IMMUNE SYSTEM FOR STUDENT COPY - PowerPoint Presentation

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IMMUNE SYSTEM

FOR STUDENT COPY

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Key attributes of immune system

4 attributes that characterize the immune system as a whole

specificity

antigen-antibody specificity

diversity

react to millions of antigens

memory

rapid 2° response

ability to distinguish self vs. non-self

maturation & training process to reduce auto-immune disease

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Immune System

must be able to identify

nonself

from self

detection determined by molecular recognition of receptor & cell-identity markers molecules

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Innate Immunity

nonspecific defense that is active immediately upon infection

found in all animals & plants

includes:

outer covering

skin

chemical secretions

@ openings to interior of body

Mucous membranes

Sweat glands

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Innate Immunity

defenses that body naturally has:

Skin

S

ecretions

Phagocytes

Natural killer cells

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Barrier Defenses

epithelial tissues block entry of many pathogens

skin

mucous membranes

line organs that have opening to outside of body

mucus: viscous fluid that blocks microbes & other particles

saliva, tears have “washing” action keeping microbes from colonizing

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Barrier Defenses

cellular secretions

lysozyme

kills by breaking down cell walls

saliva, tears dilute & prevent colonization

sweat pH 3 – 4

stomach pH 2

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Adaptive Immunity

found only in vertebrates

very specific

aka

acquired immune response

activated after innate responses & develops more slowly

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2nd line: Internal, broad range patrol

leukocytes

Innate, general defenserapid responsePatrolling cells & proteinsattack invaders that penetrate body’s outer barriers leukocytesphagocytic white blood cellscomplement systemanti-microbial proteinsinflammatory response

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Internal Innate Defenses

1. phagocytes cells that can detect fungi & bacteria then engulf them

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Types of Phagocytic Cells(#4)

Neutrophils

circulate in blood

attracted by signals sent from infected cells

Macrophages

larger cells migrate thru tissues or reside permanently in organs/tissues likely to have invaders

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Types of Phagocytic Cells

3.

Dendritic

cells

mainly found in tissues

with

contact

to outside

(skin)

stimulate adaptive immunity after engulfing pathogen

4.

Eosinophils

found beneath mucous membranes

low

phagocytic

activity

speciality

: able to defend against parasitic worms



secrete enzymes

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Neutrophils

60 to70 % of all WBCsActive phagocytesNumber increases rapidly during short term or acute infections

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Eosinophils

2 to 4 % of all WBCsIncrease during allergy attacksReact to parasitic wormsInactivate some inflammatory chemicals

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Lymphocytes

20 to 25 % of all WBCsProvides Immunity (eg. Killer T-Cell)Produces antibodiesNucleus fills most of the cell

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Inflammatory Response

innate immune defense triggered by physical injury or infection of tissue involving the release of substances that promote swelling, enhance the infiltration of WBCs, & aid in tissue repair & destruction of invading pathogens

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Inflammatory Response

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Histamine

1 of inflammatory signaling moleculesstored in granules of mast cells (in CT)

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Fever: Abnormally High Body Temperature

Hypothalamus normally set at 37°C.

Gram-negative

endotoxin

cause phagocytes to release interleukin–1 (IL–1).

Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature.

Body increases rate of metabolism and shivering which raise temperature.

When IL–1 is eliminated, body temperature falls (crisis).

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Fever

AdvantagesIncrease transferrinsIncrease IL–1 activity

DisadvantagesTachycardiaAcidosisDehydration

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Some Pathogens Evade Innate Immunity

Bacteria:some have outer capsule that interferes with recognition & phagocytosisStreptococcus pneumoniae

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Natural Killer Cells

circulate thru body detecting

abnl

surface proteins of cells infected with virus or cancer cells

on detection

 secrete chemicals that kill affected cell

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Natural Killer Cells perforate cellsrelease perforin proteininsert into membrane of target cellforms pore allowing fluid to flow into cellcell ruptures (lysis)apoptosis

Destroying cells gone bad!

perforin puncturescell membrane

cell

membrane

natural killer cell

cell membrane

virus-infected cell

vesicle

perforin

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Anti-microbial proteins

Complement system

~20 proteins circulating in blood plasmaattack bacterial & fungal cellsform a membrane attack complexperforate target cellapoptosiscell lysis

plasma membrane of invading microbe

complement proteinsform cellular lesion

extracellular fluid

complement proteins

bacterial cell

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Specific defense lymphocytesB lymphocytes (B cells)T lymphocytes (T cells)antibodies immunoglobulinsResponds to…antigens specific pathogens specific toxinsabnormal body cells (cancer)

3rd line: Acquired (active) Immu

nity

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4 Major Characteristics of Acquired Immunity

immense diversity of lymphocytes & receptors

enables immune system to detect pathogens never before encountered

adaptive immunity normally has “self” tolerance

arises as B cell matures

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4 Major Characteristics of Adaptive Immunity

cell proliferation triggered by activation greatly increases the # of B and T cells

there is a stronger & more rapid response to

agn

previously encountered

immunological memory occurs after mature lymphocyte encounters & binds to a specific

agn

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“self”

“foreign”

How are invaders recognized: antigens

Antigensproteins that serve as cellular name tagsforeign antigens cause response from WBCsviruses, bacteria, protozoa, parasitic worms, fungi, toxins non-pathogens: pollen & transplanted tissueB cells & T cells respond to different antigensB cells recognize intact antigenspathogens in blood & lymphT cells recognize antigen fragmentspathogens which have already infected cells

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Thymus

organ in thoracic cavitysome new lymphocytes travel from bone marrow  thymus & are “taught” how to respond in immune attack  mature into T cells

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Lymphocytes

B cellsmature in bone marrowhumoral response system “humors” = body fluidsproduce antibodiesT cells mature in thymuscellular response systemLearn to distinguish “self” from “non-self” antigens during maturationif they react to “self” antigens, they are destroyed during maturation

bone marrow

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B cells

Humoral response = “in fluid”defense against attackers circulating freely in blood & lymphSpecific responseproduce specific antibodies against specific antigenTypes of B cellsplasma cellsimmediate production of antibodiesrapid response, short term releasememory cellslong term immunity

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Antibodies

Proteins that bind to a specific antigen

multi-chain proteins produced by B cellsbinding region matches molecular shape of antigenseach antibody is unique & specific millions of antibodies respond to millions of foreign antigenstagging “handcuffs”“this is foreign…gotcha!”

each B cell has ~100,000 antigen receptors

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antigen

antigen-

binding site on antibody

variable

binding region

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Structure of antibodies

light chains

antigen-binding

site

heavy chains

antigen-binding

site

light

chain

light

chain

heavy

chains

B cell

membrane

variable region

antigen-binding site

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How antibodies work

macrophage

eating tagged invaders

invading pathogens tagged with antibodies

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B Cell Activation

starts when

agn

binds to a B cell

agn

receptor

ends with B cell secreting soluble form of its

agn

receptor = antibody (

aby

) or immunoglobulin (

Ig

)

abys

have same “Y” shaped organization as the B cell

agn

receptor

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B cell immune response

tested by

B cells(in blood & lymph)

10 to 17 days for full response

invader

(

foreign antigen

)

B cells + antibodies

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recognition

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clone

1000s of clone cells

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plasma cells

release antibodies

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memory cells

“reserves”

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captured

invaders

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Humoral ImmunityB-Cells

Long Term MemoryB-Cells make antibodies which trigger a T-Cell reaction to kill the invaderVaccines, Chicken Pox, Viral Infections

Humoral

Immunity

(Go animation)

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Types of Antibodies

IgG

major immunoglobulin in extra vascular spaces

crosses placenta

IgA

in secretions

IgM

1

st

immunoglobulin to be made by fetus

very good at clumping microorganisms

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Types of Antibodies

IgD

mostly found on B cell surfaces

IgE

involved in allergic reactions

levels rise in

helminthic

parasitic

infections (worms)

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Antibody Function

do not kill pathogensbind to agns  inactivation or destruction

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Immunological Memory

gives individual long term protection from an infection or vaccination

Primary Immune Response

produces

effector

cells from a clone of lymphocytes

peaks 10 -17 days after initial exposure

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1° vs 2° response to disease

Memory B cells allow a rapid, amplified response with future exposure to pathogen

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Humoral Immune Response

occurs in blood & lymphabys neutralize or eliminate toxins & pathogen in blood or lymphincludes a primary & secondary immune response

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Cell-Mediated Immune Response

specialized T cells destroy infected host cellsincludes primary & secondary immune responses

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Vaccinations

Immune system exposed

to harmless version of pathogen

triggers

active immunity

stimulates immune system to produce

antibodies to invader

rapid response if

future exposure

Most successful

against viral disease

s

Slide51

Jonas Salk

Developed first vaccine

against polioattacks motor neurons

1914 – 1995

April 12, 1955

Albert Sabin

1962

oral vaccine

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Obtaining antibodies from another individual Maternal immunityantibodies pass from mother to baby across placenta or in mother’s milkcritical role of breastfeeding in infant healthmother is creating antibodies against pathogens baby is being exposed toInjectioninjection of antibodiesshort-term immunity

Passive

Immunity

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Artificial Active Immunity

Immunizations: introduce

agns

to body



abys

develop giving immunity to person receiving vaccination

Jenner: took cowpox virus to induce adaptive immunity against small pox (closely related viruses)

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Small Pox Vaccination

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Tissue & Organ Transplants

MHC molecules stimulate the immune response that

 rejection

MHC molecules have many alleles and any 1 individual has many that vary in shape & charge

for most transplant recipients there will be some MHC molecules seen as foreign

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Moon Face

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Graft Versus Host Rejection

seen in bone marrow transplants

recipient’s bone marrow radiated b/4 to get rid of

abnl

cells

 also wipes out their immune system

lymphocytes in donor’s marrow react to “foreign” recipients tissues and cells

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Allergic Response

agn attaches to IgE abys on mast cellswhen cross linked  release of histamine  typical allergic symptoms of itchy eyes, sneezing, runny nose, teary eyes, smooth muscle contraction  constriction of airways

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2007-2008

What if the attacker gets past the B cells in the blood & actually infects some of your cells?

You need trained assassins to kill off these infected cells!

T

Attack

of the

Killer T cells!

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T cells

Cell-mediated responseimmune response to infected cellsviruses, bacteria & parasites (pathogens) within cellsdefense against “non-self” cellscancer & transplant cells Types of T cellshelper T cellsalerts immune systemkiller (cytotoxic) T cells attack infected body cells

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How do T cells know a cell is

infected?

Infected cells digest pathogens & MHC proteins bind & carry pieces to cell surfaceantigen presenting cells (APC)alerts Helper T cells

MHC proteins displaying foreign antigens

infectedcell

T cell

antigen receptors

T cell

WANTED

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Cytotoxic T Cells

in cell-mediated immune response

role:

effector

cells

synthesize toxic gene products that

kill

infected cells

activated by signaling molecules from helper T cells + interaction with APC

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T

Cell

response

stimulate

B cells &

antibodies

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killer

T cell

activate

killer T cells

or

interleukin 1

interleukin 2

interleukin 2

infected cell

helper

T cell

helper

T cell

helper

T cell

helper

T cell

helper

T cell

activated

macrophage

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Attack of the Killer T cells

Killer T cell

binds to

infected cell

Destroys infected body cells

binds to target cell

secretes perforin proteinpunctures cell membrane of infected cell

infected celldestroyed

cell

membrane

Killer T cell

cell membrane

target cell

vesicle

perforin

punctures

cell membrane

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HIV & AIDS

Human Immunodeficiency Virusvirus infects helper T cellshelper T cells don’t activate rest of immune system: T cells & B cellsalso destroy T cellsAcquired ImmunoDeficiency Syndromeinfections by opportunistic diseasesdeath usually from other infectionspneumonia, cancer

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How to protect yourself…

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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

Slide69

Allergies

exaggerated hypersensitivity reactions to

allergens

:

agn

that triggers exaggerated immune response

most involve

aby

of

IgE

class

example:

hayfever

agn

on surface of pollen grains

Slide70

Autoimmune Diseases

Immune system reacts to some molecules of self

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Stress & the Immune System

psychological stress disrupts immune system by altering interplay of the nervous system endocrine system & immune system

rest important for immunity

adults with < 7 hrs sleep/

nite

:

3x

more likely to get sick when exposed to cold virus as those who average 8 hrs sleep/

nite

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Lymphatic System

network of vessels that connect lymphatic tissues thru out body

ECF

 lymph vessels  lymph nodes  lymph vessels  venous drainage

some macrophages in lymph nodes

Slide73

Lymphatic System