2. Hematopoiesis
• The process of
formation and
development of
blood cells.
• Hematopoietic
stem cell-
-pleuripotent
-can differentiate
into various cell
types like
erythrocytes,
granulocytes,
monocytes, mast
cells etc.
Source: Kuby Immunology 5th edition
3. Regulation of hematopoiesis
• Growth factors: CSFs and Erythropoietin
• Various transcription factors
• Production and destruction of mature blood cells should
be equal so as to maintain the pool of cells
• Cytokines, expression of receptors, induction of
apoptosis etc. are the ways of regulation of
hematopoiesis
Apoptosis Vs. Necrosis
Shardul Joshi
4. Cells of Immune system
Lymphocytes
• B- lymphocytes:
- Mature in bursa of Fabricius or bone marrow
- Synthesize and secrete/display antibodies
- Class II MHC molecules- Professional APC
- Present antigens to TH cells
- B cells expressing antibodies against self antigens
die due to apoptosis
- B7-1 (CD80) and B7-2 (CD86) present on B cells
are important in co-stimulation
Shardul Joshi
5. Lymphocytes
• T- lymphocytes:
- Mature in thymus
- Express TCR which recognizes presented antigen
- Also express CD28 molecule- B7 receptor
- MHC class restriction:
- TH cells i.e. CD4+ cells are class II restricted,
hence they’re stimulated by foreign antigen
presented by APCs
- TC cells or CTLs i.e. CD8+ cells are class I
restricted, these are stimulated by self antigen
presented by altered self cells
- TS cells- presence not proved
Shardul Joshi
6. Lymphocytes
• Null/ NK cells:
- Don’t express any molecule that distinguishes B/T
cells. Also don’t secrete antibodies
- No specificity and memory
- IMP role in defence against virus infected and tumor
cells. Altered self cells
- NK cell receptors distinguish abnormalities like
reduction in the number of Class I MHC molecules
- Some virus infected and tumor cells display pre-exposed
antigens. Antitumor or antiviral antibodies
bind to these antigens.
- CD16 on NK cells bind to Fc region of IgG and
subsequently destroy these cells this is known as
antibody dependent cell-mediated cytotoxicity (ADCC)
Shardul Joshi
7. Myeloid
• Mononuclear phagocytic system
- Monocytes in blood and macrophages in tissues
- Mɸ are larger with more intracellular organelles and
better phagocytic ability than monocytes
- Lungs- Alveolar Mɸ, Connective tissues- Histiocytes,
Liver- Kupffer cells, Kidney- Mesangial cells,
Brain- Microglial cells, Bone- Osteoclasts
- Express class II MHC molecules and are APCs
- After phagocytosis, ingested matter is digested by
lysozyme and other hydrolytic enzymes inside a
phagolysozome
- Reactive oxygen intermediates, reactive nitrogen
intermediates are mechanisms of oxygen dependent
killing.
- Defensins, TNF, Lysozyme and other hydrolytic
enzymes are required for oxygen independent killing.
Shardul Joshi
8. Granulocytes
• Neutrophils/PMN
- Multilobed nucleus and granulated cytoplasm
- Stains with both acidic and basic stains
- First to arrive at the site of infection
- Leukocytosis (indicates infection): increase in the
number of circulating neutrophils
- Employ both oxygen dependent and independent
pathways like Mɸ
- Larger respiratory burst and higher levels of
defensin expression than Mɸ
Shardul Joshi
9. • Eosinophils
- Bilobed nucleus and granulated cytoplasm
- Stains with acidic stain like eosin red
- Motile and phagocytic
- Secreted contents of eosinophilic granules may
damage parasitic membrane
- Eosinophils are associated with parasitic diseases
- The inappropriate release of content in their
granules can cause host cell damage which may
lead to fibrosis
Shardul Joshi
10. • Basophils
- Only present in the bloodstream, and represent <1%
of circulating WBC.
- They are non-phagocytic cells.
- They play a major role in the allergic response.
- They release their granules (containing histamine,
serotonin, heparin, prostaglandin, etc into the
bloodstream following exposure to specific allergens).
- They bear receptors that bind to Fc of IgE
When an individual is exposed to an allergen, specific
IgE is produced which binds to the basophil surface
- Upon re-exposure to the allergen, the allergen binds
to IgE on the surface of basophils resulting in
degranulation
Shardul Joshi
11. • Mast cells
- Precursors are released from bone marrow into
blood
- Differentiate only when they enter the tissues
- They are present in skin, connective tissues and
mucosal epithelial tissues
- They also have large number of histamine
containing granules
- Along with basophils, mast cells play an important
role in allergic responses
Shardul Joshi
12. • Dendritic cells
- Covered with long membrane extensions like dendrites
- Most potent professional APCs
- Constitutively express high levels of MHC II and co-stimulatory
B7
- Epidermis/ mucous membranes- Langerhans cells
Heart, lungs kidney etc.- Interstitial dendritic cells
Thymus medula and sec lymphoid tissues-
Interdigitating
Blood- Circulating dendritic cells/ veiled cells
- Follicular dendritic cells- present in lymph follicles
- No MHC II expression. High levels of membrane
receptors for antibody and complement binding
- May have role in B-cell development and activation
Shardul Joshi
13. Organs of
Immune system
• Primary: Thymus and bone
marrow where lymphocytes
mature
• Secondary: Lymph nodes,
spleen, mucosal associated
lymphoid tissues (MALT) and
gut associated lymphoid
tissues (GALT)
• Tertiary: Cutaneous
associated lymphoid tissues
(CALT)
SourceS:h Karduubl JyosIhmi munology 5th edition
14. • Flat, bilobed, capsule
• Trabeculae -separate
lobules
• Cortex & medula-stromal
cell network
which has Mɸ,
epithelial & dendritic
cells
• Contribute to growth
& maturation of
thymocytes
Source: Kuby Immunology 5th edition
Thymus
T-cell maturation and selection
• TCR antigenic diversity by random gene rearrangements
• Cells unable to recognize self MHC molecules or those with high affinity for
self MHC alone or in conjugation with self antigen are eliminated by PCD
Immune system development and function
• Thymus increases in size till puberty and then atrophies
• It is important for development of immune system in early age
• Thymectomy at early age results in very less number of T- cells
Shardul Joshi
15. Lymphatic system
• Blood plasma seeps through capillaries
• Much of interstitial fluid returns to blood
• Remainder, called as lymph flows into lymphatic
capillaries and lymph vessels
• This lymph returns to blood through thoracic duct
which empties into left subclavian vein
• Primary lymph follicles have follicular dendritic
cells and resting B-cells
• Secondary follicles are formed after exposure to
antigen. These contain concentrically packed B-cells
surrounding a germinal center
• GC contains Th cells & dividing B-cells, selection
of most specific B-cells occurs here
Shardul Joshi
16. Lymph nodes
• Encapsulated, bean shaped
• Thee parts cortex, paracortex
and medula
• Cortex- B-cells, Mɸ and follicular dendritic cells
• Paracortex- T-cells and interdigitating dendritic
cells. This is thymus dependant area
• Medula- Mostly plasma cells
• Initial activation of B-cells in paracortex
• Lymph nodes are first organized lymphoid
structures to encounter an antigen
• These have many primary and secondary
lymphoid follicles
Kuby Immunology
5th edition
Shardul Joshi
17. • Splenic artery
carries blood
borne antigens
& lymphocytes
to spleen
• Red pulp- Mɸ
destroy old and
defunct RBCs
• Mɸ contain
RBCs/ HB/ iron
pigments
Source: Kuby
Immunology 5th edition
Blood
filtration
Spleen
• White pulp- surrounds splenic artery branches and forms
periarteriolar lymphoid sheath (PALS) which has T-cells
• Marginal zone which surrounds PALS is rich in B-cell containing
primary lymphoid follicles
• Interdigitating dendritic cells trap antigen in Marginal zone and
present it to TH cells in PALS.
• Activated TH & B cells migrate to marginal zone- sec lymph follicles
Shardul Joshi
18. MALT
Peyer’s patches
• Found within sub-mucosal layer of intestinal lining these
are nodules of 30-40 lymphoid follicles
• M cells in mucosal lining lack villi and have deep
pockets filled with cluster of Mɸ, B and T-cells
• M cells endocytose and deliver antigen to immune cells
in these pockets
• B cells secrete sIgA which crosses epithelial cells and
then can neutralize antigens
Tonsils
• Tongue base- lingual, sides & back of mouth- palatine,
roof of nasopharynx- adenoids
• Contain lymphocytes, Mɸ, granulocytes & mast cells,
lymphoid follicles
Shardul Joshi
19. CALT
• Epidermis contains interepidermal
lymphocytes
• Most T-cells in MALT and CALT are CD8+
cells which express γδ TCR which have
limited antigen diversity
• It is thought that their diversity is limited to
antigens that may enter through epidermal
or mucosal routes
• Langerhans cells are APCs in epidermis
• Keratinocytes can sometimes be induced to
express MHC II but aren’t professional APCs
Shardul Joshi
Professional APCs- Dendritic cells, B-cells, Macrophages
Class II MHC molecules are expressed by professional APCs and Class I MHC molecules are expressed by all nucleated cells
Co-stimulation- it is stimulatory when B7 interacts with CD28 and suppressive when it interacts with CTLA-4.
CD28 is expressed by both resting and activated T cells whereas CTLA-4 expression increases by CD28 generated co-stimulatory response.
PCD- programmed cell death
Thymectomy after puberty may not hamper immune function to as great extent as it will before puberty
Graft of thymus from young donor will show better development of immune function in thymectomized adults than graft from adult donor
Both experiements were conducted on mice