Acquired Immune

Response

Sanjaya AdikariDepartment 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

Inactive/Naive Activated cellsEffector cells

Few surface molecules Many surface molecules

Becomes larger in size

Proliferate and produce more cells

Release peptides and lipids

Increased ability to migrate

Macrophage

epithelium

Macrophage

Common receptors for immune cells of many animals

Detect pathogen associated molecular patterns

Macrophages

Opsonization by Complement proteins

epithelium

Toll-like receptor

Toll-like receptors

Pathogen-associated molecular patterns

Phagosome Lysosomes

Phagolysosome

H2O2 O2-

NO

Activated macrophage

Prostaglandins, Leukotrienesand Platelet activating factor

Flow increasedVelocity reduced

Lipid mediators ofinflammation

Increased diameter

Increased permeability

Increased expression of adhesion molecules

Phagosome Lysosomes

Phagolysosome

H2O2 O2-

NO

Activated macrophage

ChemokinesCytokines

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

A

A

Neutrophil

H2O2 O2- NO

Body tissue

Body tissue

Body tissue

activated

activated

activated

Cytokines

Mediators of

Chemokines Mediators of infl.

Cytokines

Chemokines

Cytokines

Cytokines

Cytokines

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 cytokinesEg. 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

Kill

Body cells

Kill

Body cells

From Innate to Adaptive

Cells activated during the innate

immune response bridge the gap

between the innate and the adaptive

systems

Dendritic cells and Macrophages

Adaptive Immune Response

Dendritic cells

epithelium

TT

T

Antigen presentation

Antigen presenting cells(APC)

Toll-like receptors

T T

Dendritic cell or

macrophage

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

T BT BT B

MatureDC

TT

ImmatureDC

Circulation

TBT

BT B

TB

TB

T

B

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

B7= CD80 & CD86

MHC I

B-7

MHC II

Antigen presenting cell

Cell-cell interaction molecules on DC and T cells

TCR

CD8

CD28TCR

CD4

CD28

CD4+ helper T cell

CD8+cytotoxic T cell

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 HLAMHC – Major histocompatibility complexHLA – Human leukocyte antigen

DC-T cell interaction

1st signal – determines antigen

specificity

2nd signal – triggers T cell proliferation

Dendritic cells send two signals to T cells

TCR

CD4+ helper T cell

CD4MHC II

immature DC

1st signal

TCR

CD4

CD28

B-7

Increase proliferation

MHC II

mature DC

2nd signal

CD4+ helper T cell

Secrete IL-2 (growth factor of T cells)

B7= CD80 & CD86

MHC I

B-7

MHC II

Antigen presenting cell

Cell-cell interaction molecules on DC and T cells

TCR

CD8

CD28TCR

CD4

CD28

CD4+ helper T cell

CD8+cytotoxic T cell

MHC IMHC II

APC

TCR

CD8

TCR

CD4

Vesicle Cytoplasm

Intravesicular pathogensExtracellular pathogensToxins

T helper cells(Th cells)

Th1 cells

Th2 cells

Th0 cells

Cytokines

Cytokines

Cytokines

Cytokines Cytokines

Cytokines

Th1 cells

IFN-

IFN-

IFN-IFN-

IFN-

Cytokines

Cytokines

Cytokines

Cytokines

Cytokines

Th2 cells

IL-4

IL-4IL-4

IL-5

IL-5

IL-10IL-10

IL-10

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

Mycobacterium leprae grows in macrophage vesicles.

Clinical relevance of Th1 vs Th2To destroy bact. need to activate macrophages by Th1 cells

Th2 response is a waste

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

MHC II

B cell

BCR

MHC II

BCR

MHC II

BCR

MHC II

TCR

CD4

CD4+ T helper cell

B cell

IL-4IL-5IL-6

IL-10

Th2

B cellPlasma cell

Ab mediated response(Humoral immunity)

IL-4, IL-5, IL-10

MHC II

TCR

CD4

CD4+ T helper cell

B cell

IFN-IFN-

Th1

InhibitionInhibition

Cell mediated response

TCR

CD8+cytotoxic T cell

CD8MHC I

immature DC

1st signal

TCR

CD8

CD28

B-7

Increase proliferation

MHC I

mature DC

2nd signal

CD8+cytotoxic T cell

Secrete IL-2

TCR

CD8MHC I

mature DC

effectorCD8+cytotoxic T cell

Infected Tissue

Kill

IFN-

CD4 T cells

CD8 T cells

cytokines

chemokines

Kills virus or intracellular pathogen infected body cells

MHC I

MHC IMHC II

cytokines

chemokines

B cells

Cell mediated response

Antibody mediated response

Immunologicalmemmory

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