Understanding The Immune System

IMMUNOLOGY

Prof. Nagwa Mohamed Amin Aref

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The Immune System

SARS virus

Parasite in red blood cell

Fungus

Bacteria

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Markers of Self

Muscle cell

Nervecell

Epithelialcell

Leukocyte

Class I MHC self-marker protein

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Markers of Non-Self

Non-self leukocyte

Antibody

Epitope Class I MHC protein

Epitope

Antibody

Antigen

Antigen

Bacteria

Non-self nerve cell

SARS virus

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Markers of Self:Major Histocompatibility Complex

Antigenic peptide

Antigen-presenting cell uses MHC Class I or II

Cell membrane

MHC Class II

Antigenic peptide

Viral infection

Infected cell

MHC Class I

Antigenic peptide

MHC Class I

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Organs of the Immune System

Tonsils and adenoids

Lymph nodes

Bone marrow

Appendix

Lymphatic vessels

Lymph nodes

Thymus

Peyer’s patches

Spleen

Lymphatic vessels

Lymph nodes

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Lymphatic System

Lymph node Lymphatic vessel

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Lymph Node

Germinal center

Vein

Cortex

Paracortex

Incoming lymphatic vessel

Outgoing lymphatic vessel

Artery

Medulla

Follicle

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Cells of the Immune System Bone graft

Multipotentialstem cell

Hematopoieticstem cell

Platelets

Macrophage

ErythrocytesEosinophil

Neutrophil

Megakaryocyte

Mast cell

Basophil

T lymphocyte

Natural killer cell

Dendritic cell

B lymphocyte

Lymphoid progenitor cell

Myeloid progenitor

cell

Monocyte

Marrow

Bone

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B Cells

Plasma cell

Class II MHC and processed antigen are displayed

Antigen-presenting bacteria

Antigen

Antigen-specific B cell receptor

AntibodiesB cell

Activated helper T cell

Lymphokines

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Antibody

Assembled antibody molecule

Heavy chain

Antigen-bindingregion

Constant region

Light chain

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Immunoglobulins

IgA

IgM

IgG, IgD, IgE, and IgA

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Antibody Genes

Assembled antibody molecule

VDJ

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Gene components scattered through one chromosome

Heavy chain

Antigen-binding region

Constant region

Light chain

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DD

JJJJ

C

Rearranged gene

components encoding a heavy chain

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T Cells

Activated killer cellActivated helper T cell

Resting cytotoxic T cellResting helper T cell

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Cytokines

Mature helper T cell

MonokinesLymphokines

Macrophage

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Killer Cells: Cytotoxic Ts and NKs

Killer cell

Target-oriented granules

Surface contact

Target cell

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Phagocytes and Their Relatives

Monocyte

Dendritic cell

Eosinophil

Neutrophil

Basophil

Mast cell

Macrophage

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Phagocytes in the Body

Brain: microglial cells

Joint:synovial A cells

Precursors in bone marrow

Lymph node: resident and recirculating

macrophages

Blood: monocytes

Kidney:mesangial

phagocytes

Spleen: macrophages

Liver: Kupffer cells

Lung:alveolar

macrophages

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Complement

C9Enzyme

C2

C5C3b

C3aC3

C4Antigen

IgG

C1C8

C7

C6

C5b

C5b

C5a

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Mounting an Immune Response

Complement

VirusKiller cell

B cell

Antibodies

T cell

Lymphokines

Macrophage

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Antigen Receptors

Killer cell

Infected cellAntigen-presenting cell Antigen-presenting cell

CD8 protein

Cell membrane MHC

Class IMHC Class I

Antigenic peptide

T cell receptor

CD4 protein

Cell membrane MHC

Class II

Antigenic peptide

T cell receptor

Cell membrane

Antigen

Antigen-specific receptor

Helper T cellB cell

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Activation of B Cells to Make Antibody

Antigen-presenting cell

Antigen

Circulating antibody

Antigen is processedClass II MHC

Antigen

Activated helper T cell

Class II MHC and processed antigen are displayed

Antibodies

Plasma cellAntigen-presenting cell

Antigen-specific B cell receptor

B cell Lymphokines

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Activation of T Cells: Helper

Activated helper T cell

Monokines

MHC Class II

T cell receptor

Antigen-presenting cell

CD4 protein

Antigenic peptide

Antigen is processed

Resting helper T cell

Class II MHC

Lymphokines

Helper T cell receptor recognizes processed antigen plus Class II MHC

Macrophage

Processed antigen and Class II MHC are displayedAntigen

Helper T cell

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Activation of T Cells: Cytotoxic

Processed antigen and Class I MHC

Lymphokines

Class I MHC

Class II MHC

Processed antigen and Class II MHC are displayedAntigen

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

Macrophage

Monokines

Cyt

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xic

T c

ell

Infe

cted

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MHC Class I

Antigenic peptide T cell receptor

CD8 protein

Resting helper T cell

Cytotoxic T cell

Cytotoxic T cell becomes activated

Antigen (virus)

Processed antigen (viral protein)

Cell dies

Infected cell

Activated cytotoxic T cell

Activated helper T cell

Antigen is processed

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Regulatory T Cells

Regulatory T cells

Mature dendritic

cell

Regulatory T cell

Proliferation

T cells compete forcytokine signals

T cells competefor same antigen

CytotoxicT cell

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Immunity: Active and Passive

Artificially acquired

Passive immunityActive immunity

Naturally acquired Naturally acquired

Artificially acquired

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Disorders of the Immune System: Allergy

Plasma cell

Interleukins

Mature helper T cell

B cell

IgEAllergen

SymptomsMediators

Mast cell

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Disorders of the Immune System:Autoimmune Disease

Cytotoxic T cell

Pancreas

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

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Disorders of the Immune System: AIDS

Virus protein

Virus RNA

New virus particle

Virus DNA

Cell DNA

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Human Tissue Typing for Transplants

HLA

ACBD

Leukocyte

Chromosome 6

MHC protein

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“Privileged” Immunity

Chorionic villi

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Immunity and Cancer

Antibody

Helper T cell

Natural killer cell

Cancer cell

Macrophage

Cytotoxic T cell

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Immunotherapy

Antibody

Breast cancer cell

Growth factor

Herceptin blocks receptor

Growth slows

Radioisotope

Antigen

Lymphoma cell Lymphoma cell

destroyed

Herceptin

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Dendritic Cells That Attack CancerComplex binds to dendritic cell precursor

T cells attack cancer cell

Dendritic cell displays tumor antigen and activates T cells

Cancer cell

T cell

Tumor antigen

Tumor antigen is linked to a cytokine

Dendritic cell matures and is infused back into patient

Complex is taken in by dendritic cell precursor

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The Immune Systemand the Nervous System

Thymosins

Macrophage

B cell

T cell

Thymus

Brain

Bonemarrow

Neuroendocrine and autonomic pathways

Immunotransmitters (feedback, regulation and modulation)

Lymphokines Monokines

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Hybridoma Technology

Antibody-producing plasma cells

Antigen

Cells fuse to make hybridomas Cancerous

plasma cells

Monoclonal antibodies are purified

Desired clones are cultured and frozen

Hybridomas are kept alive in mouse

Clones are tested for desired antibody

Individual hybridoma cells are cloned

Hybridoma cells grow in culture

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Genetic Engineering

A plasmid (ring of DNA) is isolated from a bacterium

The new gene directs the bacterium to make a new protein product such as interferon

When the bacterium divides and replicates, it copies itself and the recombinant DNA

The recombinant plasmid is inserted back into the bacterium

The gene is inserted into the plasmid, where it fits exactly. This is recombinant DNA

A gene for protein, taken from another cell, is cut with the same enzyme

An enzyme cuts the DNA at specific sites

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The SCID-hu Mouse

Mouse kidneys

Immuno-incompetent SCID mouse

Immature human immune tissue

Immature human immune cells

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Thank you