Cells Of The Immune System

INTRODUCTION

• Most of the immune system derive from

Hematopoietic stem cell.
• All blood cells arise from a type of cell called the
hematopoitic stem cell (HSC).
• Stem cells are cells that can differentiate in to other
cell types.
• They are self renewing-they maintain their population
level by cell division.
 Hematopoiesis
• HSC (Hematopoietic Stem Cell)
– Reside in Bone Marrow
– Pluripotent
– 1 HSC Per 50,000 BM Cells (~3x108 cells in Mouse
Bone Marrow)
– Extremely Proliferative If Need Arises
• HSC Differentiates to LPC (lymphoid progentor cell) or
MSC (myeloid stem cell)
• Growth Factors and Cytokines Determine Path
• Once LPC or MSC, Committed
• Stromal Cells Are Supporting Cells In BM (endothelial, fat
cells, fibroblasts, macrophages)
Hematopoietic Growth Factors
• Colony Stimulating Factors
– 4 types
• Multi-CSF (IL-3)
• M-CSF (Macrophage CSF)
• G-CSF (Granulocyte CSF)
• GM-CSF (Granulocyte Monocyte CSF)
• EPO (erythropoietin)
– Induces production of RBCs
Hematopoiesis
 Regulation of Hematopoiesis
Hematopoiesis is regulated by complex mechanisms that
affect all of the individual cell types.
• Control of the levels and types of cytokines produced by
bone-marrow stromal cells
• The production of cytokines with hematopoietic activity
by other cell types, such as activated T cells and
macrophages
• The regulation of the expression of receptors for
hematopoietically active cytokines in stem cells and
progenitor cells.
• The removal of some cells by the controlled induction of
cell death.
 Cell Death
• Orderly Self Destruction and Disorderly
• Neutrophils (5.0 x 1010) Last For a Few Days
• Aberrant Apoptosis Can Give Rise To Leukemia
• Apoptosis (orderly)
– Reduction In Cell Volume
– Chromatin Condensation
– DNA Degradation
– M Ingest Membrane Bound Bodies
– No Inflammation
• Necrosis
– Bursting of Cell Due To Injury
– Contents Released To Environment
– Inflammation
Cells of the Immune System

Differential count:
 Cells of the Immune System
• Lymphoid Cells
– B-cells, T-cells and Null cells (NK cells)
– 20-40% of body’s leukocytes
– 99% of lymph node
– If inactivated said to be naïve
– Nucleus occupies almost entire cell
– 6 m diameter
Lymphoid Cells
 Identifying Cell Using the CD
Nomenclature
• CD Cluster Of Differentiation
• Over 300 CD Markers
• T cells, CD4 or CD8 and CD3
• B cells, CD19
• NK cells, CD56
• Monocytes/Macrophages CD14
• Dendritic Cells, CD1c (Human), CD11c (mouse)
 Lymphocytes are the central cells of the immune system,
responsible for adaptive immunity and the immunologic
attributes of diversity, specificity, memory, and self/nonself
recognition.

 The lymphocytes are subdivided into three

Populations
B cells (B lymphocytes)
T cells (T lymphocytes) and
natural killer cells (NK cells)
on the basis of function and cell-membrane components.

 The other types of white blood cells play important roles,

engulfing and destroying microbes, presenting antigens and
secreting cytokines.
 B CELL

B lymphocytes mature within the bone marrow; when they

leave it, each expresses a unique antigen-binding receptor on
its membrane.

The binding of the antigen to the antibody causes the cell to

divide rapidly; its progeny differentiate into memory B cells
and effector B cells called plasma cells
 T Cell
• T lymphocytes also arise in the bone marrow.
• Unlike B cells, which mature within the bone
marrow, T cells migrate to the thymus gland to
mature. During its maturation within the thymus, the
T cell comes to express a unique antigen-binding
molecule, called the T-cell receptor, on its
membrane.
• Unlike membrane-bound antibodies on B cells,which can
recognize antigen alone, T-cell receptors can recognize only
antigen that is bound to cell-membrane proteins called major
histocompatibility complex (MHC) molecules.
• There are two types of MHC molecules,
1.Class I MHC-which are expressed by nearly all nucleated
cells of vertebrate species, consist of a heavy chain linked to a
small invariant protein called beta 2-microglobulin.
2.Class II MHC molecules, which consist of an alpha and a
beta glycoprotein chain, are expressed only by antigen-
presenting cells.
• There are two well-defined subpopulations of T cells: T
helper (TH) and T cytotoxic (TC) cells.

• Although a third type of T cell, called a T suppressor (TS) cell,

has been postulated, recent evidence suggests that it may not
be distinct from TH and TC subpopulations.

• T helper and T cytotoxic cells can be distinguished from one

another by the presence of either CD4 or CD8 membrane
glycoproteins on their surfaces T cells displaying CD4
generally function as TH cells, whereas those displaying CD8
generally function as TC Cells.
The Role of MHC molecules in antigen recognition by T cell
 ANTIGEN-PRESENTING CELLS
• Activation of both the humoral and cell-mediated branches of
the immune system requires cytokines produced by TH cells.
• To ensure carefully regulated activation of TH cells, they can
recognize only antigen that is displayed together with class
MHC II molecules on the surface of antigen-presenting cells
(APCs).
• These specialized cells, which include macrophages, B
lymphocytes, and dendritic cells.
ANTIGEN-PROCESSING AND PRESENTATION
Functions of Humoral and Cell-Mediated Immune
response
 Null Cells
• The natural killer cell was first described in 1976,when it was
shown that the body contains a small population of large,
granular lymphocytes that display cytotoxic activity against a
wide range of tumor cells in the absence of any previous
immunization with the tumor.
• NK cells were subsequently shown to play an important role
in host defense both against tumor cells and against cells
infected with some, though not all, viruses.
 Mononuclear Cells
• Monocytes in Blood, Macrophages in Tissues
– Monocytes 5-10 times smaller than M
• Macrophages Increases Phagocytic Ability
• Secretes cytokines and Produces Hydrolytic Enzymes
• Named Based on Tissue They Reside
 Alveolar macrophages in the lung
 Histiocytes in connective tissues
 Kupffer cells in the liver
 Mesangial cells in the kidney
• Activated By Phagocytosis or Cytokines (IFN)
• Antigen Presenting Capacity Thru MHC II
Monocyte vs Macrophage
Macrophage - Effective APC
Mediators of antimicrobial and cytotoxic activity of
macrophages and neutrophils
 Phagocytosis
Macrophages are capable of ingesting and digesting exogenous antigens, such as
whole microorganisms and insoluble particles, and endogenous matter, such as
injured or dead host cells, cellular debris, and activated clotting factors.
• If cells are under attack they release histamine.

• Histamine plus chemicals from pathogens mean

neutrophils are attracted to the site of attack.

• Pathogens are attached to antibodies and neutrophils

have antibody receptors.

• Enodcytosis of neutrophil membrane  phagocytic

vacuole.

• Lysosomes attach to phagocytic vacuole  pathogen

digested by proteases
 GRANULOCYTIC CELLS

The granulocytes are classified as

• neutrophils
• eosinophils or
• basophils

on the basis of cellular morphology and cytoplasmic

staining characteristics. The neutrophil has a multilobed nucleus
and a granulated cytoplasm
 Neutrophils
Neutrophils are produced by hematopoiesis in the bone marrow.
They are released into the peripheral blood and circulate
for 7–10 h before migrating into the tissues, where they have
a life span of only a few days.
• 60% of WBCs ‘Patrol tissues’ as they squeeze out of the
capillaries.

• Large numbers are released during infections Short lived – die

after digesting bacteria

• Dead neutrophils make up a large proportion of puss.

 Eosinophil

Eosinophils, like neutrophils, are motile phagocytic cells that

can migrate from the blood into the tissue spaces.
 Eosinophil

Eosinophils, like neutrophils, are motile phagocytic cells that

can migrate from the blood into the tissue spaces.
 Basophil

Basophils are nonphagocytic granulocytes that function by

releasing pharmacologically active substances from their cytoplasmic
granules.
These substances play a major role in certainllergic responses.
 Dendritic Cells
• The dendritic cell (DC) acquired its name because it is
coveredwith long membrane extensions that resemble the
dendrites of nerve cells.

• There are many types of dendritic cells, although most mature

dendritic cells have the same major function, the presentation
of antigen to TH cells.

• Four types of dendritic cells are known:

 Langerhans cells
 interstitial dendritic cells
 myeloid cells and
 lymphoid dendritic cells.
 Dendritic Cells
The only antigen presenting cells that can activate naïve T
cells