*1.3.3 Natural killer cells (NK)*

Natural killer cells (NK) have no CD markers on the surface so they are usually called null cells [3].

It is important to know that B-cells are able to be APC by internalization of Ag inside the cell and do the processing and presenting, which will be discussed later. Also Dendric cells (DC) are cells found only in the mammalian immune system; their function is to engulf and process Ag then present it on the surface to other immune cells. Found in tissues that in contact with external environment such as skin, lung, stomach and intestine [2].

### **1.4 Mucosal immune response**

In the mucosal surfaces and sites, the mucosal immune response come to play role in resistance against infection establishment. Many lymphoid tissues are associated with mucosa which are usually called mucosa-associated tissues play major role in protection since they are rich with both T-cells and B-cells, produce many types of Lymphokines that acts as signals of the immune system actions, produce IgA (sIgA Secretory IgA); the main effective immunoglobulin type in the surfaces of the body and the most important part is that mucosal surfaces have the receptors of microbiota that play as a biological barrier and support innate immunity. Many secretions are also produced by the mucosa to protect surfaces like gastric acid and continuous mucous secretion and shedding helps in renewing normal flora population and shed colonized pathogens.

Mucosa-Associated Lymphoid Tissues (MALT) Include the lymphoid tissues of the intestinal tract, genitourinary tract, tracheobronchial tree, and mammary glands. All of the mucosa-associated lymphoid tissues are unencapsulated and contain both T and B lymphocytes [2, 5].

#### **1.5 Gut-associated lymphoid tissue (GALT)**

It is found along the digestive tract. Three major areas of GALT that can be identified are the tonsils, the Peyer's patches, located on the submucosa of the small intestine, and the appendix. In addition, scanty lymphoid tissue is present in the lamina propria of the gastrointestinal tract [3, 5].


Physiological roles of secondary lymphoid organs:


#### **1.6 Antibody mediated immune response (humeral mediated immunity, HMI)**

B-cells have normal Ag receptors on the surface they are natural Igs, these Igs are able to form Ag-Ab complex on the surface of B-cell. This complex will be internalized inside B-cell, then the foreign Ag will be processed within B-cell and presented (or polypeptides from it) on the surface of B-cell near MHC class II and now B-cell is APC.

T-helper (Th) cells come near the APC B-cell and by the help of TCR and CD4; Th will interact and communicate with APC B-cell and Th cell will be activated and release cytokines or lymphokines (IL-2, IL-4, IL-5 and IFN-γ), these products will induce other B-cells for dividing, proliferation and differentiation. IgM will be the first Ig produced then B- cell will switch to make IgG. This response is called T-dependent Ag immune response. The other type of response is T-independent Ag immune response, this type of Ag stimulates B-cells without need for T-helper lymphocytes interfere [1, 2].

After B-cells activation, series of events happen (proliferation, clonal expansion, division and maturation), ending with Ab and memory B-cells production. These series of events called B-cell Maturation. During the second exposure to the same Ag that started the first immune response (perhaps after year from first exposure), the B-memory cells will remember the Ag and will be activated and divide into a clone of plasma cells to start the Secondary immune response (Memory response) [3].

Antibodies or Immunoglobulins (Ig) that are produced after specific humoral response are in five types; IgG; IgM, IgA, IgD and IgE based on differences in the amino acid sequences in the constant region of the heavy chains. In addition, the classes of immunoglobulins can be divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains [1].

**IgG immunoglobulin:** is a Monomer, have4 subclasses (IgG1, IgG2, IgG3 and IgG4), the subclasses differ in the number of disulfide bonds and length of the hinge region. IgG is the major Ig in serum and extra vascular spaces of total serum Igs. Able

#### Salmonella *and the Immune System DOI: http://dx.doi.org/10.5772/intechopen.95673*

to cross placenta transfer is mediated by receptor on placental cells for the Fc region of IgG, able to fix complement an binding to cells - Macrophages, monocytes, PMN's and some lymphocytes have Fc receptors for the Fc region of IgG. The term opsonin is used to describe substances that enhance phagocytosis. IgG is a good opsonin [2].

**IgM immunoglobulin:** is a pentamer, but it can also exist as a monomer. It is the third most common serum Ig and it is the first Ig to be made by the fetus and the first Ig to be made by B cells when it is stimulated by antigen. This type of Ig is a good complement fixing Ig. Thus, IgM antibodies are very efficient in leading to the lysis of microorganisms. Also a good agglutinating Ig. Thus, IgM antibodies are very good in clumping microorganisms for elimination from the body [5].

**IgA immunoglobulin: is** a monomer but IgA found in secretions is a dimer. When IgA is found in secretions is also has another protein associated with it called the secretory piece or T piece (sIgA), this secretory piece is made in epithelial cells and is added to the IgA as it passes into the secretions. The secretory piece helps IgA to be transported across mucosa and also protects it from degradation in the secretions. It is the second most common serum Ig and the major class of Ig in secretions - tears, saliva, colostrum, and mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity but does not fix complement [5].

**IgD immunoglobulin: is** a monomer **and** found in low levels in serum; found on B cell surfaces where it functions as a receptor for antigen also does not bind complement [5].

**IgE immunoglobulin**: **is** a monomer and rare on serum. It has role in allergic reactions and does not fix complement [5].

#### **1.7 Cell mediated immune response (cellular mediated immunity, CMI)**

This response occurs against cells, which are called Target cells. During both HMI and CMI, T-helper cells recognize foreign Ag processed on the surface of APC. If this Ag was processed and presented near MHC class II, then Th cells will activate HMI by B- cells activation, but if the presented Ag on APC was near MHC class I, then Th cells will activate CMI by activation of Tc, NK and MØ. Th cells able to activate and regulate CMI and HMI by many cytokines production.

In addition, in both CMI and HMI, when Th cells recognize the foreign Ag, Th cells will start T-cells activation by series of events (expanding, clonal proliferation and differentiation), then become mature to give specific activated T-helper cells in HMI and give specific activated T-helper cells and memory T-cells in CMI [2, 5].

Role of CMI response: is the defense against Tumor cells or cancer cells, Grafts Rejection, against Intracellular parasite infected cells with foreign Ag presented near MHC class I. Target cell is the infected cell with parasite and Types 4 hypersensitivity (Delayed type of hypersensitivity) [5].

#### *1.7.1 Activation of CMI cells*

When T-helper cells recognize foreign Ag on the surface of target cell in association with (or near) MHC class I. The TCR and CD4+ play role in recognition. Then Th cell will be activated and produce cytokines (especially IL-2 and IFN- γ). These cytokines will activate Tc CD8+ cells, MØ and NK cells. This activation will increase these cells ability for killing and became more effecter.

#### *1.7.2 Mode of action for killing target cells*

After T-cytotoxic cells and NK cells activation by Th cells, T-cytotoxic cells come into close contact with target cell; they will bind to the Ag by their specific Ag receptors. While NK cells will attach to Ag (on Target cell surface) by their nonspecific receptors for Ag.

T-cytotoxic cells and NK cells will kill target cells by the following mechanisms [1–5]:


This type of CMI occurs when the foreign Ag persist for long time (e.g. *Mycobacterium tuberculosis* infection is long standing intracellular infection), also, against some kinds of cancer cells [2, 5].
