IM1003: Medical Immunology
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IM1003: Medical Immunology Introduction to immunological disease principles Prof. L. Ziegler-Heitbrock. The complement system. C1qrs. C3. C4C2. antibody. C3a. C3b. C56789. bacteria. C5b678. C5a. PolyC9. chemotaxis. Membrane attack complex. MBL: mannose binding lectin.

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IM1003: Medical Immunology Introduction to immunological disease principles Prof. L. Ziegler-Heitbrock

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Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

IM1003: Medical Immunology

Introduction to immunological

disease principles

Prof. L. Ziegler-Heitbrock


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

The complement system

C1qrs

C3

C4C2

antibody

C3a

C3b

C56789

bacteria

C5b678

C5a

PolyC9

chemotaxis

Membrane

attack

complex


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

MBL: mannose binding lectin

Ante-antibody

Hoffman et al. (1999) Science 284:1313-8


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

granulocytes

macrophages

Phagocytosis and intracellular killing


Innate immune response

Innate Immune Response

Invasion

of the same

Microbe

Invasion

of Microbe


2 systems of immune defence

2 systems of immune defence

Innate

(present from the beginning)

Fixed repertoire

Recognises rough differences

Soluble mediators

(complement, MBL)

Cells

(granulocytes, macrophages)

Adaptive

(acquired during life)

Flexible repertoire

Recognises subtle differences

Memory

Soluble mediators

(antibodies)

Cells

(B cells, T cells)


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

B

T

Effector Cells of the Adaptive Immune System

B cell receptor

Proteins

Sugars

Lipids

Anything

T cell receptor

Proteins


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

Fab

Fab

Fc

Antibody

Immunoglobulin (Ig)


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

B

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?


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

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


Adaptive immune response

Adaptive Immune Response

More and better

B and T cells

Invasion

of the same

Microbe

Invasion

of Microbe


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

Immune Defence Against Infection

T

T

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


What can go wrong with the immune response

What can go wrong with the immune response ?

a)Hyper reactivity

Allergy

Autoimmunity

  • Immunodeficiency

  • Malignancy


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

IgE


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

type I

antigen

Type I allergy

house dust mite

IgE

Fc receptor

mast cell degranulation


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

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


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

type III

Lupus erythematodis

immune complex deposition

tissue

C3a

C5a

basement

membrane

polymorphs


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

type IV

CD4+ T helper cell

activated macrophage or dendritic cell

IFNg

Type IV (delayed) allergy

latex


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

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 (Grave’s disease)


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

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)


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

type I

type II

antigen

IgE

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

Helper T cell

activated macrophage or dendritic cell

tissue

C3a

C5a

IFNg

basement

membrane

polymorphs

type II

Stimulating

antibody

Blocking

antibody


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

What is the basis of tolerance ?

Autoreactive

Deletion

B

Receptor down

regulation

B

Blockade of

signalling

B

IL-10

Suppression by

Cytokines

B


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

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



OH

NHCOCH3

CH3

OH

B

OH

OH

B


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

If tolerance breaks down antibodies against self are produced.

(TSHR), (AChR) = Autoimmune disease


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

Immunodeficiencies

Innate system

Adaptive system

Inborn

MBL deficiency

(airway infection)

NADPH-oxidase 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)

(airway 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.


Im1003 medical immunology introduction to immunological disease principles prof l ziegler heitbrock

Malignancies of the Immune System

Termed Leukemia or Lymphoma

Granulocytes Myeloid Leukemia

T LymphocytesT cell Leukemia

B LymphocytesB cell Leukemia

B LymphocytesB 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.


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