Chapter 3 The Immune System

Chapter 3 The Immune System

Why is the Immune System Important? Why is the Immune System Relevant to HIV?

T Lymphocyte Infected by HIV

Brief History of Immunology Immunity- Observation reported in 430 BC after epidemic in Athens Greece-People that survived disease like plague did not get sick again Variolation - Practiced in 15th Century (Chinese and Turks) inoculation of people with dried pustules caused by small pox. People still died but ~10 times less frequently Vaccination- Edward Jenner (1798). Made observation that Cowpox which causes a mild disease protected people (milkmaids) from Smallpox Vaccines- First produced against other organisms in late 1800s. Louis Pasteur generated vaccines to Fowl Cholera, Anthrax, and Rabies

Antibodies produced by B-B lymphocytes T-lymphocytes & other white cells

Before we talk about the immune system, we have to talk about the circulatory system and blood Blood is composed of fluids plasma and cells Used to transport nutrients and oxygen to tissues/organs Also removes harmful C0 2 from system and other waste products Cells of blood protect against infection by foreign agents For example: Platelets are needed for wound repair

Many of the cells in the blood are the critical players in the immune system that protects us from infection from: (1) viruses-which are sub-cellular agents (2) bacteria-single cell microorganisms (3) protozoa- more complex-single cell microorganism like amoebas (4) Fungy-complex single or multicellular organism such as yeast and mold (5) Multicellular organism large complex multicellular organisms such as roundworms and tapeworms

The cells of the blood have a limited lifespan of days to weeks depending of the cell type so they need to be constantly replenished by special cells called stem cells that give rise to all blood cells Stem cells reside in the bone marrow they make more of themselves as well as differentiate into other cell types If you kill Stem cells in a human or animal, they become immunodeficient and can die Differentiation of different cell types requires specific growth factors and a specific micro-environment.

Two main types of cells in blood (1) Red Blood Cells or RBCs compose the majority of cells of blood and carry Oxygen and C0 2 (2) White Blood cells (many different kinds) are mostly involved in immune surveillance These cells can be specific or non-specific in the way they respond to a microbe or foreign agent The cells that are non-specific: recognize bacteria and other invaders non-specifically specifically- they interact with and kill bacteria by swallowing them whole they are called phagocytes (Greek work to eat). Macrophages and monocytes eat dead or infected cells found in blood and tissues-are in pus and neutrophils that kill bacteria

Other cells such as Mast cells, eosinophils and basophils help eliminate larger parasites such as protozoa and worms by releasing toxic substances that kill the invaders Interestingly, antibodies can help eliminate large organisms by acting as signals for cells to attack see Fig. 3.4 in book

All Blood Cells Come From a Special Cell Hematopoietic Stem Cell Progenitors give rise to all Blood cells See Fig 3-33

Where do lymphocytes come from? Thymus T-Cells Lymph nodes Spleen } T+B-cells Bone Marrow B-cells See Fig 3-13 Circulatory System Is Very Important to Immune System

Antibody are our smart bombs Have region that specifically interacts with foreign particles called antigens See Fig 3-83

B-lymphocytes are antibody factories See Fig 3-113

Antibodies against bacteria or foreign molecules enhance destruction by macrophages/monocytes monocytes Antibodies to parasites help white cells to recognize and destroy Y Y Y Y Y Y See Fig 3-43

Antibodies Receptor that evolved to combat disease each antibody recognizes only one specific antigen An antigen is a chemical or molecule that induces or elicits an immune response -such as the production of a spec. antibody

Theoretically, antibodies can be produced to just about any foreign substance Antibodies are highly specific for example: An antibody can distinguish one protein from another by a single amino acid difference

Binding site resemble Enzyme binding sites

A second exposure to the same antigen induces a faster & stronger r response Amount of specific Antibody Secondary Primary Exposure to Antigen 10 20 30 40 50 Days See Fig 3-133

Antibodies are important tools Protein identification Localization of proteins in cells Cell isolation Protein purification Gene cloning Therapy against diseases and venoms

Each B cell Produces a Single Type of Antibody Specific Ligand /Antigen To produce the billions of different antibodies necessary to combat disease, billions of antibody genes must have evolved to encode this information B-Cell This theory was based on the idea of One Gene = One Protein Would need more genes than coded for in the genome

1987 Nobel Prize Susumu Tonegawa Demonstrated that the variable region and the constant regions were rearranged in B-cell B tumors (myelomas)

V Variable Region Gene Rearrangement V D J J J ~ 200s ~50 ~10 V J Cµ Enh ~~~~~~~~~~~~~~~~~~~~~~~~ See Fig 3-103 VDJCµ mrna

Lymphocyte-specific gene rearrangements is mediated by a specific enzyme complex enzymes Deleted DNA

T cells have similar receptors as B cells related to antibodies See Fig 3-163

Antigen Stimulated T-Helper T Cells are Essential for a Functional Cellular and Humoral Immune Response foreign antigen T H CD4 positive T-Helper Cell Hormones called cytokines See Fig 3-153 Fig 3-18/193

Because Macrophages eat microbes and other things, they are excellent processors of antigens Y segments of microbe are sent to surface

Macrophages are excellent Antigen Presenting Cells self or foreign peptide MHC I or II CD4 or CD8 T-cell Antigen Receptor T-cell

Cytotoxic T-Cell (CTL) See Fig 3-183 TCR peptide MHC I Kill only virus infected cells due to peptide presented by Class I MHC Like Smart Bombs T cells hit only specific targets Can also kill cancerous cells (tumors) if express abnormal proteins