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IMMUNE DEFENCE OFHUMAN BODY

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IMMUNITY

immunitas

IMMUNE SYSTEM (IS) = the cells andmolecules responsible for immunity

IMMUNE RESPONSE (IR) = the

collective and coordinated response tointroduction of a foreign substance(antigen = Ag)

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IMMUNE SYSTEM

ROLES OF THE IMMUNE SYSTEM:

To identify non-self To immune recognition acts through

specific receptors

To neutralize and eliminate

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IMMUNITY

natural (native, innate)(immunity of the species) genetic inherited

acquired (specific)(individual)

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NATURAL IMMUNITYMain features

It is present in all representants of thespecie without exception

It was generate and improved through along period of time (philogenetic)

It is non-specific and it is not dependent

on the non-self agent; It is a genetic trait and

It is inherited

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A. Passive Factors (tissue)

1. Skin . It is a barrier for the penetration of microorganisms, when it is normal (intact)

2. Mucous membranes a barrier withprotective role

3. Micro-bio-organisms present localy (acompetitive action)

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B . Humoral Factors

Active factors which help to realize thenatural resistance of the body

They are present in blood, lymph, joint fluid, cerebro-rahidian fluid, in diferent secretions: milk, saliva, tears, etc.

The most important humoral factors arelyzozim, properdine, complement system, lizin, spermin

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C . C ell Factors

They have the main role in initial, rapid phaseof defence against infections

Non-specific effectors Cells,

They act through: phagocytosis and pinocytosisand they induce the distruction ofmicroorganisms Neutrophils

Eosinophils

Basophils and mast cells Platelets

Monocytes/macrophages

NK C ells

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ACQUIRED IMMUNITY

the capacity of the immune respons to respond to an antigen

It acts: active - direct stimulation of theimmune system by the antigen

It acts: passive transfer of Antibodies(Ab) (serotherapy) (deliberately) ortransplacentar (from mother to fetus),

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Ac tive Immunity

in a n atural way after an infec tion

Used in different methods of vacc in ati on

Vaccin classification according to their origin: bacterian or viral,

natural or attenuated (their virulence) or killed,

natural or produced by genetic enginery

They may be administrated once (unique dose)or may need more administration (rapel, boost,revaccination)

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P assive Immunit y

Gained in a natural way : naturaltransfer of Abs transplacentary frommother to child

Gained artificialy by inoculation of Absfrom a pacient who suffered and wascured from a disease

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IMMUNE TOLERANCE

Absence of a specific reaction of thelymphoid tissue to an antigen, when theAg is administrated in a certain dose,rythm and/or route

N atural Toleran c e

Acquired Toleran c e

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ANTIGENs (Ags)

Molecular structure which are recognizedin specific way by the cells of the immunesystem as different from the self-cells ofthe body

The agent which induces an immune response

H exogene (out of the organism),

H endogene (from the organism)- they are self-modified (altered) molecules of the body (ex. old, tumoral)

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Receptors for Ags

Any molecule which is recognized asforeign by the specific lymphocyte (ly)receptors which are called Antigen

receptor (Ag R)F There are two types:

Present on T ly, called TCR

Present on B ly surface, BCR. They arealso called membrane immunoglobulins(mIg)

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Epitop

Not the entire molecule of the Ag reactswith the ly receptor, but only a small part of the Ag = epitop (on the Ag!)(Antigenic determinant)

Epitop is a small part - diameter about

3nm, which interacts with a smallportion of the specific receptor = paratop(on the receptor or on the Ab)

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Immune Reactions induced by theAgs

Activation of ly which carry specific receptors

Induction of specific Abs synthesis

Induce immune memory

Induce specific immune effector response:

HNo immune response Immune tolerance

HA proper immune response Protection

H An immune response which is unproperly or inexcess Lack of defence, Hypersensitivity,Autoimmunity,

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1.Ag dependent c ondition

The molecule must be forei gn , non self. Usually there is no IR against self,

Molec ular wei ght should be over (>)40kDa.

The struc t ure of the molec ule bothc hemi c aly and spac ely is important

It must remain for a ti me in organism

Quantity (dose) to be administrated

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2 .H ost dependent c onditions

Spec ie

Age of the body

Physiologi c al c ondition of the body

The way of inoc ulation

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S pec ial S y stem: hapten - c arrier

Substances with a lower molecular weight (< 1.000 Da), are not able to induce anIR, unless they a link to a protein of thebody (in special conditions) = hapten

They must be covalently bound to a larger

molecule = c arrier (protein)

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H apten - c arrier s y stem

xsubstances which are haptene

Metals (nichel, crom),

Small polyzaharids, phosphocolin (present on surfaces of

some microbs),

Numerouse chemical substances (drugs,

colorants, dinitro- and trinitro-clorobenzen, oligonucleotides etc),

Vegetal origin substances (vegetal oils from plants)

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MHC Antigens

Major Histocompatibility antigens (molecules) =MHC

There are two class: I and II

HLA (human leukocyte antigens)

Major role in presentation of the Ag to T cellsrole in individual recognition (specific for eachperson) very important in transplants

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MH C Anti gens

C lass I MH C Anti gens

Membrane glicoprotein encoded by genes of class IMHC system

Present on the membrane of all nucleated cells of the organism.

They represent classic Ags of transplant .

role in presentation of some epitops produced by

fragmentation of endogene Ags to T cytotoxic lyCD8 positive cells (Tc)

The have a long polypeptidic chain E non-covalently associated with small polypeptides = 2microglobulin

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MH C Anti gens

C lass II MH C Anti gens Membrane heterodimeric glicoprotein

encoded by genes of class II MHC

Structure: two polypeptidic chains:E

chain(different of E chain of class I MHC) and chain

They are selectively express on the surface of Agpresenting cells (APC): monocytes, macrophages,

dendritic cells, B ly They present to T helper/inducer (Th) ly, CD4

pozitive. They present epitops produced bycleavage of exogene Ags in APC lyzozoms.

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LYMPHOID ORGANS

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LYMFOID ORGANS

Primary lymphoid organs Thymus Bone Marrow

Secundary lymphoid organs (periferic) Lymph nodes Spleen Tonsils

Peyers patches Appendix

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Primary lymphoid organs

1. Thymus

a lymphoepitelial organ formed by twolobs united by an istm

situated in superior 1/3 of mediastin

Has precursoar cells of lymphocytes,named prothymocytes,

Differention process T Lymphocyte

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1. Thymus

Here the production of lymphocytes iscontinue and it is realized in the absenceof any Ag stimuli

It produce the immunological maturationof T normal lymphocytes

Has two zone: Cortical Zone

Medular Zone

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2 . Bone Marrow

It the place for stem cells which are sopluripotent, they generate precursoar

cells: mieloide and lymphoid it is able to autoregenerate

it induces differention

Blood cells - granulocytes, erythrocytes,

megacariocytes, monocytes orlymphocytes (B lymphocytes)

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Secundary lymphoid organs

lymphocytes (T and B) migrate throughblood in secundary lymphoid organs

in perinatal period

Complet Immune Response

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1.Lymph nodes

Small, nodular lymphoidstructure,

localized:

on lymphatic vases

in the hil of parenchimatosorgans

Cortical zone mainly

B ly are present, at external part

Medular zone mainly

T ly, in the central part

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1.Lymph nodes

contain 3 types of cells:

lymphoid cells (T, B) immunocompetent macrophage-mononuclear cells

Dendritic cells and conjunctive cells

duble function: exclusion of patogens (phagocytosis of

macrophages)

development of specific IR

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2. Spleen

The larger lymphoid organ

conjunctive capsule white pulp and red pulp

in white pulp the lymphoid zone thereare two aria:

one thymo-independent B ly one thymo-dependent T ly

there are also macrophages and dendritic cells,plasmocytes

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2. Spleen

Red Pulp

Formed by vascular synusoids with manymacrophages

Destruction of senescent erythrocytes

It is a reservoire of erythrocytes

Other roles

Collects and destroys alterated cells

it a reservoire of iron

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3. Tonsils

maintain a balance of different bacterian

populations from mouth cavity protects the upper airways

4. Peyers patches

lymphoid cells associated to smallintestinal mucosa

local immune defence

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5. Appendix lymphoid organ associated to digestive tract

Aggregation of lymphoid tissue mainly B ly

and plasmocytesthere are many other aggregation of

lymphoid cells

trachea, bronchia, skin, kidney, brain local or general reaction of defence

through macrophages

And other cells that can present Ag

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CELLS OFSPECIFIC IMMUNE RESPONSES

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IMMUNE CELLS

Are:

lymphocytes - T and B,

Ag presenting cells (APC).

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1. LYMPHOCYTES

small cells from white blood cells,

round, � of 8-15 m, with a large, round

nucleus recognize and react with "nonself" through

membrane receptors specific for Ags(BCR, TCR).

receptors of each cells are able to recognizeonly one antigenic determinant (epitop)

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1. LYMPHOCYTES

T lymphocytes (cells) (thymo-dependent)

B lymphocytes (cells) (bone marrow-dependent)

NK cells - kill, without MHC restriction

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1. LYMPHOCYTES - roles

They react with Ag (for which they havespecific receptors) and they became activeand they can divide = clonal expansion

The recognition of Ag with the epitop fromthe membrane receptors induce theactivation and transformation of thelymphocytes in immune effector cells

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1. LYMPHOCYTES - roles

activate lymphocytes secrete mediators cytokines - which induce movementsand amplify in a non-specific way theeffector cells activity

keep immunological memory after first contact with the Ag,

some lymphocytes may act directly onone target cell direct cytotoxic effect

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B Ly mphoc y tes (B ly)

activated after Ag stimulation, theyproliferate and than they differentiate in

plasmocytes, secret Abs memory B lymphocyte at a second

contact with the Ag, they quickly areactived and they transform inplasmocytes which secret high amount of Ig with high affinity

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T Ly mphoc y tes (T ly)

Receptor for Ag of T ly (TCR) recognizethe Ag only when is presented by MHCmolecules

1. T helper/induc tor Ly mphoc y tes (T h, T H , CD4+)

2 . T c y totoxi c Ly mphoc y tes (T c or T C L, CD8+)

3 . T regul atory

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ANTIGEN PRESENTING CELLS (APC)

1. Macr ophages

recognize

phagocyte prepare intracytoplasmatic the non-self

molecules/microorganisms which laterare presented to T ly in a properstructure

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ANTIGEN PRESENTING CELLS (APC)

2 . D endr iti c Cell s

In the hole body (anywhere)

important role in induction of the IR They have the abi l ity t o sti mulate T

l y

3 . Ast r oc ytes 4. Lan ger hans c ell s

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