phagocytic leukocyte Immune Lymphatic System AP Biology lymphocytes

phagocytic leukocyte Immune / Lymphatic System AP Biology lymphocytes attacking cancer cell lymph system 2007 -2008

Avenues of attack § Points of entry digestive system u respiratory system u urogenital tract u break in skin u § Routes of attack circulatory system u lymph system u AP Biology

Why an immune system? § Attack from outside u animals must defend themselves against invaders (pathogens) § viruses w HIV, flu, cold, measles, chicken pox § bacteria w pneumonia, meningitis, tuberculosis Lyme disease § fungi w yeast (“Athlete’s foot”…) § protists w amoeba, malaria § Attack from inside u AP Biology cancers = abnormal body cells

Lymph system Production & transport of leukocytes Traps foreign invaders lymph vessels (intertwined amongst blood vessels) AP Biology lymph node

Development of Red & White blood cells inflammatory response Red blood cells fight parasites Leukocytes AP Biology Lymphocytes develop into macrophages short-lived phagocytes 60 -70% WBC

Lines of defense § 1 st line: Non-specific barriers u broad, external defense § “walls & moats” u skin & mucous membranes § 2 nd line: Non-specific patrols u broad, internal defense § “patrolling soldiers” u leukocytes / phagocytic white blood cells § 3 rd line: True immune system u specific, acquired immunity § “elite trained units” u lymphocytes & antibodies § B cells & T cells AP Biology

1 st line: Non-specific External defense § Barrier § skin Lining of trachea: ciliated cells & mucus secreting cells § Traps § mucous membranes, cilia, hair, earwax § Elimination § coughing, sneezing, urination, diarrhea § Unfavorable p. H § stomach acid, sweat, saliva, urine § Lysozyme enzyme § digests bacterial cell walls § tears, sweat AP Biology

2 nd line: Non-specific patrolling cells bacteria § Patrolling cells & proteins u attack pathogens, but don’t “remember” for next time § leukocytes w phagocytic white blood cells w macrophages, neutrophils, natural killer cells AP Biology § complement system w proteins that destroy cells § inflammatory response w increase in body temp. w increase capillary permeability w attract macrophages macrophage yeast

Leukocytes: Phagocytic WBCs § Attracted by chemical signals released by damaged cells u u ingest pathogens digest in lysosomes § Neutrophils u u most abundant WBC (~70%) ~ 3 day lifespan § Macrophages u “big eater”, long-lived § Natural Killer Cells destroy virus-infected cells AP Biology & cancer cells u

Destroying cells gone bad! § Natural Killer Cells perforate cells release perforin protein u forms pore allowing fluid to flow in & out of cell u cell ruptures (lysis) u natural killer cell perforin AP Biology perforin punctures cell membrane vesicle cell membrane virus-infected cell

Anti-microbial proteins § Complement system ~20 proteins circulating in blood plasma u attack bacterial & fungal cells when activated u § apoptosis w cell lysis extracellular fluid complement proteins form cellular lesion plasma membrane of invading microbe AP Biology complement proteins bacterial cell

Inflammatory response § Damage to tissue triggers local non-specific inflammatory response u MAST CELLS release chemical signals § histamines & prostaglandins u capillaries dilate, become more permeable (leaky) § delivers macrophages, RBCs, platelets, clotting factors w fight pathogens w clot formation u increases temperature § decrease bacterial growth § stimulates phagocytosis AP Biology § speeds up repair of tissues

Fever § When a local response is not enough u system-wide response to infection u activated macrophages release cytokines (signals) § triggers hypothalamus in brain to readjust body thermostat to raise body temperature u higher temperature helps defense § inhibits bacterial growth § stimulates phagocytosis § speeds up repair of tissues § causes liver & spleen to store iron, reducing blood iron levels w bacteria need large amounts AP Biology of iron to grow

3 rd line: Acquired (active) Immunity § Specific defense with memory B cell u lymphocytes § B cells § T cells u antibodies § a. k. a. immunoglobulins § Responds to… u antigens w specific pathogens & toxins w abnormal body cells (cancer) AP Biology

How are invaders recognized? § Antigens u Foreign invader that stimulates an immune response Antigenbinding sites Antibody A Antigen Antibody B AP Biology Antibody C Epitopes (antigenic determinants)

Lymphocytes § B cells u u mature in bone marrow humoral response system § “humors” = body fluids § attack pathogens still circulating in blood & lymph u produce antibodies § T cells u u mature in thymus cell-mediated response system § attack invaded cells § “Maturation” u AP Biology learn to distinguish “self” from “non-self” antigens § if react to “self” antigens, cells are destroyed during maturation bone marrow

B cells § Attack, learn & remember pathogens circulating in blood & lymph § Produce specific antibodies § against specific antigen Types of B cells u plasma cells § immediate production of antibodies § rapid response, short term release u memory cells § continued circulation in body § long term immunity AP Biology

Y Y Y antigenbinding site on antibody YY Y Y tagging “handcuffs” antigen Y Y YY Y Y u Y YY Y § millions of antibodies respond to millions of foreign antigens Y Y u Y multi-chain proteins (quarternary structure) binding region matches molecular shape of antigens each antibody is unique & specific Y u Y YY Y § Proteins that bind to a specific antigen u Y YY Y Antibodies Y YY Y Y Y variable binding region AP Biology each B cell has ~50, 000 antibodies

Y YY Y Structure of antibodies s light chain B cell membrane AP Biology s s s s s s Y s s Y Y YY Y s s s Y s variable region s YY Y Y s s Y Y Y antigen-binding site light chain heavy chains light chains antigen-binding site heavy chains antigen-binding site

What do antibodies do to invaders? neutralize Y Y Y invading pathogens tagged with antibodies Y macrophage eating tagged invaders AP Biology capture precipitate apoptosis

§ 1 st immune response § activate complement proteins u Y 0 Ig. G Y Y Antibody levels Ig. M Y u Y § Immunoglobulins Ig. M Y Classes of antibodies invading Exposure pathogens to tagged with antigen antibodies 2 macrophage eating tagged invaders Weeks 4 Ig. G § 2 nd response, major antibody circulating in plasma § promote phagocytosis by macrophages u Ig. A § in external secretions, mucus, sweat & mother’s milk u Ig. E § promote release of histamine & lots of bodily fluids § evolved as reaction to parasites § triggers allergic reaction u AP Biology Ig. D § B cell communication & development 6

10 to 17 days for full response YY Y Y YY Y Y Y Y YYYY YY Y Y Y Y Y YY Y Y YY Y Y Y YY Y release antibodies Y Y plasma cells AP Biology recognition YY YY YY Y Y Y Y YY Y Y macrophage Y Y Y Y YY Y captured invaders Y YY Y “reserves” Y B cells + antibodies Y YY Y tested by B cells (in blood & lymph) invader (foreign antigen) memory cells Y YY Y B cell immune response clones 1000 s of clone cells

Vaccinations § Immune system exposed to harmless version of pathogen u stimulates B cell system to produce antibodies to pathogen § “active immunity” rapid response on future exposure u creates immunity without getting disease! u § Most successful against viruses AP Biology

1914 – 1995 Jonas Salk April 12, 1955 § Developed first vaccine u against polio § attacks motor neurons Albert Sabin 1962 oral vaccine AP Biology

Polio epidemics 1994: Americas polio free AP Biology

Passive immunity § Obtaining antibodies from another individual u maternal immunity § antibodies pass from mother to baby across placenta or in mother’s milk § critical role of breastfeeding in infant health w mother is creating antibodies against pathogens baby is being exposed to § Injection u Direct transfer of antibodies § After rabies bite AP Biology u Short-term protection b/c no memory-B cells

What if the attacker gets past the B cells in the blood & actually infects (hides in) some of your cells? You need “trained assassins” (cytotoxic “killer” T cells) to recognize & kill off these infected cells! AP Biology 2007 -2008

How is any cell tagged with antigens? § Major histocompatibility (MHC) proteins u u u proteins which constantly carry bits of cellular material from the cytosol to the cell surface “snapshot” of what is going on inside cell give the surface of cells a unique label or “fingerprint” MHC protein Who goes there? self or foreign? T or B cell MHC proteins displaying self-antigens AP Biology

How do T cells know a cell is infected? § Infected cells digest some pathogens u MHC proteins carry pieces to cell surface § foreign antigens now on cell membrane § called Antigen Presenting Cell (APC) w macrophages can also serve as APC § tested by Helper T cells infected cell MHC proteins displaying foreign antigens TH cell T cell with antigen receptors AP Biology

T cells § Attack, learn & remember pathogens hiding in infected cells u u recognize antigen fragments also defend against “non-self” body cells § cancer & transplant cells § Types of T cells u helper T cells § alerts rest of immune system via cytokines (signals) u cytotoxic T cells § attack infected body cells u memory T cells § long term immunity AP Biology T cell attacking cancer cell

T cell (“cell-mediated”) response tok clones YY Y Y Y Y Y Y recognition s YY Y helper T cell AP Biology ine YY Y cy YY Y helper T cell stimulate B cells & antibodies YY Y APC: activated macrophage helper T cell activate cytotoxic T cells Y or to y c Y cytokines s e kin Y helper T cell killer T cell Y APC: infected cell recognition

Attack of the Cytotoxic T cells § Destroys infected body cells binds to target cell u secretes perforin protein u § punctures cell membrane of infected cell w apoptosis Cytotoxic T cell binds to infected cell AP Biologydestroyed vesicle cell membrane perforin punctures cell membrane target cell membrane

Immune response pathogen invasion antigen exposure skin free antigens in blood antigens on infected cells macrophages (APC) humoral response alert B cells Y Y Y antibodies Y AP Biology Y Y cellular response alert T cells memory T cells Y Y Y memory B cells Y Y helper T cells Y plasma B cells skin cytotoxic T cells

Cell-mediated immune response Humoral immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate B cell Gives rise to Plasma cells AP Biology Memory B cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Helper T cell Gives rise to Active and memory helper T cells Secreted cytokines activate Cytotoxic T cell Gives rise to Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues

Immune system & Blood type blood type antigen on RBC antibodies in blood donation status A type A antigens on surface of RBC anti-B antibodies __ B type B antigens on surface of RBC anti-A antibodies __ AB both type A & type B antigens on surface of RBC no antibodies universal recipient O no antigens on surface of RBC anti-A & anti-B antibodies universal donor Matching compatible blood groups is critical for blood transfusions A AP person Biologyproduces antibodies against foreign blood antigens

HIV & AIDS § Human Immunodeficiency Virus u virus infects helper T cells § helper T cells don’t activate rest of immune system: killer T cells & B cells § AIDS: Acquired Immuno. Deficiency Syndrome infections by opportunistic diseases u death usually from u “opportunistic” infections u § pneumonia, cancers AP Biology HIV infected T cell

Immune system malfunctions § Auto-immune diseases u immune system attacks own molecules & cells § Type I diabetes w Antibodies attack insulin-producing pancreatic cells § lupus w antibodies against many molecules released by normal breakdown of cells § rheumatoid arthritis w antibodies causing damage to cartilage & bone § multiple sclerosis w T cells attack myelin sheath of brain & spinal cord nerves § Allergies u AP Biology over-reaction to environmental antigens § allergens = proteins on pollen, dust mites, in animal saliva § stimulates release of histamine inflammation