Introduction to Immunology

Dr Andrew Williams

andrew.williams@ucl.ac.uk
Why do we need an immune system?
Part 1 - Immunology – an introduction

• Immunology – the study of the structure and function of the

immune system

• The role of the immune system is to provide protection

against infectious disease

• Provide immunity to re-infection – immune memory

• Maintain tissue homeostasis – avoid host damage

• Encompasses many disciplines

• Inflammation, allergy, autoimmunity, transplant science,

cancer biology, biochemistry, development, neuroscience
The immune system in health and disease
Infectious disease Rheumatoid arthritis
Neurology

Obesity

Inflammatory
The immune system bowel disease

Diabetes
Transplantation

Allergy
Types of pathogen

What sort of pathogens infect animals (humans)?

Multi-layered immune system

Skin
Mucosal layers

Humoral factors
Antimicrobials

Phagocytes
Innate immune cells

Antibodies
B cells
T cells
Barrier defence
Barrier defence
Site Mechanism
Respiratory tract Mucus and nasal secretions
Muco-ciliary clearance
Sneezing
Cough reflex
Gastrointestinal tract Acidic pH
Peristalsis
Vomiting
Commensal flora
Antimicrobial peptides
Glycocalyx
Digestive enzymes
Mucous coat
Urogenital tract Acidic pH
Mucus secretion
Antimicrobial peptides
Eye conjunctiva Alkalinity of tears
Eyelids and lashes
Cilia
Skin/exocrine glands Sweat
RNAse enzymes
Antimicrobial peptides
Stages of an immune response

Recognition of
Pathogens
(non-self)

Innate immune system

Immune system regulators

Effector function

Immune effector functions

Killing of pathogen
Killing of tumour
History of immunology – where did it begin?

Edward Jenner (1749-1823) Father of vaccination

Jenner, cowpox and the first vaccine
Jenner’s vaccine trial

Small pox scabs Phipps experimentally

collected from inoculated with
ill patient smallpox

Cowpox isolated from James Phipps inolulated

Sarah Nelmes (milkmaid) with cowpox NO SMALLPOX
(mild illness)
Vaccination provides immunity

Jenner first to empirically demonstrate

the induction of immunity

Vaccines protect against the disease

that you are being immunised against

Somehow, our immune system is able

to remember the vaccine

Provide protection at a later date

How does the immune system provide protection?

How is immunity generated?
Are soluble factors involved or is protection cell-based?
Passive immunisation and serum therapy

Father of serum therapy

and
Father of bacteriology

Both interested in the bacteria

that causes diphtheria

Causative agent of disease

(Koch) - Germ theory

Development of antitoxin
(von Behring)

Emil von Behring Robert Koch

(1854-1917) (1843-1910)
Generation of serum diphtheria anti-toxin

serum
(anti-toxin)
immunise
PROTECTED

Immunise infected

virulent
diphtheria
DISEASED
Toxin
avirulent strain

Passive immunisation
Humoral immunity and antibodies

Proposed the side-chain theory

Chemical interaction between toxin and side-chain

Interaction very specific - ANTIBODIES

More bound toxin, more antibodies – immunisation

Antibodies in serum provided protection

Paul Ehrlich
(1854-1915)
Cellular immunity and phagocytes

Cells could easily be observed

These cells were highly motile

Responded to injected particulates

Cells ate and removed particles – phagocytosis

Élie Metchnikoff Phagocytes important for host immunity

(1845-1916)
Cellular and humoral immunity

Cellular Immunity Humoral immunity

Directed by immune cells Soluble molecules

Non-specific (innate) Highly specific (antibodies)

Phagocytosis Neutralising

Intracellular Extracellular

Interaction

Fathers of immunology

Nobel Prize
(1908)

Metchnikoff Ehlrich
Anatomy of the immune system

Immune cells develop in

primary lymphoid tissues

Immune responses generated in

secondary lymphoid tissue

Other organs can house

tertiary lymphoid tissues
(infection/inflammation)
Haematopoiesis

White blood cells (leukocytes)

Develop in bone marrow

Thrombocytes
(platelets)

Granulocytes

Myeloid cells

Lymphocytes
Mucosal associated lymphoid tissue

MALT – mucosal associated lymphoid tissue

GALT – gut associated lymphoid tissue

NALT – nasal associated lymphoid tissue

BALT – bronchial associated lymphoid tissue

EALT – eye associated lymphoid tissue

CALT – conjunctiva associated lymphoid tissue

GENALT – (uro) genital associated lymphoid tissue

Gut associated lymphoid tissue

GC

Lymphoid follicle
Innate and adaptive immune cells

Innate Adaptive

Neutrophil T helper cell

(CD4+)
Eosinophil NK cell
Granulocytes Cytotoxic T cell
Basophil (CD8+)

Mast cell
B cell

Macrophage
Plasma cell
Myeloid
Monocyte
cells

Dendritic cell Lymphocytes

Innate versus adaptive immune systems
Innate Adaptive

Rapid response Delayed response

Non-specific response to Highly specific response to

conserved molecules antigen
Response fixed Response changes over time
(non adaptive) (adaptive)
No immune memory Immune memory

Structural, humoral and cell- Humoral and cell-mediated

mediated
Evolutionarily conserved Only found in higher vertebrates
Kinetics of an immune response
Self vs non-self

Tumour antigens

What other molecules does

the immune system
recognise?

Pathogen molecules

Allergens

Transplanted tissue

Toxins

Pollutants
How do we know we have an infection?
Fungi
TLR3
viral dsRNA Mannose
receptor Phagocytosis

Intracellular killing

PRRs ROS production

Activation
Cytokine release

TLR2
TLR4
Inflammation
PGN
LPS
PAMPs

Gram +ve bacteria

Gram -ve bacteria
Self versus non-self
Immunologists love cytokines!
Phagocytosis

Phagocytosis
(cell eating)
Inflammation is immune mediated

calor, dolor, rubor, tumor (heat, pain, redness and swelling)

Inflammation is immune mediated
Neutrophil effector functions

Cytokine release
Neutrophil granules – degranulation

https://www.youtube.com/watch?v=VT7knZ6_8rk
Neutrophil extracellular traps (NETs)

JCB vol. 198 no. 5 773-783

Innate and adaptive systems interact

Innate Immune system Adaptive immune system

Innate immunity leads to adaptive immunity

microbe

Antibody
invasion
Cytotoxicity

activation antigen
processing

antigen B cell
presentation
LYMPH NODE

T cell
B cells produce antibody
Antibody has several functions

Opsonisation Opsonisation
ADCC Phagocytosis
Complement
Neutralisation activation
Two types of T cell

Provides help

Activating signals

Enhances
Cytotoxic
Effector functions
Kills infected
cells

Kills tumour
cells
T helper cells

Link between adaptive and innate immunity T helper cells provide co-stimulation
to B cells
Cytotoxic T cells
Kinetic of an immune response

Protected from a previously encountered infection - immunity

Not protected from a new infection
Immune memory
Part II – Tolerance and transplantation

Syngeneic graft
Same person, genetically identical

Allogeneic graft
Same species, not genetically
identical

Xenogeneic graft
Different species, not genetically
identical
Tolerance – tissue rejection Self vs non-self

Leukocytes

T cells

Response
independent of
antibodies Successful Tissue
graft Rejection
Xenotransplant rejection – hyperacute and acute
Complement dependent cytotoxicity Antibody dependent cellular cytotoxicity

α1,3-Gal - Galα1-3Galβ1-4GlcNAc - α1,3-Galactosyltransferase

Porcine endothelial cells share α1,3-Gal with various microbes
Primates (humans) do not express α1,3-Gal
Antibody-dependent cellular cytotoxicity (ADCC)

Antibody-dependent
Complement-
cellular cytotoxicity
dependent
(ADCC)
cytotoxicty
(CDC)
Killing of transplanted
cells
Innate immune cell xenotransplant rejection

NK cells
1. Missing ‘self’’
2. NKG2D
3. ADCC
4. Cytokines

Macrophages
1. Galectin-3
2. T cell activation
3. SIRPα (lack of
CD47 inhibition)
Acute and chronic inflammation

Acute inflammation Chronic inflammation

Acute and chronic inflammation

Strong response Poor response

Summary

• Several layers of the immune system:

anatomic, chemical, innate and adaptive

• Innate immunity provides natural immunity

evolutionary conserved
no immune memory, rapid

• Adaptive immunity provides immune memory

acquired over time
T cells and B cells, slower to develop

• Anatomy of the immune system

systemic and mucosal lymphoid tissue

• Transplant rejection
recipient immune response to donor tissue
acute and chronic inflammation