Immunology

1. 1. Lymphoid cells T cells 4. Mast cells
B cells
NK cells
(Null cells)
2. Mononuclear
cells
Monocytes 5. Dendritic
cells
Langerhans cells
Interstitial DC
Macrophages Interdigitating
DC
Circulating DC
3. Granulocytic
cells
Neutrophils
Eosinophil
Basophil
Cells of the immune system

3. II Mononuclear cells
Monocytes and macrophages
Monocytes in Blood, M in Tissues

4. Bone marrow haematopoietic stem cell precursors
called as monoblasts
Differentiate into
promonocytes
Enter into blood
promonocytes
Blood
Differentiate into
Mature monocytes
(circulates in blood for app 8 hrs and enlarges
during that time)

5. Enlarged monocytes migrate to tissues
Tissue
Enlarged monocyte
Differentiate into
Macrophage

6. Mechanism of pathogen clearance by monocytes
- By phagocytosis of Ag
2 subpopulations of monocytes
1. CD14++ monocyte (the classical monocyte, which is
characterized by high level expression of the CD14 cell
surface receptor)
2. CD14+CD16+ monocyte (the non-classical, pro-
inflammatory monocyte with low level expression of
CD14 and with additional co-expression of the CD16
receptor)

7. Monocytes in diagnosis
 Monocytosis - is the state of excess monocytes in the
peripheral blood. It may be indicative of various disease states
 A high count of CD14+CD16+ monocytes is found in severe
infection (sepsis)
 a very low count of these cells is found after therapy with
immuno-suppressive glucocorticoids

8. Monocyte vs M

9. Macrophages are
 5-10 times larger than monocytes
 has more organelles like lysosomes
 Has increased phagocytic activity
 Produce large no of hydrolytic enzymes
 Secrete large variety of soluble factors
Macrophage
hydrolytic
enzymes
soluble factors

10. Macrophages
Some are fixed at
certain tissues (not
motile)
Some are free and motile
(travel by ameboid movement
in the tissues)
Nomenclature of Macrophages in tissues
Alveolar macrophages - lung
Histiocytes - connective tissues
Kupffer cells - liver
Mesangial cells - kidney
Microglial cells - brain (neural tissue)
Osteoclasts - bone
Epitheliod cells - granulomas
Sinusoidal lining cells - Spleen

11. Alveolar macrophages (in lungs)
- First line of defense against both living pathogens
and nonliving particulates, that enter from the
inspired air.
- Alveolus of lung contains both dendritic cells and
macrophages, as major immune cells
- Dendritic cells of alveolar lining of lung-
responsible for-adaptive immunity (antigen
specific response)
- Macrophages of alveolar lining of lung-
responsible for-innate immunity (not antigen
specific)

12. Resting macrophages
Activated macrophages
Stimulus for activation
-phagocytosis of a pathogen
-cytokines (INF-g) secreted by activated TH
-mediators of the inflammatory response
-components of bacterial cell walls

13. Resting Vs Activated Macrophages
Activated macrophages – more effective in eliminating pathogen
Activated
macrophage
greater
phagocytic
activity
increased ability
to kill ingested
microbes
increased
ability to
activate T
cells
increased
secretion of
inflammatory
mediators
secrete various
cytotoxic
proteins for
eliminating
broad range of
pathogens

14. The photomicrographs below show a human macrophage
engulfing and internalising the yeast Candida albicans.

15. Macrophages
-Their role is to phagocytose (engulf and then digest) cellular
debris and pathogens and
-to stimulate lymphocytes and other immune cells to respond
to the pathogen.

16. What is opsonisation?
Coating of Ag/pathogen with Ab or C3b
C3b
AntigenAb Ab
Ab
Ab Ab
Antigen
C3bC3b
C3b
C3b
Opsonin
1. C3b
2. Ab
What are opsonins?

17. How are the pathogens phagocytosed by macrophages?
Through Fc and Complement receptors

18. Opsonization with Ab
C3b
Opsonization with complement
Opsonization- coating of microbes with Ab/complement
components
C3b R

19. Receptors on macrophage Opsonic
Receptors
for
phagocytosis
1. Integrins
2. Fc receptors
Called as opsonic
receptors
They function in
phagocytosis and
endocytosis of
complement- or
antibody-
opsonised
particles,
respectively
AntigenAb Ab
Ab
Ab Ab
Antigen
C3bC3b
C3b
C3b

20. non-Toll-like receptors
(NTLR)
which include the family
of scavenger receptors
and the C-type lectins
Opsonic R and NTLRs
have effect on NF-kB
regulate production of
pro-inflammatory
mediators

21. Toll-Like receptors (TLR)
Are non-opsonic surface
receptors
do not mediate
phagocytosis/endocytosis
but are important sensors
of bacteria, fungi and
viruses

22. Some TLR are located
within vacuoles and
play a role in
recognition of
intracellular pathogens

23. Cytosolic viruses and
bacterial products are
recognised by the NOD-
like receptors (NLR) and
RIG-like helicases
(RLH)