Adaptive Immune response and humoural immune response.ppt

Immunology

1. Cells and organs of the
immune system

2. Hematopoiesis
Allbloodcellsarisefromatypeofcellcalledthehematopioeticstemcell
(HSC).It’sremarkablethateveryfunctionallyspecialized,matureblood
cellarisefromanHSC.
Stemcellsarecellsthatcandifferentiateintoothercelltypes.Theyare
self-renewing,maintainingtheirpopulationlevelbycelldivision.
Earlyinhematopoiesis,amultipotentstemcelldifferentiatesalongone
oftwopathways,givingrisetoeithera:
1.Lymphoidprogenitorcell,ora
2.Myeloidprogenitorcell.
*Progenitorcellshavelostthecapacityforself-renewalandarecommited
toaparticularcelllineage.

3. Lymphoid progenitor cells:
give rise to B, T, and NK cells.
Myeloid progenitor cells:
generate progenitors of red blood cells
(erythrocytes), many of the various white blood
cells (neutrophils, eosinophils, basophils,
monocytes, mast cells, dendritic cells) ,and
platelet-generating cells called megakaryocytes.
Hematopioesis is regulated at the genetic level, e.x
of these genes is (GATA-2) gene.

5. Cells of the Immune System

6. Lymphocytesarethecentralcellsoftheimmunesystem,responsiblefor
adaptiveimmunityandtheimmunologicattributesofdiversity,specificity,
memory,andself/nonselfrecognition.
Theothertypesofwhitebloodcellsplayimportantroles,engulfingand
destroyingmicroorganisms,presentingantigens,andsecretingcytokines.
LymphoidCells:
Lymphocytesconstitute20%–40%ofthebody’swhitebloodcellsand99%of
thecellsinthelymph.Theselymphocytescontinuallycirculateintheblood
andlymphandarecapableofmigratingintothetissuespacesandlymphoid
organs,therebyintegratingtheimmunesystemtoahighdegree.
Thelymphocytescanbebroadlysubdividedintothreepopulations:
*Bcells,*Tcells,and*naturalkillercells—onthebasisoffunctionandcell-
membranecomponents.
Naturalkillercells(NKcells)arelarge,granularlymphocytesthatdonot
expressthesetofsurfacemarkerstypicalofBorTcells.

7. B Lymphocytes (B cells)
•Derived it’s letter designation from it’s site of maturation, in the
bursa of fabricius in bird; and in bone marrow where is it’s major
site of maturation in a number of mammalian species including
humans and mice.
•Mature B cells display of membrane-bound immunoglobulin
(antibody) molecules, which serve as receptor for Ag (BCR) .
•The binding of the Ag to the Ab causes the cell to divide rapidly;
its progeny differentiate into :
1. Effector cells called Plasma cells ,which produce the Ab in a
form that can be secreted and have little or no membrane-bound
Ab. They are end-stage cells and do not divide.
2.Memory B cells, which have a longer life span than naïve cells,
and they express the same membrane-bound Ab as their parent B
cell.

8. B-Cell receptor

10. T-Lymphocytes (T-cell)
•It derive it litter designation from their site of
maturation in the thymus.
•During its maturation within the thymus, the T
cell comes to express on its membrane a
unique Ag-binding molecule called the T-cell
receptor.
•TCR recognize Ag that is bound to cell
membrane proteins called major
histocompaibility complex (MHC).

12. •There are two well-defined subpopulations of T cells:
1. T-helper (T H) cells, and
2. T-cytotoxic (T C) cells.
recently a third T-cell subpopulation,
3. T-regulatory ( T reg)cells .
T helper cells characterize by the presence of CD4 membrane
glycoproteins on their surfaces.
T cytotoxic cells express CD8 membrane glycoproteins on their
surfaces.
The ratio of T Hto T C is about2:1 in normal human peripheral blood,
but it may be significantly altered by immunodeficiency diseases,
autoimmune diseases, and other disorders .

13. NATURAL KILLER CELLS
Itislymphocytesthatdisplaycytotoxicactivityagainstawiderangeof
tumorcellsintheabsenceofanypreviousimmunizationwiththe
tumor.NKcellsweresubsequentlyshowntoplayanimportantrole
inhostdefensebothagainsttumorcellsandagainstcellsinfected
withsome,thoughnotall,viruses.Thesecells,whichconstitute
5%–10%oflymphocytesinhumanperipheralblood,donotexpress
themembranemoleculesandreceptorsthatdistinguishT-andB-
celllineages.
Theycanrecognizepotentialtargetcellsintwodifferentways:
1.areductioninthedisplayofclassIMHCmolecules:
NKcellsexpressnon-TCR-relatedreceptorcalledKiller-cell
inhibitoryreceptor(KIR),whichbindtoMHCclassIAg.
2.theimmunesystemhasmadeanantitumororantiviralantibodiesare
boundtotheirsurfaces.BecauseNKcellsexpressCD16,a
membranereceptorforFcregionofIgGmolecule,theycanattach
totheseantibodiesandsubsequentlydestroythetargetedcells.This
isanexampleofaprocessknownasantibody-dependentcell
mediatedcytotoxicity(ADCC).

14. NK cell(KIR) Normal cell
(MHC I)
No lysis

15. •NK cell(KIR) virus-infected or tumor
lysis

17. Mononuclear Phagocytes
The mononuclear phagocytic system consists of monocytes circulating in the
blood and macrophages in the tissues.
*Phagocytosisofparticulateantigensservesasaninitialactivatingstimulus.
*macrophageactivitycanbefurtherenhancedbycytokinessecretedby
activatedTHcells,bymediatorsoftheinflammatoryresponse,andby
componentsofbacterialcellwalls.
*Oneofthemostpotentactivatorsofmacrophagesisinterferongamma(IFN-γ)
secretedbyactivatedTHcells.
ActivatedmacrophagesalsoexpresshigherlevelsofclassIIMHCmolecules,
allowingthemtofunctionmoreeffectivelyasantigen-presentingcells.Thus,
macrophagesandTHcellsfacilitateeachother’sactivationduringthe
immuneresponse.
activated macrophages secrete:
1. a collection of cytokines, such as interleukin 1 (IL-1), TNF-αand interleukin
6 (IL-6), that promote inflammatory responses.
2. Complement proteins.
3. The hydrolytic enzymes contained within the lysosomes of macrophages.
4. TNF-α, that can kill a variety of cells.

18. Macrophagesaredispersedthroughoutthebody.Sometakeupresidencein
particulartissues,becomingfixedmacrophages,whereasothersremain
motileandarecalledfree,orwandering,macrophages.Freemacrophages
travelbyamoeboidmovementthroughoutthetissues.Macrophage-likecells
servedifferentfunctionsindifferenttissuesandarenamedaccordingtotheir
tissuelocation:
1. Alveolar macrophages in the lung.
2. Histiocytes in connective tissues.
3. Kupffer cells in the liver.
4. Mesangial cells in the kidney.
5. Microglial cells in the brain.
6. Osteoclasts in bone.

19. Granulocytic Cells:
The granulocytes are classified as neutrophils, eosinophils, or basophils on the basis of
cellular morphology and cytoplasmic staining characteristics.
Neutrophils:
are produced by hematopoiesis in the bone marrow. In response to many types of
infections, the bone marrow releases more than the usual number of neutrophils
and these cells generally are the first to arrive at a site of inflammation. The
resulting transient increase in the number of circulating neutrophils, called
leukocytosis, is used medically as an indication of infection.
Movement of circulating neutrophils into tissues, called extravasation, takes
several steps:
1.the cell first adheres to the vascular endothelium.
2. then penetrates the gap between adjacent endothelial cells lining the vessel
wall.
3. and finally penetrates the vascular basement membrane, moving out into the
tissue spaces.
A number of substances generated in an inflammatory reaction serve as
chemotactic factors that promote accumulation of neutrophils at an inflammatory
site. As for example complement components.

20. Like macrophages, neutrophils are active phagocytic cells. Phagocytosis by
neutrophils is similar to that described for macrophages, except that the lytic
enzymes and bactericidal substances in neutrophils are contained within primary
and secondary granules.
Neutrophils are in fact much more likely than macrophages to kill ingested
microorganisms. Neutrophils exhibit a larger respiratory burst than macrophages
and consequently are able to generate more reactive oxygen intermediates
and reactive nitrogen intermediates.
Eosinophils
like neutrophils, are motile phagocytic cells that can migrate from the blood into
the tissue spaces. Their phagocytic role is significantly less important than that of
neutrophils, and it is thought that they play a role in the defense against parasitic
organisms

21. Basophils
are nonphagocytic granulocytes that function by releasing
pharmacologically active substances from their cytoplasmic granules.
These substances play a major role in certain allergic responses.
Mast-cell
Mast-cell precursors, which are formed in the bone marrow by
hematopoiesis, are released into the blood as undifferentiated cells; they
do not differentiate until they leave the blood and enter the tissues. It
plays an important role in the development of allergies.

22. Dendritic cell (DC)
acquired its name because it is covered with
long membrane extensions. There are many
types of dendritic cells, although most mature
dendritic cells have the same major function,
the presentation of antigen to TH cells. Four
types of dendritic cells are known:
1. Langerhans cells.
2.Interstitial dendritic cells.
3. Myeloid cells.
4. Lymphoid dendritic cells. Each arises from
hematopoietic stem cells via different
pathways and in different locations.
They all constitutively express high levels of
both class II MHC molecules and members of
the co-stimulatory B7 family.
For this reason, they are more potent antigen-
presenting cells than macrophages and B cells,
both of which need to be activated before they
can function as antigen-presenting cells
(APCs).

23. Another type of dendritic cell, the follicular dendritic cell, does not arise in bone
marrow and has a different function from the antigen-presenting dendritic cells.
Follicular dendritic cells do not express class II MHC molecules and therefore do not
function as APCs for TH-cell activation. It express high levels of membrane receptors for
antibody, which allows the binding of Ag-Ab complexes. The interaction of B cells with this
bound antigen can have important effects on B cell responses.

24. Organs of immune system

25. Organs of the Immune System
Thesecanbedistinguishedbyfunctionastheprimaryandsecondarylymphoid
organs.
*Thethymusandbonemarrowaretheprimary(orcentral)lymphoidorgans,where
maturationoflymphocytestakesplace.
*Thelymphnodes,spleen,andvariousmucosalassociatedlymphoidtissues(MALT)
suchasgut-associatedlymphoidtissue(GALT)arethesecondary(orperipheral)
lymphoidorgans,whichtrapantigenandprovidesitesformaturelymphocytesto
interactwiththatantigen.
*Inaddition,tertiarylymphoidtissues,whichnormallycontainfewerlymphoidcells
thansecondarylymphoidorgans,canimportlymphoidcellsduringan
inflammatoryresponse.Mostprominentofthesearecutaneous-associated
lymphoidtissues(CALT).
Oncematurelymphocyteshavebeengeneratedintheprimarylymphoidorgans,they
circulateinthebloodandlymphaticsystem(anetworkofvesselsthatcollectfluid
thathasescapedintothetissuesfromcapillariesofthecirculatorysystemand
ultimatelyreturnittotheblood).

26. The human lymphoid system.
Bone marrow
Adenoids
Tonsil
Payer's patches
Thymus
Lymph nodes
Spleen
Tissue lymphatics