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ORGANIZATION OF
THE IMMUNE SYSTEM
Objectives
◆Identify the major componentsofthe lymphatic system
(organs, cells andvessels) andexplain their functions
◆List the primary andsecondary lymphoid organs
◆Discuss the development oflymphoid organs in brief
◆Explain the functions ofthe immune system
Introduction
Thereis ahugenumber
ofmicroorganisms
in our environment
thatcaninfectus,but
weare remaining
uninfected How are we defending them?
Our immune system defends these organisms
and provides immunity to infection
Introduction
Immunity State
ofprotection from
infections or
resistance to
infections
Immune system
Collections ofcells,
tissues and molecules
thatmediate
resistance to infections
Immune response
The coordinated
reaction ofcells and
molecules to eliminate
theinvading organisms
Major components of the
Immune System
◆Lymphoidorgans
• Primary or central
• Secondaryor peripheral
◆Lymphatic vessels
◆Cells
• Lymphocytes
• Antigenpresentingcells
• Other leukocytes
◆Molecules
• Antibody
• Complement
• Cytokines
Primary or Central
Lymphoid Organs
◆These organs are the sites of maturation of
lymphocytes before they encounter any antigen
◆Primary or centrallymphoid organs include
1. Bone marrow
2. Thymus
Primary Lymphoid Organs
Bone Marrow
Found in the medullary cavity of compactbones and interstices of spongy bone
Consists of haematopoitic and stromal tissue
Stromal tissue support maturationof cellsby providing growth factorsand cytokines
Thymus
◆It is aflat,bi-lobed organ situated
above the heart
◆At birth it weighs 10- 15 gm
◆Its size increases up to puberty
(30- 40 gm)
◆Subsequently its size reduces and
muchofthe organ is replaced by fat
◆Each lobeis surrounded bya
connectivetissue capsule that sends
trabeculae inside and divide it in to
lobules
Primary Lymphoid Organs
Thymus
◆Eachlobuleis organized into
•Outer cortex:Denselypacked
withmaturing T cells called
thymocytes
•Innermedulla:Sparsely populated
withthymocytes
◆Boththecortex andmedulla are
crisscrossedbyastromal- cell
networkconsistingof thymic
epithelialcells, dendritic cells,and
macrophages
◆SiteofmaturationofT cells
Primary Lymphoid Organs
Secondary or peripheral lymphoid organs include
1. Lymph nodes
2. Spleen
3. Mucosa associated lymphoid tissue (MALT)
• Tonsils
• Peyer’s patches
• Lymphocytes in the mucosa ofGIT
, Respiratory and Urinary tract
1. Cutaneous associated lymphoid tissue (CALT)
CALT is some times called tertiary lymphoid organ
Secondary or Peripheral
Lymphoid Organs
Lymphoid Organs
Secondary or Peripheral
Lymphoid Organs
◆These organs are the sites of interaction of mature
lymphocytes with antigens and antigen presenting cells
(APCs)
◆Mature lymphocytes from circulation migrate and
reside in these organs
◆Microorganisms and APCs carrying microbial or
tumour antigens also migrate to these organs through
blood or lymph
◆Lymphocytes, antigens and APCs come in close
proximity and can interact in these organs
Secondary or Peripheral
Lymphoid Organs
◆These organs also bring different types oflymphocytes
(helper T cells,cytotoxicT cells and B cells) in close
proximity
◆This close proximityofdifferent types of lymphocytes
optimizes their interaction with each other bydirect
contactor by cytokines
◆Interaction between different lymphocytes
generates effective immune response
Secondary Lymphoid Organs
Lymph nodes
◆Lymph nodes are nodular aggregates
of lymphoid tissues located along
lymphatic channels throughout the
body
◆Fluid (lymph) from epithelia,
connective tissue and most
parenchymal organs is drained by
lymphaticchannels to lymphnodes
Lymph nodes
◆Encapsulated bean (or kidney)
shaped structures containinga
reticular network packed with
lymphocytes and APCs
◆Morphologically, alymph node can
be divided into three roughly
concentricregions
•Cortex: Rich in B cells, also contains
macrophagesanddendritic cells
•Paracortex: Rich in T cells,also contains
macrophagesanddendritic cells
•Medulla: Contains T cells, B cells and
Plasmacells
Secondary Lymphoid Organs
Lymph nodes
◆Lymph enter into the lymph nodes through
afferent lymphatic vessels and exit through the
efferentlymphatic vessel
◆Microorganisms carried in lymph come in
contact with lymphocytes and APCs while
passing through the lymph nodes
◆In addition, APCs can pick up microbes from
tissue and parenchymal organs and transport
them to the lymph nodes through lymphatic
channels
◆Antigens that enter through tissue and
parenchymal organs interact with lymphocytes
in the lymph nodes and induce immune
response
Secondary Lymphoid Organs
Secondary Lymphoid Organs
Spleen
Itissurrounded by
connective tissue
capsulethatsends
trabeculae insideand
divideitinto
compartments
•Red pulp: Network of sinusoids, populated with macrophages, numerous red
bloodcells andafew lymphocytes
•White pulp: Surrounds the branches of the splenic artery, forming periarteriolarlymphoid
sheath(PALS) populatedmainlybyT lymphocytes
• Primary lymphoidfollicles: Attached to PALS rich inB cells
• Marginalzone:Peripheralto PALScontainLymphocytesandmacrophages
Secondary Lymphoid Organs
Spleen
◆Largest secondary lymphoid organ
◆Morerecirculating lymphocytes pass through the
spleen daily than alllymph nodes combined
◆Blood borne microorganismsenter spleen, interact
with APCs and lymphocytes and induce immune
response
◆Site ofclearance ofimmune complexes
MucosaAssociated Lymphoid Tissue
(MALT)
◆Group of lymphoid tissues located under the
epithelium of the gastrointestinal, respiratory and
urogenital systems
◆Their structure ranges from loose, barely organized
clusters of lymphoid cells in the mucosa (e.g. in lamina
propria)to well organized structureslike
•
•
Tonsils
Peyer’spatches
◆Majority of the lymphocyte in MALT are memorycells
Secondary Lymphoid Organs
Secondary Lymphoid Organs
Tonsils
◆Palatine,nasopharyngeal, lingualandtubaltonsilsform Waldeyer’s ringatthesiteof
entryofpathogensthroughdigestive andrespiratorytracts
◆Contain lymphocytes, macrophagesandplasmacells
Secondary Lymphoid Organs
Peyer’s patches
◆Present inthesubmucosal layer
of the ilium beneath the lamina
propria
◆These are nodules of 30–40
lymphoidfollicles
◆Lamina propria of the intestine
also contains lymphocytes,
plasma cellsand macrophages
Secondary Lymphoid Organs
Collection oflymphocytes under the epithelium ofskin Majority
are memorycells
These arethe sites ofimmune responses to antigensthat
breach the epithelium of skin
At any time, more than half ofthe body’
s
lymphocytes are in the MALT and CALT
reflecting their large size
Cutaneous AssociatedLymphoid Tissue(CALT)
Lymphatic Vessels
◆Lymphatic vessels from tissue drain
to the regional lymph nodes
through afferentlymphaticvessels
◆Efferent lymphatic vessels from
these nodes drain into another
group oflymphnodes
Lymphatic Vessels
◆Efferent lymphatic vessels form
lymphatic trunks that ultimately
drain into lymphatic ducts
(thoracic duct on the left and right
lymphatic duct on the right side)
◆Thoracic duct and right lymphatic
duct drain into the internal jugular
veins at their junction with
subclavian veins
◆Thereby it carries fluid from
tissue to the blood circulation
Lymphatic Vessels
◆Lymph maypick up microorganisms and cancer cells from
tissue and parenchymalorgans,bring them to lymph
nodes where they comein contactwith APCs and
lymphocytes and induce immune response
◆Macrophages,dendritic cells and lymphocytes that
migrateto tissues can also returnbackto circulation
through lymphatic vessels
◆So lymphatic system is an important part ofthe
immune system
Lymphocyte Recirculation
Lymphocytesare recirculating
cellsthat migrate to secondary
lymphoid organs in search of
antigens
Iftheydo not encounter
antigen,theycan comeback to
thecirculation again
Cells of the Immune System
◆Cells ofthe immune system
are generated in the bone
marrow
◆The process of generation
is called haematopoisis
◆The microenvironmentofthe
bone marrow stroma supportcell
generationand maturation
◆From bone marrow the cells
are released into the circulation
Cells of the Immune System
Functionally cells of the Immune System
can be classified as
1. Immunocompetentcells
2. Antigen presenting cells
3. Effector cells
Cells of the Immune System
Immunocopmpetent cells ICC
◆Capable of recognizing specific antigens and
providing immune response to that particular antigen
◆These cells possess 4 attributes of adaptive immunity
1. Antigenic specificity
2. Diversity
3. Immunological memory
4. Self/non-self recognition
◆Only mature T and B lymphocytes have
these characteristic attributes and are called
ICC
Cells of the Immune System
Immunocopmpetent cells
TH= T Helper,TC= T Cytotoxic
Cells of the Immune System
Lymphocytes
◆Constitute20-40% of circulating WBC population
◆O nly cells that bear specific receptors for antigens
◆All lymphocytes are morphologically similar but they
differin lineage, function and phenotype (e.g.CD
molecules)
◆Lymphocyte population can be classifiedas
•
•
•
B lymphocytes
T lymphocytes
Natural Killer (NK) cells
CD= Cluster of Differentiation
NK cellsdo not bear specific receptors for antigen
Cells of the Immune System
Antigenpresentingcells(APCs)
◆APCs arespecializedcellsthatdisplayantigenson their surface
byMHC molecules to activateT lymphocytes
◆Thecommon portalsofentry ofmicroorganisms-the skin,
gutandtherespiratorytractcontainAPCs intheir epithelium
◆Thesecells cancaptureantigens,transport themto
peripherallymphoid organs and displaythemto T cells
Cells of the Immune System
◆ProfessionalAPCs include:
• Dendriticcells
• Macrophages
• B lymphocytes
◆APCs express both Class I and Class II
MHC molecules on their surface to
display antigento T cells
◆Theyalso expressB7 (B7.1 and B7.2)
molecules to provide co-stimulatory
signalto activateT cells
Antigen presenting cells (APCs)
Signal1: Stimulatory signal
Signal2: Co-stimulatory signal
TC
Cells of the Immune System
Effector cells
Cells thateliminatemicrobes
◆Lymphocytes
◆Neutrophils
◆Monocytes and Macrophages
◆Eosinophils
◆Basophils and Mastcells
◆NaturalKiller (NK) Cells
• Plasmacells
•Derived fromB lymphocytes
•Produceantibodies
•Antibodieseliminateextracellular pathogens
•Effector THcells
to eliminate intracellular pathogens
• Cytotoxic T cells
• Derived from CD8+ T lymphocytes
• Induce apoptosis of infected cells
• Derived from CD4+ T lymphocytes
• Produce cytokines that activate macrophages Cellmediated
Cells of the Immune System
Effector cells
Effector Lymphocytes
Humoral
Immunity
Immunity
Effector cells
Other effector cells and their roles in Innate and Adaptive Immunity
Cells of the Immune System
Cells Role in Innate Immunity Role in Adaptive Immunity
Neutrophils Phagocytosis ADCC
Macrophage
s
(Monocytes)
Phagocytosis ADCC
Pathogen elimination by TH
cells
Type IV Hypersensitivity
Eosinophils ADCC in parasitic
infections
Type I Hypersensitivity
Mast cells
and
Basophils
Inflammation Type I Hypersensitivity
NK cells Kill virus infected and tumour
cells
ADCC
ADCC= Antibody dependent cell mediated cytotoxicity
Functions of the Immune System
◆The main function of the immune system is
defense against microbial infections
• Preventsentryoforganisms insidethebody
• Kills and eliminates organisms that enter the body and
preventsestablishmentofinfection
• Eradicatesestablishedinfection
◆Another major function of the immune system is
protection from tumours
• Continuoussurveillance for tumour cells
• Killany tumour celldeveloped
(Tumour developonlywhenitcanevadethe immune surveillance)
Importance of the Immune
System
◆Individuals withdefective immune responses are susceptibleto
serious,life-threateninginfections
◆Stimulating immune responses by vaccination is the most
effectivemethod for protecting frominfections
◆Immune response is a barrier to successful organ
transplantation
◆Clinical trials are showing that cancers can be treated by
stimulatingtheimmuneresponse
◆Abnormal immune response (hypersensitivity and
autoimmunity) may cause diseases with serious morbidity and
mortality
Further Review
◆Abbas AK, Lichman AH. Basic Immunology.
5TH edition. Elsevier, 2015.

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ORGANIZATION OF IMMUNE SYSTEM 1,2.pdf

  • 2. Objectives ◆Identify the major componentsofthe lymphatic system (organs, cells andvessels) andexplain their functions ◆List the primary andsecondary lymphoid organs ◆Discuss the development oflymphoid organs in brief ◆Explain the functions ofthe immune system
  • 3. Introduction Thereis ahugenumber ofmicroorganisms in our environment thatcaninfectus,but weare remaining uninfected How are we defending them? Our immune system defends these organisms and provides immunity to infection
  • 4. Introduction Immunity State ofprotection from infections or resistance to infections Immune system Collections ofcells, tissues and molecules thatmediate resistance to infections Immune response The coordinated reaction ofcells and molecules to eliminate theinvading organisms
  • 5. Major components of the Immune System ◆Lymphoidorgans • Primary or central • Secondaryor peripheral ◆Lymphatic vessels ◆Cells • Lymphocytes • Antigenpresentingcells • Other leukocytes ◆Molecules • Antibody • Complement • Cytokines
  • 6. Primary or Central Lymphoid Organs ◆These organs are the sites of maturation of lymphocytes before they encounter any antigen ◆Primary or centrallymphoid organs include 1. Bone marrow 2. Thymus
  • 7. Primary Lymphoid Organs Bone Marrow Found in the medullary cavity of compactbones and interstices of spongy bone Consists of haematopoitic and stromal tissue Stromal tissue support maturationof cellsby providing growth factorsand cytokines
  • 8. Thymus ◆It is aflat,bi-lobed organ situated above the heart ◆At birth it weighs 10- 15 gm ◆Its size increases up to puberty (30- 40 gm) ◆Subsequently its size reduces and muchofthe organ is replaced by fat ◆Each lobeis surrounded bya connectivetissue capsule that sends trabeculae inside and divide it in to lobules Primary Lymphoid Organs
  • 9. Thymus ◆Eachlobuleis organized into •Outer cortex:Denselypacked withmaturing T cells called thymocytes •Innermedulla:Sparsely populated withthymocytes ◆Boththecortex andmedulla are crisscrossedbyastromal- cell networkconsistingof thymic epithelialcells, dendritic cells,and macrophages ◆SiteofmaturationofT cells Primary Lymphoid Organs
  • 10. Secondary or peripheral lymphoid organs include 1. Lymph nodes 2. Spleen 3. Mucosa associated lymphoid tissue (MALT) • Tonsils • Peyer’s patches • Lymphocytes in the mucosa ofGIT , Respiratory and Urinary tract 1. Cutaneous associated lymphoid tissue (CALT) CALT is some times called tertiary lymphoid organ Secondary or Peripheral Lymphoid Organs
  • 12. Secondary or Peripheral Lymphoid Organs ◆These organs are the sites of interaction of mature lymphocytes with antigens and antigen presenting cells (APCs) ◆Mature lymphocytes from circulation migrate and reside in these organs ◆Microorganisms and APCs carrying microbial or tumour antigens also migrate to these organs through blood or lymph ◆Lymphocytes, antigens and APCs come in close proximity and can interact in these organs
  • 13. Secondary or Peripheral Lymphoid Organs ◆These organs also bring different types oflymphocytes (helper T cells,cytotoxicT cells and B cells) in close proximity ◆This close proximityofdifferent types of lymphocytes optimizes their interaction with each other bydirect contactor by cytokines ◆Interaction between different lymphocytes generates effective immune response
  • 14. Secondary Lymphoid Organs Lymph nodes ◆Lymph nodes are nodular aggregates of lymphoid tissues located along lymphatic channels throughout the body ◆Fluid (lymph) from epithelia, connective tissue and most parenchymal organs is drained by lymphaticchannels to lymphnodes
  • 15. Lymph nodes ◆Encapsulated bean (or kidney) shaped structures containinga reticular network packed with lymphocytes and APCs ◆Morphologically, alymph node can be divided into three roughly concentricregions •Cortex: Rich in B cells, also contains macrophagesanddendritic cells •Paracortex: Rich in T cells,also contains macrophagesanddendritic cells •Medulla: Contains T cells, B cells and Plasmacells Secondary Lymphoid Organs
  • 16. Lymph nodes ◆Lymph enter into the lymph nodes through afferent lymphatic vessels and exit through the efferentlymphatic vessel ◆Microorganisms carried in lymph come in contact with lymphocytes and APCs while passing through the lymph nodes ◆In addition, APCs can pick up microbes from tissue and parenchymal organs and transport them to the lymph nodes through lymphatic channels ◆Antigens that enter through tissue and parenchymal organs interact with lymphocytes in the lymph nodes and induce immune response Secondary Lymphoid Organs
  • 17. Secondary Lymphoid Organs Spleen Itissurrounded by connective tissue capsulethatsends trabeculae insideand divideitinto compartments •Red pulp: Network of sinusoids, populated with macrophages, numerous red bloodcells andafew lymphocytes •White pulp: Surrounds the branches of the splenic artery, forming periarteriolarlymphoid sheath(PALS) populatedmainlybyT lymphocytes • Primary lymphoidfollicles: Attached to PALS rich inB cells • Marginalzone:Peripheralto PALScontainLymphocytesandmacrophages
  • 18. Secondary Lymphoid Organs Spleen ◆Largest secondary lymphoid organ ◆Morerecirculating lymphocytes pass through the spleen daily than alllymph nodes combined ◆Blood borne microorganismsenter spleen, interact with APCs and lymphocytes and induce immune response ◆Site ofclearance ofimmune complexes
  • 19. MucosaAssociated Lymphoid Tissue (MALT) ◆Group of lymphoid tissues located under the epithelium of the gastrointestinal, respiratory and urogenital systems ◆Their structure ranges from loose, barely organized clusters of lymphoid cells in the mucosa (e.g. in lamina propria)to well organized structureslike • • Tonsils Peyer’spatches ◆Majority of the lymphocyte in MALT are memorycells Secondary Lymphoid Organs
  • 20. Secondary Lymphoid Organs Tonsils ◆Palatine,nasopharyngeal, lingualandtubaltonsilsform Waldeyer’s ringatthesiteof entryofpathogensthroughdigestive andrespiratorytracts ◆Contain lymphocytes, macrophagesandplasmacells
  • 21. Secondary Lymphoid Organs Peyer’s patches ◆Present inthesubmucosal layer of the ilium beneath the lamina propria ◆These are nodules of 30–40 lymphoidfollicles ◆Lamina propria of the intestine also contains lymphocytes, plasma cellsand macrophages
  • 22. Secondary Lymphoid Organs Collection oflymphocytes under the epithelium ofskin Majority are memorycells These arethe sites ofimmune responses to antigensthat breach the epithelium of skin At any time, more than half ofthe body’ s lymphocytes are in the MALT and CALT reflecting their large size Cutaneous AssociatedLymphoid Tissue(CALT)
  • 23. Lymphatic Vessels ◆Lymphatic vessels from tissue drain to the regional lymph nodes through afferentlymphaticvessels ◆Efferent lymphatic vessels from these nodes drain into another group oflymphnodes
  • 24. Lymphatic Vessels ◆Efferent lymphatic vessels form lymphatic trunks that ultimately drain into lymphatic ducts (thoracic duct on the left and right lymphatic duct on the right side) ◆Thoracic duct and right lymphatic duct drain into the internal jugular veins at their junction with subclavian veins ◆Thereby it carries fluid from tissue to the blood circulation
  • 25. Lymphatic Vessels ◆Lymph maypick up microorganisms and cancer cells from tissue and parenchymalorgans,bring them to lymph nodes where they comein contactwith APCs and lymphocytes and induce immune response ◆Macrophages,dendritic cells and lymphocytes that migrateto tissues can also returnbackto circulation through lymphatic vessels ◆So lymphatic system is an important part ofthe immune system
  • 26. Lymphocyte Recirculation Lymphocytesare recirculating cellsthat migrate to secondary lymphoid organs in search of antigens Iftheydo not encounter antigen,theycan comeback to thecirculation again
  • 27. Cells of the Immune System ◆Cells ofthe immune system are generated in the bone marrow ◆The process of generation is called haematopoisis ◆The microenvironmentofthe bone marrow stroma supportcell generationand maturation ◆From bone marrow the cells are released into the circulation
  • 28. Cells of the Immune System Functionally cells of the Immune System can be classified as 1. Immunocompetentcells 2. Antigen presenting cells 3. Effector cells
  • 29. Cells of the Immune System Immunocopmpetent cells ICC ◆Capable of recognizing specific antigens and providing immune response to that particular antigen ◆These cells possess 4 attributes of adaptive immunity 1. Antigenic specificity 2. Diversity 3. Immunological memory 4. Self/non-self recognition ◆Only mature T and B lymphocytes have these characteristic attributes and are called ICC
  • 30. Cells of the Immune System Immunocopmpetent cells TH= T Helper,TC= T Cytotoxic
  • 31. Cells of the Immune System Lymphocytes ◆Constitute20-40% of circulating WBC population ◆O nly cells that bear specific receptors for antigens ◆All lymphocytes are morphologically similar but they differin lineage, function and phenotype (e.g.CD molecules) ◆Lymphocyte population can be classifiedas • • • B lymphocytes T lymphocytes Natural Killer (NK) cells CD= Cluster of Differentiation NK cellsdo not bear specific receptors for antigen
  • 32. Cells of the Immune System Antigenpresentingcells(APCs) ◆APCs arespecializedcellsthatdisplayantigenson their surface byMHC molecules to activateT lymphocytes ◆Thecommon portalsofentry ofmicroorganisms-the skin, gutandtherespiratorytractcontainAPCs intheir epithelium ◆Thesecells cancaptureantigens,transport themto peripherallymphoid organs and displaythemto T cells
  • 33. Cells of the Immune System ◆ProfessionalAPCs include: • Dendriticcells • Macrophages • B lymphocytes ◆APCs express both Class I and Class II MHC molecules on their surface to display antigento T cells ◆Theyalso expressB7 (B7.1 and B7.2) molecules to provide co-stimulatory signalto activateT cells Antigen presenting cells (APCs) Signal1: Stimulatory signal Signal2: Co-stimulatory signal TC
  • 34. Cells of the Immune System Effector cells Cells thateliminatemicrobes ◆Lymphocytes ◆Neutrophils ◆Monocytes and Macrophages ◆Eosinophils ◆Basophils and Mastcells ◆NaturalKiller (NK) Cells
  • 35. • Plasmacells •Derived fromB lymphocytes •Produceantibodies •Antibodieseliminateextracellular pathogens •Effector THcells to eliminate intracellular pathogens • Cytotoxic T cells • Derived from CD8+ T lymphocytes • Induce apoptosis of infected cells • Derived from CD4+ T lymphocytes • Produce cytokines that activate macrophages Cellmediated Cells of the Immune System Effector cells Effector Lymphocytes Humoral Immunity Immunity
  • 36. Effector cells Other effector cells and their roles in Innate and Adaptive Immunity Cells of the Immune System Cells Role in Innate Immunity Role in Adaptive Immunity Neutrophils Phagocytosis ADCC Macrophage s (Monocytes) Phagocytosis ADCC Pathogen elimination by TH cells Type IV Hypersensitivity Eosinophils ADCC in parasitic infections Type I Hypersensitivity Mast cells and Basophils Inflammation Type I Hypersensitivity NK cells Kill virus infected and tumour cells ADCC ADCC= Antibody dependent cell mediated cytotoxicity
  • 37. Functions of the Immune System ◆The main function of the immune system is defense against microbial infections • Preventsentryoforganisms insidethebody • Kills and eliminates organisms that enter the body and preventsestablishmentofinfection • Eradicatesestablishedinfection ◆Another major function of the immune system is protection from tumours • Continuoussurveillance for tumour cells • Killany tumour celldeveloped (Tumour developonlywhenitcanevadethe immune surveillance)
  • 38. Importance of the Immune System ◆Individuals withdefective immune responses are susceptibleto serious,life-threateninginfections ◆Stimulating immune responses by vaccination is the most effectivemethod for protecting frominfections ◆Immune response is a barrier to successful organ transplantation ◆Clinical trials are showing that cancers can be treated by stimulatingtheimmuneresponse ◆Abnormal immune response (hypersensitivity and autoimmunity) may cause diseases with serious morbidity and mortality
  • 39. Further Review ◆Abbas AK, Lichman AH. Basic Immunology. 5TH edition. Elsevier, 2015.