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Sistemul limfatic Organe si tesuturi limfoide

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7/28/2019 Immuno 4 Sistem Raspuns Imun

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Sistemul limfatic

Organe si tesuturi limfoide

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Cells of the specific immune

systemT cell B cell

•Involved with cell mediatedimmunity

•Two types:

helper T cells (CD4) cytotoxic T cells (CD8)

•Generally eliminate intracellular pathogens

•Involved with humoralimmunity

•Secrete antibodies

•Generally eliminate extracellular pathogens

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Lymphatic System: Overview

Function:

Drain fluid fromaround cells

Absorb fat fromintestines

Circulate lymph Filter lymph

Immunity

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ANATOMY OF THE IMMUNE SYSTEM

The immune

system is localizedin several parts ofthe body

– immune cells

develop in theprimary organs - bone marrowand thymus

(yellow)– immuneresponses occur in thesecondaryorgans (blue)

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The bursa of Fabricius in birds

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Eosinofil

Monocit

Macrofag

Neutrofil

Basofil

Originea celulelor implicate în răspunsul imun  

Celula stem

Hematopoietica

B

TimusNK

Celula

dendritica

Mastocit

Plasmocit

CD4

T

Progenitor mieloid

Progenitor  limfoid

CD8

IL1,3,6

IL7

GM CSF M CSF

IL 3

G CSF

IL 5

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Lymphocyte Maturation

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ANATOMY OF THE IMMUNE SYSTEM

Bone marrow – blood-producing tissue located inside certainbones (5% BW)– blood stem cells give rise to all of the different types of

blood cells

Thymus – glandular organ near the heart – where T cells learn

their jobs

Spleen – serves as a filter for the blood– removes old and damaged red blood cells– removes infectious agents and uses them to activate cells

called lymphocytes

Lymph nodes – small organs that filter out dead cells,antigens, and other “stuff” to present to lymphocytes 

Lymphatic vessels – collect fluid (lymph) that has “leaked” outfrom the blood into the tissues and returns it to circulation

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B-CELL DEVELOPMENT 

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B-CELL DEVELOPMENT 

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Thymus

A bilobed organ in mediastinumabove the heart

The size of the thymus varieswith age

– In infants, it is found in theinferior neck and extendsinto the mediastinum whereit partially overlies the heart

– It increases in size and is

most active during childhood– It stops growing during

adolescence and thengradually atrophies

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T-CELL DEVELOPMENT 

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T-CELL DEVELOPMENT 

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Steps in T cell development

Step 1. Positive selection occurs in the thymic cortex

T cells (CD4+CD8+) that

recognise foreign antigenpresented in the form ofantigen/MHC complexes byantigen-presenting cellswithin the thymus are

allowed to live

This is called positiveselection

MHC self-recognition

molecules

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Steps in T cell development

Step 2. Negative selection 

occurs in the thymic medulla.

T cells are presented with selfantigen/MHC complexes byantigen-presenting cells withinthe thymusIf T cells bind and recognisethese self antigens they are

destroyed by apoptosisThe immune system destroys T cells specific for self-antigen

This is called negative

selection

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T-CELL DEVELOPMENT 

The result is a T cellrepertoire thatrecognisesforeign antigen

and is toleranttowards selfantigen

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Know your Flow!

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Spleen Largest lymphoid

organ In upper left

quadrant ofabdomen

Has a hilum and a

capsule Sinuses contain

blood instead oflymph

Filters blood

– Worn out RBC

– Bacteria

Lymphocytes

Monocytes

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Structure of the Spleen

Surrounded by a fibrouscapsule, it has trabeculae thatextend inward and containslymphocytes, macrophages,and huge numbers oferythrocytes and platelets

Two distinct areas of thespleen are:

– White pulp – areacontaining mostlylymphocytes suspended onreticular fibers andinvolved in immunefunctions

– Red pulp – remainingsplenic tissue (MQ)concerned with disposing

of worn-out RBCs andbloodborne pathogens

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Additional Spleen Functions

Stores breakdown products of RBCs forlater reuse

– Spleen macrophages salvage and storeiron for later use by bone marrow

Site of fetal erythrocyte production(normally ceases after birth)

Stores blood platelets

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Lymph

Fluid of the lymphatic systemSimilar to blood plasma and interstitial fluid

Lymphatic Vessels 

Transport lymphLymph is returned to the circulatory system at either theright or left subclavian veins

Lymph Nodes500-600, 1-10 mm Filter lymph, Microorganisms, Cancer cells, LymphocytesMonocytes

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Lymph Nodes

Lymph is filtered throughlymph nodes

Found in clusters

Vary in size Principal groupings in deepthoracic, abdomen andcervical, axillary, inguinalregions.

Provide biological filtration Site of cancer growth and

metastasis

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Lymph Node

Capsule, cortex and medulla: Cortex contains lymph

nodules Follicular dendritic cells

Germinal centers – B cellsproliferate Lymphatic vessels enter

node on convex side Lymph passes through

irregular channels calledsinuses

Leaves node through oneor two efferent vessels atthe hilum or hilus

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Flow of lymph

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MALT 

MALT – mucosa-associatedlymphatic tissue iscomposed of:

– Peyer’s patches, tonsils,and the appendix(digestive tract)

– Lymphoid nodules in thewalls of the bronchi(respiratory tract)

MALT protects thedigestive and respiratorysystems from foreignmatter 

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Tonsils

Lymphoid tissue of tonsils containsfollicles with germinal centers

Tonsil masses are not fully encapsulated Epithelial tissue overlying tonsil masses

invaginates, forming blind-ended crypts

Crypts trap and destroy bacteria and

particulate matter

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Tonsils

Simplest lymphoid organs;form a ring of lymphatic tissuearound the pharynx

Location of the tonsils– Palatine tonsils – either

side of the posterior endof the oral cavity

– Lingual tonsils – lie at thebase of the tongue

– Pharyngeal tonsil – posterior wall of thenasopharynx

– Tubal tonsils – surroundthe openings of theauditory tubes into thepharynx

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Aggregates of Lymphoid Follicles

Peyer’s patches – isolated clusters of lymphoidtissue, similar to tonsils– Found in the wall of the distal portion of the

small intestine– Similar structures are found in the appendix

Peyer’s patches and the appendix: – Destroy bacteria, preventing them from

breaching the intestinal wall– Generate “memory” lymphocytes for long-

term immunity

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Gut associated lymphoid tissue (GALT ) - tonsils,adenoids, Peyer’s patches, appendix

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Gut associated lymphoid tissue (GALT ) - tonsils,adenoids, Peyer’s patches, appendix

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Lymphatic vessels

Resemble veins (same 3 layers)

Found throughout body except:– Avascular tissues

– Central nervous system

– Splenic pulp

– Bone marrow

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Lymphatic vessels join to formlymphatic trunks

Lymphatic trunks join to form :•Thoracic duct (3/4 of body)

•Right lymphaticduct (drains rightarm, and right sideof head, neck andupper torso)

These empty intosubclavian veins at

 junction withinternal jugularvein.

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Fluid Movement

Formation of lymph:

Fluid leaves capillaries bydiffusion and filtration

Escaped proteins

If lymph flow blocked =tissue swelling or edema

Specialized lymphaticcapillaries in vili of smallintestine transport lipids -they are called lacteals, andthe fluid is called chyle.

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Edema

Accumulation ofinterstitial fluid

Causes of Edema 

Blockage of lymphaticsystem

Increased pressure inveins

Lack of albumin

– Decreases fluidreturning to bloodcapillaries by osmosis

Inflammation

O i f th i

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Overview of the immune response:

(Fig. 22.6, p. 762, Madigan et al.)

Cellmediated(CMI)

Antibody

mediated(humoral)

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Provides the key for the immune system

to recognize the presence of 

intracellular microorganismsMHC proteins are ignored by T cells if 

they are complexed with self protein

fragments

Antigen Recognition

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If MHC proteins are complexed with

endogenous or exogenous antigenic

peptides, they: – Indicate the presence of intracellular 

infectious microorganisms

 –

 Act as antigen holders – Form the self part of the self-antiself 

complexes recognized by T cells

Antigen Recognition

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T C cells are activated by antigen fragmentscomplexed with class I MHC proteins

APCs produce co-stimulatory molecules that arerequired for T C activation

TCR that acts to recognize the self-antiselfcomplex is linked to multiple intracellular signaling

pathways Other T cell surface proteins are involved in

antigen binding (e.g., CD4 and CD8 help maintaincoupling during antigen recognition)

T Cell Activation: Step One – Antigen Binding

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Figure 21.16

T Cell Activation: Step One – Antigen Binding

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Before a T cell can undergoclonal expansion, it mustrecognize one or more co-stimulatory signals

This recognition may require

binding to other surfacereceptors on an APC– Macrophages produce

surface B7 proteinswhen nonspecificdefenses are mobilized

– B7 binding with the CD28 receptor on the surfaceof T cells is a crucial co-stimulatory signal

Other co-stimulatory signalsinclude cytokines and

interleukin 1 and 2

T Cell Activation: Step Two – Co-stimulation

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Depending on receptor type, co-stimulators cancause T cells to complete their activation orabort activation

Without co-stimulation, T cells:– Become tolerant to that antigen

– Are unable to divide

– Do not secrete cytokines

T cells that are activated:– Enlarge, proliferate, and form clones

– Differentiate and perform functionsaccording to their T cell class

T Cell Activation: Step Two – Co-stimulation

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Mediators involved in cellular immunity, includinghormonelike glycoproteins released by activated T cells and macrophages

Some are co-stimulators of T cells and T cellproliferation

Interleukin 1 (IL-1) released by macrophages co-stimulates bound T cells to:

– Release interleukin 2 (IL-2)– Synthesize more IL-2 receptors

Cytokines

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IL-2 is a key growth factor, which sets upa positive feedback cycle that encourages

activated T cells to divide– It is used therapeutically to enhance thebody’s defenses against cancer 

Other cytokines amplify and regulate

immune and nonspecific responses

Cytokines

H l ll ( )

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Helper T Cells (T H)

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T H cells interact directlywith B cells that haveantigen fragments ontheir surfaces bound toMHC II receptors

T H cells stimulate B cells

to divide more rapidly andbegin antibody formation

B cells may be activatedwithout T H cells bybinding to T cell–independent antigens

Most antigens, however,require T H co-stimulationto activate B cells

Cytokines released by T H amplify nonspecificdefenses

Helper T Cell

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T C cells, or killer T cells, are the only T cellsthat can directly attack and kill other cells

They circulate throughout the body in search

of body cells that display the antigen to whichthey have been sensitized Their targets include:

– Virus-infected cells

– Cells with intracellular bacteria or parasites– Cancer cells– Foreign cells from blood transfusions or

transplants

Cytotoxic T Cell (T c)

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T-CELL FUNCTIONS

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T-CELL FUNCTIONS

Mechanisms of T Action

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Mechanisms of T c Action

Figure 21.18a, b

A Cytotoxic T Cell Attacking and Killing a Virus

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A Cytotoxic T Cell Attacking and Killing a Virus-Infected Target Cell

Here, the smaller cytotoxic T cell or Tc (arrow) is attacking and killing a

much larger virus-infected cell. The T cell will survive while the infected

cell is destroyed.

CELLS alive!

h ll

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Suppressor T cells (T S) – regulatorycells that release cytokines, which

suppress the activity of both T cellsand B cells

Gamma delta T cells (T gd) 5 – 10% of

all T cells found in the intestines thatare triggered by binding to MICAreceptors

Other T Cells

S l ti f B ll b ti ( l l l ti )

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Different types of B cells havedifferent receptor molecules.

When a pathogen (germ) “lockson” to a receptor, that type of Bcell is selected.

The selected B cell dividesrapidly to make lots of copiesof itself. The copies make lotsof antibodies against thepathogen.

Selection of B cells by antigen (clonal selection)

 

 

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Plasma cells secrete antibody at a high rate but can no longer respond toantigen or helper T cells. 

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Clonal Selection Theory (continued)

Some of the cellsbecome plasmacells that secreteprimary response.

Others become

memory cells thatsecreteantibodies duringthe secondaryresponse.

Antigens selectlymphocytes thatare already ableto makeantibodies.

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Memory & specificity – key features

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Memory & specificity key featuresof the adaptive immunity

Cinetica răspunsului imun la o infecţie

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Cinetica răspunsului imun la o infecţievirală tipică