Antigens (foreign cells and molecules) ~ viruses ~ bacteria ~ foreign tissue ~ molecules Some cause disease

3 Lines of defense against disease Skin and mucous membranes (non- specific) Inflammatory response (non-specific) Immune Response (specific) Exam

Skin cells with bacteria (green rods) hair Skin cells with bacteria (green rods)

3 Lines of defense against antigens Skin and mucous membranes (non-specific) Inflammatory response (non-specific) Immune Response (specific)

Neutrophil, a type of lymphocyte which scavenges for antigens http://www.beyondbooks.com/lif71/images/00016305.jpg

Lymphocytes on wall of blood vessel http://darwin.bio.uci.edu/~cchughes/Media/VessSEM.jpg

Inflammatory Response Histamine released by damaged cells Inflammatory Response Antigens Skin cells Bacteria and other antigens Neutrophils leak out and eat antigens Histamine causes blood vessels to leak Capillary with Neutrophils and other blood cells Same process in allergic reactions to pollen, chocolate, etc.

Inflammatory Response Cut in skin Damaged cells releases histamine Neutrophils (WBC) eat bacteria by phagocytosis Histamine causes capillaries to open up (distended) White blood cells go to injury site.

Neutrophil or macrophage eating bacteria

3 Lines of defense against antigens Skin and mucous membranes (non-specific) Inflammatory response (non-specific) Immune Response (specific)

Immune Response – specific antigen Bone EXAM Immune Response – specific antigen Bone marrow Unspecialized stem cell Thymus Gland B-cell T-cell macrophage

30,000 antibodies seconds / cell Antigen Helper T cell Macrophage Suppressor T cell B cell Killer T cell plasmacyte Complex formed = antigen + macrophage + B cell + Helper T cell EXAM 30,000 antibodies seconds / cell

Antigen – antibody complex reduces capacity of antigen to cause disease

Rhinovirus with antigenic sites brightly colored

Antibodies attached to the antigenic sites of the Rhinovirus

Specific antibody against specific virus Specific antibody-antigen (virus) complex – neutralizes virus

How can 35000 genes make millions of protein antibodies? Pre-existing in the human body is at least one specific pre-antibody producing cell (B-Cell) for every possible antigen – literally millions. How? How can 35000 genes make millions of protein antibodies? One gene = one protein

How do we make so many antibodies or proteins? Humans and other mammals can make a specific antibody for every antigen to which it is exposed 1000 antigens = 1000 antibodies 1,000,000 antigens = 1,000,000 antibodies 1,000,000,000 antigens = 1,000,000,000 antibodies 1 gene = 1 protein (antibody) 1,000,000 antibodies = 1,000,000 genes Humans have about 35,000 genes How do we make so many antibodies or proteins?

Barbara McClintock proposes (1948) that DNA shuffling makes new genes Makes protein or antibody X DNA New arrangement makes protein or antibody Y EXAM Barbara McClintock proposes (1948) that DNA shuffling makes new genes

Watson, Crick, Wilkins get Nobel Prize for DNA Rosalind Franklin Otto Hahn gets Nobel Prize for discovery of nuclear fission Barbara gets Nobel Prize (1983) for gene shuffling……………. and a postage stamp Barbara McClintock Lise Meitner

Clonal Selection theory B cells for Viruses A, B, C, D, E……………X, and billions more antigens Virus X B-cell for Virus X Virus X + B cell for Virus X combine Clonal Selection theory B cell X is cloned memory B cell X for Virus X Plasmacyte (formed from B-cell X) makes Antibody X specific for virus X Antibody X neutralizes Virus X

Memory B-cells specific for antigen X Pre-existing specific B-cells for all antigens Clonal Selection Theory Specific antigen X Cloning of specific B-cell for antigen X Memory B-cells specific for antigen X Figure: 27-04 Title: B Cells and Antibody-Mediated Immunity Caption: B Cells and Antibody-Mediated Immunity. Cloned plasmacytes make only antibodies for antigen X Antigen X + Antibody X complex

Days EXAM Second exposure First exposure Amount of antibody 0 7 14 0 7 14 0 7 14 Days

Figure: 27-05 Title: Prepared for an Invasion Caption: The memory cells produced by the body during a first attack by an invader allow it to mount a faster, more vigorous defense should the same invader attack a second time.

No antibody production Day 1 B cell meets antigen No antibody production Day 1 Ribosomes start to appear Day 2 Endoplasmic reticulum appears Day 3 More ribosomes and E.R. Day 4 Antibodies produced Day 5

B cell before contact with antigen – little or no rough endoplasmic reticulum or ribosomes B cell 5 days after contact with antigen – extensive Rough Endoplasmic Reticulum and ribosomes

Macrophage eating cancer cell (yellow) T cell killing cancer cell (yellow) Notice all that’s left is cytoskeleton (yellow)

Why is cancer a disease of aging?

Human age Immune system Incidence of cancer Relative activity 1 10 20 30 40 50 60 70 80 Human age

Autoimmune disease – immune system attacks self = rheumatoid arthritis = immune system attacks joints EXAM Figure: 27-09 Title: When the Body Attacks Itself Caption: Rheumatoid arthritis has so disfigured this person’s hands that simply signing a greeting card has become a difficult act. Rheumatoid arthritis is an autoimmune condition.

Multiple sclerosis = Autoimmune disease = T cells attack nerve cells

Immune cells release histamine when they encounter allergen (antigen such as pollen, chocolate, peanuts, etc.) allergen Immune cell Allergy = overreaction to antigen Histamine causes sneezing, runny nose, swollen eyes, swollen throat, etc.