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phagocytic leukocyte. Fighting the Enemy Within !. Immune / Lymphatic System. lymphocytes attacking cancer cell. lymph system. Avenues of attack. Points of entry digestive system respiratory system urogenital tract break in skin Routes of attack circulatory system lymph system.

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slide1

phagocytic leukocyte

Fighting theEnemy Within!

Immune / LymphaticSystem

lymphocytes

attacking

cancer cell

lymph

system

slide2

Avenues of attack

  • Points of entry
    • digestive system
    • respiratory system
    • urogenital tract
    • break in skin
  • Routes of attack
    • circulatory system
    • lymph system
why an immune system
Why an immune system?
  • Attack 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, meningitis, tuberculosisLyme disease
      • fungi
        • yeast (“Athlete’s foot”…)
      • protists
        • amoeba, malaria
  • Attack from inside
    • cancers = abnormal body cells

Mmmmm,

What’s in your lunchbox?

nonspecific vs specific defenses
Nonspecific vs. Specific Defenses
  • Three cooperative lines of defense have evolved to counter threats posed by bacteria and viruses.
  • Two of these are nonspecific - that is, they do not distinguish one infectious agent from another.
lines of defense
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 = phagocytic WBC
  • 3rd line: True immune system
    • specific, acquired immunity
      • “elite trained units”
    • lymphocytes & antibodies
      • B cells & T cells

Bacteria & insectsinherit resistance.

Vertebratesacquire immunity.

1st line non specific barriers
1st line: Non-specific barriers
  • Mechanical Barriers that physically block pathogens from entering the body. The skin is the most important mechanical barrier.
  • It is the single most important defense the body has.
1st line non specific barriers1
1st line: Non-specific barriers
  • Chemical Barriers destroy pathogens on the outer body surface, at body openings, and on inner body linings. Sweat, mucus, tears, and saliva all contain enzymes that kill pathogens. Urine is too acidic for many pathogens, and semen contains zinc, which most pathogens cannot tolerate.

In addition, stomach acid kills pathogens that enter the GI tract in food or water

1st line non specific barriers2
1st line: Non-specific barriers
  • Biological Barriers are living organisms that help protect the body.

Millions of harmless bacteria live on the human skin. Many more live in the GI tract.

The harmless bacteria use up food and space so harmful bacteria cannot grow.

1st line non specific external defense
1st line: Non-specific External defense
  • Barrier
      • skin
  • Traps
      • mucous membranes, cilia,hair,

earwax

Lining of trachea: ciliated cells & mucus secreting cells

1st line non specific external defense1
1st line: Non-specific External defense
  • Elimination
      • coughing, sneezing, urination, diarrhea
  • Unfavorable pH
      • stomach acid, sweat, saliva, urine
  • Lysozyme enzyme
      • digests bacterial cell walls
      • tears, sweat
2nd line non specific patrolling cells
2nd line: Non-specific patrolling cells

bacteria

  • Patrolling cells
    • attack pathogens, but don’t “remember” for next time
      • leukocytes
        • phagocytic white blood cells
        • macrophages, neutrophils, natural killer cells

macrophage

Phagocyte & yeast

2nd line non specific patrolling cells1
2nd line: Non-specific patrolling cells
  • Proteins
      • complement system
        • proteins that destroy cells
      • inflammatory response
        • increase in body temp.
        • increase capillary permeability
        • attract macrophages
leukocytes phagocytic wbcs
Leukocytes: Phagocytic WBCs
  • Attracted 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
destroying cells gone bad
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
    • cell ruptures (lysis)
      • apoptosis

vesicle

natural killer cell

perforin

cell membrane

perforinpuncturescell membrane

cell membrane

virus-infected cell

anti microbial proteins
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

extracellular fluid

complement proteinsform cellular lesion

plasma membrane of invading microbe

complement proteins

bacterial cell

inflammatory response
Inflammatory response
  • Damage to tissue triggers local non-specific inflammatory response
    • release chemical signals
      • histamines & prostaglandins
    • capillaries dilate, becomemore permeable (leaky)
      • delivers macrophages, RBCs, platelets, clotting factors
        • fight pathogens
        • clot formation
    • increases temperature
      • decrease bacterial growth
      • stimulates phagocytosis
      • speeds up repair of tissues
fever
Fever
  • When a local response is not enough
    • system-wide 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
3rd line acquired active immunity
3rd line: Acquired (active) Immunity
  • Specific defense with memory
    • lymphocytes
      • B cells
      • T cells
    • antibodies
      • immunoglobulins
  • Responds to…
    • antigens
      • cellular name tags
        • specific pathogens
        • specific toxins
        • abnormal body cells (cancer)

B cell

specific defenses the 3 rd line of defense
Specific Defenses: The 3rd Line of Defense
  • While microorganisms are under assault by phagocytic cells, the inflammatory response, and antimicrobial proteins, they inevitably encounter lymphocytes, the key cells of the immune system.
  • Lymphocytes generate efficient and selective immune responses that work throughout the body to eliminate particular invaders:
    • This includes pathogens, transplanted cells, and even cancer cells, which they detect as foreign.
humoral and cell mediated immunity
Humoral and Cell-Mediated Immunity
  • The immune system can mount two types of responses to antigens: a humoral response and a cell-mediated response.
    • Humoral immunityinvolves B cell activation and results from the production of antibodies that circulate in the blood plasma and lymph.
      • Circulating antibodies defend mainly against free bacteria, toxins, and viruses in the body fluids.
    • In cell-mediated immunity, T lymphocytes attack viruses and bacteria within infected cells and defend against fungi, protozoa, and parasitic worms.
      • They also attack “nonself” cancer and transplant cells.
  • The humoral and cell-mediated immune responses are linked by cell-signaling interactions, especially via helper T cells.
b s and t s
B’s and T’s
  • The vertebrate body is populated by two main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells).
  • They are said to display specificity.
    • A foreign molecule that elicits a specific response by lymphocytes is called an antigen:
      • Including molecules belonging to viruses, bacteria, fungi, protozoa, parasitic worms, and nonpathogens like pollen and transplanted tissue or organs.
lymphocytes

bone marrow

Lymphocytes
  • B cells
    • mature in bone marrow
    • humoral response system
      • “humors” = body fluids
      • attack pathogens still circulating in blood & lymph
    • produce antibodies
  • T cells
    • mature in thymus
    • cellular response system
      • attack invaded cells
  • “Maturation”
    • learn to distinguish “self” from “non-self” antigens
      • if react to “self” antigens, cells are destroyed during maturation
how are invaders recognized
How are invaders recognized?
  • Antigens
    • cellular name tag proteins
      • “self” antigens
        • no response from WBCs
      • “foreign” antigens
        • response from WBCs
        • pathogens: viruses, bacteria, protozoa, parasitic worms, fungi, toxins
        • non-pathogens: cancer cells, transplanted tissue, pollen

“self”

“foreign”

b cells
B cells
  • Attack, learn & remember pathogens circulating in blood & lymph
  • Produce specific antibodiesagainst specific antigen
  • Types of B cells
    • plasma cells
      • immediate production of antibodies
      • rapid response, short term release
    • memory cells
      • continued circulation in body
      • long term immunity
antibodies
Antibodies
  • One way that an antigen elicits an immune response is by activating B cells to secrete proteins called antibodies.
  • This structure of a lymphocyte’s receptors is determined by genetic events that occur during its early development.
    • As unspecialized cells differentiate into a B or T lymphocyte, segments of antibody genes are linked together by a type of genetic recombination in the DNA, generating a single functional gene for each polypeptide of an antibody or receptor protein.
    • This process occurs before any contact with foreign antigens and creates an enormous variety of B and T cells in the body, each bearing antigen receptors of particular specificity.
    • This allows the immune system to respond to millions of antigens.
antibodies1

Y

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Antibodies

Y

Y

  • Proteins that bind to a specific antigen
    • multi-chain proteins
    • binding region matches molecular shape of antigens
    • each antibody is unique & specific
      • millions of antibodies respond to millions of foreign antigens
    • tagging “handcuffs”
      • “this is foreign…gotcha!”

Y

Y

Y

antigen-binding site on antibody

Y

antigen

Y

Y

Y

variable binding region

Y

Y

each B cell has ~50,000 antibodies

structure of antibodies

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

antigen-binding site

variable region

s

s

s

s

s

s

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s

light

chain

s

s

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heavy

chains

s

s

s

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s

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s

s

s

s

s

s

Structure of antibodies

Y

Y

Y

Y

Y

Y

Y

light

chain

Y

Y

B cell

membrane

what do antibodies do to invaders

Y

Y

Y

Y

Y

Y

invading pathogens tagged with antibodies

macrophageeating tagged invaders

What do antibodies do to invaders?

neutralize

capture

precipitate

apoptosis

first exposure to antigen
First Exposure to antigen:
  • The selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to an antigen is the primary immune response.
    • About 10 to 17 days are required from the initial exposure for the maximum effector cell response.
    • During this period, selected B cells and T cells generate antibody-producing effector B cells, called plasma cells.
    • While this response is developing, a stricken individual may become ill, but symptoms of the illness diminish and disappear as antibodies and plasma cells clear the antigen from the body.
secondary response
Secondary Response
  • A second exposure to the same antigen at some later time elicits the secondary immune response.
    • This response is faster (only 2 to 7 days), of greater magnitude, and more prolonged.
    • In addition, the antibodies produced in the secondary response tend to have greater affinity for the antigen than those secreted in the primary response.
b cell immune response

Y

Y

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invader(foreign antigen)

B cells + antibodies

memory cells

“reserves”

recognition

Y

capturedinvaders

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

macrophage

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

clones

1000s of clone cells

plasma cells

release antibodies

10 to 17 days for full response

B cell immune response

tested by B cells

(in blood & lymph)

active immunity
Active Immunity
  • Immunity conferred by recovering from an infectious disease such as chicken pox is called active immunity because it depends on the response of the infected person’s own immune system.
    • Active immunity can be acquired naturally or artificially, by immunization, also known as vaccination.
    • Vaccines include inactivated toxins, killed microbes, parts of microbes, and viable but weakened microbes.
    • These no longer cause disease, but they can act as antigens, stimulating an immune response, and more important, immunological memory.
vaccinations
Vaccinations
  • Immune system exposed to harmless version of pathogen
    • stimulates B cell system to produce antibodies to pathogen
      • “active immunity”
    • rapid response on future exposure
    • creates immunity without getting disease!
  • Most successful against viruses
polio epidemics
Polio epidemics

1994: Americas polio free

passive immunity
Passive immunity
  • Obtaining antibodies from another individual
    • maternal immunity
      • antibodies pass from mother to baby across placenta or in mother’s milk
      • critical role of breastfeeding in infant health
        • mother is creating antibodies against pathogens baby is being exposed to
  • Injection
    • injection of antibodies
    • short-term immunity
slide36

T

What if the attacker 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!

Attackof the Killer T cells!

But how do T cellsknow someone ishiding in there?

how is any cell tagged with antigens

MHC protein

T or Bcell

MHC proteins

displaying self-antigens

How is any cell tagged with antigens?
  • Major histocompatibility (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”

Who goes there?

self or foreign?

how do t cells know a cell is infected

MHC proteins displaying foreign antigens

TH cell

WANTED

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

infectedcell

T cell with antigen receptors

t cells
T cells
  • Attack, learn & remember pathogens hiding in infected cells
    • recognize antigen 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
      • attack infected body cells
    • memory T cells
      • long term immunity

T cell attacking cancer cell

t cell response

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

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Y

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Y

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Y

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Y

killerT cell

APC:activated

macrophage

activatekiller T cells

stimulateB cells &antibodies

APC:infected cell

helperT cell

helperT cell

helperT cell

helperT cell

helperT cell

Y

Y

Y

Y

Y

Y

Y

Y

T cell response

recognition

interleukin 2

interleukin 1

or

interleukin 2

clones

recognition

attack of the killer t cells
Attack of the Killer T cells
  • Destroys infected body cells
    • binds to target cell
    • secretes perforin protein
      • punctures cell membrane of infected cell
        • apoptosis

vesicle

Killer T cell

Killer T cellbinds toinfected cell

cell membrane

perforinpuncturescell membrane

cell membrane

infected cell

destroyed

target cell

immune response

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

antibodies

antibodies

Y

Y

Y

Y

Y

Y

Y

Y

Immune response

pathogen invasionantigen exposure

skin

skin

free antigens in blood

antigens on infected cells

macrophages

(APC)

humoral response

cellular response

alert

alert

helperT cells

B cells

T cells

plasmaB cells

memoryB cells

memoryT cells

cytotoxicT cells

hiv aids
HIV & AIDS
  • Human Immunodeficiency Virus
    • virus infects helper T cells
      • helper T cells don’t activate rest of immune system: killer T cells & B cells
      • also destroys helper T cells
  • AIDS: Acquired ImmunoDeficiency Syndrome
    • infections by opportunistic diseases
    • death usually from
    • “opportunistic” infections
      • pneumonia, cancers

HIV infected T cell

slide44
AIDS

The HIV virus fools helper T-cells into thinking its proteins are “self,” and so is able to infect the cells that trigger specific immunity.

The virus forces T-cells to make more viruses, killing the T-cells when the new viruses burst out.

stage 1 primary

Short, flu-like illness - occurs one to six weeks after infection

Mild symptoms

Infected person can infect other people

Stage 1 - Primary
stage 2 asymptomatic

Lasts for an average of ten years

This stage is free from symptoms

There may be swollen glands

The level of HIV in the blood drops to low levels

HIV antibodies are detectable in the blood

Stage 2 - Asymptomatic
stage 3 symptomatic

The immune system deteriorates

Opportunistic infections and cancers start to appear.

Stage 3 - Symptomatic
opportunistic infections associated with aids

CD4<500

Bacterial infections

Tuberculosis (TB)

Herpes Simplex

Herpes Zoster

Vaginal candidiasis

Hairy leukoplakia

Kaposi’s sarcoma

Opportunistic Infections associated with AIDS
opportunistic infections associated with aids1

CD4<200

Pneumocysticcarinii

Toxoplasmosis

Cryptococcosis

Coccidiodomycosis

Cryptosporiosis

Non hodgkin’s lymphoma

Opportunistic Infections associated with AIDS
health care follow up of hiv infected patients

For all HIV-infected individuals:

CD4 counts every 3–6 months   

Viral load tests every 3–6 months and 1 month following a change in therapy   

PPD   

INH for those with positive PPD and normal chest radiograph   

RPR or VDRL for syphilis  

Toxoplasma IgG serology   

CMV IgG serology   

Pneumococcal vaccine   

Influenza vaccine in season   

Hepatitis B vaccine for those who are HBsAb-negative   

Haemophilus influenzae type b vaccination    

Papanicolaou smears every 6 months for women

HEALTH CARE FOLLOW UP OF HIV INFECTED PATIENTS
aids prevention
AIDS Prevention
  • HIV is a fragile virus that cannot live outside the human body for more than a few minutes.
  • Preventing HIV spread comes down to preventing exposure to body fluids of an infected person.
helping the immune system
Helping the immune system
  • Medical science has created to systems for augmenting the human immune system:
    • Antibiotics (NOT the same as antibodies)
    • Vaccines
how antibiotics work
How antibiotics work
  • Antibiotics help destroy bacteria (but not viruses).
  • Antibiotics work in one of several ways:
    • Slowing bacteria reproduction.
    • Interfering with bacterial cell wall formation.
antibiotic myths
Antibiotic myths
  • Antibiotics are not antibodies.
  • Antibiotics do not weaken our immune system. They help it by weakening bacteria.
  • Humans do not become “immune” to antibiotics.
  • Bacteria that resist antibiotics and are not completely destroyed may multiply, producing more antibiotic-resistant bacteria.
immune system malfunctions
Immune system malfunctions
  • Auto-immune diseases
    • immune system attacks own molecules & cells
      • lupus
        • antibodies against many molecules released by normal breakdown of cells
      • rheumatoid arthritis
        • antibodies causing damage to cartilage & bone
      • diabetes
        • beta-islet cells of pancreas attacked & destroyed
      • multiple sclerosis
        • T cells attack myelin sheath of brain & spinal cord nerves
  • Allergies
    • over-reaction to environmental antigens
      • allergens = proteins on pollen, dust mites, in animal saliva
      • stimulates release of histamine
slide59

It’s safe

to Ask Questions!