defense mechanism against pathogensbs.kaist.ac.kr/~metastasis/files/chapter 53 immunology.pdf ·...

Defense mechanism against pathogens

Immune SystemWhat is immune system?

Cells and organs within an animal’s body that contribute to immune defenses against pathogens (병원체)

Bacteria -Major entry points ;open wounds, inhalation, and ingestion

Parasites -Fungi, worms -Damage host by using host nutrients or secreting toxic chemicals

Viruses -May kill host cell rapidly or lie dormant for a period -May cause cancer

The job of the immune system is to 1) keep pathogens out and

2) keep pathogens if they enter the body

Immune SystemTypes of Immune system

1) Innate immune system (non-specific)

2) Adaptive immune system

Immune SystemTypes of Immune system

1) Innate immune system (non-specific)

Defense system present at birth

Protect against foreign cells or matters regardless what they are

Doesn’t require prior exposure to invaders

Innate Immune System

• First line of defense

=> If the first line of defense fails

• Second line of defense

Keep pathogens out

Players: •skin (protects body against several pathogens •stomach acid (kill pathogens including bacteria)

•mucus: trap pathogens

Kill pathogens

Players: • Phagocytes

Innate Immune System

• Second line of defense

Kill pathogens

Phagocytes : cells capable of phagocytosis (engulfing particulate matter and destroy = Eat it up)

- Present in all classes of animals- Most fundamental and ancestral of body defenses- In vertebrates, most are leukocytes (WBC) e.g., neutrophils, macrophages, natural killer (NK) cells, Basophils, - Dendritic cells

- Mast cells

Innate Immune System

• Second line of defense

Kill pathogens

Cells involved in the innate immune system

Innate Immune System

Innate Immune System

Bacterium

phagosome

Lysosome

The bacterium (upper right) is engulfed in a section of the cell's membrane

Form a structure called a phagosome

Fuse with lysosomes

Digestive enzymes in lysosomesdestroy bacterium

Innate Immune System

• Second line of defense

Kill pathogens

Phagocytes : cells capable of phagocytosis (engulfing particulate matter and destroy = Eat it up)

- Present in all classes of animals- Most fundamental and ancestral of body defenses- In vertebrates, most are leukocytes (WBC) e.g., neutrophils, macrophages, natural killer (NK) cells, Basophils, - Dendritic cells

- Mast cells

Can recognize general features of cancer or virus-infected cells and kill them

Innate Immune System

Innate Immune System

• Second line of defense

Inflammation

Small injuries e.g., cuts

- Symptoms: redness, swells, pus, heat

Why do these symptoms occur? Inflammatory response

- Innate local response to infection or injury

- Destroys or inactivates foreign invaders, clears infected area of dead cells and sets stage for tissue repair

Innate Immune SystemInflammation

Injury introduce bacteria⇒Mast cells secrete

Histamine and endothilial cells secrete nitric oxide=> Dilation of vessel

Capillaries dilate and become Leaky

⇒Fluid and leukocytes enter the site of wound

neutrophil

Neutrophils and otherphagocytes engulf and destroy bacteria

=> Capillaries return to normal

Innate Immune SystemInflammation

Innate Immune System

Other types of innate immune system

Players : Antimicrobial proteins (proteins involved in killing microbes 미생물)Interferon

Secreted by most cellsInhibits viral replication inside host cellsNot specific to a particular virus

ComplementKills microbes without phagocytosisUses membrane attack complex (MAC) to create channels in microbial plasma

membrane (=poke holes in the membrane of microbes)Causes microbe to burst

Innate Immune System

Complement

Immune System

Innate immune system (non-specific)

•Defense system present at birth

•Protect against foreign cells or mattersregardless what they are

•Doesn’t require prior exposure to invaders

Acquired immune system (specific)

•Involves antigen (항원) :any molecule thatthe host doesn’t recognize as itself

•Requires exposure to foreign substances

Aquired Immune System

•Players

Lymphocytes (림프구): •Type of white cells

•Required for the acquired immune system

Cytotoxic T cells :directly kill target

Helper T cells :Assist in activating BCells and cytotoxic T cells

Aquired Immune System

3 stages of response1)Antigen encounter and recognition by lymphocytes

2) Lymphocyte activation and cell division to produce effector cell andmemory cells

3) Attack launched by activated lymphocytes and/or their secretions

Aquired Immune System3 stages of response

1) Antigenencounterand recognitionby lymphocytes

•During its development, each lymphocyte synthesizes a membranereceptor that can bind to a specific antigen

•Antigens that bind to a lymphocyte receptor are recognized by thelymphocyte

•Each lymphocyte is specific for just one type of antigen

Antigen

Aquired Immune System3 stages of response

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

Antigen

•Upon binding the antigen, lymphocyte undergoes cell division•progeny all express the same receptor :clonal selection•B cells proliferate into plasma cells that make antibodies (each B cell can secreteonly one particular type of antibody (항체)

Aquired Immune System3 stages of response

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

3) Attack againstspecific antigen

Antigen

Effector cells carry out the attackMemory cells that remain poised for future attacks

Secrete antibody that bind to antigen(humoral immunity)

Directly attack antigen bearing cells(cell-mediated immunity)

Aquired Immune System3 stages of response

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

3) Attack againstspecific antigen

Antigen

Later, plasma cells and cytotoxic T cells die to prevent excessive immune response

Memory cells persist, waiting future attacks

Humoral Immunity (체액면역)B cells and Humoral immunity

Humoral Immunity (체액면역)Antibody

Constantregion

Variableregion

Immunoglobulin protein familyEach composed of 4 interlinked polypeptides

2 long heavy chains2 short light chains

Constant region : identical for all antibodies of a given class Variable region : antigen binding site, each ab has different variable region => bind to different antigen

Humoral Immunity (체액면역)B cells do not attack pathogens directly. Instead, secrete antibody( Ab)

Ab can in activate pathogens by

1) Physically link the pathogens to phagocytes, complement proteins and NK cells

2) Ab directly binds to toxin of pathogen: inhibit the function of toxin

Aquired Immune System3 stages of response

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

3) Attack againstspecific antigen

Antigen

Pathogen present

Antigens such as proteins from pathogens are broken downin endosome

Fragments of antigen (epitope)are complexed with MHCII

Transported to plasma membrane

Epitope-MHC complex is recognizedby T cell receptor

T-cell activation e.g., cytokine secretion : IL2 => promote division of helper

T cells

Helper T- Cell activationAntigen presenting cells

Phagocytosis by macrophage orNK cells

Pathogen

Helper T-cell receptor

cytokine secretion : IL2

B Cell activation by activated T-cells

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

3) Attack againstspecific antigen

Antigen

Memory cells persist, waiting future attacks

Activated helper Tcell

Bind to B-cellpresenting sameantigen=> promoteclonal selection

B Cell activation by activated T-cells

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

3) Attack againstspecific antigen

Antigen

humoral immunity

Summary of events in a humoral immune response

Summary of events in a humoral immune responseMost of eventhappen within alymph node

Bacteriaenterthe body

Bacteria are carriedinto lymph nodeand phagocytosisby macrophageoccurs

phagocytosis by B cells and B cell present Ag

1

2

Macrophagepresent Ag toa helper Tcells andsecret IL1

helper T cell isactivated-> secret IL2and othercytokines->Division

Activated Helper Tcellbind to B celldisplaying the sameantigen

Activation of B cells

Some B cells-> plasma cells

Other B cells-> Memory B cells

Antibody secretionby B cells->destroy bacteria

Cell mediated immunity

1) Antigenencounterand recognitionby lymphocytes

2) Lymphocyte activation and cell division

3) Attack againstspecific antigen

Antigen

Memory cells persist, waiting future attacks

Cell mediated immunityCytotoxic Tcell binds to thesurface of virusinfected cells

Cytotoxic T cellsbind to othervirus-infected cells

Helper T cell activation(same mechanism as inhumoral immune response)-> promote proliferastion andthe activation of Cytotoxic Tcells

Cytotoxic T cells secrete perforin-> inserted into the plasma membrane ofvirus-infected cells -> Cells burst

Some cytotoxic T cells do not complete full activation and remain as memory cells

Cell mediated immunity

Immune memory

Primary immune response•Initial exposure to an antigen•Antibody productionis slower andlower

Secondary immune response•Subsequent exposure to same antigen•Faster and larger antibody production•Memory B cells quickly stimulated to differentiate and multiply•Immunological memory