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