The Immune System
Classes of Antibodies and Their Functions Class - Function -
IgA - ~10-15%, Found in mucus, tears, saliva, and milk Prevents pathogens from adhering and penetrating membranes IgD - ~ 0.2% Part of B cell antigen receptor. Important in B cell activation IgE - < 0.1%, Attracts eosinophils to site of parasitic infections. Attaches to basophils and mast cell, stimulates them to release histamine, accordingly plays a role in allergic and hypersensitivity reactions IgG - Constitutes 80% of circulating antibodies. Only antibody that crosses placenta and provides passive immunity to fetus. Protects against bacteria and viruses[ neutralizes toxins. IgM - ~ 5 -10% Main antibody secreted in primary immune response. Effective in agglutination
Types of Antibodies
IgG, IgA, IgM, IgD and IgE
Complement Activation
IgM or IgG bind to antigen and initiate complement activity leading to lysis
Antigen Recognition
Immune cells have antigen receptors that recognize antigens Recognition occurs by identifying the reciprocating shape " shape to shape recognition"
Hyperesnsitivity / Intolerance
Immune system causing tissue damage as it fights off a perceived threat that would normally be harmless Reactions may be damaging, uncomfortable, sometimes fatal.
Autoimmune Disease
Immune system loses ability to differentiate between self and non self and ultimately destroys itself. E.G. systemic lupus erythematosus: an inflammatory disease when immune system attacks own tissues.
Specific Defenses
Immunity- 3rd line of defense Recognizes and attacks specific foreign substances Can keep memory of the invading organism
Disorders of Immune System
Immunodeficiencies Severe Combined Immunodeficiency (SCID) Acquired Immune Deficiency Syndrome (AIDS) Autoimmune Disease
Severe Combined Immunodeficiency (SCID)
Immunodeficiency A congenital condition that produces a deficit of B & T cells
Acquired Immune Deficiency Syndrome (AIDS)
Immunodeficiency Infection with HIV (human immunodeficiency virus) that cripples the immune system by interfering with helper T cells
Sequence of Cellular Immunity
Infected or cancerous cells displays abnormal epitope on MHC II protein Helper T cell binds to antigen and releases cytokines to activate cytotoxic T cell In response to cytokines, cytotoxic T cell will clone itself to make more cytotoxic t cells that are sensitized to that antigen The cytotoxic T cell binds to the infected cell and secretes perforins and granzymes that destroy the cell and cause apoptosis
The Course of a Fever
Infection and pyrogen secretion Hypothalamic thermostat is reset to higher set point Onset (body temperature rises) Stadium (body temperature oscillates around new set point) Infection ends, set point returns to normal Defervescence (body temperature returns to normal)
Second Line of Defense
Internal Defenses Cells and Chemicals Leukocytes and Macrophages (Phagocytosis) Antimicrobial Proteins (interferon) Natural Killer Cells Inflammation Fever
Natural Example -
Just happens Breastfeeding, placenta antigens
Effects of Aging
Little effect on lymphatic system Decreased ability of helper T cells to proliferate in response to antigens Decreased primary and secondary antibody responses Decreased ability of cell-mediated immunity to resist intracellular pathogens
Classes of MHC Proteins
MHC proteins are specific proteins located on the surface of an individual's cells. They are unique to each individual. They have two functions: self recognition and antigen-presentation. There are two classes of MHC proteins: Class I and Class II
Vasodilation & Increased Permeability of Vessels
Mast cells detect injury , release histamine Histamine increases blood flow (hyperemia) to injury site, increases vascular permeability, allowing fluid, phagocytes, and other immune cells to enter infected tissue →swelling Occurs within minutes producing heat, redness & edema Blood-clotting factors leak into tissues trapping microbes
Precipitation
May form antigen-antibody complex which precipitates. Removed by phagocytes
Mechanisms of Action by Antibodies Against Antigens
Neutralization/Inactivation Agglutination Precipitation Complement Activation
Phagocytic Cells Types - Monocytes Develop Into -
Neutrophils target bacteria Monocytes leave the circulation and go into tissues Eosinophils target parasites Dendritic Cells antigen-presenting cells Macrophages engulf and destroy foreign particles
First Line of Defense
Nonspecific Surface (external) barriers Skin and mucous membranes and their secretions
Categories of Immune Defenses
Nonspecific / Innate Defenses Specific Defenses
The Immune System True Organ System Resistance Susceptibility
Not an organ system, but a cell population that inhabits all organs and defends the body from disease The lymphatic system The ability to ward off disease Lack of resistance
Class I MHC Location - Presents Antigen To -
On surface of all nucleated body cells Cytotoxic T cell
Class II MHC Location - Presents Antigen To -
On surface of antigen-presenting cells (macrophages, dendritic cells, B cells) Helper T cell
The process in which antibodies coat foreign pathogens is called _____.
Opsonization
Complement Activation Triggers the Following Immune Responses
Opsonization and phagocytosis Inflammation Cytolysis
Discrimination Between Self and Non-Self in Specific Immunity Self - Non-Self -
Own tissue → no immune response Foreign antigen → trigger immune response Immunocompetent cells - B cells and T cells
Active Example -
Person makes own antibodies Exposure to the pathogen
Passive Ex -
Person receives antibodies from someone else Antibody transfer
Antibody Opsonization
Process by which the pathogen is marked for ingestion and eliminated by the phagocytes
Antimicrobial Proteins 3 Types of Antimicrobial Proteins in Blood and Interstitial Fluid
Proteins that inhibit microbial reproduction and provide short-term, nonspecific resistance to pathogenic bacteria and viruses Transferrins - iron binding proteins inhibit bacterial growth by reducing available iron Complement system Interferon (IFN)
Abscesses and Ulcers
Pus - dead phagocytes, damaged tissue cells & fluid Abscess - accumulation of pus in a confined space not open to the outside Pimples and boils Ulcer - open sore People with poor circulation (diabetics with advanced atherosclerosis) stasis ulcers in tissues of legs due to poor oxygen & nutrient supply to tissues
Stages of the Third Line of Defense
Recognize Respond To Remember
Costimulation of T cells
Second check to ensure T cell is really bound to a foreign antigen CD4 (for Th) and CD8 (for Tc) proteins are coreceptors, the second signal (costimulation) required for activation CD4 and CD8 are related to interleukins
T cells Must Have
Self-Recognition - be able to recognize own MHC Self-Tolerance - lack reactivity to peptide fragments from own proteins
Cytolysis
Several complement molecules join together to form a large ring shaped protein called membrane attack complex (MAC) MAC bores holes in the bacterial cell membrane which will result in cytolysis
First Line of Defense Physical Barriers Chemical Barriers
Skin Mucous membrane Cilia Skin - sweat, oil (acidic) Stomach lining Saliva, tears Urine Vaginal secretions coughing, sneezing, vomiting
Dematomes
Skin area that is supplied mainly from one spinal nerve
Haptens
Small foreign and complex molecules with reactivity but no immunogenicity. To elicit an immune response, they must attach to body proteins. Ex) penicillin, poison ivy
Successful Costimulation
will trigger clonal selection
Characteristics of Specific Immunity
Specificity - ability to recognize and respond to specific pathogens Memory - ability to remember previous encounters with a particular foreign substance and respond rapidly 2nd time Discrimination between self and non-self Self : own tissue → no immune response Non-Self: foreign antigen → trigger immune response Immunocompetent cells : B cells and T cells
IgD Class - Function -
~0.2% Part of B cell antigen receptor. Important in B cell activation
IgA Class - Function -
~10-15%, Found in mucus, tears, saliva, and milk Prevents pathogens from adhering and penetrating membranes
IgM Class - Function -
~5 -10% Main antibody secreted in primary immune response. Effective in agglutination
External Barrier
Structures, chemicals, processes that work to prevent pathogens entering the body
General Characteristics of T cells
T cell has specific receptors for a particular microbe T cell will only react with antigen presented by APC Unlike B cells, T cells produce no antibodies NK cells destroy a wide variety of infected cells
Antigen Presentation
T cells only recognize antigens presented with an antigen-presenting cell (APC) Macrophages, dendritic cells, reticular cells and B cells function as APCs Normal body cells can also present antigens when they are infected or have cancer APCs process and present antigens with major histocompatibility complex (MHC) proteins to the T cell receptor MHCs act as "identification tags" that label body cells as "self" and are unique for each individual, except identical twins
Immunocompetence
The ability of the body to produce a normal immune response following exposure to an antigen During maturation, lymphocytes become tagged with antigen receptors Mature B and T cells then travel to the lymph nodes and spleen where they have their first encounter with antigens and become immunocompetent
Allergic Reaction
The body's way of responding to an "invader" The body senses an antigen → trigger the immune system Its overreaction to a harmless substance (an allergen) is called a hypersensitivity reaction, or an allergic reaction
Inflammation
The complement system actively regulates various steps of an inflammatory response Complement binds to mast cells and basophils causing them to release histamine. Complement attracts neutrophils and macrophages to the site → destroy pathogen Initiated by damaged tissue regardless of type of damage Processes of inflammation Mobilization of body defenses - vasodilation and increased permeability Containment and destruction of pathogens Tissue cleanup and repair Response initiated by chemical mediators
Which line of defense has the ability to keep memory of the invading organism?
Third
Cytokine Therapy
Uses cytokines (interferon) Alpha-interferon used to treat kaposi's sarcoma, genital herpes, hepatitis b and c & some leukemias Beta-interferon used to treat multiple sclerosis Interleukin-2 used to treat cancer (side effects)
3 Stages of Inflammation
Vasodilation & Increased Permeability of Vessels Phagocyte Emigration Tissue Repair
Second Line of Defense Internal Non-Specific Defenses Chemical Mediators
When pathogens succeed in penetrating the skin and mucous membrane Phagocytes Natural Killer Cells Antimicrobial Proteins Inflammation Fever
Importance of Helper T Cells
Without them there is no adaptive immune response because the they direct or help complete the activation of all other immune cells
Basic Structure of Antibody
Y-shaped molecule consists of four polypeptide chains, two shorter light chains & two longer heavy chains Each antibody has two antigen-binding sites at tips of variable region Some antibodies have complement-binding sites. Antibodies do not destroy antigens, but rather inactivate them and tag them for destruction.
Immunodeficiencies
congenital or acquired conditions
Types of T Cells and Their Purpose
cytotoxic T (Tc) cells: killer T cells (T8, CD8, or CD8+) "Effectors" of cellular immunity; carry out attack on enemy cells Helper T (Th) cells: T4, CD4, CD4+ Help promote Tc cell, B cell action and nonspecific Resistance Regulatory T (Tr) cells: T-regs (aka suppressor T cell) Inhibit multiplication and cytokine secretion by other T cells; limit immune response Like Th cells, Tr cells can be called T4, CD4, CD4+ Memory T (Tm) cells Descend from the cytotoxic t cells Responsible for memory in cellular immunity
Anergy
recognition without costimulation (in both B and T cells) leads to prolonged state of inactivity
For B cells to become activated and make antibodies:
1. B cell must encounter the antigen 2. Costimulation by IL-2 (and other cytokines) produced by Th cells needed.
Nonspecific / Innate Defenses Defenses - Present - Protection From - Consists of - Lacks - Memory - Used -
1st and 2nd defenses Present at birth Wide variety of invaders recognized as "non-self cells" Cells & proteins that are always present and ready to mobilize and fight microbes The ability to recognize specific pathogens Unable to keep memory of the invading organism Non-specific/innate immunity is used by a host immediately or within several hours after exposure to almost any microbe
IgE Class - Function -
< 0.1%, Attracts eosinophils to site of parasitic infections. Attaches to basophils and mast cell, stimulates them to release histamine, accordingly plays a role in allergic and hypersensitivity reactions
Cell-Mediated Immunity
A form of specific defense in which T lymphocytes directly attack and destroy diseased or foreign cells The immune system remembers the antigens and prevents them from causing disease in the future
Antigen Processing
APC encounters antigen Internalizes it by endocytosis & digests into fragments Relevant fragments (epitopes) are displayed combined with MHC protein Helps T cells recognise antigens as foreign not self -class I MHC (MHC-I) - built into all body cell membranes except rbcs (no nucleus) -class II MHC (MHC-II) - only on APCs Tc cells respond only to MHC-I proteins Thr cells respond only to MHC-II proteins interleukins coordinate immune activity
Immunogenicity
Ability to provoke immune response by stimulating specific lymphocytes & specific antibodies
Reactivity
Ability to react with activated lymphocytes & antibodies
Third Line of Defense
Acquired (adaptive)/specific immunity. Involves the activation of widely distributed cells that recognize specific foreign substances and act to neutralize or destroy them. Against pathogens able to evade/overcome innate immune defenses. Components are normally silent unless activated by presence of an antigen. Stages: recognize, respond to, remember
Monoclonal Antibodies
Antibodies against a particular antigen can be harvested from blood Growing a clone of plasma cells to produce identical antibodies difficult Fused B cells with tumor cells that will grow in culture producing a hybrid cell (hybridoma) Antibodies produced called monoclonal antibodies Used clinically for diagnosis -- strep throat, pregnancy, allergies, hepatitis, rabies, cancer
Neutralization/Inactivation
Antibodies mask and block antigen's pathogenic effects
Agglutination.
Antibody binds to multiple antigens and immobilizes them. Form clumps which phagocytes ingest
Pathogen
Any microorganism that causes disease Infectious organisms, toxic chemicals, radiation
Antigens Required Characteristics -
Any substance that can mobilize the immune system & provoke an immune response (e.g. pollen, microbes, toxins) Get past the body's nonspecific defenses Immunogenicity - ability to provoke immune response by stimulating specific lymphocytes & specific antibodies Reactivity - ability to react with activated lymphocytes & antibodies
receiving someone else's antibodies as a treatment for rabies would be considered:
Artificial Passive Immunization
Natural Killer (NK) Cells
Attack virus-infected body and cancer cells Attack cells with unusual plasma membrane proteins May release perforins→ cytolysis of target May release granzymes → digest proteins and cause apoptosis without killing microbes → phagocytosis
Immunocompetent Cells
B Cells T Cells
Lymphocytes
B cells produced in and mature in bone marrow . concentrate in lymph nodes and spleen responsible for humoral immunity differentiate into plasma cells which secrete antibodies T cells produced in bone marrow, migrate to & mature in thymus develop surface antigen receptors to become immunocompetent positive selection: survive negative selection: killed After maturation, B and T cells circulate in the blood and lymph
Artificial Example -
Caused by man (often using a needle) Vaccines
Types of Adaptive Immunity Responding Cell - Antigen - Antigen Presentation - Outcome -
Cell Mediated Immunity T lymphocytes (Cytotoxic T and Helper T) Intracellular antigens eg-Infected cell (virus inside cell), cancer cell, transplanted cell, bacteria Requires antigen-presenting cell Cytolysis of infected cell by Cytotoxic T cell Humoral Immunity B lymphocyte Small extracellular antigens in body fluids Does not require antigen-presenting cell Antibody secretion by plasma cells
Phagocytosis
Cells attacked by pathogen release histamine Histamine + other chemicals attract neutrophils Endocytosis of neutrophil membrane = phagocytic vacuole
Self-Recognition and Self-Tolerance
Cells that can't recognize own MHC undergo apoptosis Tolerance: prevents immune system from responding to self-antigens T and B cells that recognize self peptide fragments are eliminated deletion - undergo apoptosis anergy - remain alive but are unresponsive
Pyrogens
Chemicals that effectively alter the "thermostat setting" of the hypothalamus to elevate body temperature and cause fever.
Phagocyte Emigration
Chemotaxis Within an hour, neutrophils followed by monocytes Pus may form
Effects of Complement Activation Pathways
Classical Pathway - Initiated by antigen-antibody complex Alternative Pathway - Initiated by abnormal pathogen surface such as bacterial or fungal cell wall
cd
Cluster of Differentiation
Opsonization
Coating the surface of the pathogen thus making it more recognizable to phagocytic cells.
IgG Class - Function -
Constitutes 80% of circulating antibodies. Only antibody that crosses placenta and provides passive immunity to fetus. Protects against bacteria and viruses[ neutralizes toxins.
Fever
Defense mechanism that can destroy microbes Infection and inflammation → abnormally high temperature Certain bacterial or viral infections cause production of pyrogens May also inhibit the growth of many pathogens Intensifies effects of interferons Increases phagocytosis inhibits growth of some microbes Speeds up body reactions to enable body repair
Antibody-Mediated/Humoral Immunity
Different B cells recognize and respond to different antigens. B cells remain in lymphatic tissue and wait for antigens. Once activated, differentiate into plasma cells that secrete antibodies Antibodies mark antigens for later destruction Combines with epitope on antigen Stages: Recognition, Attack, Memory for B cells to become activated and make antibodies: 1.B cell must encounter the antigen 2. costimulation by IL-2 (and other cytokines) produced by Th cells needed.
Stages of Phagocytosis
Engulfing a pathogen Formation of a phagosome Digestion of the pathogenic particle in phagolysosome Expulsion of undigested materials from cell
Epitopes of Antigens
Epitopes (antigenic determinants): Small regions on antigen which trigger immune response. Different epitopes on same antigen result in different antibodies
Immunological Memory
First encounter with antigen, you have few B cells or Tc cells against that antigen = primary response Second exposure to antigen presence of memory cells → faster and stronger response Memory B cells quickly differentiate into plasma cells and produce higher concentration of antibodies memory cells survive for 20 years or more Antibody titer measure of immunological memory The first antibodies produced are IgM. Several days later, IgG is produced - single unit antibodies, abundant in serum, cross the placenta, and longest half-life
Interferons (IFN)
Glycoprotein produced by virally infected cells. Of no benefit to the cell that secretes them. Leave infected cells to uninfected neighboring cells and protect them from becoming infected by producing antiviral proteins which interfere with viral replication IFNs also enhance phagocytosis & suppress growth of tumors. Enhances macrophage, nk cells, tc cell & b cell activity
Complement System
Group of 30 or more proteins synthesized by the liver and involved in both nonspecific and specific immunity Circulate in the blood in inactive form Activated by presence of a pathogen → pathogen destroyed by cytolysis, immune clearance, inflammation, phagocytosis
Types of T Cells
Helper (TH) Cytotoxic (TC) Memory (TM) Regulatory (TR)
B cells are most important in the _______ immunity type of _______ immunity
Humora Specific