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Immunology Lecture 3rd

Cells of Immune System

BY
Dr. Humera Kausar
March 2015

Cells of the Immune System

Cells of the Immune System


Leucocytes

Immune
Cells

Myeloid
cells

Lymphoid
cells

Granulocytic

Monocytic

T cells

B cells

Neutrophils
Basophils
Eosinophils

Macrophages
Kupffer cells
Dendritic cells

Helper cells
Suppressor cells
Cytotoxic cells

Plasma
cells

NK cells

Cells of the innate immune system:


Phagocytes
Monocytes/macrophages
Neutrophils/PMNs/

NK cells
Basophils and mast cells
Eosinophils

Phagocytic Cells Mononuclear


PROMONOCYTES
MONOCYTES
MACROPHAGES

(Fixed or Free)

Brain ---------Microglial cells


Lungs ------------Alveolar cells
Liver ----------------- Kupffer cells
Connective tisues-----Histocytes
Kidney ---------------------Mesangial cells
Bones ------------------------ Osteoclasts

Skin ------------------------Langerhans cells

Macrophages

Macrophage

Characteristic nucleus
lysosomes
CD14 membrane
marker protein

Macrophages
Activated by variety of stimuli in the course of an
immune response.
Activated macrophages are more effective then
resting ones in eliminating potential pathogen.
Activated macrophages secreted various cytotoxic
proteins that help to eliminate broad range of targets
including
o
virus infected cells
o
Tumor cells
o
Intracellular bacteria

Also act as antigen presenting cells

Macrophage as an antigen presenting cells

Granulocytes

Neutrophils
Polymorphonuclear (PMN) leukocyte.

Has multilobed nucleus and granulated cytoplasm.


Stains with both acidic and basic dyes.

Constitute 50% to 70% of the circulating


leukocytes.
After release in to the blood, circulates 7 10 hours
before migrating in to the tissues.
Life span is few days. (3 days)

Neutrophils (PMNs)

CD66 membrane
marker protein
Neutrophil
Geimsa stains

GRANULOCYTES

Neutrophils

First cells to arrive at the site of inflammation.


In response to many types of infections the bone
marrow releases increased number of circulating
neutrophils called leukocytosis.
Act as phagocytic cells.

Neutrophils

GRANULOCYTES

Lytic enzymes and bactericidal substances in


neutrophils are contained within primary and
secondary granules.
Larger denser primary granules are a type of
lysosome containing

peroxidase, lysozyme, various hydrolytic enzymes


Smaller secondary granules contains,

collagenases, lactoferrin,

lysozyme

Both primary and secondary granules fuse with


phagosomes.

Neutrophil

GRANULOCYTES

Eosinophils
Stain with acid dye eosin red.

Has bilobed nucleus and granulated cytoplasm.


Constitute 1% to 3% of WBC population.

Like neutrophils, motile phagocytic cells that can


migrate from blood into tissues.
Phagocytic role of eosinophils are less significant
than that of neutrophils.
Play a role in the defense against parasitic
organisms by secreting contents of eosinophilic
granules, which damage the parasite membrane.

Eosinophil

GRANULOCYTES

Basophils
Basophil has a lobed nucleus and heavily granulated

cytoplasm.
Stains with basic dye methylene blue.
Non phagosytic granulocyte.
Constitute <1% of circulating WBC.
Function by releasing pharmacological active
substances from cytoplasmic granules.

Play a major role in certain allergic responses.

Basophil

Mast Cells
By hematopoiesis, released into the blood as

undifferentiated cells.
Do not differentiate until they leave the blood and
enter the tissues, including
skin, connecting tissue of various organs,
mucosal epithelial tissues of respiratory,
genitourinary & digestive tracts
Like circulating basophils, mast cells have large
numbers of cytoplasmic granules that contains
histamines and other pharmacological active
substances.
Play an important role in the development of allergies.

MEDIATORS RELEASED

Prostaglandin D2
Platelet Activating Factor
Tryptase
Heparin
Histamin
IL-4, IL-5, IL-6, IL-8
TNF

CAUSING

Vasodilation,
increased vasopermeability,
contraction of smooth muscles,
bronchoconstriction,
increased eosinophil, neutrophil & monocyte
chemotaxis,
anticoagulation,
increased fibroblast proliferation,
platelet activation

Dendritic Cells
Activation of T cells and
initiate adaptive immunity
Found mainly in lymphoid
tissue
Function as antigen
presenting cells (APC)
Most potent stimulator of
T-cell response

Dendritic Cells

Dendritic Cells
DC covered with long membranous extensions
that resemble the dendrites of nerve cells.
Display class I & class II MHC.
B and T lymphocytes are the mediators of
immunity, but their function is under the
control of dendritic cells.

Dendritic cells in the periphery capture and


process antigens.

Dendritic Cells
Express lymphocyte co-stimulatory molecules,
(B7, CD40)
Migrate to lymphoid organs and secrete
cytokines to initiate immune responses.

They not only activate lymphocytes, they also


tolerize T cells to antigens that are innate to the
body (self-antigens), thereby minimizing
autoimmune reactions.

Dendritic cells initiate antigenspecific immune responses


most efficient of all APCs
high MHC class I, II & costimulators
efficient cross presentation
stimulate nave T cells (CD4, CD8)
initiate Ag-specific immune responses

All immunization strategies must target DCs

Immature:
antigen
capture

Mature:
antigen
presentation

Cells of the immune system:


APC
Cells that link the innate and adaptive arms
Antigen presenting cells (APCs)
Heterogenous population with role in innate immunity
and activation of Th cells
Rich in MHC class II molecules

Examples

Dendritic cells
Macrophages
B cells
Others (Mast cells)

Cells of Adaptive Immune


System
T cells and B cells

Cells of the Adaptive Immune System:


Lymphocytes (Lymphoid Cells)
B cells
Plasma cells (Ab producing)
Memory cells

T cells
Cytotoxic (CTL)
Helper (Th)
Th1
Th2

Null cells (NK cells)

Lymphoid Cells
Contributes 20-40% of bodys WBCs,
Nave or unprimed cells are small, motile, nonphagocytic cells.

Can not be distinguished morphologically.


Resting cells are in G0 phase of cell cycle.

Small lymphocytes are 6 um in diameter.


Cytoplasm barely covers the rim around
nucleus.

Lymphoid Cells

Have,
o densely packed chromatin

o few mitochondria
o poorly developed endoplasmic reticulum

o Golgi apparatus
Life span of effector cell is few days to few
weeks.

B-Lymphocytes
Derived its name from its site of maturation in the
Bursa of fabricius in birds and Bone marrow in humans
Plasma cells (Ab producing)
Memory cells

B-CELL RRECEPTORS

Membrane bond Ig molecules


i.e.,1.5 x 105 molecules/cell
CD 45
(Marker B220)
MHC II (Antigen Presenting
receptor)
CD35
(Complement receptor)
CD21
(Complement receptor)
CD32
(Fc RII)

T-CELL RRECEPTORS

TCR
Thy 1 (1st receptor remains
throughout life span of the cell)
CD4 (T- helper cell)
CD8 (T- cytotoxic cell)
Ratio of Th : Tc = 2:1

Specificity of adaptive immune


response
Resides with Ag
Receptor on T and B
cells
TCR and BCR both
specific for only ONE
antigenic determinant
TCR is monovalent
BCR is divalent

T cell

TCR

BCR

B cell

Ag

T-Lymphocytes
T- helper cell vs T cytotoxic cell)

T helper cells and (TH) Class II MHC proteins


Specialized TH cell involved in
the inflammatory response

Cell-cell interaction mediated


by the TCR and the class II
MHC-antigen complex activates
The TH cell which produces
cytokines
TNF-alpha (tumor necrosis factor)
IFN-gamma (interferon)
GM-CSF (granulocyte-monocyte
colony stimulating factor)
These cytokines further stimulate
macrophages to increase phagocytic
activity and to in turn produce cytokines
that promote inflammation

Cytotoxic T cells (Tc) and Class I MHC proteins


The cell-cell interaction between
the infected cell and the Tc
cell is mediated by the
MHC/antigen complex and TCR

The Tc cell produces cytotoxic proteins


perforinsproduce holes or pores in the
target cell and granzymes enter the
virus infected cell causing apoptosis or
programmed cell death
The cytotoxic proteins only affect those
cells to which the Tc cell has specifically
interacted

NATURAL-KILLER CELLS

NATURAL-KILLER CELLS

Fails to express membrane molecules that


distinguished B and T cells.

Fails to express antigen binding receptors.


Constitute 5% - 10% of lymphocytes in human
peripheral blood.

NK cells have ability to recognize tumor or


virus infected cells.
NK cells express membrane receptor CD16 for
a specific region of antibody molecule (ADCC).

Cells of the Immune System


Human red blood cells
(red), activated platelets
(purple) and white blood
cells - monocyte (green)
and T lymphocyte
(orange).
Colorized-SEM
(scanning electron
micrograph)
Magnification:-1200x-(Based on an image
size of 1 inch in the
narrow dimension)



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