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Understanding Cancer and Related Topics

Understanding The Immune System

Developed by:
Lydia Schindler
Donna Kerrigan, M.S.
Jeanne Kelly
Brian Hollen
Illustrates the immune system, a complex
network of specialized cells and organs that
distinguishes between self and foreign
molecules inside the body. Explains that a
malfunctioning immune system can cause
allergies or arthritis and can fail to stop the
growth of cancer cells.

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The Immune System
Bacteria Parasite in red blood cell

SARS virus Fungus

R
Markers of Self

Epithelial Muscle cell


cell

Leukocyte

Nerve
cell

Class I MHC self-marker protein

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Markers of Non-Self
Bacteria SARS virus

Antigen Epitope

Antibody

Non-self nerve cell Non-self leukocyte

Antigen Epitope
Class I MHC protein

Antibody
R
Markers of Self:
Major Histocompatibility Complex
Antigenic Antigenic Antigenic
peptide peptide peptide
Viral
infection
MHC MHC MHC
Class I Class I Class II

Antigen-presenting cell
Infected cell uses MHC Class I or II

Cell
membrane

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Organs of the Immune System

Tonsils and adenoids


Lymph nodes
Lymphatic vessels

Thymus
Lymph nodes

Spleen

Peyer’s patches
Appendix
Lymph nodes
Bone marrow Lymphatic vessels

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Lymphatic System

Lymph node Lymphatic vessel

R
Lymph Node

Incoming lymphatic vessel

Germinal
center

Follicle
Paracortex

Cortex
Medulla

Outgoing lymphatic vessel


Vein
Artery
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Cells of the Immune System
Bone graft
Macrophage
Mast cell

Eosinophil
Marrow Erythrocytes
Basophil

Monocyte Megakaryocyte
Bone
Hematopoietic
stem cell

Multipotential
stem cell Myeloid
progenitor Neutrophil
cell
Platelets

Lymphoid progenitor cell

T lymphocyte Dendritic cell

B lymphocyte R

Natural killer cell


B Cells

Antigen-specific Class II MHC and


B cell receptor processed antigen
are displayed

Antigen

B cell Antibodies

Lymphokines Plasma cell

Antigen-presenting Activated
bacteria helper T cell
R
Antibody
Heavy chain

Light chain

Antigen-binding
region

Constant region

Assembled antibody molecule R


Immunoglobulins

IgG, IgD, IgE, and IgA

IgA

IgM
Antibody Genes
V

V
Heavy chain

V Light chain

D V
D D Antigen-
J binding region

J Constant
J region
J C
J
Rearranged Assembled
gene antibody
components molecule
C encoding a
heavy chain
Gene components
scattered through R

one chromosome
T Cells
Resting helper T cell Resting cytotoxic T cell

Activated helper T cell Activated killer cell

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Cytokines

Lymphokines Monokines

Mature helper T cell Macrophage

R
Killer Cells: Cytotoxic Ts and NKs

Killer cell Target cell

Target-oriented
granules
Surface contact

R
Phagocytes and Their Relatives

Monocyte

Eosinophil

Mast cell

Macrophage Dendritic cell

Neutrophil

Basophil

R
Phagocytes in the Body
Brain:
microglial cells

Lung:
alveolar
macrophages
Liver: Kupffer
cells Spleen:
macrophages
Kidney:
mesangial Blood:
phagocytes monocytes
Lymph node:
resident and
Precursors in bone
recirculating
marrow
macrophages

Joint:
synovial A cells R
Complement

C2 C3 C3a C5a C7

C1
C6 C8
C5b
IgG

C5b
C4 Enzyme C3b C5
Antigen
C9

R
Mounting an Immune Response

Lymphokines Complement
T cell
Antibodies Macrophage
B cell

Killer cell
Virus

R
Antigen Receptors

B cell Killer cell Helper T cell

Antigen-
specific T cell T cell
receptor receptor receptor
CD8 CD4
Antigen protein Antigenic protein Antigenic
peptide peptide
Cell Cell Cell
membrane MHC membrane MHC membrane MHC
Class I Class I Class II

Antigen-presenting cell Infected cell Antigen-presenting cell

R
Activation of B Cells to Make Antibody

Circulating antibody

Antigen

Antigen-specific Class II MHC Antigen-presenting cell


B cell receptor and
processed
Antigen is antigen are
Antigen Class II MHC processed displayed

B cell Lymphokines Antibodies

Antigen- Activated
presenting cell helper T cell Plasma cell R
Activation of T Cells: Helper
Antigen is Processed antigen
processed and Class II MHC
Antigen are displayed

Macrophage

Class II MHC Helper T cell receptor


recognizes processed
Monokines antigen plus Class II
MHC
Antigen-presenting cell

Resting helper T cell

Lymphokines

MHC Class II
Activated helper T cell
Antigenic peptide
T cell receptor

CD4 protein

Helper T cell
Activation of T Cells: Cytotoxic
Antigen is Processed antigen
processed and Class II MHC
Antigen are displayed

Macrophage

Class II MHC Resting helper T cell


Monokines receptor recognizes
processed antigen
Resting helper T cell plus Class II MHC

Lymphokines
Activated helper T cell

Class I MHC
Processed antigen and Class I MHC
Infected cell Cytotoxic T cell
becomes activated
Antigen (virus)
MHC Class I CD8 protein
Cytotoxic T cell

Activated
Infected cell

cytotoxic T cell

Processed antigen
(viral protein)

Cell Cytotoxic T cell


dies R

Antigenic peptide T cell receptor


Regulatory T Cells
T cells compete T cells compete for
for same antigen cytokine signals

Cytotoxic
T cell

Mature
dendritic
cell

Regulatory
T cells
Regulatory
T cell

Proliferation

R
Immunity: Active and Passive
Active immunity Passive immunity

Naturally acquired Naturally acquired

Artificially acquired Artificially acquired


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Disorders of the Immune System: Allergy

Interleukins Allergen IgE

Mediators
Symptoms
B cell Plasma cell Mast cell
Mature
helper
T cell

R
Disorders of the Immune System:
Autoimmune Disease

Pancreas

Cytotoxic T cell

Beta cell

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Disorders of the Immune System:
Immune Complex Disease
Glomerular basement
membrane of kidney

Large complex

Endothelial cell

Small complex R
Disorders of the Immune System: AIDS
Virus protein

Virus RNA

Virus DNA

Cell DNA

New virus
particle
R
Human Tissue Typing for Transplants

HLA
Chromosome 6

D B C A

Leukocyte

MHC protein
R
“Privileged” Immunity

Chorionic villi

R
Immunity and Cancer
Antibody

Macrophage

Cancer cell
Helper T cell

Natural
killer cell Cytotoxic T cell

R
Immunotherapy
Radioisotope Herceptin
Growth Herceptin
Antibody factor blocks
receptor

Antigen

Breast
cancer cell
Lymphoma
cell Lymphoma cell
destroyed

Growth slows
R
Dendritic Cells That Attack Cancer
Dendritic cell
Complex binds matures and is
to dendritic cell infused back into
precursor patient

Tumor antigen

T cell
Tumor
antigen is
linked to a Complex is
cytokine taken in by
dendritic cell
precursor

Dendritic cell
displays tumor
antigen and
activates T cells

Cancer cell

T cells attack cancer cell R


The Immune System
and the Nervous System
Brain

Neuroendocrine Thymus Immunotransmitters


and autonomic (feedback, regulation
pathways and modulation)

Bone Thymosins
marrow

T cell
Lymphokines
Monokines
Macrophage
B cell R
Hybridoma Technology
Antigen

Cells fuse
to make
hybridomas Cancerous
plasma cells

Antibody-producing
plasma cells Clones are tested for
desired antibody

Hybridoma cells
grow in culture

Individual hybridoma Desired


cells are cloned clones are
cultured
and frozen
Hybridomas are
kept alive in mouse

Monoclonal antibodies R

are purified
Genetic Engineering
A plasmid (ring of DNA) is
isolated from a bacterium

An enzyme cuts the


DNA at specific sites

A gene for protein, taken


from another cell, is cut The recombinant
with the same enzyme plasmid is
inserted back into The new gene
the bacterium directs the
The gene is inserted into the bacterium to
plasmid, where it fits exactly. make a new
This is recombinant DNA protein
product such
as interferon

When the bacterium


divides and replicates,
it copies itself and the
recombinant DNA
R
The SCID-hu Mouse

Immature human
immune tissue

Immature human
immune cells

Mouse kidneys

Immuno-incompetent SCID mouse

R
We would like to hear from you . . .
If you have questions about this tutorial’s content, suggestions for new topics, or
other feedback on the Web site, please send an e-mail to kerrigad@mail.nih.gov.
If you have questions about this tutorial’s artwork or want permission to use it,
please send an e-mail to beankelly@verizon.net.

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