Key Molecules in immune response
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| Key Molecules in immune response :
Antigens , antibodies , MHC, TCR, adhesion molecules (CD), Cytokines. Several types of molecules play vital roles in immune responses. Antibodies are substances which provoke an immune response. Antibodies are not only the surface receptors of B cells that recognize specific antigens, but once the appropriate B cells are activated and differentiate into plasma cells; antibodies also are secreted into blood and body fluids in large quantities to prevent that antigen from causing damage. T cell have similar receptors for recognizing antigens, Known as T-cell receptors. Major histocompatibility complex (MHC) molecules provide a means of self recognition and also play a fundamental role in T lymphocyte effector functions. Effector mechanisms are often dependent on messages from initiating or regulating cells, soluble mediators which carry message between cells are known as interleukins or cytokines. Antigens: Antigens are able to provoke an immune response and react with the immune products. They react both with the T-cell recognition receptor and with antibody. An antigenic molecule may have several antigenic determinants (epitopes), each epitope can bind with an individual antibody, and a single antigenic molecule can therefore provoke many antibody molecules with different binding sites. Some low molecular –weight molecules, called haptens, are unable to provoke an immune response themselves, although they can react with existing antibodies. Such substances need to be coupled to carrier molecule in order to have sufficient epitopes to be antigenic. For some chemicals, such as drugs, the carrier may be a host (auto) protein. The tertiary structure as well as the amino acid sequence, is important in determining antigenicity. Pure lipids are not immunogenic and nucleic acids are also poor antigens. Antigens are conventionally divided into: Thymus dependent antigens which are required T-cell participation to provoke the production of antibodies; most proteins and foreign red cells are examples. Thymus-independent antigens require no T-cell cooperation for antibody production; they directly stimulate specific B lymphocytes by virtue of their ability to cross-link antigen receptors on the B-cell surface, produce predominantly IgM and IgG2 antibodies and provoke poor immunological memory. Such antigens include bacterial polysaccharides (found in bacterial cell walls). Endotoxin another thymus-independent antigen, not only causes specific B-cell activation and antibody production but acts as a polyclonal B-cell stimulant as well. Factors other than the intrinsic properties of the antigen can also influence the quality of the immune response. Factors influencing the immune response to an antigen, i.e its immunogenicity. 1-Nature of molecules
2- Dose
3- Route of entry
4- Addition of substances with synergistic effects
5- Genetic factors of recipient animal
Non-specific immunity ( Innate Immunity) Introduction During evolution, an extremely complex system of anti-infections defenses has emerged. But at the same time as vertebrates and mammals developed their defenses, microbes continued evolving as well, and many became adept at avoiding the consequences of the anti-infections defense mechanisms. The interplay between host defenses, microbial virulence, and microbial evasion mechanisms determines the outcome of the constant encounters between host and pathogenic organisms.
State of being immune. Immune: Having a high degree of natural or acquired resistance to a disease. By extension, the term indicate the altered state of an individual that result from immunization with any antigen. An animal can be immune by means of exposure to natural infection, antigen and vaccine. Immunology: Science deals with study the immune response. Immune response: Specific response of an animal to antigenic stimulation. The immune response may take the form of antibody production, cell-mediated immunity or tolerance. II. Nonspecific Anti-Infectious Defense Mechanisms Nonspecific defense mechanisms play a most important role as a first line of defense, preventing penetration of microorganisms beyond the outer exposed surfaces of the body. The following is a brief description of the most important nonspecific defense mechanisms. 
Innate immunity ( Non specific immune response) 
First line: 1) Mechanical barriers - Intact skin - Mucous coat - Mucous secretion - Blinking reflex and tears - The hair at the nares - Coughing and sneezing reflex 2) Chemical & biochemical inhibitors - Sweet and sebaceous secretion - Hydrolytic enzymes in saliva - HCl of the stomach - Proteolytic enzyme in small intestine - Lysozyme in tears - Acidic pH in the adult vagina 3) Normal bacterial flora - Competition for essential nutrients - Production of inhibitory substances
Specialized cells for capture, Ingestion and destruction of invading microorganisms * Polymorphonuclear leucocytes, mainly neutrophils: granulocytes circulate in blood * Mononuclear cells (macrophages) - Monocytes in blood - Histocytes in connective tissues - Fixed reticuloendothelial cells in liver spleen, lymph nods, bon marrow B- Soluble factors 1- Acute phase protein (Plasma protein, CRP=C reactive protein, Fibrin.) 2- Complement (proteins in serum, body fluids) 2- Interferons (Proteins against viral infections) 3- Properdin (Complement activation) 4- Beta lysine (Antibacterial protein from Platelets) 5- Lactoferrrin,Transferrin (Iron binding protein) 6- Lactoperoxidase (Saliva & Milk) 7- Lysozyme (Hydrolyze cell wall) Interferons: Proteins usually produced by virally infected cells * Types of interferon's: 1- Alpha interferon Secreted by Macrophages Induced by Viruses or Polynucleotide 2- Beta interferon Secreted by Fibroblasts, Viruses 3- Gamma interferon T- lymphocytes, Specific antigens
1) Activate T-cells 2) Activate macrophages 3) Activate NK Phagocytosis The engulfment, digestion, and subsequent processing of microorganisms by macrophages and neutrophils 1) Chemotaxis & attachment: a- Attraction by chemotactic substances (microbes, damaged tissues) b- Attachment by receptors on surfaces of phagocytes 2) Ingestion: * Phagocyte pseudopodia surround organism forming phagosom * Opsinins and co-factors enhance phagocytosis * Fusion with phagocyte granules and release digestive, toxic contents 3- Killing (two microbicidal routes) a- Oxygen depended system (powerful microbicidal agents) Oxygen converted to superoxide, anion, hydrogen peroxide, activated oxygen and hydroxyl radicals. b- Oxygen-independent system (anaerobic conditions) Digestion and killing by lysozyme. Lactoferrin, low pH, cationic proteins and hydrolytic and Proteolytic enzymes .
Various cells internalize (endocytose) and break down foreign macromolecules. Specialized cells (blood Monocytes, neutrophils, and tissue macrophages) internalize. (Phagocytose), kill, and digest whole microorganisms. As a microbe penetrates beyond the skin or mucosal surface, it will encounter cells able to ingest it. Two types of cells are particularly adept at no immune Phagocytosis: tissue macrophages and granulocytes (particularly neutrophils).This non-immune Phagocytosis involves a variety of recognition systems. About 90% of invaded microbe was eliminated by phagocytosis.
Tissue damage and infection induce leakage of vascular fluid, containing serum proteins with antibacterial activity, and influx of phagocytic cells into the affected. D- Including fever and release of interferon’s, activated when infectious agents manage to invade, particularly effective in preventing viral replication. E- Activation of the Complement System :
F. Acute Phase Reaction and Leukocyte Chemotaxis. The initial recognition by phagocytes and the activation of the complement system by the alternative pathway, by themselves, may not be sufficient to eradicate the invading microorganism, but the response is quickly amplified by a multitude of cytokines released by macrophages activated as a consequence of Phagocytosis.
G. Natural Killer (NK) Cells are able to destroy viral infected cells as a consequence of the delivery of an activating signal in the absence of an inhibitory signal. H. g/D T Lymphocytes are predominantly localized to the mucosal epithelia, where they appear to recognize infected epithelial cells by a non-immunological mechanisms (i.e., not involving the T-cell receptors), which are subsequently destroyed. I. Natural Antibodies Preexisting antibodies may play a very important anti-infectious protecting role. Natural antibodies may arise as a Consequence of cross-reactions, as exemplified in the classic studies concerning the isoagglutinins of the ABO blood group system (i.e., circulating antibodies that exist in a given individual and are able to agglutinate erythrocytes carrying alloantigen of the ABO system different from those of the individual himself). A. The Origin of the AB Isoagglutinins 1. Chickens are able to produce agglutinins recognizing the AB alloantigen, but only when fed conventional diets; chicks fed sterile diets do not develop agglutinins. Furthermore, anti-A and anti-B agglutinins develop as soon as chicks fed sterile diets after birth are placed on conventional diets later in life. 2. These observations pointed to some dietary component as a source of immunization. It was eventually demonstrated that the cell wall polysaccharides of several strains of enterobacteriaceae and the AB oligosaccharides of human erythrocytes are structurally similar. 3. Newborn babies of blood groups A, B, or O do not have either anti-A or anti-B isohemagglutinins, but will develop them during the first months of life, as they get exposed to common bacteria with polysaccharide capsules. However, newborns are tolerant to their own blood group substance, so they will only make antibodies against the blood group substance that they do not express. Blood group AB individuals never produce AB isoagglutinins. B. Other Mechanisms for the Generation of Natural Antibodies. Cross-reaction is probably the most common explanation for the emergence of “natural” antibodies, but other mechanisms, such as the mitogenic effects of Tindependent antigens and the nonspecific stimulatory effects of lymphokines released by antigen-stimulated T Lymphocytes, which could activate B cells responding to other antigens, could explain the rise of “nonspecific “Immunoglobulin’s that is observed in the early stages of the humoral response to many different antigens. C. The Significance of “Natural” Antibodies. “Natural” antibodies may play an important protective role,. It is logical to assume that such cross-immunizations may be rather common and play an important protective role against a variety of infectious agents.
Include the following:
Including the integrity of the epithelial and mucosal surfaces, the flow of mucosal secretions in the respiratory tract, the acidity of the gastric contents, and the secretion of lysozyme in tears, saliva, and most secretions. The importance of these barriers is apparent from the prevalence of infections when their integrity is compromised.
Skin mechanical barrier retards entry of microbes. Acidic environment (pH 3–5) retards growth of microbes. Mucous membranes normal flora competes with microbes for attachment sites and nutrients. Mucus entraps foreign microorganisms. Cilia propel microorganisms out of body.
Skin fatty acid secretions Oral cavity Enzymes & Abs in saliva Respiratory system hair in nasal passage, enzyme, Abs Gastric system low pH of stomach, enzymes and Abs in secretion Eyes Lysozyme Genitourinary system low PH
Resistance Mechanism
Comparative between Innate and acquired immunity
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