The Immune System and

Lymphoid Organs

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 Immune system
• Provides defense or immunity against infectious agents.
• Divided into Innate and adaptive immunity
• Innate immunity:- nonspecific.
• Adaptive immunity:- specific
• Primary lymphoid organs:- thymus and the bone marrows
• Secondary lymphoid organs:- lymph nodes, spleen, diffuse lymphoid
tissue found in mucosa of GIT .
• Mucosa associated lymphoid tissue (MALT)
 Innate immunity
• Involves immediate, nonspecific actions including physical barriers i.e.
skin, mucous membranes of GIT, RT, and UGT
• Pathogens penetrating these barriers are picked up by Neutrophils
and other Leukocytes.
• Toll like receptors (TLRs) on leukocytes recognize and bind to the
invaders.
• Natural killer cells destroy infected host cells and certain tumorigenic
cells.
Innate immunity
Production of antimicrobial agents by leukocytes
ØHydrochloric Acid production:- either kill microorganisms directly or (−)
ØDefensins:- produced by leukocytes and various epithelial cells that kill
bacteria by disrupting cell wall.
ØLysozyme:- enzyme made by neutrophils and cells of epithelial barriers,
which hydrolyses bacterial cell wall components.
ØComplement proteins:- proteins in blood plasma , mucus and
macrophages that react with bacterial surface component to aid their
removal.
ØInterferons:- factors from leukocytes and virus-infected cells that signal NK
cells to kill such cells and adjacent cells to resist viral infection
Adaptive immunity
• Acquired gradually by exposure to microorganisms
• Is more specific and slower to respond.
• Involves B and T-lymphocytes.
• Antigens presented to lymphocytes by Antigen Presenting Cells (APCs)
• APCs are usually derived from monocytes
• Aimed at specific microbial invaders
• Involves production of memory lymphocytes so that a similar
response can be mounted very rapidly if that invader ever appear
again.
 Cytokines
• Cells in the immune system use cytokines to communicate with each
other to coordinate defensive measures.
• Involved in both innate and adaptive immunity.
• They are a diverse group of peptides and glycoproteins examples
include:-
ØTumour necrosis factors ( TNF α and β)
ØInterleukins (IL)
ØInterferons (INF)
ØGrowth Factors (GF)
Cytokines
Responses induced by cytokines include:-
ØChemotaxis due to the production of chemokines.
ØIncreased mitotic division in certain leukocytes due to produced GFs
ØStimulation or suppression of the lymphocyte activities in adaptive
immunity caused by interleukins.
ØStimulated phagocytosis or directed cell killing by innate immune
cells.
 Antigen and antibodies
• Antigen:- a molecule that is recognized by cells of the adaptive
immune system.
• Epitopes:- antigenic determinants on antigens
• Immune response to antigens can be cellular or humoral
• Antibodies:- is a glycoprotein of immunoglobulin family that interacts
specifically with an antigenic determinants.
• Antibodies are secreted by plasma cells
Structure of an antibody
• Two identical light chain
• Two identical heavy chain bound
by disulfide bonds.
• Constant Fc region
• Variable region
• Two Antigen binding sites per
antibody, both for the same
antigen.
 Classes of antibodies
Five classes of immunoglobulins
Immunoglobulin G
IgG:- most abundant of all, 75 – 85 %
ØProduction increases during immune response following infection
ØIgG is highly soluble,
Østable
ØT1/2 of 3 weeks.
ØCrosses placental barrier into fetal circulation, confers passive
immunity till newborn’s own immunity develops.
Immunoglobulins
Immunoglobulin A
ØIgA:- present in almost all exocrine secretions in a dimeric form
Øassociated with mucosal lining
ØFound in tears, saliva, milk and mucus
Immunoglobullin M
IgM:- constitutes 5 – 10 % of all
ØPentameric
Øproduced in an initial response to an antigen.
Øinvolved in complement system
ØAct as antigen receptor in triggering B-cell activation.
Immunoglobulins
Immunoglobulin E
ØIgE:- usually a monomer
ØBound to mast cells and basophils
ØInduces the release of bioactive substances e.g. histamine, heparin,
leukotrienes.
ØInvolved in allergic reactions
 Immunoglobulins
Immunoglobulin D
ØIgD:- least abundant in plasma.
ØLeast understood of all antibodies
ØMonomer
ØAntigen receptor for triggering B cell activation.
Actions of antibodies
• Neutralisation of toxins
• Agglutination of bacterial cells
• Precipitation of soluble antigens
• Opsonisation
• Complement activation
• NK cells activation;- release perforins and granzymes
 Antigen Presentation
• Antigen presenting proteins are parts of Major Histocompatibility
Complex MHC.
• MHC class I and II
• Human Leukocytes Antigens HLAs coded by genes.
• Recognition of “self” and “non-self”.
• MHC class I:- present on all nucleated cells
• MHC class II:- present only on cells of the mononuclear phagocytic
system.
Cells of the Adaptive
Immunity
Antigen Presenting Cells (APCs)
• Most are part of mononuclear phagocytic system including all
macrophages and dendritic cells in lymphoid organs.
• Features common to all APCs are expression of MHC class II and an
endocytic system
Lymphocytes
• Both B and T cells regulate and carry out adaptive immunity
• In adults stem cells for all lymphocyte are in red bone marrow
• Cells of major lymphoid lineage mature and become functional in two
primary lymphoid organs.
• Cells to become B-lymphocytes remain and differentiate further in
bone marrow.
• Progenitor for T-lymphocytes move to the thymus.
• After maturation in primary centres B and T cells circulate to the
secondary lymphoid organs
 T-Lymphocytes
• Long lived lymphocytes, about 75% of circulating lymphocytes.
• Recognise antigenic epitopes via T-cell receptors TCRs.
• T-lymphocytes are MHC restricted.
T-lymphocyte subtypes include:-
ØHelper T-lymphocytes (Th cells)
ØCytotoxic T lymphocytes (CTLs)
ØRegulatory T cells
ØGamma and delta T lymphocytes
Helper T-lymphocytes (Th cells)
vC/rised by CD4 coreceptors for binding MHC II, with TCRs
vProduce cytokines that promote differentiation of :-
v B cells into plasma cells.
vMacrophages to become phagocytic
vActivate cytotoxic T lymphocytes
vInduce inflammatory reactions
vPersist as memory helper T cells
Cytotoxic T lymphocytes (CTLs)
• Are CD8+ cells
• Their TCRs together with CD8 core-receptors bind specific Ags
displaying MHC class I
• Also called killer T cells
• Release perforins and granzymes which trigger apoptosis.
• Differentiates to memory cytotoxic T cells
 Regulatory T cells
• Also known as T regs or suppressor T cells
• Displays CD4+ and CD 25+ markers
• Involved in immune tolerance ( self or none self)
• Produce peripheral tolerance to supplement central tolerance in the
Thymus.
 Gamma-delta T-Lymphocytes
• Contain the γ and δ chains instead of α and β chains
• Migrate to the epidermis and mucosal epithelia and do not recirculate
to secondary lymphatic organs.
• Functions like innate immune cells, in the front lines against invading
microorganisms.
 B-Lymphocytes
• In B lymphocytes , surface receptors for antigens are monomers of
IgM or IgD, with B cells covered by B cell receptors BRCs
• Antigens are presented on MHC class II molecules of B cells.
• B cells proliferates into Plasma cells
• Plasma cells produce antibodies
• Antibodies are involved in the humoral immunity
• Some B cells remain as memory B cells involved in adaptive immunity
Lymphoid Organs
Lymphoid organs
• Lymph nodes
• Spleen
• Thymus
• Tonsils
• Small intestine & appendix aggregated lymphoid nodules
Lymph Nodes
Lymph nodes
• Are been shaped, blood vessels enter and leave the node at its
concavity.
• Several lymph vessels enter the node on its convex part.
• Usually a single lymph vessel leave the node through its hilum.
• Made up of the cortex and the medulla.
• Cortex contain densely parked lymphocytes hence stains darkly.
• Cortex also contain Lymphatic follicles or lymphatic nodules.
• Each nodule has a paler staining germinal centres surrounded by a
zone of densely packed lymphocytes.
Lymph Nodes
• CT making up a capsule surrounds the lymph node.
• Some elastic fibres and smooth muscles may be present.
• Trabeculae or septa extend into the node from the capsule and divide
into the node into nodules.
• Hilum is occupied by a mass of dense fibrous tissue.
• Reticular fibres occupy the greater substance of the node
• Reticular cells present in the node:- fibroblasts or phagocytic????.
 Cells of the Lymph Node
1. Lymphocytes
ØEnter LN from blood and some from lymph.
ØBoth B and T- lymphocytes are preset in the LN
ØThe Lymphatic nodules constitute the B-lymphocytes.
ØGerminal centres constitutes the lymphoblasts believed to have
been stimulated by Antigens to multiplicate.
ØB-lymphocytes mature into plasma cells seen mainly in the Medullary
cords.
ØSome B lymphocytes remain as memory cells
Cells of the Lymph node
• T lymphocytes are present in the paracotex of the LN and medullary
cords.
• T cells enter LN from blood and leave the node via efferent lymph
vessel
2. Reticular cells
ØFound in association with the reticular fibres, they are the fibroblast
of the LN.
Cells of the Lymph node
3. Macrophages
ØMore numerous in the medulla than the cortex.
Øhave antigen presenting function
ØDendritic antigen presenting cells are also present
4. Endothelial cells
ØPericytes and smooth muscle cells are also present around the blood
vessels.
Circulation of lymph in Lymph node
• Lymph enter the node via several afferent vessel
• Enter perivascular sinus from which a number of radial cortical
sinuses run through the cortex towards the medulla.
• Reaching the medulla , they join to form larger medullary sinuses.
• From the medullary sinuses originate usually one efferent lymph
vessel through which lymph leave the node.
Blood supply to the Lymph Node
• Arteries enter the LN at the hilum
• Pass through the medulla to the cortex to end into arterioles and
capillaries.
• Post capillary venules in the LN are lined by cuboidal endothelium.
Functions of the Lymph Nodes
• Centre of lymphocyte production
• Removal of particulate matter from lymph by macrophages
• Production of antibodies by Plasma cells in LN
The Spleen
Spleen
• Is the largest lymphoid organ of the body.
• Except at the hilum, the spleen is covered by serous coat of peritoneum.
• Deep to the serous coat is the capsule from which extends the trabeculae into
the spleen substance.
• Capsule and trabeculae are made up of fibrous tissue in which elastic fibres are
abundant.
• Spaces between the trabeculae are pervade by a network of reticular fibres.
• Fibroblasts (reticular cells) and macrophages are also present in the reticulum.
• Interstices of reticulum is pervaded by lymphocytes, blood vessels and blood cells
and macrophages.
Circulation through the Spleen
• On reaching the hilum of spleen, the splenic artery divide into about
five branches that enter the spleen.
• Each branch subdivide as they traverse the trabeculae and arterioles
arising from this enter inter-trabecular substance of the spleen.
• For some distance, the arterioles are surrounded by dense sheath of
lymphocytes constituting the white pulp of the spleen.
• Arterioles then divide into a number of straight arteries called
penicilli.
• Each penicilli shows a localized thickening of it walls called ellipsoid.
Circulation through the Spleen
• Distal to the ellipsoid the vessel dilates to form an ampulla, the walls of
which become continuous with the reticular framework.
• As a result, blood flows into spaces lined by reticular cells, coming into
contact with lymphocytes there.
• The part of the spleen that is infiltrated by the blood in this way is called
Red pulp, therefore circulation in the red pulp is an “open circulation” in
contrast to the closed circulation in the white pulp.
• Blood in red pulp is then collected by sinusoids that drains into veins in the
trabeculae.
• Endothelial cells of the sinusoid are banana shaped and are called stave
cells.
 White Pulp
ØIs made up of lymphocytes that surround arterioles…and follow the
branching pattern of the arterioles.
ØContain the lymphatic nodules like those seen in the lymph nodes known
as Malpighian bodies.
ØEach nodule has a germinal centre and a surrounding cuff of densely
packed lymphocytes.
ØNodules are easily distinguished from those of the lymph node by the
presence of an arterioles in each of them (central artery) placed
eccentrically.
ØFunction of white pulp is similar to that of the cortical tissue of the lymph
node…most cells being the T-lymphocytes.
ØLymphatic nodules are aggregation of B-lymphocytes and germinal centres
are areas of where B–lymphocytes are dividing.
The Red Pulp
• is like a sponge….permiated by spaces lined by reticular cells.
• Intervals between the spaces are filled by B-lymphocytes as well as T-
lymphocytes, macrophages and blood cells.
• Cells are arranged as cords (splenic cords, of Billroth) and the cords
form a network.
• Red pulp immediately surrounding the white pulp is the marginal
zone which has rich network of sinusoids.
Functions of the Spleen
• Centre of both T and B lymphocytes multiplication.
• Is the only site where an immune response can be started against
antigens present in circulating blood.
• Destruction of RBCs by MNPS cells
• Haematopoietic centre in foetal life.
• Store blood that can be thrown into circulation when required.
ØSplenomegaly……..?????. and splenectomy.
The Thymus
Thymus
• Is a bilobed structure in the mediastinum
• Involved in central tolerance, prevents autoimmunity
• Fully formed and functional at birth.
• Remains large and active in T-cell production until puberty, during
which in undergoes involution.
• Decreases greatly in size and activity and becoming largely filled with
adipose tissue.
• Has a vascularized CT capsule that extend into the parenchyma,
dividing the organ into many incompletely separate lobules.
Thymus
• Lobules have outer darkly basophilic cortex.
• More lightly stained medulla.
• Staining difference is due to greater density of lymphoblasts in the
medulla than small lymphocytes in the cortex.
• Does not receive lymphatics but give off efferent lymphatic vessels.
• There are three major types of Thymic Epithelial Cells (TECs) namely:-
ØSquamous TECs
ØStellate TECs
ØOther squamous cortical TECs
Cells in the cortex of the Thymus
1. Squamous Thymic Epithelial Cells
ØForm a layer joined by desmosomes and occluding junctions
ØLine the CT of the capsule and septa
ØForm Blood-Thymus barrier preventing unregulated exposure of
thymocytes to antigens.
2. Stellate TECs
ØForm a cytoreticulum to which macrophages and developing
lymphocytes attach
ØThey are APCs, expressing MHC class II molecules
Cells in the cortex of the Thymus
3. Other Squamous cortical TECs
Ø also express MHC class II molecules
ØContribute to the functional corticomedullary barrier between two
regions of each lobule.
Thymus
• Large aggregates of TECs,
sometimes concentrically
arranged seen in the medulla
known as Hassall corpuscles.

• Secret several cytokines that

control activities of the local
dendritic cells and development
of regulatory T-cells.
Functions of the Thymus
• Positive selection in the cortex:- T cells with functional TCRs that recognize
both MHC class I and II.
• Negative selection in the medulla:- survival of T cells that do not tightly
bind self antigens presented on dendritic ells.
• Expression of the TCRs
• Expression of CD4 and CD8 markers
• T-Cells proliferation
• Central immunotorelance:- deletion of self- reactive T cells in the Thymus.

vMyasthenia gravis????
Mucosa-Associated
Lymphoid Tissue
(MALT)
MALT
• Aggregation lymphoid tissue seen in GIT, RT and UGT.
MALT have some features in common:-
ØHave lymphatic nodules like LN which contain B-lymphocytes and
have germinal centres and diffuse areas containing T-lymphocytes.
ØThey are present in the lining epithelium of the mucosa and lie in the
substantia propria while larger aggregates can extend into
submucosa.
ØThey are not surrounded by the capsule nor do they have CT septa.
ØAs a rule, they do not receive afferent lymph vessels, hence they do
not serve as filters of lymph but centres of lymphocytes production.
MALT
• In RT they are present in the walls of the trachea and large bronchi
and they are referred to as Bronchial associated lymphoid tissue
(BALT).
• In GIT they are referred to as Gut associated lymphoid tissue (GALT)
and they are as follows:-
• Palatine tonsil
• Lingual tonsils
• Tubal tonsils
• Solitary lymphatic follicles
• Payer’s patches
M-Cells????
Palatine Tonsils
• Each palatine tonsil (left and right) consist of diffuse lymphoid tissue
in which lymphatic nodules are present.
• Is covered by stratified squamous epithelium that extend into the
substance of the tonsil in the form of several tonsilar crypts.
• Numerous mucous glands open into the crypts.
Tonsilitis????
Pharyngeal Tonsil
• Mass of lymphoid tissue present on the posterior wall of the
nasopharynx (single).
• Covered by pseudostratified ciliated columnar epithelium
• Lack crypts
Adenoids????
Lingual Tonsil
• Situated along the base of the tongue
• Covered by stratified squamous epithelium….with crypts.
• Lack distinct capsule