Infectious Disease Book

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Immunity

Aka: Immunity, Immune System, Immune Status, Immunology, Innate Immunity, Adaptive Immunity
  1. See Also
    1. Humoral Immunity (Immunoglobulin)
    2. T-Lymphocyte
    3. B-Lymphocyte
    4. Antigen Processing
    5. Complement Pathway
    6. Immunodeficiency
  2. Definitions
    1. Immune System
      1. Defense mechanism against both errant native cells and foreign organism or substance invasion
        1. Distinguishes self from non-self
        2. Eliminates foreign organisms and substances
      2. Responses include humoral immune response and the cell-mediated response
        1. Organs (Thymus, Spleen, Tonsils, Lymphatic System, hematopoetic system)
        2. Cells (Lymphocytes, Granulocytes, Monocytes, Macrophages)
        3. Molecules (antibodies, complement, Cytokines)
    2. Innate Immunity (Natural Immunity)
      1. Generalized, immediate immune response not reliant on prior exposure
      2. Predates the evolution of the more specific Immunity provided by antibodies and Lymphocytes
    3. Adaptive Immunity
      1. Organism specific Immunity that relies on prior "memory" of exposure
      2. Immune System evolved beyond the more primitive Innate Immunity
        1. Humoral Immunity (Antibody and B Cell response)
        2. Cell mediated Immunity (T Cell Response)
    4. Phagocyte (and Phagosome, Phagocytosis)
      1. Immune cells (Neutrophils and Monocytes/Macrophages) are White Blood Cells that engulf pathogens and foreign material
      2. Phagosomes are the membrane engulfed pathogens
      3. Often combined with lysis by Lysozymes
    5. Lysosome (and Lysozyme)
      1. Lysozyme-containing vacuoles produced in cellular golgi apparatus
      2. Lysomsomes fuse with Phagosomes, resulting in pathogen lysis (esp. Bacterial cell walls)
      3. Lysosomes, like Phagosomes, are found in Phagocytes (Macrophages and Neutrophils)
    6. Opsonin (and Opsonization)
      1. Proteins (e.g. Antibody, complement, C-Reactive Protein) that bind a pathogen surface, targeting it for Phagocytosis
  3. Types: Innate Immunity (Natural Immunity)
    1. Physical Barriers
      1. Skin
      2. Mucosa (e.g. respiratory and gastrointestinal tract)
      3. Cilia (e.g. respiratory)
    2. Inflammatory Response
      1. C-Reactive Protein
        1. Increases with inflammation and tissue injury
        2. Binds Bacterial surface and facilitates Phagocytosis (by Macrophages and Neutrophils)
      2. Prostaglandins and Leukotrienes
        1. Fatty Acids released from injured cells, as well as Mast Cells
        2. Promote inflammation (e.g. vascular permeability, Neutrophil chemotaxis, stimulate nociceptors)
      3. Kinin peptides (kallidin and bradykinin)
        1. Short-lived inflammatory proteins that increase vascular permeability and result in arteriolar dilitation
      4. Cytokines
        1. Cytokine types include Interleukin, Interferon, Tumor Necrosis Factor, Colony-Stimulating Factor, TGF-beta
        2. Glycoproteins act in inflammatory and immune response via cell to cell communication
        3. Released from cells in response to a trigger (e.g. Antigen binding) and bind and activate Target Cells
    3. Secretion Contents
      1. Lysozyme (e.g. in tears, Saliva and in Neutrophils)
        1. Enzymatically degrades cell walls
      2. Acid destroys acid-labile organisms
        1. Sweat Lactic Acid
        2. Stomach Gastric Acid (Hydrochloric Acid)
    4. Phagosomes (Phagocytosis)
      1. Phagocytes such as Neutrophils (PMNs) and Macrophages attract and engulf organisms (Phagocytosis)
      2. Phagocytes attract organisms which in turn activate Phagocytosis
      3. Phagosomes are later lysed via Lysosomes (as below)
        1. Phagocytosis.jpg
    5. Lysosomes
      1. Neutrophil's and Macrophage's (Phagocytes) golgi apparatus produce Lysosomes (vacuoles) that contain Lysozyme
      2. Lysosomes fuse with Phagosomes to produce phagolysosomes, degrading the engulfed organisms
      3. Lysosomes may also release their contents extracellularly to lyse larger targets too large to engulf
    6. Natural Killer Cells (NK cells)
      1. Lymphocytes providing protection against Intracellular Bacteria and viruses
      2. NK cells bind Major Histocompatibility Complex 1 (MHC-1)
        1. MHC-1 is present on normal cells and it inactivates NK cells
        2. MHC-1 is NOT expressed by infected cells
          1. NK activating receptor Ligand is expressed
          2. NK cells bind infected cells and destroy them
      3. NK cell mechanisms of infected cell destruction
        1. Cytoplasmic granules
          1. Perforin
            1. Generates pores on cells targeted for destruction
          2. Granzyme
            1. Induces programmed cell death (apoptosis) on entry into Target Cells
        2. Cytokines
          1. Interferon-Gamma (IFN-g)
            1. Activates Macrophages for Phagocytosis
      4. Image: NKC Mediated Destruction of Infected Host Cells
        1. NaturalKillerCells.jpg
    7. Complement Pathway
      1. Images
        1. idComplementPathway.jpg
      2. Activation
        1. Classical Pathway (C1, C2, C3, C4)
          1. C1 binds Antigen-Antibody complex
        2. Alternate Pathway (Properdin, Factor B, Factor D, C3)
          1. Activation via microbe cell surface
        3. Lectin Pathway (Mannose Binding Lectin or MBL)
          1. Mannose Binding Lectin (MBL) binds mannose on microbe surface
          2. Mannose Binding Lectin Associated Proteases (MASP-1, MASP-2) are activated
          3. Classical Pathway (above) is stimulated
      3. Enzyme C3 Convertase (C3bBb or C4b2a) Formation
        1. Enzyme C3 Convertase splits C3 into C3a and C3b
        2. C3a stimulates inflammation (attracts Neutrophils, histamine release)
        3. C3b stimulates Phagocytosis, inflammation (as with C3) and lysis (see below)
      4. Opsonization
        1. Microbe coated with an Opsonin, an Antibody or complement (e.g. C3b)
        2. Surface Opsonins target microbes for Phagocytosis
      5. Phagocytosis
        1. Phagocytes such as Neutrophils (PMNs) and Macrophages attract and engulf targeted organisms
      6. Inflammation (via C3a, C5a)
        1. Chemoattraction of Neutrophils
        2. Anaphylatoxic activation of Mast Cells and Basophils to degranulate, releasing histamines and vasoactives
          1. Inflammation occurs when histamine-induced capillary dilation results in fluid and protein release
      7. Lysis
        1. C3b splits C5 into C5a and C5b
        2. Membrane attack complex or MAC (C5b, C6, C7, C8, C9) binds microbe surface
        3. MAC promotes microbe lysis by creating holes in microbe surface, resulting in leak
  4. Types: Adaptive Immunity
    1. Humoral Immunity (B-Cells and Antibodies)
      1. Humoral Immunity (i.e. antibodies) targets extracellular pathogens
      2. B Cells
        1. Derivation
          1. Fetal Liver
          2. Bone Marrow Pluripotent Stem Cells
        2. Peripheral Migration to Secondary Lymphoid Tissue
          1. Spleen
          2. Lymph Nodes
          3. Peyer's Patches (Small Bowel)
        3. Activation
          1. Images
            1. BCellActivation.jpg
          2. Recognition
            1. Antigen binds B-Lymphocyte Surface Receptor (BCR)
            2. BCR binding activates B-Lymphocyte
              1. T-Cell Independent Antigen (e.g. inert Antigens) alone activate B-Cells
              2. T-Cell Dependent Antigen (e.g. microbes) require added stmulus (e.g. T Cells)
          3. B-Cell Proliferation
            1. Activated Lymphocytes proliferate
          4. B-Cell Differentiation
            1. Plasma Cells (Antibody producing cells)
              1. Survive for days to weeks producing antibodies, and without replicating
            2. Memory Cells
              1. Remain in B-Lymphocyte pool ready to respond to the same Antigen in future
              2. Future Antigen response is known as secondary immune response
      3. Antibodies
        1. Images
          1. idAntibody.jpg
        2. Immunoglobulin (Ig)
          1. Immunoglobulins (or antibodies) are Y-Shaped glycoproteins generated by Plasma Cells
          2. Immunoglobulin stem (Fc) is composed of 2 identical heavy chains
          3. Two Immunoglobulin Arms emanate from the stem
            1. Each arm is composed of 2 heavy chains and 2 light chains
            2. The end of each arm contains an Antigen binding site (Fab)
          4. Immunoglobulins have 2 forms
            1. Membrane bound Immunoglobulins (on surface of B-Cell)
            2. Secretory Immunoglobulin (unbound, free-floating)
              1. Monomeric antibodies exist as single Antibody molecules (IgE or IgG)
              2. Multimeric antibodies exist as multiple joined antibodies (IgA or IgM)
                1. Connected with J Chains
        3. Immunoglobulin G (IgG and subclasses IgG1-4)
          1. Monomer accounting for 75% of all Antibody, and has a serum half-life of 23 days
          2. Responsible for long lasting Immunity (secondary immune response) and Type 2 Hypersensitivity
        4. Immunoglobulin A (IgA and subclasses IgA1, IgA2)
          1. Dimer (2 Antibody molecules) when secretory Ig and accounts for 10-15% of all Antibody
          2. Serum half life of 6 days
          3. Present in body secretions (e.g. tears, Saliva, milk) and responsible for mucosal Immunity
        5. Immunoglobulin M (IgM)
          1. Pentamer (5 Antibody molecules) when secretory Ig
          2. Responsible for early, primary Antibody response
        6. Immunoglobulin E (IgE)
          1. Long stem (Fc) monomeric Antibody with serum half-life of only 2.5 days
          2. Reacts to allergans (Type 1 Hypersensitivity) and Parasitic Infections
        7. Immunoglobulin D (IgD)
          1. Monomer with serum half life of 3 days
          2. Membrane bound surface Antibody
    2. Cell-Mediated Immunity (T-Cells)
      1. Cellular Immunity (i.e. T Cells) target Intracellular Pathogens (e.g. viruses and Intracellular Bacteria)
      2. T-Cells
        1. Derived in Bone Marrow
        2. Migrate to Thymus
          1. Maturation and Differentiation into two cell lines with different T-Cell Receptors (CD4 and CD8)
        3. Release into peripheral circulation
      3. T-Cell Surface Receptors
        1. T-Cell Receptors (TCR)
          1. Bind the Antigen on the Antigen Presenting Cell
          2. TCR Types
            1. TCR-alpha-beta (TCRab+)
            2. TCR gamma-delta (TCRgd+)
        2. T-Cell Co-Receptors
          1. CD4 binds MHC Class 2 - peptide/Antigen complex on surface of Antigen Presenting Cells (APC)
            1. Only Dendritic Cells, Macrophages, B-Cells (B-Lymphocyte) present MHC Class 2
          2. CD8 binds MHC Class 1 - peptide/Antigen complex on surface of Antigen Presenting Cells (APC)
            1. Any nucleated cell can present MHC Class 1
      4. T-Cell Types
        1. Effector Cells
          1. T-Helper Cells (CD4+ Cells)
            1. Releases Interferon
              1. Stimulates Phagocytosis by Macrophages
              2. Activates Natural Killer Cells
              3. Suppresses viral replication
            2. Releases interleuken 2
              1. Promotes T-Cell proliferation (esp. memory cells)
              2. Promotes B-Cell proliferation (memory cells and plasma cells)
          2. T-Cytotoxic Cells (CD8+ Cells)
            1. Target and destroy tumor cells and virus-infected cells
        2. Other Cells
          1. Memory Cells
          2. Apoptosis of some cells not otherwise differentiated
      5. Naive T-Cell Activation
        1. TCellActivation.jpg
        2. T-Cell Receptor (TCR) binds to MHC-Antigen complex on Antigen Presenting Cells
        3. T-CellSurface CD28 binds to B7 Ligand on Antigen Presenting Cell
        4. T-CellSurface LFA-1 (Lymphocyte Function Associated Antigen) binds ICAM1 on Antigen Presenting Cells
        5. Interleukin-2 (IL2) produced by naive T Cells
          1. Stimulate T Cell proliferation
  5. Resources
    1. Immune System (Wikipedia)
      1. https://en.wikipedia.org/wiki/Immune_system
  6. References
    1. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL
    2. Guyton and Hall (2006) Medical Physiology, p. 419-50

Immune system (C0020962)

Definition (NCI_NCI-GLOSS) The complex group of organs and cells that defends the body against infection or disease.
Definition (NCI) The complex group of organs like thymus, spleen, tonsils, lymphatic system, hematopoetic system and cells like lymphocytes, granulocytes, monocytes and macrophages that defends the body against infection or disease. It consists of a complex interrelated cellular, molecular and genetic component.
Definition (MSH) The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
Definition (CSP) includes the thymus, spleen, lymphatic system, bone marrow, tonsils, and Peyer's patches, and the migratory cells these organs generate: lymphocytes, granulocytes, and cells of the monocyte- macrophage type.
Concepts Body System (T022)
MSH D007107
SnomedCT 116003000
LNC LP30062-1, MTHU013246
English Immune System, Immune Systems, System, Immune, Systems, Immune, Immune system structure, Immune system structure (body structure), Structure of immune system (body structure), Structure of immune system, Structure of immune system, unspecified, immune systems, immune system, Immune system, allergic/immunologic body system, allergic/immunologic organ system, body system, allergic/immunologic, immunologic/allergic organ system, organ system, allergic/immunologic
Swedish Immunsystemet
Czech imunitní systém
Finnish Immuunijärjestelmä
Russian IMMUNNAIA SISTEMA, ИММУННАЯ СИСТЕМА
Portuguese Sistema Imunológico, Sistema Imune, Sistema Imunitário
Croatian IMUNOLOŠKI SUSTAV
Latvian Imūnā sistēma
Polish System odpornościowy, Układ immunologiczny, System immunologiczny
Norwegian Immunsystem
Spanish Sistema Inmune, Sistema Inmunitario, estructura del sistema inmunológico (estructura corporal), estructura del sistema inmunológico, sistema inmune, sistema inmunológico, Sistema Inmunológico
French Système immunitaire
German Immunsystem
Italian Sistema immunitario
Dutch Immuunsysteem, Systeem, immuun-
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Immunity (C0020964)

Definition (HL7V3.0) <p><b>Definition:</b>Testing has shown that the patient already has immunity to the agent targeted by the immunization.</p>
Definition (NCI) The protection against infectious disease conferred by the immune response. It encompasses the capacity to distinguish foreign material from self, and to neutralize, eliminate, or metabolize that which is foreign.
Definition (NCI_NCI-GLOSS) The condition of being protected against an infectious disease. Immunity can be caused by a vaccine, previous infection with the same agent, or by transfer of immune substances from another person or animal.
Definition (MSH) Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.
Definition (CSP) nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.
Definition (NOC) Natural and acquired appropriately targeted resistance to internal and external antigens
Concepts Physiologic Function (T039)
MSH D007109
SnomedCT 58915005
HL7 IMMUNE
English Immunity, Immune Status, Immune state, biological immunity, immunity, immune status, Immune status, Immune status (observable entity), Immune state, NOS, Immunity, NOS, Immune status, NOS
Dutch immuunstatus, Immuniteit
French Etat immunitaire, Immunité
German Immunstatus, Abwehrbereitschaft, Abwehrkraft, Immunität
Italian Stato immunitario, Immunità
Portuguese Status imunológico, Imunidade
Spanish Estado inmunológico, estado inmunológico, estado inmunitario, estado inmune, estado inmune (entidad observable), estado inmunitario, SAI, estado inmunológico (entidad observable), inmunidad, Inmunidad
Japanese 免疫状態, メンエキジョウタイ
Swedish Immunitet
Czech imunita, Imunitní stav
Finnish Immuniteetti
Russian IMMUNITET, ИММУНИТЕТ
Croatian IMUNOST
Polish Odporność, Stan uodpornienia
Hungarian Immun állapot
Norwegian Immunitet, Immunologisk motstandskraft
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Immunity, Innate (C0020969)

Definition (MSH) The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Definition (GO) Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. [GO_REF:0000022, GOC:add, GOC:ebc, GOC:mtg_15nov05, GOC:mtg_sensu]
Concepts Organism Attribute (T032)
MSH D007113
English Immunity, Non Specific, Immunity, Non-Specific, Natural Immunity, Non-Specific Immunity, innate immune response, nonspecific immune response, native immunity, Innate Immunity, Immunity, Natural, Immunity, Innate, Innate Immune Response, Immune Response, Innate, Immune Responses, Innate, Innate Immune Responses, non-specific immunity, innate immunity, Native Immunity, Immunity, Native, Natural immunity, natural immunity
Swedish Immunitet, naturlig
Czech imunita přirozená, imunita vrozená, imunita nespecifická
Finnish Luonnollinen immuniteetti
French Immunité non spécifique, Immunité innée, Immunité naturelle, Réponse immune innée, Réponse immunitaire innée, Immunité native
Italian Immunità nativa, Immunità non specifica, Immunità naturale, Immunità innata, Risposta immune innata
Russian IMMUNITET ESTESTVENNYI, IMMUNITET NESPETSIFICHESKII, SOPROTIVLIAEMOST' BOLEZNIAM, SOPROTIVLIAEMOST' ESTESTVENNAIA, ИММУНИТЕТ НАСЛЕДСТВЕННЫЙ, ИММУНИТЕТ ЕСТЕСТВЕННЫЙ, IMMUNITET NASLEDSTVENNYI, IMMUNITET VROZHDENNYI, ИММУНИТЕТ ВРОЖДЕННЫЙ, ИММУНИТЕТ НЕСПЕЦИФИЧЕСКИЙ, СОПРОТИВЛЯЕМОСТЬ БОЛЕЗНЯМ, СОПРОТИВЛЯЕМОСТЬ ЕСТЕСТВЕННАЯ
Japanese 免疫-自然, 疾病抵抗性, 自然抵抗力, 自然抵抗性, 免疫-非特異的, 非特異免疫, 自然免疫, 自然耐性
Spanish Inmunidad Innata, Inmunidad Natural, Inmunidad Nativa, Inmunidad no Específica
Portuguese Imunidade Inata, Imunidade Natural, Imunidade não Específica, Imunidade Nativa
Croatian IMUNOST, PRIRODNA
Polish Odporność gatunkowa, Odporność naturalna, Odporność wrodzona, Odporność dziedziczna, Odporność nieswoista, Odporność konstytucyjna, Odporność fizjologiczna, Odporność genetyczna
Norwegian Medfødt immunforsvar, Nativ immunitet, Medfødt immunrespons, Uspesifikt immunforsvar
German Abwehrkraft, natürliche, Immunität, natürliche, Immunität, unspezifische, Widerstandskraft, natürliche
Dutch Natuurlijke immuniteit, Aangeboren immuniteit, Immuniteit, aangeboren, Immuniteit, natuurlijke, Immuniteit, niet-specifieke, Niet-specifieke immuniteit
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Immunology (C0152036)

Definition (NCI_NCI-GLOSS) The study of the body's immune system.
Definition (NCI) The study of the immune system and its reaction to pathogens, as well as its malfunctions (autoimmune diseases, allergies, rejection of organ transplants).
Definition (PSY) Medical science dealing with the study of immunity. Used for the scientific discipline or the immunological processes themselves.
Definition (CSP) branch of biomedical science concerned with the response of the organism to antigenic challenge, the recognition of self and foreign substances, and the biological, serological and physical chemical aspects of immune phenomena.
Concepts Biomedical Occupation or Discipline (T091)
MSH D000486
English Immunology, IMMUNOLOGY, IMMUNOL, Immunologic, immunology (field), immunologies, immunology, Immunology (Including BRMP), Immunology (NCI Program)
Dutch immunologie, Immunologie
Japanese 免疫学, メンエキガク
Czech imunologie, Imunologie
Portuguese Imunologia
Spanish Inmunología
French Immunologie
German Immunologie
Italian Immunologia
Hungarian Immunológia
Norwegian Immunologi
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Adaptive Immunity (C0678209)

Definition (MSH) Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).
Concepts Physiologic Function (T039)
MSH D056704
SnomedCT 191441008, 192360000, 63546004
Spanish inmunidad: adquirida, Inmunidad Adquirida, Inmunidad Adaptativa, inmunidad adquirida (función biológica), inmunidad adoptiva (calificador), inmunidad adoptiva (entidad observable), inmunidad adoptiva, inmunidad adquirida (concepto no activo), inmunidad adquirida (entidad observable), inmunidad adquirida (función), inmunidad adquirida, inmunidad adquirida, función (entidad observable), inmunidad: adquirida (entidad observable), tipo de inmunidad: adquirida (entidad observable), tipo de inmunidad: adquirida
English Acquired immunity, function, Adoptive immunity, function, Adoptive Immunity, Acquired Immunity, Immunity, Adaptive, Immunity, Acquired, Immunity, Adoptive, acquired immunity, Adoptive immunity (biological function) (finding), Adaptive Immunity, Adoptive immunity, Acquired immunity, function (observable entity), Acquired immunity, Adoptive immunity, function (observable entity), Acquired immunity (function), Adoptive immunity (biological function) [Ambiguous], Adoptive immunity (qualifier value)
French Immunité acquise, Immunité adaptative, Immunité adoptive
German Adaptive Immunität, Erworbene Immunität, Immunität, adaptive
Italian Immunità adattativa
Portuguese Imunidade Adquirida, Imunidade Adaptativa
Russian IMMUNITET ADAPTIVNYI, ИММУНИТЕТ АДАПТИВНЫЙ, ПРИОБРЕТЕННЫЙ ИММУНИТЕТ, PRIOBRETENNYI IMMUNITET, АДАПТИВНЫЙ ИММУНИТЕТ, ADAPTIVNYI IMMUNITET
Croatian Not Translated[Adaptive Immunity]
Czech specifická imunita, imunita adaptivní, získaná imunita
Swedish Adaptiv immunitet
Polish Odporność nabyta
Japanese 適応免疫, 獲得免疫, 免疫-適応, 後天免疫, 後天性免疫, 免疫-後天性, 免疫-獲得
Norwegian Adaptiv immunitet, Ervervet immunitet
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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