Elements of innate and Elements of innate and acquired immunityacquired immunity

E. coli bacteria adhering to the surface of epithelial cells of the urinary tract

Figure 2.1The developmental pathway of various cell types from pluripotential bone marrow stem cells.

This granulocyte has very tiny light staining granules (the granules are very difficult to see). The nucleus is frequently multi-lobed with lobes connected by thin strands of nuclear material. These cells are capable of phagocytizing foreign cells, toxins, and viruses.

When taking a Differential WBC Count of normal blood, this type of cell would be the most numerous. Normally, neutrophils account for 50-70% of all leukocytes. If the count exceeds this amount, the cause is usually due to an acute infection such as appendicitis, smallpox or rheumatic fever. If the count is considerably less, it may be due to a viral infection such as influenza, hepatitis, or rubella.

Neutrophil

This granulocyte has large granules (A) which are acidophilic and appear pink (or red) in a stained preparation. This micrograph was color enhanced to illustrate this feature. The nucleus often has two lobes connected by a band of nuclear material. (Does it looks like a telephone receiver?) The granules contain digestive enzymes that are particularly effective against parasitic worms in their larval form. These cells also phagocytize antigen - antibody complexes.

These cells account for less than 5% of the WBC's. Increases beyond this amount may be due to parasitic diseases, bronchial asthma or hay fever. Eosinopenia may occur when the body is severely stressed.

Eosinophil

The basophilic granules in this cell are large, stain deep blue to purple, and are often so numerous they mask the nucleus. These granules contain histamines (cause vasodilation) and heparin (anticoagulant).

In a Differential WBC Count we rarely see these as they represent less than 1% of all leukocytes. If the count showed an abnormally high number of these cells, hemolytic anemia or chicken pox may be the cause.

Basophil

The lymphocyte is an agranular cell with very clear cytoplasm which stains pale blue. Its nucleus is very large for the size of the cell and stains dark purple. This cell is much smaller than the three granulocytes (which are all about the same size). These cells play an important role in our immune response. The T-lymphocytes act against virus infected cells and tumor cells. The B-lymphocytes produce antibodies.

This is the second most numerous leukocyte, accounting for 25-35% of the cells counted in a Differential WBC Count. When the number of these cells exceeds the normal amount, one would suspect infectious mononucleosis or a chronic infection. Patients with AIDS keep a careful watch on their T-cell level, an indicator of the AIDS virus' activity.

Lymphocyte

Distinctive membrane molecules on lymphocytes

This cell is the largest of the leukocytes and is agranular. The nucleus is most often "U" or kidney bean shaped; the cytoplasm is abundant and light blue (more blue than this micrograph illustrates). These cells leave the blood stream (diapedesis) to become macrophages. As a monocyte or macrophage, these cells are phagocytic and defend the body against viruses and bacteria.

These cells account for 3-9% of all leukocytes. In people with malaria, endocarditis, typhoid fever, and Rocky Mountain spotted fever, monocytes increase in number.

Monocyte

Development of dendritic cells & macrophages

Macrophages are 5 - 10 fold largerthan monocytes, and contain moreorganelles, especially lysosomes.

Alveolar macrophages in the lungHistiocytes in connective tissuesKupffer cells in the liverMesengial cells in the kidneyMicroglial cells in the brainOsteoclasts in bone

SEM micrograph of follicular dendritic cells showing long, beaded dendrites

- Langerhans cells- Interstitial dendritic cells- Interdigitating dendritic cells- Circulating dendritic cells (veiled cells)

Phagocytosis and processing of exogenous antigen by macrophages

The background cells in this micrograph are erythrocytes (red blood cells). These cells are non-nucleated, biconcave discs that are filled with hemoglobin. The primary function of these cells is to carry oxygen from the lungs to the body cells.

Woman usually have 4-5 million erythrocytes per cubic millimeter of blood, men have 5-6 million. If this number is considerably higher, polycythemia may be the cause. If the number is considerably less, the person has anemia.

Erythrocyte

Sickle cell anemia is an inherited condition which results in some erythrocytes being malformed. The gene for this condition causes the hemoglobin to be incorrectly formed, which in turn causes some erythrocytes to take on a crescent shape. These cells are not able to carry adequate amounts of oxygen to cells.

Phagocytic defenses

Phagocytes : - class of cells capable of ingestion (engulfment) & destruction of microorganisms - recruited to site of inflammation - two cell types

1) neutrophil (PMN) - 1st to accumulate around invaders & initiate phagocytosis

2) tissue & blood borne macrophages (mononuclear phagocytes - migrate to site & initiate phagocytosis

Figure 2.2Endocytosis and phagocytosis by macrophages.

Figure 2.3A polymorphonuclear leukocyte (surrounded by erythrocytes in a blood smear) with a trilobed nucleus and cytoplasmic granules. (Photograph courtesy of Dr. A. C. Enders, School of Medicine, University of California, Davis).

Figure 2.4A scanning electron micrograph of a macrophage with ruffled membranes and a surface covered with microvilli. (Photograph courtesy of Dr. K. L. Erickson, School of Medicine,

University of California, Davis)

Figure 2.5Schematic representation of NK cell inhibitory receptors and killing.

Inflammation

- Def: Tissue reaction to infection or injury, characterized by erythema, swelling, heat, pain & loss of normal tissue function- Necessary for proper functioning of host defenses

Erythema : due to increased blood flowSwelling : due to increased extravascular fluid & phagocytic infiltrationHeat : due to increased blood flow & pyrogensPain : due to tissue distruction & irritation of sensory nerve receptors

Major events in the inflammatory response

Tissue bactericides

Substance Source Composition Activity

LysozymeSerum, saliva,

sweat, tearsprotein bacteriolysis

Lactoferrin &transferrin

Serum, tissues,secretions

glycoprotein Iron binding

PeroxidaseSaliva, tissues(neutrophils)

protein oxidation

Fibronectin Serum, mucosa glycoproteinOpsonization,

clearance

Interferons Virus inf. cells protein Virus resistance

InterleukinsMacrophages,lymphocytes

proteinActivation of

immune system

Complement serum proteinsLysis,

inflammation

Figure 2.6The distribution of lymphoid tissues in the body.

Roles of various lymphoid tissuesin immune system function

Generating bone marrow source of lymphocytesstem cells

Regulating thymus, BM sites of regulation ofproduction bursa lymphocyte development

Providing spleen, BM site of lymphocyte-Agenvironment lymph nodes interactionsfor cell-Ag tonsilsinteraction Peyer’s patch

Primary lymphoid organs- maturation of lymphocytes

- removal of self-reactive lymphocytes

• Thymus– differentiation of T cell lymphocytes

• Bone Marrow (bursa of Fabricus in birds)– differentiation of B lymphocytes

Rat thymus

Thymus

1. Lymphoepithelial organ2. Differentiation of T lymphocytes3. Only 5 - 10% of maturing T cells survive4. Size

1) relative size greatest in newborn2) absolute size greatest in puberty3) atrophy after puberty

5. Maturation of T cells - mainly during fetal development and for a short time after birth

Figure 2.7The cellular organization of the thymus.

Thymus & tolerance

- Tolerance results if host lacks T cells with receptors specific for Ag

- Range of T cell receptors (TCR) determined in thymus

BM stem cells

React w/ self MHCPositive selection

Thymocyte proliferation

React w/ “self” thymocytesNegative selection

Apoptosis

Secondary lymphoid organs- angen-induced activation of lymphocytes

• Spleen (filters blood)

• Lymph nodes (filter lymph)

• Mucosa-associated lymphoid tissue (MALT)

– Gut-associated lymphoid tissue (GALT)• Peyer’s patches, tonsils, appendix, …….

– Bronchus -associated lymphoid tissue (BALT)• diffused aggregates of lymphocytes

Spleen

- Removes Ag & aged blood cells- Stores RBC & platelets- Site for Ab production & effector T cells- Consists of

red pulp - storage of RBC & Ag trappingwhite pulp - immune response

Figure 2.8Schematic views and light micrograph of a section of spleen.

Rich in lymphocytes

Erythrocytes &macrophages

B cells

Macrophages

T cells

Derived from follicles after Ag stimulation

Response of spleen to antigen

Ag trapped in spleed

macrophages in marginal zone, red pulp

primary follicles in white pulp

Ab producing cells in primary follicles

germinal center in primary follicles

Figure 2.9(A) A diagrammatic representation of a section of a lymph node. (B) A section through a lymph node showing the capsule, the subcapsular sinus, the medulla (upper left), and the cortex with secondary follicles containing germinal centers. Also shown (upper right) is a follicle without a germinal center.

Lymphatic vessels

Structure of M cells and production of IgA at inductive sites

Figure 2.10Circulation of lymph and fate of antigen following penetration through (1) the bloodstream, (2) the skin, and

(3) the gastrointestinal or respiratory track.

Figure 2.11The interrelationship between innate and acquired immunity.