Transcript Cells and Organs Of Lymphoid System

Defense Cells in the Blood: The Leukocytes
All leukocytes critical to body defense.
blood - 5,000-10,000 leukocytes per cubic millimeter (mm3)
five major types:
Lymphocytes,
Neutrophils,
Basophils,
Eosinophils,
Monocytes.
DEVELOPMENT OF IMMUNE CELLS
Bone marrow  hemopoetic pluripotent stem cell
Major cell lines:
TPO- trombopoetin
- lymfoid (T Ly,B Ly, NK)
- myeloid (granulocytes,
Mo/Ma)
- erythroid
- megakaryocyte
LYMPHOCYTES
-
lymphoid tissue (Ly, Primary, Secondary LO) accounts for about 2% of body weight.
109 lymphocytes produced each day by the human body.
The average adult has about 1012 total lymphocytes
Lymphocytes comprise 20% of all leukocytes
Lymphocytes normally represent 25-40% of the WBCs (1,500-4,500/mm3 of blood).
a. Lymphocytes mediate the specific immune responses.
b. Only a small proportion of the body's lymphocytes are found in the blood.
The majority are found in lymphoid tissue.
c. Lymphocytes circulate back and forth between the blood and the lymphoid
system of the body.
d. They have a life span of days to years.
e. There are 2 major populations of lymphocytes:
LYMPHOCYTES
1. B-lymphocytes (B-cells) mediate humoral immunity (antibody production).
- 10-20% of all lymphocytes.
- They become antibody -producing plasma cells.
2. T-lymphocytes (T-cells)
mediate cellular immunity (cytotoxic and helper T-Ly and cytokines) and
regulate the immune responses.
- 60-80% of the lymphocytes are T-lymphocytes.
Based on markers on their surface, there are two major classes of T-Ly:
T LYMPHOCYTES
a. TH-lymphocytes (CD4+ T-lymphocytes) have CD4 molecules on their surface
and function to regulate the immune responses through
cytokine production.
- recognize protein Ag
b. TC-lymphocytes (CD8+ T-lymphocytes) have CD8 molecules on their surface.
They differentiate into T8-supressor cells and cytotoxic Tlymphocytes (CTLs).
- recognize protein Ag
c. CD4-CD8- T-lymphocytes have neither CD4 nor CD8 molecules on their surface.
- recognize lipid and lipoglycan Ag
TH1 and TH2 cells
There are two subsets of helper T-lymphocytes based on the combinations of cytokines
they are able to produce: TH1 cells and TH2 cells.
a. TH1 cells secrete the cytokines
interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and
tumor necrosis factor beta (TNF-beta) –
stimulate the cell-mediated immune responses that help the body destroy
cells infected with intracellular pathogens.
This killing of intracellular microbes is carried out by Ma and Tc-Ly.
These cytokines also stimulate certain T8-lymphocytes to secrete chemokines that block HIV from
replicating in CD4+ cells. The interferon-gamma produced by the TH1 cells also
blocks the secretion of IL-4 and IL-10 by TH2 cells.
b. TH2 cells secrete the cytokines
interleukin-4, -5, -6, -10, and -13 (IL-4, IL-5, IL-6, IL-10, IL-13) –
increase production of antibodies that help remove extracellular MIO, toxins,
and allergic antibodies (IgE).
These cytokines also activate mast cells and eosinophils. The IL-4 produced by the TH2 cells also suppresses
the secretion of IL-2 and interferon-gamma by TH1 cells while IL-10 blocks T8-lymphocytes from
producing chemokines.
B LYMPHOCYTES
B-lymphocytes refer to lymphocytes that are produced in the bone marrow and
require bone marrow stromal cells and their cytokines for maturation.
the body has 107 - 109 distinct clones of B-lymphocytes,
over 100,000 identical B-cell receptors (surface immunoglobulin-sIg)
capable of binding Ag
B LYMPHOCYTES
103 and more same BCR on the surface
BCR bind soluble antigens – internalisation – processing – coopertion to TH activation TH – cytokine production – dif. B Ly
BCR
B Ly
mitóza a
diferenciácia
Plazmatická
bunka
NK (NATURAL KILLER CELLS
NK = lymphocytes without sIg a TCR.
All NK express CD16 (receptor for Fc fragment IgG) and CD 56
CD16 enables NK killing of target cells opsonized by IgG.
NK eliminate
- tumor cells (not expressing MHC I. class molecules)
- cells infected by viruses
KIR – killer cell inhibitory
receptors
LAK - NK activated
in vitro IL-2
- more effective against
tumors than
NK
terčová b.
NK
NEUTROPHILS
Neutrophils are the most abundant of the leukocytes
-account for 54-75% of the WBCs.
-An adult = 3,000-7,500 neutrophils/mm3 of blood
the number may increase two- to three-fold during active infections.
a. Neutrophils are important phagocytes.
b. Their granules contain various agents for killing microbes.
(lysozyme, lactoferrin, acid hydrolase, and myeloperoxidase)
- kill microbes intracellularly during phagocytosis
- often released extracellularly - they kill not only microbes but also surrounding cells
c. release the enzyme kallikrein which catalyzes the generation of bradykinins that
- promote inflammation by causing
- vasodilation, ↑ vascular permeability, ↑ mucous production.
- are chemotactic for leukocytes
d. release enzymes which catalyze the synthesis of prostaglandins
- promote inflammation (vasodilation, ↑ capillary permeability.
- cause constriction of smooth muscles, enhance pain, and induce fever.
e. short-lived, having a life span of a few hours to a few days, and do not multiply.
The bone marrow makes about 80,000,000 new neutrophils per minute.
EOSINOPHILS
- comprise 1-4% of the WBCs (50-400/mm3 of blood).
a. Their granules contain destructive enzymes for killing infectious organisms.
(acid phosphatase, peroxidases, proteinases)
b. They are capable of phagocytosis
c. release contents of granules into the surrounding environment to kill microbes e.c.
d. The substances they release defend primarily against fungi, protozoa, and parasitic
worms - too big to be phagocytosed
e. They may moderate inflammatory destruction in order to prevent serious
tissue damage.
f. Their life span is 8-12 days.
BASOPHILS
make up 0-1% of the WBCs (25-100/mm3 of blood).
a. Basophils release histamine which promotes inflammation
by causing vasodilation, increasing capillary permeability, and increasing mucous
production. Basophils also release heparin, PAF, and SRS-A.
b. Their life span is probably a few hours to a few days.
MONOCYTES
make up 2-8% of the WBCs (100-500/mm3 of blood).
a. Monocytes are important phagocytes.
b. Monocytes become macrophages and dendritic cells when they
leave the blood and enter the tissue.
Macrophages and dendritic cells are important in phagocytosis and
aid in the immune responses.
They produce a variety of cytokines that play numerous roles in body defense.
c. They are long-lived (life span of months) and can multiply.
Primary (central) lymphoid organs
two major primary lymphoid organs
1. bone marrow - in which B cells develop
2. thymus - in which T cells develop
Progenitor cells from the bone marrow migrate to the thymus gland to
develop into T lymphocytes.
The thymus is a bilobed structure, whose size reaches its maximum at birth,
then atrophies with age.
- The cortex contains mostly immature thymocytes, some of which mature
and migrate to
- the medulla, where they learn to discriminate between self and nonself during
fetal development and for a short time after birth. T cells leave the medulla
to enter the peripheral blood circulation, through which they are transported
to the secondary lymphoid organs
Secondary lymphoid organs
two major functions:
1.they trap and concentrate foreign substances,
2.they are the main sites of production of antibodies and antigen-specific T cells.
Secondary lymphoid organs include:
Spleen, which is responsive to blood-borne antigens;
Lymph nodes, which protect the body from antigens that come from skin or
internal surfaces via the lymphatic system;
Mucosa-associated lymphoid tissue (MALT) - scattered along mucosal linings,
which protects the body from antigens entering the body directly through
mucosal surfaces.
SPLEEN
Function: - antibodies synthesis and release into circulation.
- site of destruction of aged both platelets and erythrocytes
(hemocatheresis).
The spleen composition - two types of tissue: red pulp and the white pulp.
The red pulp contains plasma cells, resident macrophages, erythrocytes, platelets,
granulocytes and lymphocytes.
The white pulp contains the lymphoid tissue clustered around a central arteriole in an
arrangement known as a PeriArteriolar Lymphoid Sheath (PALS).
- T cells around the central arteriole,
- B cells are organized into either primary follicles (unstimulated), or secondary follicles
(stimulated by contact with antigen) that contain a germinal center complete with
memory cells.
About 50% of spleen cells are B Ly and
30-40% are
T cells.
Arterial blood lymphocytes enter the spleen through
the trabecular artery and
return to venous circulation through the trabecular vein.
LYMPH NODE
- ovoid structures usually less than 1 cm in diameter
- placed in the neck, axillae, groin, mediastinum and abdominal cavity, where they act
to filter antigens from the interstitial tissue fluid and the lymph during its passage from
the periphery to the thoracic duct.
Somatic lymph nodes protect the skin
Visceral lymph nodes protect the respiratory, digestive and genitourinary tracts ar
The lymph node consists of
- B cell area - cortex,
- T cell area - paracortex
- central medulla, which contains a mix of
B cells, T cells, plasma cells and Ma.
B cells are arranged in:
- primary follicles -containing unstimulated
B cells, and
- secondary follicles with germinal centers
- containing antigen-stimulated B cells
Mucosa-associated lymphoid tissue (MALT)
The bulk of the body's lymphoid tissue (>50%) is found associated with
the mucosal system.
MALT is composed of:
1. gut-associated lymphoid tissues (GALT) lining the intestinal tract,
2. bronchus-associated lymphoid tissue (BALT) lining the respiratory tract,
lymphoid tissue lining the genitourinary tract.
3. Genitourinary tract associated lymphoid tissue (GUALT)
The major effector mechanism of MALT
secretion of immunoglobulin A (sIgA) directly onto the mucosal epithelial surfaces.
Examples of MALT - Peyer's patches lining the small intestine,
- tonsils
- appendix.
Diffuse accumulations of lymphoid tissue are seen in the lamina propria of the
intestinal wall. The intestinal epithelium overlying the Peyer's patches is specialized
to allow the transport of antigens into the lymphoid tissue. This particular function is
carried out by epithelial cells termed "M" cells, so called because they have
numerous microfolds on their luminal surface.
M cells absorb, transport, process and present antigens to subepithelial lymphoid cells.
Circulation of lymphocytes
1-2% of all lymphocytes recirculate each hour, allowing a large number of
antigen-specific lymphocytes to come into contact with the appropriate
antigen within the peripheral lymphoid organs. Lymphocyte traffic is
directed by the cuboidal endothelial cells lining the high endothelial venules
of the lymph nodes. When activated, the endothelial cells express adhesion
molecules that act as a kind of "glue" for the lymphocytes, preferentially
retaining and recruiting lymphocytes to the site of antigen localization. The
adhesion molecules expressed by MALT differ from those expressed by
systemic lymphoid organs. Thus, lymphoid cells stimulated in the MALT
tend to "home" back to the MALT, while systemic lymphocytes stay in the
periphery. Furthermore, adhesion molecules expressed by the HEVs differ
from those expressed at sites of inflammation. The adhesion molecules fall
into four families of structurally-related molecules—the immunoglobulin
supergene family, integrins, selectins and carbohydrate ligands.