Ch 43- Immune system

Function of Immune system

• To defend the body against disease

• Pathogens – agents of disease (bacteria, viruses, protists)

Immune system• Non specific immunity (Innate immunity)

– All animals & plants have defenses effective immediately upon infection

• Specific immunity• (Adaptive or Acquired immunity)

– All vertebrates have immunity after exposure to specific pathogens (slower response).

1. Non-specific (Innate) Immunity

– 1st line of defense: barrier– Skin, mucous membrane, secretions

– 2nd line of defense: internal defenses– Phagocytosis, natural killer cells,

antimicrobial proteins, inflammatory response

Invertebrate defenses

• 1st barrier – exoskeleton made of chitin• Digestive system is protected by a chitin-

based barrier and lysozyme, an enzyme that breaks down bacterial cell walls

• The immune system recognizes bacteria and fungi by structures on their cell walls

Pathogen

PHAGOCYTICCELL

VacuoleLysosomecontainingenzymes

Hemocytes - circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria

- also secrete antimicrobial peptides that disrupt the plasma membranes of fungi and bacteria

Non-specific immunity in Vertebrates

• Include barrier defenses, phagocytosis, antimicrobial peptides

• Unique to vertebrates: natural killer cells, interferons, inflammatory response

Barrier defenses

• Skin• Mucous membranes• Body secretions: saliva ,mucus, tears • Low pH in skin & membranes

Phagocytosis

• “Cell eating” – white blood cells ingest invading pathogens

• Engulfs microbe & fuses with lysosyme to destroy it

• White blood cell attacking bacterium• http://www.youtube.com/watch?v=qvGVoxdy

-yM

• Phagocytes use Toll-like receptors (TLRs) that recognize molecular patterns characteristic of certain pathogens

• This increases efficiency of phagocytes– i.e. one type recognizes double stranded RNA (in

viruses)• Flagellin – protein found in bacteria flagella

Types of phagocytes in mammals

2 main types:• Neutrophils – short lived white blood cells

– move through bloodstream• Macrophages – largest phagocytes

– Found fixed in parts of lymphatic system (spleen, lymph nodes, thymus)

– Some travel throughout body

Other cells• Dendritic cells – phagocytic - in tissues,

stimulate adaptive immunity

• Eosinophils – (low phagocytic) help defend against multicellular invaders, release destructive enzymes

• Natural killer cells– Destroy virus-infected body cells, cancer cells– Attack cells membrane, so cell lyses

Lymphatic system

• A network of vessels that distributes lymph through the body

• Lymph nodes hold many macrophageshelp trap foreign substances

Thymus

AdenoidTonsils

Lymphaticvessels

Spleen

Lymphnodes

Lymphnode

Bloodcapillary

Interstitialfluid

Tissuecells

Lymphatic vesselLymphatic vessel

Masses ofdefensive cells

Antimicrobial proteins

• Proteins involved in attacking microbes or stopping their reproduction

• Lysozyme- present in tears & saliva, mucous

• Complement proteins – 30 serum proteins – carry out steps to lyse microbes

• Interferons – secreted by virus-infected cells, induce neighboring cells to produce chemicals to inhibit viral reproduction

Inflammatory response

• Response to cut or entry of microorganisms• Area becomes inflamed, red, swollen

• Result of chemical signals-– From invader– Nearby mast cells release histamines – released by

body cells in response to injury– Histamines dilate capillaries and increase permeability,

so fluid & clotting elements leave can enter site

Acute inflammatory responsehttp://www.youtube.com/watch?v=suCKm97yvyk

Inflammatory responsePathogen Splinter

Mastcell

Macro-phage

Capillary

Redblood cells

Neutrophil

Signalingmolecules

Movementof fluid

Phagocytosis

• Clotting begins• Other cells release chemokines, which attract

phagocytes to area• Phagocytes consume pathogens & debris• Pus - a fluid rich in white blood cells, dead

pathogens, and cell debris from damaged tissues

http://www.youtube.com/watch?v=CmbWE3jLUgM&list=UUDwoLF9pXx4RgB7BgmsnY0w

2. Specific Immunity

• Specific immune responses to particular microorganisms

• Found in vertebrates• Lymphocytes – type of white blood cells

– 2 types:– T cells – mature in thymus– B cells – mature in bone marrow

Antigens• Substances that can

elicit a response from a B or T cell

• B or T cells have antigen receptors specific for parts of that pathogen – so they can recognize specific antigens

Antigen receptors

Mature B cell Mature T cell

Recognizing antigens

• The specificity of the T & B receptors (and antibodies) is a result of shuffling and recombining several gene segments to produce the protein

• There are more than 1 million different B cells and 10 million different T cells

• Due to random arrangment, some receptors are specific for epitopes on organism’s own molecules, so B & T cells must be tested for self- reactivity.

http://www.youtube.com/watch?v=JiOwZsTO02w

• B cells:• Mature in bone marrow• Produce antibodies

• Receptors bind to intact antigens

• T cells:• Mature in thymus• Do not produce antibodies• Receptors bind to antigens

displayed by antigen-presenting cells (APCs) on their MHCs

Both: Activated by cytokines, from helper T cells

– MHC – major histocompatability complex – cell surface glycoproteins that differ among individuals

- aid in recognition of “self”

- Class I – found on nearly all body cells- can present fragments of proteins made by

infecting microbes to cytotoxic T cells

- Class II – made by some cells of immune system- macrophages & B cells- molecules collect remnants of microbes and

present them to helper T cells

Clonal selection

• Activation occurs when antigen binds to B or T cell.

• Clones formed in clonal selection – two types produced:– Effector cells – fight the antigen– Memory cells – have receptors for same antigen, so

allow quick response to subsequent infection

– http://www.youtube.com/watch?v=HUSDvSknIgI

Responses

• Primary response- when body first exposed to antigen and lymphocyte is activated

• Secondary response – when same antigen is encountered later, faster more efficient response due to memory cells

Primary immune responseto antigen A producesantibodies to A.

Secondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B.

Exposureto antigen A

Exposure to antigens A and BTime (days)

Ant

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ion

(arb

itrar

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its)

104

103

102

101

100

0 7 14 21 28 35 42 49 56

Antibodiesto A Antibodies

to B

Cell- mediated immunity

• Activation & clonal selection of cytotoxic T- cells

• Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens.

• T-cells are trained in thymus• T- cells are chosen that have correct receptors to

recognize MHC molecules• T- cells that can recognize MHC molecules

complexed with foreign peptide are allowed to pass out of thymus

• Cytotoxic T cells (Killer T cells) bind to class 1 MHC molecules, display fragments on surface of body cells. Destroy infected cells.

• Helper T-cells: secrete cytokines in response to interaction with class 2 MHC molecules – stimulate & activate both cytotoxic T cells & B cells

• Memory T cells – recognize & respond to antigen once it has already been encountered.

• http://www.youtube.com/watch?v=1tBOmG0QMbA

Humoral response

• Activation & clonal selection of effector B cells• Fight pathogens in body fluids• Activated B cells produce plasma & memory

cells• Plasma cells –(effector cells) produce

antibodies• Memory cells – for secondary response

• Antibodies – soluble proteins secreted by B cells during an immune response

• Antibodies destroy antigens through:– Neutralization: bind & block activity of antigen– Lysis: caused by activation of complement system-

form a hole in membrane of pathogen– Agglutination: clumping of bacteria or viruses– Opsonization: results in increased phagocytosis of

antigen (attracts macrophages)

• Humoral response:• http://www.youtube.com/watch?v=hQmaPwP

0KRI&list=UUDwoLF9pXx4RgB7BgmsnY0w&index=7

• Specific immunity• http://www.dnatube.com/video/194/Specific-

Adaptive-immunity-humoral-and-cell-mediated

• Active immunity – when body is exposed directly to pathogen, body responds

• (infection, vaccination)

• Passive immunity – when an individual receives antibodies

• (to fetus from mother across placenta)

What can go wrong-

• Over reaction of immune system – allergies

• Reaction against self – autoimmune disease

• Defects or problems with immune system - immunodeficiency

• Allergy reaction animation

• http://www.youtube.com/watch?v=IGDXNHMwcVs

• Our immune system/ autoimmune diseases• http://www.youtube.com/watch?v=MI-

BLaj5nFk