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IM1003 Medical Immunology Introduction to
immunological disease principles Prof. L.
Ziegler-Heitbrock
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The complement system
C1qrs
C3
C4C2
antibody
C3a
C3b
C56789
bacteria
C5b678
C5a
PolyC9
chemotaxis
Membrane attack complex
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MBL mannose binding lectin
Ante-antibody
Hoffman et al. (1999) Science 2841313-8
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granulocytes
macrophages
Phagocytosis and intracellular killing
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Innate Immune Response
Invasion of the same Microbe
Invasion of Microbe
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2 systems of immune defence
Adaptive (acquired during life) Flexible
repertoire Recognises subtle differences Memory
Soluble mediators (antibodies) Cells (B cells,
T cells)
Innate (present from the beginning) Fixed
repertoire Recognises rough differences Solubl
e mediators (complement, MBL) Cells (granulocytes
, macrophages)
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Effector Cells of the Adaptive Immune System
B cell receptor
Proteins Sugars Lipids Anything
T cell receptor
Proteins
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Fab
Fab
Fc
Antibody Immunoglobulin (Ig)
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1 B cell makes 1 Antibody
During an immune response many different B cells
making many different antibodies are activated
the response is polyclonal.
For diagnostic and therapeutic purposes a
monoclonal antibody may be advantageous.
How can monoclonal antibodies be generated?
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T cell receptor (TCR) recognises foreign peptide
together with an MHC class I or II molecule (also
termed HLA molecule)
MHC molecule
T cell receptor
Foreign peptide
Major Histocompatibility Complex, Human Leukocyte
Antigen
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Adaptive Immune Response
More and better B and T cells
Invasion of the same Microbe
Invasion of Microbe
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Immune Defence Against Infection
Extracellular bacteria
anti-bacterial antibody
C
lysis, phagocytosis
Intracellular bacteria
CD4 helper cell
macrophage is activated to kill mycobacteria
IFNg
Viruses
CD8 killer cell
infected cell is killed
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What can go wrong with the immune response ?

• a) Hyper reactivity
• Allergy
• Autoimmunity
• Immunodeficiency
• Malignancy

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IgE
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type I
antigen
Type I allergy house dust mite
IgE
Fc? receptor
mast cell degranulation
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type II
Self cell surface antigen
IgG
target cell
K cell
Anti-erythrocyte antibodies leading to hemolytic
anemia
cytotoxic action
IgG
target cell
complement mediated lysis
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type III
Lupus erythematodis
immune complex deposition
tissue
C3a C5a
basement membrane
polymorphs
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type IV
CD4 T helper cell
activated macrophage or dendritic cell
IFNg
Type IV (delayed) allergy latex
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Antibody against TSH receptor
TSH
TSH receptor
Thyroid epithelial cell
Thyroid hormones
Thyroid hormones
Excessive stimulation of thyroid epithelial cells
by antibodies against TSH receptors (Graves
disease)
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Nerve ending
Acetyl choline (Ach)
Antibody against Ach receptor
Ach receptor
Muscle
Contraction
No contraction
Inhibition of neuromuscular transmission by
antibodies against the acetylcholine receptor
(myasthenia gravis)
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type I
type II
IgG
target cell
K cell
Self cell surface antigen
cytotoxic action
Fc? receptor
IgG
target cell
Mast cell degranulation
complement mediated lysis
type III
type IV
immune complex deposition
activated macrophage or dendritic cell
Helper T cell
tissue
C3a C5a
IFNg
basement membrane
polymorphs
type II
Stimulating antibody
Blocking antibody
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What is the basis of tolerance ?
Autoreactive
Deletion
B
Receptor down regulation
B
Blockade of signalling
B
IL-10
Suppression by Cytokines
B
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Usually tolerance is intact
CH2OH
CH2OH
OH
OH
??????
?????? ?? ??????
NHCOCH3
CH2
OH
H
OH
OH
CH2OH
CH2OH
CH2OH
OH
OH
OH
A
??????
A
NHCOCH3
NHCOCH3
CH3
OH
A
Anti-B
OH
OH
CH2OH
CH2OH
CH2OH
A
OH
OH
OH
??????
NHCOCH3
OH
CH3
OH
B
OH
OH
B
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If tolerance breaks down antibodies against self
are produced. (TSHR), (AChR) Autoimmune
disease
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Immunodeficiencies
Innate system
Adaptive system
Inborn MBL deficiency (airway infection) NADPH-ox
idase deficiency in phagocytes (chronic
granulomatous disease) (bacterial
abscesses) Acquired Chemotherapy induced
agranulocytosis (severe bacterial infection,
sepsis)
Inborn Selective IgA deficiency (1/600) (airway
infection) X-linked agammaglobulinemia (XLA) (air
way infection, enteroviruses) Acquired AIDS CD4
helper cell depletion (Pneumocystis, CMV)
Almost every element of the immune system can be
defective, some deficiencies are amenable to
gene therapy.
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Malignancies of the Immune System Termed Leukemia
or Lymphoma Granulocytes Myeloid
Leukemia T Lymphocytes T cell Leukemia B
Lymphocytes B cell Leukemia B Lymphocytes B
cell Lymphoma (Leukemia increased numbers of
white blood cells Lymphoma increased size of
lymph nodes) Monoclonal antibodies against the
normal leukocytes are used to classify the
leukemias and lymphomas.