Chapter 15: The Adaptive Immune Response. General Characteristics of the Adaptive Immune Response Involves specialized white blood cells known as lymphocytes

Chapter 15: The Adaptive Immune Response

General Characteristics of the Adaptive Immune Response

• Involves specialized white blood cells known as lymphocytes

• Response is highly specific (molecular specificity)

• Response generates memory

• Can discriminate between self and non-self (tolerance)

Immune cells are born in bone marrow and thymus gland

Immune cells are born in bone marrow and thymus gland

Migrate to lymphoid tissue

Migrate to lymphoid tissue

Body-circulatory system

Cells sample the environment of the body

In the secondary lymph organs, B-cells, T-cells, and Dendritic cells exchange information. T-cells activate B-cells into plasma cells that make antibodies.T-cells also activate Dendritic cells and Macrophages to kill cells. T-cells also inactivate cells that present antigens from self – healthy body cells (prevents autoimmunity)

Cells circulate looking for the invader labeled with antibodies

Antibody on microbe

NKcell

Hematopoietic stem cell(in bone marrow)

Commonlymphoid progenitor

Lymphoblasts

B cellT cell

Erythroblast Megakaryoblast

Commonmyeloid progenitor

Monoblast

MyeloblastPutative mastcell precursor

LymphocytesRed blood cell(erythrocyte)

Platelets(thrombocytes)

Megakaryocyte

Mast cell White blood cells (leukocytes)

Dendritic cellMacrophage

Naturalkiller (NK) cell

Monocyte

Granulocytes

Eosinophil NeutrophilBasophil

Self-renewal

From Last week: Innate and Adaptive immune cells—how they relate

The Cells of the Immune System• Four types of leukocytes (white blood cells)

– Granulocytes contain cytoplasmic granules

• Neutrophils engulf and destroy • Basophils involved in allergic reactions,

inflammation (Mast cells)• Eosinophils fight

parasitic worms–Also involved in

allergic reactions


Lymphoblasts

B cellT cell

Erythroblast Megakaryoblast

Commonmyeloid progenitor

MonoblastMyeloblastPutative mastcell precursor

LymphocytesRed blood cell(erythrocyte)

Platelets(thrombocytes)

Megakaryocyte

Mast cell

White blood cells (leukocytes)



Monocyte

Granulocytes

Eosinophil NeutrophilBasophil

Self-renewal

The Cells of the Immune System

• Four types of leukocytes (cont…) – Mononuclear Phagocytes

• monocytes (circulate inblood) and developinto Macrophages and Dendritic cells

– Dendritic Cells• Sentinel cells, function as “scouts”• Engulf material in tissues, bring it

to cells of adaptive immune system for “inspection”

Commonmyeloid progenitor Monoblast


Monocyte

Self-renewal

Four types of leukocytes (cont…)

LymphocytesResponsible for adaptive immunityB cells, T cells highly specific in recognition of antigenGenerally reside in lymph nodes, lymphatic tissuesNatural killer (NK) cells lack specificity


Lymphoblasts

B cellT cell

Lymphocytes


Lymphocytes are responsible for the adaptive immune response

Anatomy of the Lymphoid System• Primary Lymphoid Organs

– where the cells are made– Bone marrow and thymus

• Lymphatic Vessels—transport cells, and receive fluid from tissue—lymph

• Secondary lymphoid Organs-where cells get together and exchange antigen information

– Lymph nodes, spleen, tonsils,

peyer’s patches, MALT and SALT

SALT (skin associated lymph tissue) MALT (mucosal associated lymph tissue) and

Lumen ofintestine

Antigens

Absorptiveepithelial cellM cell

Dendriticcell

Area whereB cells gather

Lymphatic vesselsthat drain to locallymph nodes

Peyer’spatch

Area whereT cells gather

Macrophage

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Peyer’s Patch is example of secondary

lymphoid organ

Lymphaticvessel Excess tissue fluid

becomes lymph

Tissuefluid

Bloodflow

Venule Arteriole

Filtration

Absorption

Capillary


Lympth nodes—where the cells communicate

Lymph vessels take in fluid from tissue

What promotes an immune response?

• Antigens– Any molecule that reacts with antibody, B cell

receptor or T cell receptor– Composition is usually proteins or

polysaccharides– Foreign substance with MW of 10,000 daltons– Examples of antigens: bacterial capsules, cell

walls, flagella, toxins of bacteria

Small molecules are not recognized as

antigens until bound to another

Players of the Adaptive Immune Response

Activation

Proliferationand differentiation

Effector actionand consequence

Innate immunityDendritic cell

Naive cytotoxic T cell

Infected “self”cell undergoes

apoptosisAdaptive immunity(cell-mediated)

Adaptive immunity(humoral)

Antibodies Antibodies bindantigen

Naive B cell

Plasma cells

Naive helper T cell

Infected“self” cell

Macrophage withincreased killing power

Macrophage thathas engulfed

invaders

Activates T cells thatbind antigens

representing “danger”

Produceantibodies

Delivercytokines

Deliver “deathpackages”

Tc cellsTH cells


activated

activated

Bacterial cell

Antibodies

Epitopes(antigens)

Epitopes(antigens)


Antibodies bind antigens

Plasmamembrane

B-cellreceptor (BCR)

T-cell receptor(TCR)

Antigen

Antigen-bindingsite

B cell T cell

Antigen-bindingsite

CD marker

Antigen


Variableregion

Constantregion

(c)

Heavychain

Antigen-binding site

Lightchain

Fab region

Fc region

(a) (b)


Structure of an antibody

Selected B cell receives confirmation from a specific TH cell that a response is warranted(not shown here; process is illustratedin figure 15.11)

Hematopoietic stem cell

Antigen X

B cell ZB cell Y B cell Xrecognizing antigen X

B cell W

Antibodies:These neutralize theinvader and tag it fordestruction.

Plasma cells(effector B cells):These descendants ofactivated B cellssecrete large quantitiesof antibody moleculesthat bind to antigen X.

Memory B cells:These long-liveddescendants ofactivated B cellsrecognize antigen Xwhen it is encounteredagain.

Activated B cells:These cell scanproliferate becausetheir B-cell receptorsare bound to antigen Xand the cells havereceived requiredsignals from TH cells.

Activation

Proliferation anddifferentiation

Effector action

Naive B cells: Eachcell is programmed torecognize a specificepitope on an antigen;B-cell receptors guidethat recognition.

Immature B cells: Asthese develop, afunctionally limitlessassortment of B-cellreceptors is randomlygenerated.

Development


How are B cells activated?

That’s great. But, how do the cells know what is foreign and what is self?

(self vs. non-self recognition)• Self markers also known as MHC markers• MHC (major histocompatibility complex)• MHC Class I-produced by all body cells (signal

SELF—material from inside the cell)• MHC Class II-produced by dendritic cells, B cells,

and macrophages (PRESENT NON-SELF—potential invader—material outside the cell)– These cells are also called antigen presenting

cells (APCs)

B cell degrades antigen intopeptide fragments.

B-cell receptor bindsto antigen.

B-cell receptor 21

Endosome

T-cell receptor

Peptide fragments arepresented on MHC class IImolecules.

No TH cell recognizesantigen fragment;B cell becomesanergic.

B cell internalizes antigen.

TH cell recognizesantigen fragmentand activates B cell.

Cytokine delivery

4 Antigenfragment

MHC class IImolecule

Harmlessantigen

presented.

Microbialantigen

presented.

Antigen

5b

5a

3


B cell activation by Helper T cell

Anergic cells undergo cell death-elliminated

T-independent antigens activate B-cells without T cells

Opsonization by C3bInflammatory responseLysis of foreign cells

Complementsystem protein

Complement System Activation

Bacterium

Bacterium

Phagocyte

Opsonization

Neutralization

Virus

Toxin

Infected“self” cell

Antibody-Dependent CellularCytotoxicity (ADCC) Natural

killer cell

Cross-LinkingBacterium

Flagellum

Bacterium

Immobilization and Preventionof Adherence

Kills cell

What can happen when antibody binds antigen.

There are 5 classes of antibodies

• IgM

• IgG

• IgA

• IgE

• IgD

Months

Maternal IgG

Total IgG

0

Before birth Infant ageBirth

Infant IgG

100

8642864

Per

cen

t o

f n

orm

al a

vera

ge

adu

lt l

evel

of

IgG


Fig. 15.9

Naïve B cells produce IgM, then IgG antibodies

Secondaryresponse

Primaryresponse

Ag

IgM

IgG

Time after antigen (Ag) injection

MonthsDaysMonthsDays

IgG

Co

nce

ntr

atio

n o

f a

nti

bo

dy

Ag


Primary and secondary response to antigen

More about T cells—distinguish self from non-self

• Have own T cell receptor (TCR)

• Do not make antibodies

• Must recognize MHC markers which “present” antigen

T cells differ from B cells

• Must use MHC markers on host cells to recognize antigens

TC cells recognizeantigens presented onMHC class I molecules.

All nucleated cells present endogenousantigens on MHC class I molecules.

Endogenousantigen

MHC class ImoleculeCD8 T-cell receptor

CD4MHC class IImolecule

Exogenousantigen

TH cells recognize antigens presented onMHC class II molecules.

B cells and macrophages presentexogenous antigens on MHC class IImolecules.

T-cell receptor

(b)

(a)


B cell degrades antigen intopeptide fragments.

B-cell receptor bindsto antigen.

B-cell receptor 21

Endosome

T-cell receptor

Peptide fragments arepresented on MHC class IImolecules.

No TH cell recognizesantigen fragment;B cell becomesanergic.

B cell internalizes antigen.

TH cell recognizesantigen fragmentand activates B cell.

Cytokine delivery

4 Antigenfragment

MHC class IImolecule

Harmlessantigen

presented.

Microbialantigen

presented.

Antigen

5b

5a

3


Effector function of Helper-T cells

Effector function of Helper-T cells

Effector functions of Cytotoxic T cells

Natural Killer Cells…lymphocyte but not a T cell

Activation of T CellsDendritic cells in the tissue collectparticulate and soluble antigen and thentravel to the secondary lymphoid tissues.

Dendritic cells presentingmicrobial peptides produceco-stimulatory molecules.

Naive T cells that recognize antigen presentedby dendritic cells expressing co-stimulatory moleculescan become activated.

Lymphoid organ

MHC class II molecule

MHC class I molecule

Co-stimulatory molecule

T-cell receptor T-cell receptor

CD4 CD8

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 15.20


Dendritic cells presenting “self”peptides or other harmlessmaterial do not produceco-stimulatory molecules.



Naïve T cells that recognize antigen presentedBy dendritic cells not expressing co-stimulatorymolecules become anergic.

Activated T cells proliferate and differentiate.

Lymphoid organ





CD4 CD8



Dendritic cells presenting “self”peptides or other harmlessmaterial do not produceco-stimulatory molecules.



Naïve T cells that recognize antigen presentedBy dendritic cells not expressing co-stimulatorymolecules become anergic.

Activated T cells proliferate and differentiate. Anergic T cells cannot respond and eventually undergo apoptosis.

Lymphoid organ





CD4 CD8


Antibody dependent cell mediated cytotoxicity

Dendritic cell(gathers antigenfor presentationto naive T cells)

Primary lymphoid organs

Immature B cells(bone marrow)

Immature T cells(thymus)

Secondary lymphoidorgans

Naïve B cellsNaïve cytotoxicT cells (CD8)

Naïve helper T cells(CD4)

Macrophage (engulfs and destroys invaders; limited killing powers)

Infected “self” cell(harbors antigenwithin the cell)

Extracellularantigen

Dendritic cells that have gatheredantigen in the periphery present it to naïve T cells; co-stimulatory molecules are expressed if the material collected represents “danger.”

Peripheral tissues

TC cellsTH cells

MemorycytotoxicT cells

MemoryhelperT cells

TH cells activateB cells that presentspecific antigen

Plasma cellssecrete antibodies.

Antibodies(tag extracellularantigen for removal)

MemoryB cells

TH cells activate macrophages that present antigen via MHC class II molecules; also produce cytokines that determine other responses.

TC cells induce apoptosisin infected “self” cells; alsoproduce cytokines thatalert neighboring cells.

Activated macrophage (engulfs and destroys invaders; enhanced killing powers)


Documents

Chapter 15: The Adaptive Immune Response. General Characteristics of the Adaptive Immune Response Involves specialized white blood cells known as lymphocytes