Basic Clinical Immunology

Overview

Dr Joanne Pennock
School of Translational Medicine
Joanne.pennock@manchester.ac.uk

Recommended reading:
Essential of Clinical Immunology
Chapel, Haeney, Misbah & Snowdon (Authors)
5th Ed 2006, Blackwell Scientific Publications

Janeways Immunobiology
Kenneth Murphy
Garland Science 2011

Immunology timeline:
Germ
Theory
1800s
Ancient
Civilisations
430BC
8th Century

1900s
Vaccination

Germ
Theory
1800s
Vaccination

Sprang from the study of bacteria and

smallpox
Bacteria first observed.
Idea of contagion gradually evolved
1718 Lady Mary Wortley Montagu
innoculated her children against smallpox
(Constantinople)
1798 Edward Jenner successfully
demonstrated innoculation against smallpox
1884 Kochs postulates definition of a
contagious disease

1900s

Discovery of mouse MHC

Advances in microscopy
Louis Pasteur developed rabies
and anthrax vaccines first
example of attenuating bacteria
to induce immunity
Antigen:antibody theory
established
Hypersensitivity and allergy

Clonal selection theory

HLA
Antibody structure
Thymus
T & B cells
Dendritic cells
HIV
cytokines
Immune response to intra/extracellular
pathogens (Th1 vs Th2)
Regulatory T cells
Danger model
pattern recognition (TLR)

37 interleukins
Th17 cells
Native and inducible T reg cells
Human papillomavirus vaccine
Regulatory macrophages and DCs.

Barriers to infection

The skin:
3 layers protect the body from infection.

Collagen
between
layers

Epidermolysis bullosa
Caused by a defect in collagen formation

Atopic dermatitis
Often associated with mutations in Filaggrin
Secondary infections cause flare ups due to
breach of skin barrier

The lungs:

Healthy lung
tissue

Dr Keith Wheeler/ Science photo library

The lungs:
Cystic fibrosis

Normal

CF

Excessive
A severe disease
mucus causing
impairs
excessive
bacterial
mucus production in
clearance
the lungs and
resulting
pancreatic
in
ducts.
congestion
Life expectancy
and severe
30 years.
infection.

The gastrointestinal tract:

Saliva, mucus, antibodies
and constant surveillance
protect the body from
pathogens

The stomach:
Protection of gastric
epithelium by mucus
and secretion of
neutralising
bicarbonate

Gastric/duodenal ulcers
caused by:
NSAIDS (20%)
H pylori (80%)

The colon:

In the GI tract, a single layer of cells separates our

immune system from the outside world

The colon:

A protective layer
of mucus is
essential for
health

Johansson M E V et al. PNAS 2008;105:15064-15069

2008 by National Academy of Sciences

The firm mucus layer is devoid of bacteria.

The colon:

Mucus is secreted
by goblet cells

Johansson M E V et al. PNAS 2008;105:15064-15069

Muc5ac: a critical component

mediating the rejection of enteric
nematodes.
J Exp Med. 2011 May 9;208(5):893-900. Epub 2011 Apr 18.
Hasnain SZ, Evans CM, Roy M, Gallagher AL, Kindrachuk KN, Barron L,
Dickey BF, Wilson MS, Wynn TA, Grencis RK, Thornton DJ.

Wellcome Trust Centre for Cell Matrix Research, Faculty of Life

Sciences, The University of Manchester, Manchester M13 9PT,
England, UK.

The colon:

Upper layer of
mucus is
colonised by
bacteria

Johansson M E V et al. PNAS 2008;105:15064-15069

The colon:
Gut flora provides additional barrier
Essential for health and development
Different composition between individuals
Thought to out compete potential pathogens
Mutaflor
Ulcerative Colitis
Gastroenteritis
IBS
Pouchitis
Crohns disease
Each capsule 2.5-25x10(9) viable cells

The colon:
Gut flora is actively involved in the
homeostasis and maintenance of health in the
gut

E. Coli is a commenal bacterium

Species is highly diverse
Acquisition of virulence genes can
lead to pathogenicity

World's largest E. coli outbreak

kills 14 in Germany (May 2011)
3,500 infected
855 developed rare haemolytic uraemic syndrome
53 died
Enteroaggregative
strain of E. coli had
acquired Shiga toxin
which caused HUS

The gastrointestinal tract:

IgA is a GI specific
antibody
responsible for
primary defence
against bacteria

The gastrointestinal tract: IgA

http://www.calier.es/

1 in 700 Europeans are IgA deficient

The most common immunodeficiency
Many have no symptoms. BUT

Rolepatients
of IgA insuffer
the defense
against of:
IgA deficient
more episodes
IgA deficiency
often
presents
with
IgG2 mice
deficiency
respiratory
infections:
IgA
deficient
bronchitis
Increases
susceptibility
to
certain bacteria
exhibited
increased
susceptibility
to
pneumonia
intranasal
infection with Mycobacterium
chronic
diarrhea
conjunctivitis bovis BCG
sinusitis
Vaccine
Volume 23, Issue 20, 8 April 2005, Pages 2565-2572

The bladder:
No mucosal layer
Umbrella cells provide barrier function alongside 5
to 6 cell-deep epithelium

Discovery of blood & lymph systems

Leonardo da vinci 1510

Circulatory system

Lymphatic system

Lymph and blood systems are separate

Antigen: substance which provokes an immune response
May have several antigenic determinants (epitopes)
which can be recognised by antibody
Therefore a single antigen may provoke many antibody molecules
Antibody: Soluble factor secreted by plasma cell in large quantities
Prevents antigen from causing damage (inflammation)
Cytokine: Protein secreted by cells of the immune system to
orchestrate the immune response (activate, suppress,
attract)

2006 Encyclopedia Britannica

But lymph and blood interact at lymph nodes

Lymph nodes are the defence hub during infection

e.g. Head and neck lymph nodes during flu

http://effleurageholistictherapies.co.uk

Swelling of lymph nodes during infection is due

to cellular proliferation, and antibody production.

Any immune response is very much an

orchestrated event involving early nonspecific defence, quickly followed by nonspecific attack, then antigen-specific, sitespecific defence.

Any immune response is very much an

orchestrated event involving early nonspecific defence, quickly followed by nonspecific attack, then antigen-specific, sitespecific defence.

Any immune response is very much an

orchestrated event involving early nonspecific defence, quickly followed by nonspecific attack, then antigen-specific, sitespecific defence.

Any immune response is very much an

orchestrated event involving early nonspecific attack, quickly followed by antigenspecific, site-specific defence.