The Immune System

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Immune System


Overview• Barriers = 1st line of defense against pathogens

• Immune system recognizes foreign bodies

responds with the production of leukocytes and proteins

• 2 kinds of defense:

– innate immunity

– acquired immunity

INNATE IMMUNITY

Recognition of traitsshared by broad rangesof pathogens, using asmall set of receptors

•

•Rapid response

•Recognition of traitsspecific to particularpathogens, using a vastarray of receptors

•Slower response

ACQUIRED IMMUNITY

Pathogens(microorganisms

and viruses)

Barrier defenses:SkinMucous membranesSecretions

Internal defenses:Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells

Humoral response:Antibodies defend againstinfection in body fluids.

Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.


• present from birth

• recognition and rapid response rely on shared traits of pathogens

• nonspecific responses to pathogens

– external barriers

– internal cellular defense

– chemical defenses

– inflammation

Innate immunity


Barriers• Skin - continuous keratinized stratified

squamous layers of epithelium

• Mucus traps and allows for the removal of microbes

• Saliva, mucus, and tears are hostile to microbes (hydrolytic enzymes, high salinity)

• low pH of skin and digestive system prevents microbial growth


Cellular Innate Defenses• Phagocytic

leukocytes engulf pathogens in the body

• Groups of pathogens are recognized by TLR, Toll-like receptors of leukocytes

EXTRACELLULARFLUID Lipopolysaccharide

FlagellinTLR4

TLR5

Helperprotein

TLR9

TLR3

WHITEBLOODCELL

VESICLE

CpG DNA

ds RNA

Inflammatoryresponses


4 types:

– Neutrophils engulf and destroy microbes

– Macrophages (of lymphatic system) and are found throughout the body

– Eosinophils discharge destructive enzymes

– Dendritic cells stimulate acquired immunity

Phagocytic Cells


Chemical Defenses • Proteins and enzymes attack microbes directly

or impede their reproduction

• Interferon proteins:

– innate defense against viruses

– activate macrophages

• ~ 30 proteins form the complement system:

lysis of invading cells, trigger inflammation


Inflammatory Response• Following an injury, mast cells release

histamine:

Dilates blood vessels

increase local blood supply

more phagocytes and antimicrobial proteins enter tissues

• Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation


Inflammatory Response• Fever

– 100 – 102 Fahrenheit = beneficial

– Slows growth and reproduction of microbes

• denature their proteins

Pathogen Splinter

Macrophage

Mast cell

Chemicalsignals

Capillary

Phagocytic cellRed blood cells

Fluid

Phagocytosis


Natural Killer Cells• All cells in the body (except red blood cells)

have a class 1 MHC protein on their surface (major histocompatibility complex)

• Cancerous or infected cells lack this protein; natural killer (NK) cells attack these damaged cells


Innate Immune System Evasion by Pathogens

• Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis

• Ex. Tuberculosis (TB);

– kills more than a million people/year


• develops after exposure to foreign substances

• specific responses

– Antibody-mediated

– Cell-mediated response

• Slower

Acquired immunity


Lymphocyte-Dependent• lymphocytes recognize, remember, and

respond to antigens, foreign molecules

• Cytokines, secreted by macrophages and dendritic cells, recruit and activate lymphocytes

• T cells Lymphocytes mature in the thymus above the heart

• B cells mature in bone marrow


B and T-cell Specificity

• Each lymphocyte is specialized to recognize ONE specific type of antigen (foreign body)

• A single B cell or T cell has about 100,000 identical antigen receptors

• B cells give rise to plasma cells, which secrete proteins called antibodies or immunoglobulins (Ig) specific to the antigen

Fig. 43-9

Antigen-bindingsite

Antigen-binding site

Antigen-bindingsite

Disulfidebridge

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Lightchain

Heavy chains

T cell

chain chain

Disulfide bridge

Cytoplasm of T cell

(b) T cell receptor

Cytoplasm of B cell

(a) B cell receptor

B cell

V

V

C C

V

V

C C C C

VV


The Role of Antibodies• Neutralization occurs when a pathogen can no

longer infect a host because it is bound to an antibody

• Opsonization occurs when antibodies bound to antigens increase phagocytosis

• Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis

Animation: AntibodiesAnimation: Antibodies

Fig. 43-10

Antigen-binding sites

Antigen-bindingsites

Epitopes(antigenicdeterminants)

Antigen

Antibody B

Antibody CAntibody A

CC

CV

V

V

V

C


• The first exposure to an antigen

• Slow response

– B cells called plasma cells are generated,

– T cells are activated

• In secondary immune response, B-cell memory facilitate a faster, more efficient response

Animation: Role of B CellsAnimation: Role of B Cells

Primary Immune Response


Two branches of Acquired immunity

• Humoral (antibody-mediated) immune response

– activation and clonal selection of B cells, resulting in production of secreted antibodies

• Cell-mediated immune response

– activation and clonal selection of cytotoxic T cells

• Helper T cells aid both responses

Fig. 43-16

Humoral (antibody-mediated) immune response

B cell

Plasma cells

Cell-mediated immune response

Key

Stimulates

Gives rise to

+

+

++

+

+

+Memory B cells

Antigen (1st exposure)

Engulfed by

Antigen-presenting cell

MemoryHelper T cells

Helper T cell Cytotoxic T cell

MemoryCytotoxic T cells

ActiveCytotoxic T cells

Antigen (2nd exposure)

Secretedantibodies

Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.

Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.

+

+ +


Active Immunity• Active immunity develops naturally in

response to an infection

• It can also develop following vaccination

– a nonpathogenic form of a microbe or part of a microbe is used to initiate a primary immune response and immunological memory

The Immune System

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