How the Immune System Protects the Body

Peter Corless

3 November 2010

Homeostasis & the Immune System

Homeostasis is the process by which an organism maintains a stable, healthy internal environment.

The immune system is part of the overall process of maintaining homeostasis.

“Look out, dad! Here comes some e. Coli!!!”

The immune system identifies and attacks harmful invasive biological entities called pathogens, what most people call “germs.”

“Germs”Webster’s: 1 a : a small mass of living substance capable of developing into an organism or one of its parts; 3 : microorganism; especially : a microorganism causing disease; from the Latin germin- “to beget.”

Germ theory of disease replaced the Aristotelian theory of spontaneous generation (abiogenesis) c. 17th-19th Centuries.

Robert Hooke coins the term“cell” in Micrographia, 1665.

Anton van Leeuwenhoek used a microscope to see microorganisms c. 1674.

Nicolas Andry posited microorganisms cause smallpox, 1700.

Louis Pasteur disproved spontaneousgeneration by experimentation in 1861.

Plasmodium falciparum, the cause of malaria

PathogensPathogen Definition

Prions Protinaceous infecteous particles that cause mis-folded proteins. (ex: Bovine Spongiform Encephalopathy, BSE or “mad cow disease”) Currently untreatable and mostly fatal.

Viruses Genetic information (DNA) with a molecular body and a coat of protein; about 10-100 times smaller than bacteria; invade a healthy cell to replicate. (ex: Rhinovirus or “common cold”, Influenza, Hepatitis, Herpes, HIV) Some antiviral medications available.

Bacteria Prokaryotic organisms (no nucleus), usually unicellular. (ex: tuberculosis, cholera, syphilis, anthrax, bubonic plague, leprosy) Can be fought with antibiotics.

Eukaryotic Parasites • Protozoa (one-celled organisms with a nucleus, such as Plasmodium falciparum, which causes malaria)

• Helminths (multi-celled parasites, ex: flatworms & roundworms)Can be fought with various medications.

Fungi Chitinous eukaryotes (hard structure similar to insect or crab shells; not cellulose, like plants)

• Yeasts (unicellular molds)• Hyphae (multi-celled thread-like colonies)• Mushrooms (macroscopic structures)

Can be fought with fungicides.

How Small is Small?

Pathogens vary widely insize, from prions and viruses(measured in nanometers)to bacteria (measured inmicrometers) to protozoa,helminths and fungi (whichcan grow to 1 millimeter or more)

Immune System Activities

Needs to distinguish internal parts of an organism (“self”) from invasive external pathogens (“other”).

Needs to distinguish healthy parts of an organism from damaged, dead, or diseased parts (ex: cancer).

Happens at many levels of biological processes

Intracellular activity (ex: enzyme defenses against viruses, and defensin peptides)

Cellular activity (ex: phagocytosis) or

Intercellular activity (ex: intercellular signaling)

OVERLAPPING DEFENSESNO SINGLE POINT OF FAILURE

Working Down to the Bone

Bone marrow is the factory of the immune system in humans(and other vertebrates)

Initially develops blood and immune system cells

Erythrocytes (red blood cells)

Platelets

Lymphocytes (B-cells, thymocytes —immature T-cells, plus Natural Killer “NK” cells)

Granulocytes

Major Immune System OrgansThymus – Produces mature T-cells from thymocytes; central to adaptive immune system response; begins to atrophy in teen years.

Spleen – Filters blood of old red blood cells. Produces antibodies and removes bacteria; stores monocytes(immature white blood cells) that change into dentritic cells (that fight diseases on externally-exposed tissue) and macrophages (which protect internal tissues).

Lymph Nodes – Filled with lymphocytes, act as central loci to detect and fight diseases.

The immune system is comprised of many organs with interdependent functions(a few key ones are listed at right)

Innate and Adaptive Immune Systems

Plants and invertebrate animals only have innateimmune systems

Humans and other vertebrateshave both innate and adaptiveimmune systems

Innate Immune System

Creates non-specific antibodies

Promotes removal of dead cells

Reactive

Activated upon sensing of pathogen

Shuts off production of antibodieswhen pathogen no longer detected

Does not confer long-lasting or permanent immunity

Can only respond to readily-recognized pathogens

Adaptive Immune System & Hypermutation

Can be used to fight pathogens never encountered before

Activated by innate immune system responses (monitors for unusual activity)

Rapidly invents antibodies for unusual pathogens using a process called somatic hypermutation (SHM)

Creates genetically unique immunoglobin genes, with antigen receptors tailor-made to hopefully match the antigens of the detected pathogen

Has “memory” — can provide long-lasting or permanent immunization/resistance

How the Immune Response Works

http://waynejoseph.files.wordpress.com/2010/03/immune20system.jpg

Immune System Errors“Mistargeted” Somatic Hypermutation (SMH) in B-cell lymphocytes (white blood cells) can lead to cancer (lymphoma)

Hodgkin’s lymphoma (~7,000 US cases annually)

Non-Hodgkin’s lymphoma (0.2%, ~54,000 US cases annually)

Human Immunodeficiency Virus (HIV/AIDS)

Causes shut-down of immune system

Loss of T-cells leads to inability to respond to other pathogens

Pandemic; more than 25 million dead

Infects 0.8% of global population (>33 million; >1 in 200)

Severe Combined Immunodeficiency (SCID)

“Bubble Boy Syndrome” (rare; 1 in 100,000 children born)

Can be treated with bone marrow replacement

Artificial Immune SystemsHealth & Medical Technologies

Antibiotics (Antibacterial drugs)

Antiviral drugs

Surgery/Chemotherapy/Radiology/Lasers

Gene therapy

Artificial Immune Systems (AIS)

Apply computational analogies of natural immune systems to complex computing systems

Detect and prevent spread of computational “pathogens”: viruses, spam, hackers, malicious users

Referenceshttp://en.wikipedia.org/wiki/Homeostasis

http://en.wikipedia.org/wiki/Immune_system

http://en.wikipedia.org/wiki/Pathogen

http://en.wikipedia.org/wiki/Innate_immune_system

http://en.wikipedia.org/wiki/Adaptive_immune_system

http://www.thebody.com/content/art1788.html

http://en.wikipedia.org/wiki/Bacteria

http://en.wikipedia.org/wiki/Virus

http://en.wikipedia.org/wiki/Prion

http://en.wikipedia.org/wiki/Fungi

http://en.wikipedia.org/wiki/Plasmodium_falciparum

http://singularityhub.com/2010/07/27/watching-genetically-engineered-cells-kill-cancer-in-real-time/

Thank You!

Peter Corless

petercorless@mac.com

650-906-3134 (mobile)