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Acquired Immune Response. Sanjaya Adikari Department of Anatomy. Immune Response. Defense against foreign invaders or cancer cells. Immune Response. Innate Response. Acquired Response. Antibody Response. Cell mediated Response. Innate Response. Adaptive Response.

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Acquired Immune Response

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Acquired Immune Response

Sanjaya Adikari

Department of Anatomy


Immune Response

  • Defense against foreign invaders or cancer cells

Immune Response

Innate Response

Acquired Response

Antibody Response

Cell mediated Response


Innate Response

Adaptive Response


Cells of the immune system


Properties of Immune cells

Activated cells

Effector cells

Inactive/Naive

Many surface molecules

Few surface molecules

Becomes larger in size

Proliferate and produce more cells

Release peptides and lipids

Increased ability to migrate


epithelium

Macrophage


Macrophage

Common receptors for immune cells of many animals

Detect pathogen associated molecular patterns


Opsonization by

Complement proteins

epithelium

Toll-like receptor

Macrophages


Toll-like receptors

Pathogen-associated molecular patterns


Phagolysosome

H2O2 O2- NO

Lysosomes

Phagosome

Activated macrophage

Prostaglandins, Leukotrienes

and Platelet activating factor


Flow increased

Velocity reduced

Lipid mediators of

inflammation

Increased diameter

Increased permeability


Increased expression of adhesion molecules


Phagolysosome

H2O2 O2- NO

Lysosomes

Phagosome

Activated macrophage

Cytokines

Chemokines


A

A

Cytokines

Proteins released by cells that affect the behavior of other cells that bear receptors for them

Chemokines

Proteins released by cells that attract other cells that bear receptors for them


H2O2 O2- NO

Neutrophil


Body tissue

Body tissue

Body tissue


Cytokines

Cytokines

activated

Chemokines

Chemokines

Mediators of infl.

activated

Cytokines

Cytokines

activated

Cytokines

Mediators of

Chemokines


Pus cells

Pus cells


Natural Killer cells

Also called NK T cells

Larger than T and B cells

Activated during the innate response by macrophage derived cytokines

Eg. IL-12 and Interferons

Produce IFN- when activated

Kills cells infected with intracellular pathogens

Mechanism of Killing is similar to that of cytotoxic T cells


Complement system

  • Augments the opsonization of bacteria by antibodies. Hence, the name, meaning that it complements the antibodies

  • Large number of plasma proteins that react with each other following a trigger

  • Most of them are proteases that are themselves activated by proteolytic cleavage


Complement system….cont.

  • Precursor proteins are widely distributed in body fluids and tissues

  • Only activated on the surface of the pathogens

  • Once triggered it becomes a huge reaction in its successive steps


Trigger


Innate immunity - summary

  • Immune cells identify the ‘pathogen-associated molecular patterns’ on the cell membrane of pathogens

  • Pathogen is immediately destroyed

  • Neutrophils and macrophages are key players

  • Complement system plays an important role

  • Activated dendritic cells present antigens


Body cells

Kill


Body cells

Kill


From Innate to Adaptive

  • Cells activated during the innate immune response bridge the gap between the innate and the adaptive systems

  • Dendritic cellsandMacrophages


Adaptive Immune Response


epithelium

Dendritic cells


Antigen presentation

Antigen presenting cells

(APC)

Toll-like receptors

Dendritic cell

or

macrophage

T

T

T

T

T

Clonal expansion of lymphocytes


Dendritic Cells (DC)

  • Most potent APC (>>> macrophages)

  • Designated as professional APC

  • Main function is to control T and B cells through presentation of different antigens


Mature

DC

B

B

T

B

B

T

T

T

T

B

T

B

Circulation

T

B

T

T

B

T

B

T

Immature

DC


Jefford et al., Lancet, June 2001


Surface molecules on DC and T cells

  • Cell-cell interaction molecules

  • Receptors for cytokines

  • Receptors for chemokines

  • Cell adhesion molecules


MHC I

MHC II

CD8

CD4

Antigen presenting cell

B-7

TCR

TCR

CD28

CD28

B7= CD80 & CD86

CD4+ helper

T cell

CD8+cytotoxic

T cell

Cell-cell interaction molecules on DC and T cells


MHC molecules

  • Two types: MHC type I and MHC type II

  • MHC type I: Expressed in all body cells

  • MHC type II: Expressed in some immune cells

    • Dendritic cells, macrophages and B cells

  • Human counterpart is called HLA

MHC – Major histocompatibility complex

HLA – Human leukocyte antigen


DC-T cell interaction

Dendritic cells send two signals to T cells

  • 1st signal – determines antigen specificity

  • 2nd signal – triggers T cell proliferation


immature DC

CD4

MHC II

1st signal

TCR

CD4+ helper T cell


mature DC

MHC II

CD4

B-7

2nd signal

TCR

CD28

CD4+ helper T cell

Increase proliferation

Secrete IL-2 (growth factor of T cells)


MHC I

MHC II

CD8

CD4

Antigen presenting cell

B-7

TCR

TCR

CD28

CD28

B7= CD80 & CD86

CD4+ helper

T cell

CD8+cytotoxic

T cell

Cell-cell interaction molecules on DC and T cells


APC

CD8

CD4

MHC I

MHC II

TCR

TCR

Intravesicular pathogens

Extracellular pathogens

Toxins

Vesicle

Cytoplasm


Th1 cells

T helper cells

(Th cells)

Th2 cells

Th0 cells


Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

IFN-

IL-4

IFN-

IL-5

IFN-

IL-4

IL-10

IL-10

IFN-

IFN-

IL-4

IL-5

IL-10

Th1 cells

Th2 cells

Macrophage Activation

B cell Activation


Th1 cells

Produce IFN-, the main macrophage-activating cytokine.

It inhibits B cells

Th2 cells

Produce IL-4, IL-5 that activates B cells and IL-10 that inhibits macrophages

Th0 cells

Produce both Th1 and Th2 cytokines and therefore have a mixed effect


Clinical relevance of Th1 vs Th2

To destroy bact. need to activate macrophages by Th1 cells

Th2 response is a waste

Mycobacterium leprae grows in macrophage vesicles.

  • Th1 response

  • Tuberculoid leprosy

  • Few live bacteria

  • Little Ab in serum

  • Skin & PN damage due to Mac. activation

  • Slow disease, patient survives

  • Th2 response

  • Lepromatous leprosy

  • Numerous live bacteria

  • Lot of Ab in serum (ineffective)

  • Gross tissue damage & death


Humoral immune response


BCR

B cell

MHC II


BCR

MHC II


BCR

MHC II


B cell

MHC II

CD4

IL-4

IL-5

IL-6

IL-10

TCR

CD4+ T helper cell

Th2


IL-4, IL-5, IL-10

Plasma cell

B cell

Ab mediated response

(Humoral immunity)


B cell

MHC II

CD4

Inhibition

Inhibition

IFN-

IFN-

TCR

CD4+ T helper cell

Th1


Cell mediated response


immature DC

CD8

MHC I

1st signal

TCR

CD8+cytotoxic T cell


mature DC

MHC I

CD8

B-7

2nd signal

TCR

CD28

CD8+cytotoxic T cell

Increase proliferation

Secrete IL-2


Kill

IFN-

mature DC

Infected Tissue

MHC I

CD8

TCR

effector

CD8+cytotoxic T cell


Kills virus or intracellular pathogen infected body cells

CD8 T cells

MHC I

Cell mediated

response

Immunological

memmory

cytokines

MHC I

MHC II

chemokines

cytokines

CD4 T cells

chemokines

B cells

Antibody mediated response


Immunological memory

  • The ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously

  • Both T cells and B cells are left behind as memory cells following the primary immune response

  • These are a distinct populations of long lived cells, without the need to getting exposed to residual antigen, in the body


Immunological memory…cont.

  • In the presence of memory T and B cells, the naïve T and B cells are not activated upon exposure to the same antigen again (would be a waste)


Adaptive immunity - summary

  • The immune cells need to specifically identify the pathogen

  • Clonal expansion of specific immune cells

  • Takes few days to build up

  • T and B lymphocytes are key players

  • Leaves behind memory cells


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