Immuno 4 Sistem Raspuns Imun
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Transcript of 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
T
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