Immune system cells

1. Immune cells
Dr. Samuel Asamoah Sakyi
Dept. of Molecular Medicine
KSMD

2. Immune cells

3. Classification of immune cells
Cells of the innate immune system
monocyte/macrophage
neutrophil
eosinophil
basophil
dendritic cell (DC)
natural killer cell (NK cell)
Cells of the adaptive immune system
B lymphocyte
T lymphocyte

4. Cells mediating innate immunity
monocyte/macrophage
neutrophil
eosinophil
basophil
dendritic cell (DC)
natural killer cell (NK cell)

5. Origin and development of macrophages
I. monocyte/macrophage

6. monocyte macrophage
Enlarged cell size (5~10-fold)
Increased organelles
Enhanced phagocytic ability

7. Macrophages in different tissues
have various names

8. 1. Ingestion and digestion of pathogens
Functions of macrophage

9. How do Macrophages
Recognize Pathogens?

10. Pattern Recognition Receptors
(PRRs)
PRRs
Mannose receptor
Scavenger receptor
Toll-like receptor (TLR)
PRRs recognizes conserved molecular
structures on microorganisms
These molecular structures are not
expressed by host tissues

11. Mannose receptor

12. Scavenger receptor
recognize
 teichoic acid (gram-negative bacteria)
 lipopolysaccharide (LPS, gram-positive bacteria)
 phosphatidyl serine (apoptotic host cells)

15. Scavenger receptor
Phagocytosis of
apoptotic cells

16. Toll-like receptor (TLR)
 Thirteen receptors identified in mice and humans

17. Opsonic receptor
1) IgG Fc receptor (FcγR)
2) complement receptor (CR1)

18. Mechanisms of killing
phagocytosed pathogens
1) Oxygen-dependent killing
mechanisms
2) Oxygen-independent killing
mechanisms

19. 1) Oxygen-dependent killing
mechanisms
A. reactive oxygen intermediates（ROIs）
NADH/NADPH oxidase
O2 OH
. (hydroxyl radicals)
H2O2 (hydrogen peroxide)
B. reactive nitrogen intermediates（RNIs）
iNOS (induced nitric oxide synthetase)
L-arginine + O2 + NADPH NO (nitric oxide) + L-citrulline + NADP
NO reacts with O2— forming peroxynitrite
During phagocytosis, the respiratory burst occurs
O2
— (superoxide anion)

20. 2) Oxygen-independent killing
mechanisms
Lysozyme
Defensins: a group of cationic peptides
hydrolytic enzymes

21. 2. Antigen processing and presentation
Functions of macrophage

22. Functions of macrophage
3. Secretion of factors

23. Neutrophil
Eosinophil
Basophil
Granulocytes

24. II. Neutrophil
Constitute 50%–70% of the circulating WBC
Rapid responders to pathogen invasion
the first to arrive at a site of inflammation
sensitive to chemoattractants
A life span of only 2-3 days

25. The process of neutrophil extravasation
The steps in transendothelial
migration and how it is directed
are still largely unknown

26. II. Neutrophil
Potent phagocytic activity
Primary granules: a type of lysosome
contain peroxidase, lysozyme, and hydrolytic enzymes
Secondary granules:
contain collagenase, lactoferrin, and lysozyme
Produce more ROIs and RNIs
Exhibit a larger respiratory burst
than macrophages
Neutrophils are more likely than
macrophages to kill ingested pathogens

27. III. Eosinophil
Constitute 1%–3% of the circulating WBC
Contents of eosinophilic granules may
damage the parasite membrane
Help against parasites

28. IV. Basophil
＜1% of the circulating WBC
Nonphagocytic granulocytes
Pharmacologically active substances
histamine, leukotriene etc.
Involved in allergic responses

29. V. Mast cell
In mucosae and connective tissues
Not in circulation
Functionally indistinguishable from basophil

30. VI. Dendritic cell (DC)
covered with long
membrane extensions
uptake, processing and
presentation of antigens
express high levels of class
II MHC molecules and co-
stimulatory molecules

31. Interaction of DC and T cell

32. VII. Natural killer (NK) cell
 Large, granular lymphocytes with cytotoxic activity
 No specific antigen receptor
CD16 (IgG Fc receptor) and CD56: typical NK cell markers
 No thymic development
Nude Mice
lack a thymus
no T cells
have functional NK-cell populations

33. VII. Natural killer (NK) cell
The first line of defense against
 virus infected cells
 tumor cells
Cytolytic mechanisms of NK cell
 FasL-Fas pathway
 perforin/granzyme pathway
 antibody-dependent cell-mediated
cytotoxicity (ADCC)

34. The FasL-Fas pathway

35. The perforin/granzyme pathway
 The most common mechanism

36. The perforin/granzyme pathway

37. Antibody-dependent cell-
mediated cytotoxicity (ADCC)

38. The mechanism by which NK cells
recognize target cells
 NK cells express two different categories of
receptors
Activation receptors Inhibition receptors
deliver inhibition signals
deliver activation signals
The cytoplasmic tails contain the
immunoreceptor tyrosine-based
activation motif (ITAM)
The cytoplasmic tails contain the
immunoreceptor tyrosine-based
inhibition motif (ITIM)

39. Activation receptors (ARs)
 The exact nature of ARs on NK cells is not
completely clear
 Some of the candidate activation receptors
May be abnormal
patterns of
glycosylation on
the surface of
target cells
 The ligands : are not known

40. Inhibitory receptors
 Killer immunoglobulin-like receptor
(KIR)
KIR2DL, KIR3DL
 Killer lectin-like receptor
CD94/NKG2A
 Ligand: MHC class I molecules

41. Opposing Signal Model of
Cytotoxicity By NK Cells

42.  Some of the characteristics of both T cells
and NK cells
 Express T cell receptors (TCRs)
Recognition of CD1-presented antigens
 Express NK-specific markers
Kill tumor and virus-infected cells
VIII. NK T cell

43.  Cell function
monocyte/macrophage
neutrophil
eosinophil
basophil/mast cell
dendritic cell
NK cell
NKT cell
What to remember

44. Study question
 What are functions of macrophages?
1. Ingestion and digestion of pathogens
2. Antigen processing and presentation
3. Secretion of factors

45. Study question
 Explain why each of the following statements is
false.
a. Activation of macrophages increases their
expression of class I MHC molecules, making the
cells present antigen more effectively.
b. All lymphoid cells have antigen-specific receptors
on their membrane.
c. Follicular dendritic cells can process and present
antigen to T lymphocytes.

46. Study question
 (Eosinophil) is phagocytic cell important in the
body’s defense against parasitic organisms
 (Neutrophil) is generally first cell to arrive at site of
inflammation
 (Basophil) is nonphagocytic granulocytic cell that
release various pharmacologically active substances
 (Basophil) is white blood cell that migrate into the
tissues and play an important role in the
development of allergies
 (B cell) is an antigen-presenting cell that arises from
the same precursor as a T cell but not the same as
a macrophage