BASIC IMMUNOLOGY

* INTRODUCTION
Functionally, immunological competence can be divided into:
i-

Natural immunity : it is,

1. 2. 3. Genetic constitution of the host. Non specific. First line of defense. of various barriers: skin, mucous membranes, phagocytic cells...etc.

4. Consists ii- Acquired

immunity: it is

1.Specific. 2.Results from stimulation of foreign substances.

3. Involves 4. Retains

specific receptors on lymphocytes, and presentation by macrophage. memory for future exposure(retained by long living T & Lymphocytes) a) Humoral immunity (antibody production and complement) b) Cell mediated immunity (viable lymphocytes).

5.It involves:

* IMMUNE SYSTEM (LYMPHOID SYSTEM)

It consists of:

a- Central lymphoid organs: - Site of maturationof lymphoid cells. - Consist of the bonemarrow & thymus . b- Peripheral lymphoid organs: Site of reactivity of lymphoid cells. Include the spleen, lymph nodes LN), mucosa-associated lymphatic tissues ( (MALT) and lymphatic channels . MALTs are present in the gut, pharynx, bronchi, breast, genitourinarysystem, salivary and lacrirmal glands.

The resting Lymphoid tissue consists of three areas:

The cortex which contains B lymphocytes.

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The paracortex contains T lymphocytes. The medulla contains the connective tissue.

* CELLS OF THE IMMUNE SYSTEM

A) Granulocytes (50 - 75% of WBCs). B) Lymphocytes (20 - 45% of WBCs). C) Mononuclear phagocytes [Monocytes, (macrophages) 3-8% of WBCs].

1. Lymphocytes are divided into:

T lymphocytes (70% of total lymphocytes). B lymphocytes (20% of total lymphocytes). Null cells (10% of total lymphocytes).
T and B lymphocytes communicate by either direct contact or by soluble factors.

1.1 T cells:
-

Mature in thethymus by thymic epithelial cell hormones. Involved in helping B cells (Th) to become antibody-producing plasma cells. Have specific surface receptors [T-cell receptor, (TCR)] for antigen recognition. Found in paracortical and interfollicular areas of LN and spleen.

Divided intosubsets depending on their role in regulating the immune response:

o o o o -

cells.

T helper

Th) CD4 positive (

T suppressor Ts) CD8 positive cells. ( T cytotoxic Tc) CD8 positive (

cells.

Delayed hypersensitivity (TD). T-cell interaction with antigen releases non-specific factors called cytokines that amplifies the immune response. 1.2 B cells:
-

Derived from bone marrow. Involved with generation of humoral immunity .

- Have specific surface immunoglobulin for antigen recognition. - Located in germinal centers of lymph nodes and spleen. - Mature into antibody-producing plasma cells. - Antibody synthesis is inhibited by T-suppressor (Ts) cells. 1.3 Null cells:
-

- Non B non T cells. Originate in bone marrow .

2

They are either natural killer (NK) cells or antibody dependent killer (K) cells.

2. Mononuclear phagocytes
-

Present as tissue macrophages andblood monocytes. Bear surface receptors for IgG, complement and cytokines (gammainterferon, IL-4). Their primaryactivity includes:
o

Engulfment of cell debris and foreign material.

o Processing and presentation of these antigens to T and B cells.

* IMMUNE RESPONSE
- It has two limbs:
iii-

The afferent limb is concerned with antigen recognition and processing by macrophages or B-cells. The efferent limb is concerned with a series of cellular (T cell) and humoral (B cell) mechanisms against the antigen.
-

The cells are stimulated to proliferate by soluble signals between the macrophages, B-cells and T cells (interleukins). The cells will undergo blast transformation and a series of mitotic divisions leading to generation of immunoglobulin plasma cells and/or sensitized T lymphocytes capable of interacting with the original stimulus or immune tolerance. The type of immune response will depend on the antigen and the immunological maturity of the immune system. Ts cells down regulate the antibody synthesis.

- Types of Immune Response 1. Humoral response

-

Initial (primary) exposure to antigen results in the appearance of circulating immunoglobulin (Ig) mainly IgM within 3 days with maximal production at 7-10 days. Also results in the generation of memory T and B cells. Secondary exposure to the same antigen results in generation of IgG in high titers.

A) Immunoglobulin (Ig): o Glycoprotein in nature. o Present in serum and in tissue fluids. o Induced on exposure to foreign antigen.
o o

Ig consists of 2 identical heavy chains and 2 identical light chains linked together by disulphide bonds. Five types of heavy chain; G, M, A, E & D (correspond to five types of
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Igs).
o

There are 2 types of light chain: Kappa and Lambda.

B) Mechanisms of action of antibodies o Neutralization of toxins. o Promotion of phagocytosis (opsonization). o Bacterial lysis. IgG: Monomeric -

70-75% of serum immunoglobulin. Major Ab in secondary immune response. Crosses the placenta. Fixes thecomplement(all IgG classes except lgG 4). Has antitoxin activity.

IgM: (macroglobulin) [pentameric]:

-

7-10% of the total serum Igs. First Ig to appear in maturation . Found in secretions. Major Ab in primary immune response. Fixes the complement (classical pathway).

IgA: dimeric: -

15-20% of serum Igs. Predominates insecretions (colostrums, tears, saliva ...) Plays the primary role in mucosal immunity . Fixes the complement(alternative pathway).

IgE (reaginin Ab): -

Present in trace amounts in serum. Bind to receptors onbasophiles and mast cells . Has a primary role in the defense against helminthes infection . Involved in allergic reactions . Can fix the complement(alternative pathway). IgD
-

1% of serum Igs Present on circulating lymphocytes. Has unknown function may be involved in lymphocyte differentiation. ,
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B) Complement:
-

Series of nine plasma proteins that become bound to Ag-Ab complexes in specific sequence (Cascade). Contribute to humoral immunityin two ways:
iii-

Opsonization binding of complement and/or Ab to the surface of a : microorganism, attracts phagocytes and facilitates phagocytosis. Complement fixationto the surface of microorganisms results in its lysis if the complement cascade is completed.

Complement activation can occur by two routes: Classical pathway which triggered by IgG (not lgGor IgM. 4) Alternativepathway which triggered by IgA, IgE and bacterial endotoxins.

i-

ii-

II- Cell Mediated Response

-

Involves activation of cells by antigen presenting cells ( T APC). Acts against intracellular viruses, parasites and bacteria resistant to phagocytosis. Antigen presenting cells (APC) generate Interleukin 1 ( which activates T IL-1) cells to produce IL-2 that drives the activated cells to proliferate. Cell mediated cytotoxicity results from the close binding of Tc or NK cells to their target. Cytokines: -

Group of proteins released by activated lymphocytes and macrophages to modulate cellular immunity. Classified into lymphokines, interleukins and interferon. A) Lym phokines Generated by activated and B lymphocytes. T Have several actions :

o
o

Macrophage activation ( Interferon) Eosinophil activation[granulocyte-monocyte colony stimulating factor (GM-CSF)]. Leukocyte chemotaxis to site of infection. Tumor necrosis factors (TNF). Increase leukocyte turnover from stem cells [colony stimulating factors (CSF)] Increase capillary permeability. B)
-

o
o

o o

Interleukins

Generated by avariety of cellsincluding T-cell, macrophages and epithelial cells. Control cellular immune response. Involved in hemopoiesis. C) Interferon
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Generated byvirus infected cells . There are three main types alpha, beta and gamma. Function: o Interfere with virus replication. o Control cellular actions. o Control cell growth and differentiation. o Used in cancer therapy. o Used in treatment of infectious diseases.

* THE PATHOGENESIS OF IMMUNOLOGICAL MEDITATED DISEASE

Is either:
a. b. c.

Reaction to self Ags

autoimmune disease.

Exaggerated immune response hypersensitivity reactions. Inadequate immune response immune deficiency disease.

Zamzami is my name Immunology is my game