Question

Clearly describe six ways in which macrophages and lymphoctyes (both B- and/or T-cells) interact during an immune response.

Answer 1

• Immune response is initiated when; the body encounters any foreign molecules acting as exogenous or endogenous antigens).
• The innate immunity or non-specific immunity acts as the first line of defense, provides barrier against the foreign substances.
• Various cytokines released from specific cells, like interleukins (IL), tumor necrosis factor alpha (TNFα), activates the production of mature phagocytic cells, like neutrophils, macrophages and dendritic cells and induce their migration to the site of infection or invasion.
• Phagocytic cells, engulf the foreign substances by phagocytosis or endocytosis.
• The phagocytosed molecules processed and, then the peptide fragments of antigens are expressed through membrane bound glycoproteins called major histocompatibility complex (MHC).
• The antigenic polypeptide bound to MHC molecules further induces B-lymphocytes (designated from Bursa of Fabricus in birds, in humans generated in bone marrow) and T-lymphocytes (lymphocytes maturing in thymus), generating humoral or cell mediated immune responses, as well as immunogenic memory. Such specific activations lead to clonal selection, clonal expansion and clonal deletion.

Specific interactions of macrophages and lymphocytes:

1.Activation of helper T-lymphocytes (TH):

• They are mediators for the activation of both humoral or cell mediated immune responses.
• The naïve TH cells, with T-cell receptor- cluster of differentiation 3 complexes (TCR CD3), reacts to class II MHC molecules associated with antigenic polypeptide of Antigen presenting cells (Macrophages).
• This induces other T-cell surface receptors like CD28, leading to further interactions with MHCII-polypeptide complexes.
• The TH cells then proliferates and differentiates into memory cells and effector cells or mature cells with CD4 receptors. TH cells are subdivided into TH2 (activating B-cells), TH 1 (activating T-cytotoxic cells) and other subtypes, which secretes different cytokines, that induces other immune cells. TH cells also mediate clonal anargy.

2. Activation ofCytotoxic T-lymphocytes (Tc):

• T cytotoxic cells (TC)CD 8 receptors on T cytotoxic cells recognizes type I MHC molecules bound antigenic peptides, and co-stimulatory responses.
• They contribute to the cell mediate immunity. TC, then differentiates into memory cells ad effector cells called cytotoxic T-lymphocytes (CTLs). CTLs then further recognizes MHC-I complexes bound to the target cell, and thus destroy the target cell.

• Activate macrophages release cytokines- IFN-γand also antigen co-stimulatory response via CD40 receptor.

  They activates T-cytotoxic cells.

3. Activation of TREGS (T-regulatory cells):

• Certain T-cells, may suppress the immune response, these cells are called and T suppressor cells (TS ). These regulatory T-cells has CD-4 surface receptors and are also called TREGS (T-regulatory cells).
• Regulatory macrophages interact with these cells (with CD-28, CD- 86, Cd-80).
• Activation of cells results in release of certain lymphokines, interleukins, that stimulates production of granzymes, that inhibit effector cells, resulting shutting down of immune responses.

4. Activation of B cells:

• Activated macrophages release cytokines like IL3, IL-4. IL-5
• These cytokines activates TH2 cells.
• TH2 subtype in turn help in activation of B-cells
• Initiates antibody-mediated or humoral immunity, allergic reaction.

5. Interaction with TH17

• TH17 ontribute against extracellular pathogens and fungal infections.
• Activated macrophages interacts with TH17 with  IL-6 and TGF-2.
• This helps to stimulate epithelial cells to produce antimicrobial substances to aid to physiological barrier of innate immunity. Also helps in migration of neutrophils to site of infection.

6. Interaction with Th cells to eliminate Virus infected cells:

IL-12 released by activated macrophages interacts with TH1 cells. These cells inturn produce IFNγ.

The process causes apoptosis of viral infected cells.

Answer 2

The immune system is the body’s biological defense system. The main purpose of the immune system is to identify self from non-self. The immune system identifies and defends the body from non-self proteins, viruses, bacteria, fungi, parasites and other pathogens. Occasionally, the immune system can make a mistake and attack itself, resulting in autoimmune disorders.

The immune system comprises many different cells, organs, and tissues that work together to combat infection, cellular damage and disease. Cells of the immune system include white blood cells, such as macrophages, as well as T and B lymphocytes. The main lymphoid tissues of the immune system are the thymus and the bone marrow.

The immune system consists of many parts that work together to defend the body against invaders. The primary parts of the immune system include the bone marrow and thymus. The bone marrow is extremely important to the immune system because all the body’s blood cells (including T and B lymphocytes) originate in the bone marrow. B lymphocytes remain in the marrow to mature, while T lymphocytes travel to the thymus.

The thymus is a bi-lobed gland located above the heart, behind the sternum and between the lungs. The thymus is only active through puberty, then it slowly shrinks and is replaced by fat and connective tissue. The thymus is responsible for producing the hormone thymosin, which in turn aids in the production of T cells. While in the thymus, T cells multiply, acquire different antigen receptors, and differentiate into helper T cells and cytotoxic T cells. Various proteins (e.g., CD4, CD8) are expressed on the T cell surface. The thymus will have produced all the T cells an individual needs by puberty.

After the T and B lymphocytes have matured in the thymus and bone marrow, they then travel to the lymph nodes and spleen where they remain until the immune system is activated. Lymph nodes are located throughout the body. The spleen is located in the upper left area of the abdomen, behind the stomach, and under the diaphragm. The main function of the spleen is to filter the blood. Healthy red blood cells easily pass through the spleen; however, damaged red blood cells are broken down by macrophages (large white blood cells specialized in engulfing and digesting cellular debris, pathogens and other foreign substances in the body) in the spleen. The spleen serves as a storage unit for platelets and white blood cells. The spleen aids the immune system by identifying microorganisms that may cause infection.

In addition to the lymph nodes and spleen, mucosal associated lymphoid tissues (MALTs) and gut associated lymphoid tissues (GALTs) play a vital role in the immune system, although they are considered to be part of the lymphatic system. MALTs are lymphoid tissues found in parts of the body where mucosa is present, such as the intestines, eyes, nose, skin and mouth. They contain lymphocytes and macrophages that defend against pathogens attempting to enter from outside the body. GALTs are lymphoid tissues found in the mucosa and submucosa of the gastrointestinal tract, tonsils, appendix and Peyer’s patches in the small intestine.