The Immune response is the body's ability to stay safe by affording protection against harmful agents and involves lines of defense against most microbes as well as specialized and highly specific response to a particular offender. This immune response classifies as either innate which is non-specific and adaptive acquired which is highly specific. The innate response, often our first line of defense against anything foreign, defends the body against a pathogen in a similar fashion at all times. These natural mechanisms include the skin barrier, saliva, tears, various cytokines, complement proteins, lysozyme, bacterial flora, and numerous cells including neutrophils, basophils, eosinophils, monocytes, macrophages, reticuloendothelial system, natural killer cells (NK cells), epithelial cells, endothelial cells, red blood cells, and platelets.
The adaptive acquired immune response will utilize the ability of specific lymphocytes and their products (immunoglobulins, and cytokines) to generate a response against the invading microbes and its typical features are:
The inflammatory immune response is an example of innate immunity as it blocks the entry of invading pathogens through the skin, respiratory or gastrointestinal tract. If pathogens can breach the epithelial surfaces, they encounter macrophages in the subepithelial tissues that will not only attempt to engulf them but also produce cytokines to amplify the inflammatory response.
Active immunity results from the immune system's response to an antigen and therefore is acquired. Immunity resulting from the transfer of immune cells or antibodies from an immunized individual is passive immunity.
The immune system has evolved for the maintenance of homeostasis, as it can discriminate between foreign antigens and self; however, when this specificity is affected an autoimmune reaction or disease develops.
While the immune system is meant to protect the individual against threats, at times an exaggerated immune response generates a reaction against self-antigens leading to autoimmunity. Also, the immune system is not able to defend against all threats at all times.
Vaccination is required to induce an adequate active immune response to specific pathogens:
Cells of the innate immunity are:
Cells of the adaptive response are:
Mesoderm cells are induced to form hemangioblasts, a common precursor for vessels and blood cell formation. The definitive hematopoietic stem cells derive from mesoderm surrounding the aorta called aorta-gonad-mesonephros region. These stem cells colonize the liver and after that are actively produced by the bone marrow by the seventh month of gestation.
The organ systems involved in the immune response are primarily lymphoid organs which include, spleen, thymus, bone marrow, lymph nodes, tonsils, and liver. The lymphoid organ system classifies according to the following:
T lymphocytes mature in the thymus, where these cells reach a stage of functional competence while B lymphocytes mature in the bone marrow the site of generation of all circulating blood cells. Excessive release of cytokines stimulated by these organisms can cause tissue damage, such as endotoxin shock syndrome.
The immune system responds variedly to different microorganisms often determined by the features of the microorganism. These are some different ways in which the immune system acts
Immune Response to Bacteria
Response often depends on the pathogenicity of the bacteria:
Immune Response to Fungi 
Immune Response to Viruses 
Immune response to parasites:
Despite Immune response(s) generated by intact and functional Immune system we still fall sick, and this is often due to evasive mechanisms employed by these microbes. Here are some of those.
Strategies of Viruses to Evade the Immune System
Antigenic variation: It is a mutation in proteins that are typically recognized by antibodies and lymphocytes. HIV continually mutates, thus making it difficult for either the immune system to protect against it and also hinders the development of a vaccine.
By disrupting 2',5'-oligoadenylate synthetase activity or by the production of soluble interferon receptors viruses disrupt the Interferon response.
By several mechanisms, Viruses affects the expression of MHC molecules.
A virus can infect immune cells: Normal T and B cells are also sites of virus persistence. HIV hides in CD4+T cells and EBV in B cells.
Strategies of Bacteria to Evade the Immune System
Intracellular pathogens may hide in cells: Bacteria can live inside metabolically damaged host leukocytes, and escaping from phagolysosomes (Shigella spp).
Strategies of Fungi to Evade the Immune System
Strategies of Parasites to Evade the Immune System
The most important mechanisms of the immune system by which it generates immune response include:
Macrophages produce lysosomal enzymes and reactive oxygen species to eliminate the ingested pathogens. These cells produce cytokines that attract other leukocytes to the site of infection to protect the body. The innate response to viruses includes the synthesis and release of interferons and activation of natural killer cells that recognize and destroys the virus-infected cells. The innate immunity against bacterial consist of the activation of neutrophils that ingest pathogens and the movement of monocytes to the inflamed tissue where it becomes in macrophages. They can engulf, and process the antigen and then present it to a group of specialized cells of the acquired immune response. Eosinophils protect against parasitic infections by releasing the content of their granules.
Antibody-dependent cell-mediated cytotoxicity (ADCC): A cytotoxic reaction in which Fc-receptor expressing killer cells recognize target cells via specific antibodies.
Affinity maturation: The increase in average antibody affinity mostly seen during a secondary immune response.
Complement system: It is a molecular cascade of serum proteins involved in the control of inflammation, lytic attack on cell membranes, and activation of phagocytes. The system can undergo activation by interaction with IgG or IgM (classical pathway) or by involving factors B, D, H, P, I, and C3, which interact closely with an activator surface to generate an alternative pathway C3 convertase.
Anergy: It is the failure to induce an immune response following stimulation with a potential immunogen.
Antigen processing: Conversion of an antigen into a form that can be recognized by lymphocytes. It is the initial stimulus for the generation of an immune response.
Antigen presentation: It is a process in which specific cells of the immune system express antigenic peptides in their cell membrane along with alleles of the major histocompatibility complex (MHC) which is recognizable by lymphocytes.
Apoptosis: Programmed cell death involving nuclear fragmentation and the formation of apoptotic bodies.
Chemotaxis: Migration of cells in response to concentration gradients of chemotactic factors.
Hypersensitivity reaction: A robust immune response that causes tissue damage more considerable than the one caused by an antigen or pathogen that induced the response. For instance, allergic bronchial asthma and systemic lupus erythematosus are an example of type I and type III hypersensitivity reactions respectively.
Inflammation: Certain reactions that attract cells and molecules of the immune system to the site of infection or damage. It featured increased blood supply, vascular permeability and increased transendothelial migration of blood cells (leukocytes).
Opsonization: A process of facilitated phagocytosis by deposition of opsonins (IgG and C3b) on the antigen.
Phagocytosis: The process by which cells (e.g., macrophages and dendritic cells) take up or engulf an antigenic material or microbe and enclose it within a phagosome in the cytoplasm.
Immunological tolerance: A state of specific immunological unresponsiveness.
They are overreactive immune responses to antigens that would not normally cause an immune reaction.
Type 1 hypersensitivity reactions: Initial exposure to the antigen causes stimulates Th2 cells. They release IL-4 leading the B cells to switch their production of IgM to IgE antibodies which are antigen-specific. The IgE antibodies bind to mast cells and basophils, sensitizing them to the antigen.
When the body is exposed to the allergen again, it cross-links the IgE bound to the sensitized mast cells and basophils, causing the degranulation and release of preformed mediators including histamine, leukotrienes, and prostaglandins. This causes systemic vasodilation, bronchoconstriction, and increased permeability of vascular endothelium.
The reaction can be divided into two stages – 1) Immediate, in which release of preformed mediators cause the immune response, and 2) Late-phase response 8-12 hours later, in which the cytokines released in the immediate stage stimulate basophils, eosinophils, and neutrophils even though the allergen is removed.
Type 2 hypersensitivity reactions (Antibody dependant cytotoxic hypersensitivity): Immune response against the antigens present on the cell surface. Antibodies binding to the cell surface, activate the complement system and cause the degranulation of neutrophils and destruction of the cell. Such reactions can be targeted at self or non-self antigens. ABO blood group incompatibility leading to acute hemolytic transfusion reactions is an example of Type 2 hypersensitivity.
Type 3 hypersensitivity reactions are also mediated by circulating antigen-antibody complex that may be deposited in and damage tissues. Antigens in type 3 relations are soluble as opposed to cell-bound antigens in type 2.
Type 4 hypersensitivity reactions (delayed-type hypersensitivity reactions): They are mediated by antigen-specific activated T-cells. When the antigen enters the body, it is processed by antigen-presenting cells and presented together with the MHC II to a Th1 cell. If the T-helper cell has already been sensitized to that particular antigen, it will be stimulated to release chemokines to recruit macrophages and cytokines such as interferon-γ to activate them. This causes local tissue damage. The reaction takes longer than all other types, around 24 to 72 hours.
Hyperacute Rejection: In hyperacute rejection, the transplanted tissue is rejected within minutes to hours because vascularization is rapidly destroyed. Hyperacute rejection is antibody mediated and occurs because the recipient has preexisting antibodies against the graft, which can be due to prior blood transfusions, multiple pregnancies, prior transplantation, or xenografts. Activation of the complement system leads to thrombosis in the vessels peventing the vascularization of the graft.
Acute Rejection: Develops within weeks to months. Involves the activation of T lymphocytes against donor MHCs. May also involve humoral immune response, which antibodies developing after transplant. It manifests as vasculitis of graft vessels with dense interstitial lymphocytic infiltrate.
Chronic Rejection: Chronic rejection develops months to years after acute rejection episodes have subsided. Chronic rejections are both antibody- and cell-mediated. The use of immunosuppressive drugs and tissue-typing methods has increased the survival of allografts in the first year, but chronic rejection is not prevented in most cases. It generally presents as fibrosis and scarring. In heart transplants, chronic rejection manifests as accelerated atherosclerosis. In transplanted lungs, it manifests as bronchiolitis obliterans. In liver transplants, it manifests as vanishing bile duct syndrome. In kidney recipients, it manifests as fibrosis and glomerulopathy.
Graft-versus-host Disease: The onset of the disorder varies. Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells which they consider 'nonself' leading to severe organ dysfunction. It is a type 4 hypersensitivity reaction and manifests as maculopapular rash, jaundice, diarrhea, hepatosplenomegaly. Usually occurs in the bone marrow and liver transplants, which are rich in lymphocytes.
The immunological investigations for the study of innate and adaptive immunity are listed below and include the assessment of immunoglobulins, B and T-lymphocyte counts, lymphocyte stimulation assays, quantification of components of the complement system and phagocytic activity.
Quantitative Serum Immunoglobulins
IgG antibodies (post-immunization)
IgG antibodies (post-exposure)
Detection of isohemagglutinins (IgM)
Blood Lymphocyte Subpopulations
Lymphocyte Stimulation Assays
Nitroblue tetrazolium (NBT) test (before and after stimulation with endotoxin)
Complement System Evaluation
Measurement of individuals components by immunoprecipitation tests, ELISA, or Western blotting
Complement system functional studies
Measurement of complement-activating agents
Assays for complement-binding
Others complement assays
The immune system protects the body against many diseases including recurrent infections, allergy, tumor, and autoimmunity. The consequences of an altered immunity will manifest in the development of many immunological disorders some of which are listed below:
Highly specific and discriminatory immunity is of utmost importance for survival. The immune system has evolved as a collection of protective mechanisms to defend the host against a long list of potential invaders that would take advantage in immunodeficiency disorders, inflammatory diseases, cancers, and autoimmunity. This system has to be sophisticated enough to recognize "self" from "non-self" and provide help in infections, malignant tumors, organ transplantations, and various other situations the immune system encounters.
|||Arce-Sillas A,Álvarez-Luquín DD,Tamaya-Domínguez B,Gomez-Fuentes S,Trejo-García A,Melo-Salas M,Cárdenas G,Rodríguez-Ramírez J,Adalid-Peralta L, Regulatory T Cells: Molecular Actions on Effector Cells in Immune Regulation. Journal of immunology research. 2016; [PubMed PMID: 27298831]|
|||Lawrence H,Mawdesley AE,Holland JP,Kirby JA,Deehan DJ,Tyson-Capper AJ, Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation. Oncotarget. 2016 Feb 16; [PubMed PMID: 26840091]|
|||Denson LA, The role of the innate and adaptive immune system in pediatric inflammatory bowel disease. Inflammatory bowel diseases. 2013 Aug; [PubMed PMID: 23702804]|
|||Gu M, Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Cells. Current protocols in human genetics. 2018 Jul 6; [PubMed PMID: 29979824]|
|||Williamson L,Flyak AI,Kose N,Bombardi R,Branchizio A,Reddy S,Davidson E,Doranz B,Fusco ML,Saphire EO,Halfmann PJ,Kawaoka Y,Piper AE,Glass PJ,Crowe JE Jr, Early human B cell response to Ebola virus in four U.S. survivors of infection. Journal of virology. 2019 Feb 6; [PubMed PMID: 30728263]|
|||Pedraza-Sánchez S,Méndez-León JI,Gonzalez Y,Ventura-Ayala ML,Herrera MT,Lezana-Fernández JL,Bellanti JA,Torres M, Oral Administration of Human Polyvalent IgG by Mouthwash as an Adjunctive Treatment of Chronic Oral Candidiasis. Frontiers in immunology. 2018; [PubMed PMID: 30627128]|
|||Gack MU,Diamond MS, Innate immune escape by Dengue and West Nile viruses. Current opinion in virology. 2016 Oct; [PubMed PMID: 27792906]|
|||Yap GS,Gause WC, Helminth Infections Induce Tissue Tolerance Mitigating Immunopathology but Enhancing Microbial Pathogen Susceptibility. Frontiers in immunology. 2018; [PubMed PMID: 30386324]|
|||Di Rosa R,Pietrosanti M,Luzi G,Salemi S,D'Amelio R, Polyclonal intravenous immunoglobulin: an important additional strategy in sepsis? European journal of internal medicine. 2014 Jul; [PubMed PMID: 24877856]|
|||Man K,Jiang LH,Foster R,Yang XB, Immunological Responses to Total Hip Arthroplasty. Journal of functional biomaterials. 2017 Aug 1; [PubMed PMID: 28762999]|
|||Valent P,Akin C,Bonadonna P,Hartmann K,Brockow K,Niedoszytko M,Nedoszytko B,Siebenhaar F,Sperr WR,Oude Elberink JNG,Butterfield JH,Alvarez-Twose I,Sotlar K,Reiter A,Kluin-Nelemans HC,Hermine O,Gotlib J,Broesby-Olsen S,Orfao A,Horny HP,Triggiani M,Arock M,Schwartz LB,Metcalfe DD, Proposed Diagnostic Algorithm for Patients With Suspected Mast Cell Activation Syndrome. The journal of allergy and clinical immunology. In practice. 2019 Feb 5; [PubMed PMID: 30737190]|
|||Surace M,DaCosta K,Huntley A,Zhao W,Bagnall C,Brown C,Wang C,Roman K,Cann J,Lewis A,Steele K,Rebelatto M,Parra ER,Hoyt CC,Rodriguez-Canales J, Automated Multiplex Immunofluorescence Panel for Immuno-oncology Studies on Formalin-fixed Carcinoma Tissue Specimens. Journal of visualized experiments : JoVE. 2019 Jan 21; [PubMed PMID: 30735177]|
|||Hung CY,Hsu AP,Holland SM,Fierer J, A review of innate and adaptive immunity to coccidioidomycosis. Medical mycology. 2019 Feb 1; [PubMed PMID: 30690602]|
|||McCusker C,Upton J,Warrington R, Primary immunodeficiency. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2018; [PubMed PMID: 30275850]|
|||Pellicciotta M,Rigoni R,Falcone EL,Holland SM,Villa A,Cassani B, The microbiome and immunodeficiencies: Lessons from rare diseases. Journal of autoimmunity. 2019 Jan 28; [PubMed PMID: 30704941]|