1.Innate-Adaptive B9

8/8/2019 1.Innate-Adaptive B9

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Immune system -

why?


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The major types of pathogen

confronting the immune system


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Innateand

Adaptive

immunity


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Gastrointestinal,

respiratory and

Infection occur only when the pathogen can

colonize or cross through these barriers

These barriers are

permanently present.

They do not normally

increase in concentration or

respond to specific

pathogens.


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Cellular innate immunity:

Granulocytes(polymorphonuclear

leukocytes)


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Macrophages

are activated by

pathogens and

both engulf

them and initiateinflammatory

responses

Pattern recognition receptors (PRRs)

on phagocytic cells recognize and are

activated by pathogen-associated

molecular patterns (PAMPs)


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Cytokines are small proteins (~ 25 kDa) thatare released by various cells in the body,

usually in response to an activating stimulus,and they induce responses through binding to

specific receptors.

They can act in autocrine manner,affecting the behavior of the cell that

releases the cytokine, in a paracrine

manner, affecting the behavior of adjacencells and some cytokines are stable

enough to act in an endocrine manner,

affecting the behavior of distant cells.


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Infection triggers an inflammatory response


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leukocytes leave the blood and migrate to sites of infection in

a multistep process mediated through adhesive interactions

Selectins

Chemokines

Integrins


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Bactericidal agents produced or released by

phagocytes on the ingestion of microorganisms


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Mannose-

binding

lectinrecognizes

bacterial

surfaces bytheir

particular

spacing of

carbohydraeresidues


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Schematic overview of the

complement cascade


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The actions of the innateimmune systems are a

prerequisite for thedevelopment of the adaptive

immunity


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All the cellular

elements of

the bloodarise from

pluripotent

hematopoieticstem cells in

the bone

marrow


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Adaptive

immunity


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Clonal

selection


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1 lymphocyte=

1specificity


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A specific immune response,

such as the production of antibodies

or activation ofT cells against aparticular pathogen, is known as an

adaptive immune response,because it occurs during the life

time as an adaptation to infection

with that pathogen.


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The key difference between the innate

and adaptive immune systems is thatresistance to infection is not improved

by repeated infection in the innate

immune system. In contrast, theadaptive immune system will increase

the ferocity of its defense to a pathogen

with repeated infection.


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Fab

Fc

Fab


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Antibodies can participate in host defense in three main ways

FcR


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FcR


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The T-cell

receptor

resembles a

membrane-bound

Fab fragment


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TCR has

constant and

variable regionshomologous in

structure and

function to thoseof

immunoglobulins

(TCR has only a

membrane form)


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Tri-molecular interaction

MHC-Ag-TCR CD4

MHC-II

E

F

TCR

MHC-

MajorHistocompatibility complex

TCR- TCell Receptor

Ag- antigen

CD8

E F

MHC--I

TCR

Ag

Professional APC


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MHC-I molecules are expressed at

low level on the vast majority of our cells

RBCLiver

cell

MHC--I

Kidneycell

MHC-I


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MHC Class I


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CD8 T cells kill viral

infected and malignant

target cells by lythic

granules (granzyme and perforin)

and receptor-induced apoptosis

Fas Ligand

Fas

Target cell

CD8

EF

TCR

DNA fragmentation

Caspasses


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Nature reviews microbiology 3:59 (2005)

The missing

self hypothesis

Downregulation of

MHC class-I molecules

from the cell surface

by oncogenic

transformation

or virus infection

renders these cells

more susceptible

to attack by NK cells


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Professional

Antigen

PresentingCells (APCs)


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MHC Class II


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macrophages

B cells

DC

express MHC-IIand present antigen

to CD4 T cells

Professional APC

CD8

E F

MHC I

TCR

CD4

B cell

MHC II

CD4

MHC II

E F

TCR

Th di ib i f l h id i i h b d


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The distribution of lymphoid tissues in the body

Lymphatics drain

extracellular fluid (lymph)

from the peripheral tissues

into the thoracic duct

Primary

lymph nodes

peripheral

Lymph nodes

1.Innate-Adaptive B9

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