiratory tract, GI tract)

 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)
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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

 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 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?
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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

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What happens when the macrophages find an invader?
Phagocytosis

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What happens when the macrophages find an invader?
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

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What happens when the macrophages find an invader?
Phagocytosis
Call for back-up
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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)

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What happens when the macrophages find an invader?
Phagocytosis
Call for back-up
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Increased blood flow to area (redness)
Increased tissue fluid leakage (swelling)
Increased nerve activity (pain)
Cytokine production
 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 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

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The third level of defence
Edward Jenner - small pox vaccine
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1790s - small pox major health problem
Milkmaids often got cowpox
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Cowpox symptoms are like small pox
Milkmaids didn’t get small pox
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So Edward Jenner injected cow pox pus into a boy o (vacca - vaccine)
Then Jenner infected the boy with small pox…
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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 are the molecules of adaptive immunity
- Identified as proteins in the blood of immune people
Antigen binding regions (Fab)
Light chain
IgG - prototypic antibody molecule
IgG is the most common antibody
In people, there are also IgM, IgA,
IgE and IgD
All have specialised functions and distributions
Heavy chain
Effector function region (Fc)

 Antibodies are multi-functional molecules:
 Agglutinate invaders
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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
Hungry macrophage
FcR
Antibody
Bacterium

Where do antibodies come from?
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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
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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 , T
C cells search and destroy infected cells
 Helper , T
H 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

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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
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For many aspects of adaptive immunity, a two signal system is adopted
For T cells, these 2 signals are:
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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
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Both signals are the keys for activation
Either key alone - no joy
Both keys together - ACTIVATION

 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:
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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
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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

 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’
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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
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3 lines of defence- physical barriers, innate immunity, adaptive 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