The normal immune response
A normal immune response offers co-ordinated protection against foreign infections. It must ensure immunological tolerance towords self-antigen.
Types of immune response include: natural, innate immunity & acquired, adaptive immunity. First responders to infection are the natural, innate immunity. Acquired, adaptive immunity are second responders stimulated by microbes, and foreign antigens. It is important to know that an unchecked acquired, adaptive immune response sets the foundation for allergy and auto-immune diseases
The natural, acquired immunity composes of: epithelial surfaces; neutrophils; macrophages; dendritic & natural killer cells; complement system; microbe binding C-reactive protein. Phagocytic cells possess Toll-like receptors (TLRs) to recognize and initiate cellular response. Leukocytes have opsonin receptors to bind antibodies and complement. Natural killer cells and dendritic cells provide anti-viral defense.
The acquired, adaptive immunity composes of: antibodies, plasma cells, mature B & T lymphocytes. Two types of this immunity include humoral and cellular immunity.
Humoral immunity offers defense against foreign microbes and their toxins, with B lymphocytes, plasma cells & antibodies as mediators. Cellular immunity offers protection against intracellular microbes by help of T lymphocytes, and cytotoxic T cells.
Tissues of the immune system
The tissues of the immune system consist of central and peripheral lymphoid organs.
The central organs are the thymus and bone marrow where the T and B lymphocytes mature respectively. In their respective central organs, they are called naive immune cells, as they lack stimulation by any antigens yet. Naive immune cells migrate to the spleen or the lymph nodes, after developing.
The peripheral organs consist of lymph nodes; spleen, & cutaneous, mucosal associated lymphoid tissues. Among these lymphoid tissues, T and B lymphocytes are segregated respectively within T cell zones, and B cell zones. Within their specified zones, they differentiate into effector cells after encounter wither antigen and other stimulatory molecules.
The effector cells of the T lymphocytes and antibodies enter the circulation or interstitium to fight foreign bodies or microbes. Complete eradication of foreign bodies or microbes leave memory cells that immediately fight back recurrent infections. The pharyngeal tonsils and Peyer’s patches of the intestine are examples of mucosal lymphoid tissue.
Components of the immune system
Here we shall briefly examine the structures, functions of immune cells, and other molecules.
T lymphocytes: T lymphocytes mature in the thymus from where they migrate to peripheral lymphoid tissues. The T cell receptor on their surfaces help recognize antigens that display on MHC molecules. Depending on their receptors, the main types of T lymphocytes are CD4+ T lymphocytes, CD8 + T lymphocytes. CD4+ lymphocytes differentiate into TH1, TH2, & TH17 cells which are effecter T helper cells. CD8+ differentiates into cytotoxic T lymphocytes.
B lymphocytes: B lymphocytes mature in the bone marrow, after which they migrate to peripheral lymphoid organ. The B-cell antigen receptor complex on their surfaces binds antigens which causes receptor stimulation. On, stimulation, they differentiate into plasma cells that secrete antibodies that enters the circulation. Main component of this receptor complex is surface antibodies IgM & IgD that bind antigens.
Dendritic cells are antigen presenting cells (APCs) present in interstitium and under epithelia of tissues. Two types exist: follicular dendritic cell and dendritic cell. Follicular dendritic cells are APCs for the B lymphocytes. Dendritic cells are APCs for T lymphocytes in peripheral lymphoid tissues. They possess Toll-like receptors TLRs.
Their Fc & C3b receptors attach IgG and complements that coat antigens awaiting destruction.
Natural killer cells are large granular lymphocytes that can destroy tumor cells and viral infected cells. Their inhibitory receptors prevent them from harming self-antigens. Their activating receptors kill viral infected and tumor cells. CD16 molecule on their surfaces is an fc receptor for IgG-coated target cells. NK cells secrete IFN-γ that activate macrophages.
Macrophages are APCs for T lymphocytes. They possess TLRs, and opsonin receptors for antibodies and complements that phagocytize microbes, in humoral immunity. Macrophages are effector cells in cell-mediated immunity, to attack intracellular microbes after activation by T lymphocytes.
The Major Histocompatibility Complex (MHC) molecule
The Major Histocompatibility Complex (MHC) molecule, is a receptor molecule that presents peptides to T lymphocytes. Their location is on a small segment of chromosome 6, which is the major histocompatibility complex. The receptor exhibits polymorphism, in which every individual has a different receptor type.
Two types of MHC molecules include: MHC class1 & MHC class 2 molecules. M Class 1 MHC molecules are expressed on the surface of all nucleated cell and platelets. CD8+ T lymphocytes bind just to class 1 MHC molecules.
Class 2 MHC molecules are expressed on the surfaces of macrophage, dendritic cells, & B lymphocytes. CD4+ T lymphocytes only bind class 2 MHC molecules.
Mechanisms of T and B lymphocyte activation in immune response
Upon recognizing a microbe, APC expresses surface B7 proteins. The CD28 protein receptor of naive CD4+ T lymphocyte recognizes the B7 protein, causing its activation. CD4+ T lymphocyte secretes IL-2 which causes its proliferation. By help of several cytokines, it differentiates into TH1, TH2, & TH17 effector cells.
TH1 secretes IFN-γ and CD40 ligand that activate microbicidal action of macrophage against intracellular microbes. TH2 releases IL-4 that causes B lymphocyte to differentiate into IgE. It secretes IL-5 that attracts eosinophils. Eosinophils and mast cell bind to IgE-coated parasite for elimination. TH17 secretes IL-17 to recruit neutrophils and monocytes to destroy extracellular microbes.
After activation by cytoplasmic peptides presented by class I MHC molecules, CD8+ T lymphocytes differentiate into cytotoxic T lymphocytes (CTLs). CTLs migrates to cells harboring cytoplasmic microbes or tumor cells to case destruction.
B-cells antigen receptor complex is the B lymphocyte receptor. They have a better binding capacity for polysaccharides and lipids, and poorly bind to globular proteins. On binding with polysaccharides and lipids, it activates, and differentiates directly into plasma cells that secretes antibodies. Each antibody is same as surface receptors on mature B lymphocyte.
B lymphocytes only bind fewer protein antigens, which is why they require the help of CD4+ helper T lymphocytes. B lymphocytes ingest these protein antigens into peptides for display on MHC molecule. The activation of B lymphocytes begins as CD4+ lymphocyte recognizes peptides. CD4+ lymphocytes secrete CD40 ligand and IL-4 which activates B lymphocyte destruction of ingested protein. CD4+ lymphocyte causes differentiation of B lymphocytes into isotypes IgA, IgG, IgE that neutralizes other surrounding protein antigens.
Types of hypersensitivity reactions
Continuous and excessive exposure to an allergen is the causes hypersensitivity reaction. Let’s discuss the types.
Immediate type 1 hypersensitivity reaction: This reaction occurs within 5 to 30 minutes after exposure to allergens. These allergens include: penicillin, antisera, hormones, bee venoms, pollen, dust, animal dander, food. Allergens trigger IgE activation, mast cell degranulation, and eosinophil recruitment. They lead to systemic or local reaction. System reactions include: vascular shock, wide-spread edema, respiratory distress.
Local reaction include: itching, skin erythema, angioedema, bronchial asthma, allergic rhinitis.
Antibody-mediated type 2 hypersensitivity reaction: In this reaction, IgG & IgM attack normal or altered cell surface antigens. These surface antigens can be proteins in the extracellular matrix. They trigger cell injury by opsonization, phagocytosis and inflammation. Examples of this disorders include: autoimmune thrombocytopenic purpura; good pasture syndrome; myasthenia gravis; type 2 diabetes; graves disease; pemphigus vulgaris; acute rheumatic fever; vasculitis; hemolytic disease of the newborn.
Immune complex-mediated type 3 hypersensitivity: This reaction causes deposition of IgM, IgG-antigen complexes on vessels, joints, and the glomeruli. Antigens may be foreign proteins or endogenous. Antigen- antibody complexes trigger inflammation leading to tissue injury. Examples include: systemic lupus erythematosus; poststreptococcal glomerulonephritis; reactive arthritis; polyarteritis nodosa; serum sickness.
T-cell mediated type 4 hypersensitivity reaction: This reaction involves TH1, TH17, & cytotoxic T cells against self and foreign antigens. These antigens may include poison ivy, poison oak, jewelries, virus, self-proteins. Examples of disorder: type 1 diabetes; tuberculosis; rheumatoid arthritis; contact dermatitis; Guillain-Barre syndrome, multiple sclerosis; graft rejection.