SYLLABUS FOR BIOINSTRUMENTATION - SCANNING

 

IMMUNITY. INNATE IMMUNITY. STRUCTURE OF THE IMMUNE SYSTEM. IMMUNE CELLS

 

1.1.  IMMUNITY AS A WAY OF PROTECTION AN ORGANISM TO SUBSTANCES THAT HAVE SIGNS OF FOREIGNITY AND IS

PROVIDED BY A SPECIALIZED IMMUNE SYSTEM. TYPES OF IMMUNITY

 

The human body has different mechanisms of protection to genetically alien agents. They are divided into two groups – innate responses and specific or adaptive immunity. The human‟s organism has specialized structures and organs responsible for implementation of immune defence. They are connected with a special system – immune system.

 

Table 1. Synonyms for terms “innate responses” and “adaptive immunity”

Terms	Synonyms
Innate responses	Nonspecific,  innate,  species,   heritable immunity
Adaptive immunity	Specific, adaptive, individual immunity; immunity

 

Innate immunity is basic immunity, which may be genetically passed on from one generation to other generation. It does not depend on prior contacts with microorganisms. It may be non-specific when it indicates a degree of resistance to all infections.

Adaptive immunity provides the ability of an organism to resist a particular infectious agent or toxin by recognition and counteraction foreign organisms or substances by the action of specific antibodies or sensitized white blood cells.

Sometimes the term “immunity” can be used to name adaptive immunity only, sometimes – for all mechanisms joined together. It is possible to understand this difference by the context. If the question is about all mechanisms of defenсe together, it can be classified to some different types (Table 1-2).

Immune system provides some specialized machineries for direct protection of the host, direct fight with everything foreign. There are two groups of factors for both levels of defenсe - innate responses and adaptive immunity, – molecules, diluted in liquids of the body (humoral factors) and specialized cells (cellular factors).

Table 2. Types of immunity (1)

Immunity
Innate		Adaptive
Non- specific	Specific	Passive	Active
It indicates a degree of resistance to all infections	It shows resistance to particular pathogens	Natural - provides by transplacental Ig G	Natural - postinfection (after disease)
		Artificial – gamma-globulins in serum drug	Artificial – postvaccinal

 

 

Table 3. Types of immunity (2)

Level of defense	Humoral	Cellular
Innate responses	Lysozyme, complement system proteins, lysines, leukins, antiviral inhibitors, C- reactive protein, cationic and  hydrolytic  proteins, lactoferrins, etc. in blood	Phagocytes, natural killer cells
Adaptive immunity	Antibodies	T-cytotoxic (effectors)

 

 

Table 4. The differences between innate responses and specific immunity

Innate responses	Specific immunity
Response is antigen-independent	Response is antigen-dependent
There is immediate maximal response	There is lag time between exposure and maximal response
Non antigen-specific	Antigen-specific
Exposure  results  in   no   immunologic memory	Exposure    results     in     immunologic memory

 

In addition, immune system cells produce a lot of biologically active substances, which are necessary for defenсe, working with foreign agent indirectly. Another levels of cells - nonspecific and specific – are producers of these regulative molecules.

1.2.  FACTORS OF INNATE IMMUNITY

 

Innate responses have a lot of different mechanisms. Many of them, but not all, are connected with activity of immune system directly. Innate responses can be divided into 2 lines of defence. The third one is line of specific defence.

 

 

The first line of defence

(not connected with activity of immune system directly)

 

Epithelial surfaces

External physical barriers which restrict entry of pathogen. Examples: skin, mucous membranes and hair, blood clotting. The intact skin and mucous membrane covering the body gives considerable protection against bacteria on it. They provide mechanical barriers. They also provide bactericidal secretions (for second line).

Movement out of body. Examples: respiratory tract ciliated epithelium (moves particles trapped in mucus toward the pharynx), bleeding, urinating, vomiting, diarrhea, tears, coryza.

Chemical defence. Examples: the wax in the ears, the sticky mucus lines of nose and other openings, the acid in the stomach.

 

Normal microflora

Intact normal flora realises the protection of the colonized surfaces in a healthy host body. It has been discussed in several contexts.

There are three maine ways that the normal flora protects the surfaces:

1.     Competition with non-indigenous species for binding (colonization) sites. The normal flora is highly-adapted to the tissues of their host;

2.     Nonspecific antagonism to non-indigenous species. The normal flora produces a variety of metabolites and ends products that inhibit other microorganisms. These include fatty acids (lactate, propionate, etc.) and peroxides;

3.     Specific antagonism to non-indigenous species. Members of the normal flora may produce highly specific proteins called bacteriocins, which kill or inhibit other (usually closely-related) species of bacteria.

 

Areactivity of cells and tissues

This concept is about specific innate immunity (see Table 1-2). Areactivity of cells and tissues is connected with absence of cells receptors for pathogen absorption or toxins fixation. A pathogen should attach to some cells surfaces by

specific receptors of the host. Such interaction is necessary for next stage - multiplying of microbe. It means disease is not possible without attachment.

In another situation it can be because of cellular machinery has not the needs of the microorganism.

In the both examples the question is that the pathogen of one species can be not pathogenic for another one.

 

 

The second line of defence

(connected with activity of immune system directly)

Innate non-specific immune defences provide rapid local response to pathogen after it has entered host (tissue factors). If the barrier of body is overcomed by the microorganisms, a number of factors plays its role in normal tissue and body fluid. Tissue factors may be divided into: cellular and humoral factors.

Examples:

Cellular factors - leukocytes (phagocytes: macrophages and neutrophils), basophils, eosinophils; lymphatic system.

Humoral factors - organic substances present in the extracellular fluids of the body - complement cascade responses, interferon responses, lysozyme in tears, swear and saliva; lysines, leukins, antiviral inhibitors, C-reactive protein, cationic and hydrolytic proteins, lactoferrins, etc. in blood.

Fever and inflammatory responses are provided by interaction of the cellular and humoral factors.

 

 The third line of defenсe

Antigen-specific immune responses specifically target and attack invaders that go through first two lines of defenсe. Examples: antibodies and lymphocytes.

 

 1.3. STRUCTURE OF THE IMMUNE SYSTEM. CENTRAL AND PERIPHERAL ORGANS OF THE IMMUNE SYSTEM

 

The immune system (lymphatic system) is a defence system against pathogens. It is incorporated into every system of the body. The immune system has its special vessels (lymph vessels) that run through the body. White blood cells are one of the major parts of the immune system.

Central organs include bone marrow (all WBC source) and thymus (is the placement of the T-cells proliferation).

Peripheral organs include Lymph nodes, Peyer's Patches, Adenoids, Tonsils, Spleen.

The immune system has been divided into two levels by the criteria of immune cells interaction with foreign substances (antigens). Early, antigen-independent stages have place in the central organs, while contact with antigens and maturation of immune cells occurs in peripheral organs. After that, immune cells are ready to defend.

The immune system is closely connected with the circulatory system. White blood cells are present in the immune system, blood and tissues.

1.4. IMMUNE CELLS. SURFACE MARKERS (ANTIGENS) AND RECEPTORS OF THESE CELLS

 

The white blood cells are represented on the Figure 2. There are cells of innate responses and specific defence, humoral and cellular directions. 

Lymphocytes

Lymphocytes (lymphoid cells) are one of the principal leukocytes. There are three major types of lymphocytes B, NK and T. The T- and B-cells in the lymph nodes are confined to discrete zones. Thay have distinctive surface markers and functions.

B cells are called so because they are connected with a special organ “bursa” in birds. Mature B cells (Plasma cells) are the producers of antibodies or immunoglobulins - Ig (classes A, M, G, E and D). B-memory cells are capable for reacting in future. It is the essence of the humoral adaptive immunity.

Additionally, B cells present antigens (they are also classified as professional antigen-presenting cells (APCs).

NK (normal killer cells) carry out extracellular killing of the target cell – tumor cells or virus-infected cells with antibody-independent cytolytic granule

mediated or cytokine-induced NK activated cell apoptosis. It is possible for antibody- dependent cytotoxicity resulting in NK activation, release of cytolytic granules and consequent cell apoptosis. Antibody plays here recognizing role while the NK-cell is affecting participants. NK cells are representatives of innate cellular immunity that distinguishes them from another lymphocytes.

T cells are called so because they are predominantly produced in the thymus. T cells are factors of cellular adaptive immunity. The main of them are T cytotoxic (CD8 T cells) and CD4 T cells.

T cytotoxic cells are the effector cells which recognize specific antigen on the surface of the target cell and after attachment kill it extracellularly. The special proteins with enzymatic activity (perforins) are released by the cell for that. Perforins destroy cellular membrane.

 

Myeloid cells

First subgroup of this is granulocytic cells (granulocytes). There are neutrophils, basophils, mast cells and eosinophils. All these types of cells work on innate cellular area of defence. Their activity can be enhanced by feedback with adaptive level of immunity (by opsonins and IgE).

Neutrophils (microphages) are cells with phagocytic activity. They are present in blood and tissues. They migrate in injured zones very fast and take part in the inflammation reactions.

Basophils and mast cells release histamine, provide allergic response, are antiparasitic.

Eosinophils are involved in parasite defence and allergic response.

The second subgroup is monocytic cells (macrophages). This group of cells defends at the innate cellular level. In contradistinction to neutrophils, macrophages are directly connected with adaptive level of defence (with CD4 T cells). The macrophages are the main antigen-presenting cells (APCs). It has place in process of co-operation between immune cells in the process of forming an adaptive immune response.

 

Membrane markers (antigens) and receptors

There are a lot of specialized structures on the surfaces of immune cells. The functions are in direct and indirect interaction (co-operation) between immune cells in the immune response formation and realizing. Additional group of receptors are specific receptors for foreign antigens recognition. Some of them are typical of special populations and subpopulations of immune cells, so it can be used to reveal or to count them for some aims. This surface sructures are named markers of the immune cells.

Membrane markers and receptors on B-cells and T-cells

The nature of the membrane receptors for antigen on B-cells and T-cells is fairly well understood. Each B-cell has approximately 10⁵ membrane-bound antibody molecules (IgD or IgM), which correspond in specificity to the antibody that the cell is programmed to produce.

Each T-cell has about 10⁵ molecules of a specific antigen-binding T-cell receptor (TCR) exposed on its surface. The TCR is similar, but not identical, to antibody.

In addition, T-cell subsets bear some distinguishing surface markers, notably CD4 or CD8. T-cells bearing CD4 always recognize antigens in association with class II MHC proteins on the surfaces of other cells.

T-cells bearing CD8 (CD8) always recognize antigen in association with class I MHC proteins and typically function as cytotoxic T-cells.

 

Table 5. Immune cells

Cells	Characteristics	Markers	Functions
Natural cytolytic cells
Natural killer cells	Large granular lymphocytes	Fc receptors for antibody; CD16, CD56, CD57	Kill antibody- decorated cells and virus-infected or tumor cell
Phagocytic cells
Neutrophi ls (polymorp ho-nuclear leukocytes )	Granulocytes with short life span, multilobed nucleus and granules, segmented band forms	-	Phagocytise and kill bacteria
Eosinophi ls	Bilobed nucleus, heavily granulated cytoplasm	Staining with eosin	Are involved in parasite defence and allergic response
Macropha ges	See below	-	-

Antigen-presenting cells (APCs)
Monocyte s	Found in lymphocytes, blood, lungs, and other organs	Horseshoe-shaped nucleus, lysosomes	Are precursors to macrophage- lineage, lymphokine release
Macropha ges	Possible residence in tissue, spleen, lymph nodes, and other organs	Large, granular cells; Fc and C3 receptors	Initiate inflammatory and acute phase response; activated cells have antiviral, antibacterial, and antitumor activities
Langerhan s‟ cells	Presence in skin	-	Transport antigen to lymph nodes
Dendritic cells	Alpha lymph nodes, tissue	-	Are efficient antigen presenter
Microglial cells	CNS and brain	-	Produce cytokines
Kupffer‟s cells	Presence in liver	-	Filter particles from blood (e.g., viruses)
B cells	See below	-
Antigen-responsive cells
T-cells	Mature in thymus; large nucleus	CD2, CD3, T-cell receptor	Produce lymphokines
CD4 T- cells	Helper / DTH cells; activation by LPC through class II MHC antigen presentation   Th 1 subtype     Th 2 subtype	CD2, CD3,CD4, T-cell receptor,       IL-2, IFN-gamma- production   IL-4,5,6,10- production	Produce lymphokines; stimulate T- and B- cell growth; promote B-cell differentiation, antibody production Promote initial defenses (local), DTH, T cytotoxic cells. Promote humoral response

CD8 T- cytotoxic cells	Recognition of antigen presented by class I MHC antigens		CD2,CD3,CD8, T- cell receptor	Kill viral, tumor, non-self (transplant) cells; secrete TH1 lymphokines
CD 8 T- cells (suppresso r cells)	Recognition of antigen presented by class II MHC antigens		CD2,CD3,CD8, T- cell receptor	Suppress T- and B- cell response
Antibody-producing cells
B-cells	Mature in Peyer‟s patches, bone marrow, bursal equivalent; large nucleus; activation by antigens and T-cells	Surface antibody, class II MHC antigens		Produce antibody and present antigen
Plasma cells	Small nucleus, large cytoplasm	-		Are terminally differentiated, antibody factories
Other cells
Basophils/ mast cells	granulocytic	Fc receptors for IgE		Release histamine, provide allergic response, are antiparasitic

 

Notes: MHC – Major histocompatibility complex; TNF – tumor necrosis factor; CNS – central nervous system; DTH – delayed type hypersensitivity; IL – interleukin; Ig – immunoglobulin; LPS – lipopolysaccharide