Deer Park High School

Mr. Knuffke

AP Biology

Immune / Lymphatic System (Ch. 43)

Avenues of attack §  Points of entry digestive system respiratory system u  urogenital tract u  break in skin u  u 

§  Routes of attack u  u 

circulatory system lymph system

Why  an  immune  system?   •  A/ack  from  outside   –  lots  of  organisms  want  you  for  lunch!   –  animals  are  a  tasty  nutrient-­‐  &  vitamin-­‐packed  meal   •  cells  are  packages  of  macromolecules   –  animals  must  defend  themselves  against  invaders  (pathogens)     •  Viruses:    HIV,  flu,  cold,  measles,  chicken  pox   •  Bacteria:    pneumonia,  meningiHs,  tuberculosis   Lyme  disease   •  Fungi:    yeast  (“Athlete’s  foot”…)   •  ProHst:    amoeba,  malaria  

•  A/ack  from  inside   –  cancers  =  abnormal  body  cells  

Mmmmm, What’s in your lunchbox?

1

Deer Park High School

Mr. Knuffke

AP Biology Lymph  system  

Production & transport of leukocytes Traps foreign invaders

lymph vessels (intertwined amongst blood vessels)

lymph node

Development  of  Red  &  White  blood  cells  

inflammatory response

Red blood cells

fight parasites

Leukocytes Lymphocytes

develop into macrophages

short-lived phagocytes 60-70% WBC

Lines  of  defense  

•  1st  line:  Non-­‐specific  barriers   –  broad,  external  defense   •  “walls  &  moats”     –  skin  &  mucous  membranes  

•  2nd  line:  Non-­‐specific  patrols   –  broad,  internal  defense   •  “patrolling  soldiers”   –  leukocytes  =  phagocyHc  WBC  

•  3rd  line:  True  immune  system   –  specific,  acquired  immunity   •  “elite  trained  units”   –  lymphocytes  &  anHbodies   •  B  cells  &  T  cells  

Bacteria & insects inherit resistance. Vertebrates acquire immunity.

2

Deer Park High School

Mr. Knuffke

AP Biology 1st  line:  Non-­‐specific  External  defense   •  Barrier   •  skin  

•  Traps  

Lining of trachea: ciliated cells & mucus secreting cells

•  mucous  membranes,  cilia,   hair,  earwax  

•  EliminaHon   •  coughing,  sneezing,  urinaHon,  diarrhea  

•  Unfavorable  pH   •  stomach  acid,  sweat,  saliva,  urine  

•  Lysozyme  enzyme   •  digests  bacterial  cell  walls   •  tears,  sweat  

2nd  line:  Non-­‐specific  patrolling  cells     •  Patrolling  cells  &  proteins   –  a/ack  pathogens,  but  don’t   “remember”  for  next  Hme   •  leukocytes   – phagocyHc  white  blood  cells   – macrophages,  neutrophils,   natural  killer  cells     •  complement  system   – proteins  that  destroy  cells   •  inflammatory  response   – increase  in  body  temp.   – increase  capillary  permeability   – a/ract  macrophages  

bacteria

macrophage

yeast

Leukocytes:  PhagocyHc  WBCs     •  A/racted  by  chemical  signals  released  by  damaged   cells     –  ingest  pathogens   –  digest  in  lysosomes    

•  Neutrophils   –  most  abundant  WBC  (~70%)   –  ~  3  day  lifespan  

•  Macrophages   –  “big  eater”,  long-­‐lived    

•  Natural  Killer  Cells   –  destroy  virus-­‐infected  cells     &  cancer  cells  

3

Deer Park High School

Mr. Knuffke

AP Biology Destroying  cells  gone  bad!   •  Natural  Killer  Cells  perforate  cells   –  release  perforin  protein   –  insert  into  membrane  of  target  cell   –  forms  pore  allowing  fluid  to     flow  in  &  out  of  cell   natural killer cell –  cell  ruptures  (lysis)  

vesicle

•  apoptosis   perforin

cell membrane cell membrane

perforin punctures cell membrane

virus-infected cell

AnH-­‐microbial  proteins   •  Complement  system   –  ~20  proteins  circulaHng  in  blood  plasma   –  a/ack  bacterial  &  fungal  cells   •  form  a  membrane  a/ack  complex   •  perforate  target  cell   •  apoptosis   – cell  lysis  

extracellular fluid

complement proteins form cellular lesion

plasma membrane of invading microbe

complement proteins

bacterial cell

Inflammatory  response   •  Damage  to  Hssue  triggers  local   non-­‐specific  inflammatory   response   –  release  chemical  signals     •  histamines  &  prostaglandins   –  capillaries  dilate,  become   more  permeable  (leaky)   •  delivers  macrophages,  RBCs,   platelets,  clofng  factors     – fight  pathogens   – clot  formaHon  

–  increases  temperature  

•  decrease  bacterial  growth   •  sHmulates  phagocytosis   •  speeds  up  repair  of  Hssues  

4

Deer Park High School

Mr. Knuffke

AP Biology Fever     •  When  a  local  response  is  not  enough   –  system-­‐wide  response  to  infecHon   –  acHvated  macrophages  release  interleukin-­‐1   •  triggers  hypothalamus  in  brain  to  readjust  body   thermostat  to  raise  body  temperature   –  higher  temperature  helps  defense   •  inhibits  bacterial  growth   •  sHmulates  phagocytosis   •  speeds  up  repair  of  Hssues   •  causes  liver  &  spleen  to  store     iron,  reducing  blood  iron  levels   – bacteria  need  large  amounts     of  iron  to  grow  

3rd  line:  Acquired  (acHve)  Immunity   •  Specific  defense  with  memory     B cell

–  lymphocytes   •  B  cells   •  T  cells  

–  anHbodies     •  immunoglobulins  

•  Responds  to…   –  anHgens     •  cellular  name  tags   – specific  pathogens     – specific  toxins   – abnormal  body  cells  (cancer)  

How  are  invaders  recognized?   •  AnHgens   –  cellular  name  tag  proteins   •  “self”  anHgens   – no  response  from  WBCs   •  “foreign”  anHgens     – response  from  WBCs   – pathogens:  viruses,  bacteria,  protozoa,  parasiHc   worms,  fungi,  toxins     – non-­‐pathogens:  cancer  cells,  transplanted  Hssue,   pollen  

“self”

“foreign”

5

Deer Park High School

Mr. Knuffke

AP Biology Lymphocytes    

bone marrow

•  B  cells  

–  mature  in  bone  marrow   –  humoral  response  system     •  a/ack  pathogens  sHll  circulaHng  in   blood  &  lymph   –  produce  anHbodies   •  T  cells     –  mature  in  thymus   –  cellular  response  system   •  a/ack  invaded  cells   •  “MaturaHon”   –  learn  to  disHnguish  “self”     from  “non-­‐self”  anHgens     •  if  react  to  “self”  anHgens,  cells     are  destroyed  during  maturaHon  

B  cells   •  A/ack,  learn  &  remember  pathogens  circulaHng  in   blood  &  lymph   •  Produce  specific  anHbodies     against  specific  anHgen   •  Types  of  B  cells   –  plasma  cells  

•  immediate  producHon  of  anHbodies   •  rapid  response,  short  term  release  

–  memory  cells  

•  conHnued  circulaHon  in  body   •  long  term  immunity  

Y

Y

Y

YY Y

Y

Y

Y

YY Y

Y

YY Y Y

Y

Y

Y

Y

Y

Y

variable binding region

antigen

Y

antigenbinding site on antibody

YY Y

Y

Y YY Y

–  mulH-­‐chain  proteins     –  binding  region  matches  molecular  shape  of  anHgens   –  each  anHbody  is  unique  &  specific     •  millions  of  anHbodies  respond  to  millions  of     foreign  anHgens   –  tagging  “handcuffs”   •  “this  is  foreign…gotcha!”  

Y

YY Y

Y

Y

•  Proteins  that  bind  to  a  specific  anHgen  

Y

YY Y

Y

YY Y

Y

AnHbodies    

each B cell has ~50,000 antibodies

6

Deer Park High School

Mr. Knuffke

AP Biology Structure  of  anHbodies  

YY Y

Y YY Y

Y

light chain

s

s

s s

s s s s s s s

s s

s s

s s

s s

s s

s

s

s s

Y

s

s

Y

s s

light chain heavy chains

B cell membrane

Y

Y

s

YY Y Y

s

variable region

Y YY Y

s

Y

s

Y

Y

s

s

Y

Y

antigen-binding site s

light chains

antigen-binding site

antigen-binding site

heavy chains

What  do  anHbodies  do  to  invaders?   neutralize

precipitate

apoptosis

Y

Y

Y

Y

Y

invading pathogens tagged with antibodies

capture

Y

macrophage eating tagged invaders

•  Immunoglobulins  

invading Exposure pathogens to tagged with antigen antibodies Antibody levels

Classes  of  anHbodies  

IgM

IgG

–  IgM   macrophage tagged •  1st  immune  response   Y eating invaders •  acHvate  complement  proteins   Y 0 2 4 6 –  IgG   Weeks •  2nd  response,  major  anHbody  circulaHng  in  plasma   •  promote  phagocytosis  by  macrophages   –  IgA   •  in  external  secreHons,  sweat  &  mother’s  milk   –  IgE   •  promote  release  of  histamine  &  lots  of  bodily  fluids   •  evolved  as  reacHon  to  parasites   •  triggers  allergic  reacHon   –  IgD   •  receptors  of  B  cells???  

Y

Y

Y

Y

7

Deer Park High School

Mr. Knuffke

AP Biology

10 to 17 days for full response

Y

Y

Y

Y

Y

YY Y

YY Y

YY Y

YY Y

YY Y YY YY Y Y YYYY YY Y Y Y

Y

Y Y

YY Y

YY Y

YY Y YY YY Y Y YY YY Y Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

YY Y

Y

YY Y

Y

YY Y

Y

Y

release antibodies

YY Y

Y

Y Y Y

Y

plasma cells

recognition

YY YY YY Y Y Y Y YY YY Y YY Y

Y

Y

YY Y

Y

Y

Y

Y

Y

Y

Y Y

macrophage

Y

Y

YY Y

“reserves”

captured invaders

Y

B cells + antibodies

Y

Y

YY YY Y Y YY Y

memory cells

Y

YY Y

invader (foreign antigen)

Y

Y

YY Y

tested by B cells (in blood & lymph)

Y

B  cell  (aka  “humoral”)  immune  response  

clones

1000s of clone cells

VaccinaHons     •  Immune  system  exposed     to  harmless  version  of  pathogen     –  sHmulates  B  cell  system  to  produce     anHbodies  to  pathogen   •  “acHve  immunity”  

–  rapid  response  on  future  exposure   –  creates  immunity     without  gefng     disease!  

•  Most  successful     against  viruses  

Jonas  Salk   •  Developed  first  vaccine  

1914 – 1995 April 12, 1955

–  against  polio   •  a/acks  motor  neurons    

Albert Sabin 1962 oral vaccine

8

Deer Park High School

Mr. Knuffke

AP Biology Polio  epidemics  

1994: Americas polio free

Passive  immunity   •  Obtaining  anHbodies  from  another  individual     –  maternal  immunity   •  anHbodies  pass  from  mother  to  baby  across  placenta  or   in  mother’s  milk   •  criHcal  role  of  breasmeeding  in  infant  health   – mother  is  creaHng  anHbodies  against  pathogens  baby   is  being  exposed  to  

•  InjecHon   –  injecHon  of  anHbodies   –  short-­‐term  immunity  

What  if  the  a/acker  gets  past  the  B  cells  in   the  blood  &  actually  infects  (hides  in)   some  of  your  cells?   You  need  trained  assassins  to  recognize  &   kill  off  these  infected  cells!   Attack of the Killer T cells!

T

But how do T cells know someone is hiding in there?

9

Deer Park High School

Mr. Knuffke

AP Biology

How  is  any  cell  tagged  with  anHgens?   •  Major  histocompaHbility  (MHC)  proteins     –  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

How  do  T  cells  know  a  cell  is  infected?   •  Infected  cells  digest  some  pathogens   –  MHC  proteins  carry  pieces  to  cell  surface   •  foreign  anHgens  now  on  cell  membrane   •  called  AnHgen  PresenHng  Cell  (APC)   – macrophages  can  also  serve  as  APC   •  tested  by  Helper  T  cells   infected cell

WANTED

MHC proteins displaying foreign antigens TH cell

T cell with antigen receptors

T  cells  

•  A/ack,  learn  &  remember  pathogens  hiding  in   infected  cells   –  recognize  anHgen  fragments   –  also  defend  against  “non-­‐self”  body  cells   •  cancer  &  transplant  cells    

•  Types  of  T  cells   –  helper  T  cells   •  alerts  rest  of  immune  system   –  killer  (cytotoxic)  T  cells     •  a/ack  infected  body  cells   –  memory  T  cells   •  long  term  immunity  

T cell attacking cancer cell

10

Deer Park High School

Mr. Knuffke

AP Biology T  cell  (aka  “Cell  mediated”)  response  

YY Y

YY Y

Y

Y

Y

Y

Y

Y

Y

Y

YY Y

Y

YY Y

Y

Y

recognition

Y

2

Y

YY Y

helper T cell

stimulate B cells & antibodies

YY Y

clones

leu kin

YY Y

int er

helper T cell

YY Y

APC: activated macrophage

Y

interleukin 1

or

activate killer T cells

t

in helper T cell helper T cell

Y

helper T cell

killer T cell

2 kin eu erl

Y

APC: infected cell recognition

A/ack  of  the  Killer  T  cells   •  Destroys  infected  body  cells   –  binds  to  target  cell   –  secretes  perforin  protein   •  punctures  cell  membrane  of  infected  cell   – apoptosis   Killer T cell

vesicle

Killer T cell binds to infected cell cell membrane

infected cell destroyed

perforin punctures cell membrane

cell membrane

target cell

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 person produces antibodies against foreign blood antigens

11

Deer Park High School

Mr. Knuffke

AP Biology Immune  response   pathogen invasion antigen exposure

skin free antigens in blood

macrophages (APC)

humoral response alert

B cells

memory T cells

cytotoxic T cells

Y

Y

Y

Y

Y

Y

Y

Y

T cells

Y Y

Y Y Y antibodies Y

Y

Y

alert

memory B cells

Y Y

Y Y Y antibodies

helper T cells

cellular response

Y

plasma B cells

skin antigens on infected cells

HIV  &  AIDS   •  Human  Immunodeficiency  Virus   –  virus  infects  helper  T  cells   •  helper  T  cells  don’t  acHvate  rest  of  immune  system:  killer  T   cells  &  B  cells   •  also  destroys  helper  T  cells  

•  AIDS:  Acquired  ImmunoDeficiency  Syndrome   –  infecHons  by  opportunisHc     diseases   –  death  usually  from     –  “opportunisHc”  infecHons   •  pneumonia,  cancers    

HIV infected T cell

Immune  system  malfuncHons   •  Auto-­‐immune  diseases  

–  immune  system  a/acks  own  molecules  &  cells   •  Lupus:    anHbodies  against  many  molecules  released  by   normal  breakdown  of  cells   •  rheumatoid  arthriHs:    anHbodies  causing  damage  to   carHlage  &  bone   •  Diabetes:    beta-­‐islet  cells  of  pancreas  a/acked  &   destroyed   •  mulHple  sclerosis:    T  cells  a/ack  myelin  sheath  of  brain   &  spinal  cord  nerves  

•  Allergies     –  over-­‐reacHon  to  environmental  anHgens   •  allergens  =  proteins  on  pollen,  dust  mites,  in  animal   saliva   •  sHmulates  release  of  histamine  

12

Deer Park High School

Mr. Knuffke

AP Biology Make  sure  you  can  do  the  following:   1.  Explain  the  interplay  between  the  humoral  and   cell-­‐mediated  responses.   2.  Demonstrate  how  the  HIV  virus  leads  to  a   breakdown  of  the  immune  system.   3.  Explain  why  a  vaccine  works.   4.  Explain  the  causes  of  immune  system   disrupHons  and  how  disrupHons  of  the  immune   system  can  lead  to  disrupHons  of  homeostasis.  

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