Physical chemical defenses external barrier Innate general cquired immunity

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					Lecture 22: The Immune/Lymphatic System (Chapter 40)

Just a Mild Case of the Sniffles…
•Attack from outside
          –lotsof organisms want you for lunch!
          –animals are a tasty nutrient- & vitamin-packed meal
                    •cells are packages of macromolecules

                    •no cell wall

          –animals must defend themselves against invaders
                    •viruses; HIV, flu, cold, measles, chicken pox, SARS
                    •bacteria; pneumonia, meningitis, tuberculosis
                    •yeast (“Athlete’s foot”…)
                    •protists; amoeba, Lyme disease, malaria
•Attack from inside
          –defend     against abnormal body cells = cancers

Lines of Defense
•1st line: Barriers
          –broad, external defense (skin & mucus membranes)
•2nd line: Non-specific patrol
          –broad, internal defense
          –leukocytes = phagocytic WBC (macrophages)
•3rd line: Immune system
          –specific, acquired immunity
          –lymphocytes & antibodies (B cells & T cells)

1st line: External Defense
•Physical & chemical defenses
          –non-specific defense
•external barrier
          –epithelial cells & mucus membranes (skin, respiratory system, digestive system, uro-genital tract)

1st Line: Chemical Barriers on Epithelium
•Skin & mucous membrane secretions
          –sweat - pH 3-5
          –tears - washing action
          –mucus - traps microbes
          –saliva - anti-bacterial = “lick your wounds”
          –stomach acid - pH 2
          –anti-microbial proteins - lysozyme enzyme (digests bacterial cell walls)

2nd line: Internal, Broad Range Patrol
•Innate, general defense - rapid response
•Patrolling cells & proteins
          –attack invaders that penetrate body’s outer barriers
                       •leukocytes, phagocytic WBCs, complement system, anti-microbial proteins, inflammatory response

Leukocytes: Phagocytic WBCs
•Attracted by chemical signals released by damaged cells
          –enter infected tissue, engulf & ingest microbes
          –most abundant WBC (~70%)
                   –~ 3 day lifespan
          –“big eater”, long-lived
•Natural Killer Cells
          –destroy virus-infected cells & cancer cells
Destroying Cells Gone Bad!
•Natural Killer Cells perforate cells
           –release perforin protein
           –insert into membrane of target cell
           –forms pore allowing fluid to flow into cell
           –cell ruptures (lysis) (apoptosis)

Anti-Microbial Proteins
•Complement system
           –~20 proteins circulating in blood plasma
           –attack bacterial & fungal cells
                     •form a membrane attack complex
                     •perforate target cell
                     •apoptosis (cell lysis)

Inflammatory Response
•Tissue damage triggers local non-specific inflammatory response
           –release histamines & prostaglandins
           –capillaries dilate, more permeable (leaky)
                     •increase blood supply
                     •delivers WBC, RBC, platelets, clotting factors
                     •fight pathogens
                     •clot formation
                     •accounts for swelling, redness & heat of inflammation & infection

•When a local response is not enough
           –systemic response to infection
           –activated macrophages release interleukin-1
                     •triggers hypothalamus in brain to readjust body thermostat to raise body temperature
           –higher temperature helps defense
                     •inhibits bacterial growth
                     •stimulates phagocytosis
                     •speeds up repair of tissues
                     •causes liver & spleen to store iron, reducing blood iron levels
                     •bacteria need large amounts of iron to grow

•Glycoproteins that work against viruses
•Various types bond to cell receptors and induce transcription of proteins that:
           –Stop viral transcription & protein synthesis
           –Activate cytotoxic T Cells and Natural Kill Cells to destroy viral host cell
           –Activate host to present viral antigens and identify infected host to macrophages & helper T Cells
•Are anti-proliferative agents (stop mitosis) and may be used to treat tumors like melanoma
•Side effects include death of host cells, fever, general weakness
           –Extreme cases—kidney, liver, bone marrow, heart toxicity

3rd Line: Acquired Immunity
•Specific defense
                     •B lymphocytes (B cells)
                     •T lymphocytes (T cells)
           –antibodies (immunoglobulins)
•Responds to…
           –specific microorganisms, specific toxins, abnormal body cells, antigens

•B cells
           –mature in bone marrow
           –humoral response system
                     •“humors” = body fluids; produce antibodies
•T cells
           –mature in thymus; cellular response system
•Learn to distinguish “self” from “non-self” antigens during maturation – VERY IMPORTANT!

•Surface proteins; “name tags”
           –foreign antigens cause response from WBCs
           –proteins belonging:
                     •viruses, bacteria, protozoa, parasitic worms, fungi, toxins
                     •non-pathogens: pollen & transplanted tissue
•B cells & T cells respond to different antigens
           –B cells recognize intact antigens
                     •invaders in blood & lymph
           –T cells recognize antigen fragments
                     •invaders which have infected cells

Specific Immune Response
•Whether it is a primary or secondary response, the immune response starts like this:
           –A macrophage eats and digests a pathogen
           –The pathogen’s surface proteins (antigens) are displayed on the macrophage’s cell membrane
           –A Helper T Cell meets up with the macrophage
           –The macrophage secretes a chemical called Interleukin 1
           –This causes the Helper T Cell to secrete Interleukin 2
•Cell Mediated Immune Response:
           –First part of primary immune response
           –Interleukin 2 causes T cells to divide
                     •Result is defense against invaders in infected cells
                               •viruses & bacteria within infected cells, fungi, protozoa & parasitic worms
                     •Result is also defense against “non-self” cells
                               •cancer & transplant cells
•Kinds of T cells
           –helper T cells
                     •stimulate   immune system
           –killer T cells
                     •attack   infected body cells
           –suppressor T cells
                     •Turn   off the immune response

How Cells Are Tagged with Antigens
•Glycoproteins on cell surfaces have unique “fingerprint”
           –major histocompatibility proteins (MHC)
           –human leukocyte antigens (HLA)
•MHC proteins constantly export bits of cellular protein to cell surface
           –“snapshot” of what is going on inside cell

How T Cells ID Invaders
•Infected cells digest some pathogens & export pieces to MHC proteins on cell surface
           –antigen presenting cells (APC)

Attack of the Killer T Cells
•Destroys infected body cells
           –binds to target cell
           –secretes perforin protein
                     •punctures cell membrane of infected cell

•Human Immunodeficiency Virus (FYI – it’s a retrovirus that requires reverse transcriptase to make DNA from RNA)
           –virus infects helper T cells
           –helper T cells don’t activate rest of immune system: T cells & B cells
                     •also destroy T cells
•Acquired ImmunoDeficiency Syndrome
          –infections by opportunistic diseases
          –death usually from other infections
                     •pneumonia or cancer

Specific Immune Response
•Humoral Immune Response:
          •Second Phase of the primary immune response
          •Interleukin 2 secreted by T Cells activates B Cells
          •Active B Cells divide into Plasma Cells
          •Plasma cells secrete the specifically shaped proteins known as Antibodies
          •Antibodies bind to antigens and “clump”
          •Macrophages digest clumped antibody-antigen

B Cells
•Humoral response = “in fluid”
          –defense against attackers circulating freely in blood & lymph
•Specific response
          –recognizes specific antigen
          –produces antibodies against it
                     •tagging protein = immunogloblin
                    •millions of different B cells, each produces different antibodies, each recognizes a different antigen
          –types of B cells
                    •plasma cells
                               •immediate production of antibodies, short term release
                    •memory cells
                               •long term immunity

•Proteins that bind to a specific antigen
          –multi-chain proteins produced by B cells
          –antibodies match molecular shape of antigens
          –immune system has antibodies to respond to millions of antigens (invaders)
                     •tagging   system

Specific Immune Response
•Primary vs. Secondary Immune Response
          –The first time you fight off a particular pathogen it is called the Primary Immune Response
          –Your body employs B & T Cells to act as Memory Cells
          –The Secondary Immune Response occurs when you are infected with a pathogen you have already fought off
                     •Your memory cells can automatically direct your body to produce antibodies against the familiar antigen

•Immunity is resistance to a specific pathogen
          –Innate/Passive Immunity: immunity from birth through life
          –Acquired/Active Immunity: developed after birth either by fighting an infection or through vaccination.

Immune System Malfunctions
•Immune Disorders
          –Allergies: body responds to environmental Antigens
                     •Medications that attempt to lower one’s sensitivity to these allergens are called Antihistamines
          –Autoimmune diseases occur when a body cannot recognize its own cells.
                     •Lymphocytes attack body cells like they are pathogens
                                –Lupus: Connective tissues attacked; results in skin rash, joint pain, fever, fatigue, weight loss, kidney problems
                                –Type I Diabetes: beta-islet cells in pancreas that produce insulin are killed; result is inability to metabolize
                                sugar; diabetics are prone to blindness, weight loss, excessive urination, irritability, and fatigue
                                –Multiple Sclerosis: insulation surrounding nerves is destroyed; results can be disruption of nerve function,
                                paralysis, blindness, & death
                                –Rheumatoid Arthritis: joints are attacked; result is extreme pain and crippling in joints

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