IMMUNE SYSTEM

FOR STUDENT COPY

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

Immune System

• must be able to identify nonself from self

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

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

Innate Immunity

• defenses that body naturally has:– Skin– Secretions– Phagocytes– Natural killer cells

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

Barrier Defenses

• cellular secretions – lysozyme kills by breaking down cell

walls– saliva, tears dilute & prevent

colonization– sweat pH 3 – 4– stomach pH 2

Adaptive Immunity

• found only in vertebrates• very specific• aka acquired immune response• activated after innate responses &

develops more slowly

2nd line: Internal, broad range patrol leukocytesleukocytes• Innate, general defense

– rapid response

• Patrolling cells & proteins– attack invaders that

penetrate body’s outer barriers • leukocytes

– phagocytic white blood cells

• complement system– anti-microbial proteins

• inflammatory response

Internal Innate Defenses

1. phagocytes• cells that can detect fungi &

bacteriathen engulf them

Types of Phagocytic Cells(#4)

1. Neutrophils– circulate in blood– attracted by signals sent from infected

cells

2. Macrophages – larger cells migrate thru tissues or

reside permanently in organs/tissues likely to have invaders

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

Neutrophils

60 to70 % of all WBCsActive phagocytesNumber increases rapidly

during short term or acute infections

Eosinophils

2 to 4 % of all WBCsIncrease during allergy

attacksReact to parasitic wormsInactivate some

inflammatory chemicals

Lymphocytes

20 to 25 % of all WBCs

Provides Immunity (eg. Killer T-Cell)

Produces antibodies

Nucleus fills most of the cell

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

Inflammatory Response

Histamine

• 1 of inflammatory signaling molecules

• stored in granules of mast cells (in CT)

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).

Fever• Advantages– Increase

transferrins– Increase IL–1

activity

• Disadvantages– Tachycardia– Acidosis– Dehydration

Some Pathogens Evade Innate Immunity

• Bacteria:– some have outer capsule that interferes

with recognition & phagocytosis– Streptococcus pneumoniae

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

• 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

Destroying cells gone bad!

perforin puncturescell membrane

cell membrane

natural killer cell

cell membrane

virus-infected cell

vesicle

perforin

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

plasma membrane of invading microbe

complement proteinsform cellular lesion

extracellular fluid

complement proteins

bacterial cell

• Specific defense – lymphocytes• B lymphocytes (B cells)• T lymphocytes (T cells)

– antibodies • immunoglobulins

• Responds to…– antigens • specific pathogens • specific toxins• abnormal body cells

(cancer)

3rd line: Acquired (active) Immunity

4 Major Characteristics of Acquired Immunity

1. immense diversity of lymphocytes & receptors– enables immune system to detect

pathogens never before encountered

2. adaptive immunity normally has “self” tolerance– arises as B cell matures

4 Major Characteristics of Adaptive Immunity

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

4. there is a stronger & more rapid response to agn previously encountered– immunological memory occurs after

mature lymphocyte encounters & binds to a specific agn

“self” “foreign”

How are invaders recognized:

antigens • Antigens– proteins that serve as cellular name tags

• foreign antigens cause response from WBCs– 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

• pathogens in blood & lymph– T cells recognize antigen fragments

• pathogens which have already infected cells

Thymus • organ in thoracic cavity• some new lymphocytes travel

from bone marrow thymus & are “taught” how to respond in immune attack mature into T cells

Lymphocytes • 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– if they react to “self” antigens,

they are destroyed during maturation

bone marrow

B cells• Humoral response = “in fluid”– defense against attackers circulating

freely in blood & lymph• Specific response– produce specific antibodies

against specific antigen• Types of B cells

• plasma cells– immediate production of antibodies– rapid response, short term release

• memory cells– long term immunity

Antibodies • Proteins that bind to a specific antigen

– multi-chain proteins produced by B cells– 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!”

each B cell has ~100,000 antigen receptors

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antigenantigen-binding site on antibody

variable binding region

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Structure of antibodies

light chains

antigen-bindingsite

heavy chains

antigen-bindingsite

lightchain light

chain

heavychains

B cellmembrane

variable region

antigen-binding siteY

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How antibodies work

macrophageeating tagged invaders

invading pathogens tagged with antibodiesY

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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

B cell immune responsetested 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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clone1000s of clone cellsY

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plasma cellsrelease antibodies

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memory cells“reserves”

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Ycapturedinvaders

Humoral ImmunityB-Cells

• Long Term Memory• B-Cells make antibodies which

trigger a T-Cell reaction to kill the invader

• Vaccines, Chicken Pox, Viral Infections

Humoral Immunity

(Go animation)

Types of Antibodies• IgG–major immunoglobulin in extra vascular

spaces– crosses placenta

• IgA– in secretions

• IgM– 1st immunoglobulin to be made by fetus– very good at clumping microorganisms

Types of Antibodies

• IgD–mostly found on B cell surfaces

• IgE– involved in allergic reactions– levels rise in helminthic parasitic

infections (worms)

Antibody Function

• do not kill pathogens• bind to agns inactivation or

destruction

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

1° vs 2° response to disease• Memory B cells allow a rapid, amplified

response with future exposure to pathogen

Humoral Immune Response

• occurs in blood & lymph

• abys neutralize or eliminate toxins & pathogen in blood or lymph

• includes a primary & secondary immune response

Cell-Mediated Immune Response

• specialized T cells destroy infected host cells

• includes primary & secondary immune responses

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 diseases

Jonas Salk• Developed first vaccine– against polio• attacks motor neurons

1914 – 1995April 12, 1955

Albert Sabin1962oral vaccine

• 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

Passive Immunity

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)

Small Pox Vaccination

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

Moon Face

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

Allergic Response

• agn attaches to IgE abys on mast cells

• when cross linked release of histamine typical allergic symptoms of itchy eyes, sneezing, runny nose, teary eyes, smooth muscle contraction constriction of airways

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

Attackof the Killer T cells!

T cells• Cell-mediated response– immune response to infected cells• viruses, bacteria & parasites (pathogens)

within cells– defense against “non-self” cells• cancer & transplant cells

• Types of T cells– helper T cells• alerts immune system

– killer (cytotoxic) T cells • attack infected body cells

How do T cells know a cell is infected?

• Infected cells digest pathogens & MHC proteins bind & carry pieces to cell surface– antigen presenting cells (APC)– alerts Helper T cells

MHC proteins displaying foreign antigens

infectedcell

T cellantigen receptors

T cellWANTED

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

T Cell response

stimulateB cells &antibodies

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killerT cell

activatekiller T cells

orinterleukin 1

interleukin 2

interleukin 2

infected cell

helperT cell

helperT cell

helperT cell

helperT cell

helperT cell

activatedmacrophage

Attack of the Killer T cells

Killer T cellbinds to

infected cell

• Destroys infected body cells– binds to target cell– secretes perforin protein• punctures cell membrane of infected cell

infected celldestroyed

cell membrane

Killer T cell

cell membrane

target cell

vesicle

perforin puncturescell membrane

HIV & AIDS• Human Immunodeficiency Virus– 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, cancer

How to protect yourself…

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

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

Autoimmune Diseases

• Immune system reacts to some molecules of self

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

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

Lymphatic System