Understanding The Immune System IMMUNOLOGY Prof. Nagwa Mohamed Amin Aref

The Immune System SARS virus Parasite in red blood cell Fungus Bacteria

Markers of Self Muscle cell Nerve cell Epithelial cell Leukocyte Class I MHC self-marker protein

Markers of Non-Self Non-self leukocyte Antibody Epitope Class I MHC protein Epitope Antibody Antigen Bacteria Non-self nerve cell SARS virus

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

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

Lymphatic System Lymph nodeLymphatic vessel

Lymph Node Germinal center Vein Cortex Paracortex Incoming lymphatic vessel Outgoing lymphatic vessel Artery Medulla Follicle

Cells of the Immune System Bone graft Multipotential stem cell Hematopoietic stem cell Platelets Macrophage Erythrocytes Eosinophil Neutrophil Megakaryocyte Mast cell Basophil T lymphocyte Natural killer cell Dendritic cell B lymphocyte Lymphoid progenitor cell Myeloid progenitor cell Monocyte Marrow Bone

B Cells Plasma cell Class II MHC and processed antigen are displayed Antigen-presenting bacteria Antigen Antigen-specific B cell receptor Antibodies B cell Activated helper T cell Lymphokines

Antibody Assembled antibody molecule Heavy chain Antigen-binding region Constant region Light chain

Immunoglobulins IgA IgM IgG, IgD, IgE, and IgA

Antibody Genes Assembled antibody molecule VDJCVDJC Gene components scattered through one chromosome Heavy chain Antigen- binding region Constant region Light chain VVVDDJJJJCVVVDDJJJJC Rearranged gene components encoding a heavy chain

T Cells Activated killer cellActivated helper T cell Resting cytotoxic T cellResting helper T cell

Cytokines Mature helper T cell Monokines Lymphokines Macrophage

Killer Cells: Cytotoxic Ts and NKs Killer cell Target-oriented granules Surface contact Target cell

Phagocytes and Their Relatives Monocyte Dendritic cell Eosinophil Neutrophil Basophil Mast cell Macrophage

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

Complement C9 Enzyme C2 C5C3b C3aC3 C4 Antigen IgG C1 C8 C7 C6 C5b C5a

Mounting an Immune Response Complement Virus Killer cell B cell Antibodies T cell Lymphokines Macrophage

Antigen Receptors Killer cell Infected cellAntigen-presenting cell CD8 protein Cell membrane MHC 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

Activation of B Cells to Make Antibody Antigen-presenting cell Antigen Circulating antibody Antigen is processed Class II MHC Antigen Activated helper T cell Class II MHC and processed antigen are displayed Antibodies Plasma cell Antigen- presenting cell Antigen-specific B cell receptor B cell Lymphokines

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 displayed Antigen Helper T cell

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 displayed Antigen Resting helper T cell receptor recognizes processed antigen plus Class II MHC Macrophage Monokines Cytotoxic T cell Infected cell MHC Class I Antigenic peptideT 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

Regulatory T Cells Regulatory T cells Mature dendritic cell Regulatory T cell Proliferation T cells compete for cytokine signals T cells compete for same antigen Cytotoxic T cell

Immunity: Active and Passive Artificially acquired Passive immunityActive immunity Naturally acquired Artificially acquired

Disorders of the Immune System: Allergy Plasma cell Interleukins Mature helper T cell B cell IgEAllergen Symptoms Mediators Mast cell

Disorders of the Immune System: Autoimmune Disease Cytotoxic T cell Pancreas Beta cell

Disorders of the Immune System: Immune Complex Disease Glomerular basement membrane of kidney Large complex Endothelial cell Small complex

Disorders of the Immune System: AIDS Virus protein Virus RNA New virus particle Virus DNA Cell DNA

Human Tissue Typing for Transplants HLA ACBD Leukocyte Chromosome 6 MHC protein

“Privileged” Immunity Chorionic villi

Immunity and Cancer Antibody Helper T cell Natural killer cell Cancer cell Macrophage Cytotoxic T cell

Immunotherapy Antibody Breast cancer cell Growth factor Herceptin blocks receptor Growth slows Radioisotope Antigen Lymphoma cell Lymphoma cell destroyed Herceptin

Dendritic Cells That Attack Cancer Complex 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

The Immune System and the Nervous System Thymosins Macrophage B cell T cell Thymus Brain Bone marrow Neuroendocrine and autonomic pathways Immunotransmitters (feedback, regulation and modulation) Lymphokines Monokines

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

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

The SCID-hu Mouse Mouse kidneys Immuno-incompetent SCID mouse Immature human immune tissue Immature human immune cells