Adaptive and Innate Immunity

Exogenous Antigen

-Originate from microbes located outside the body's cells -Toxins, secretions, cell wall, flagella, ...

Monoclonal Antibodies

-One clonal antibody -Producing a clone of antibodies (same) against a particular antigen in Lab -Test for hepatitis

Cells

1) Neutrophils 2) Monocytes (macrophage) 3) NK cells 4) Basophils 5) Eosinophils

T Helper Cell (TH)

-Contacts the displayed antigen fragment and releases cytokines that activate B cells -B cell undergoes proliferation (clonal expansion) -Clonal selection differentiates activated B cells into: 1) Antibody-producing plasma cells 2) Memory cells 3)Clonal deletion = eliminates harmful B cells

Hematopoietic cytokines

-Control stem cells that develop into red and white blood cells

IgM

-5-10% of circulating Abs -Pentamer: 5 monomers joined by a J-chain protein -Since every monomer has two binding sites then the IgM will have 10 binding sites in all -Remains in blood vessel circulation: too large to pass through blood vessels -Agglutination: aggregating Antigens, easier to phagocytize (cause clumping of cells and viruses) -1st to appear in initial stages of infection (first response to an active/recent infection) -Diagnostically important: appearance in serum indicated a recent infection -6% of serum antibodies -Short-lived

Humoral immunity

-A type of adaptive defense -Produces antibodies that combat foreign molecules known as antigens -B cells are lymphocytes that are created and mature in red bone marrow -Recognize antigens and make antibodies -Named for bursa of Fabricius in birds -Macrophages (APC), T-Helper Cells (CD4), B cells

Cellular immunity (cell-mediated immunity)

-A type of adaptive defense -Produces T lymphocytes -Recognize antigenic peptides processed by phagocytic cells -Mature in the thymus -T cell receptors (TCRs) on the T cell surface contact antigens, causing the T cells to secrete cytokines instead of antibodies -Macrophages, T-helper cells (CD4), T Cytotoxic cells (CD8)

General Characteristics of Acquired or Adaptive Immunity

-Ability to recognize self & non-self (unresponsiveness to self) -Specificity: Antigen specific -Diversity but Inudcibility -Ability to recognize different antigens -But only respond to a specific Ag -Clonality: rapid proliferation of the cells in response to a specific Ag -Memory: ability to remember Ags -Antibody-mediated: Humoral -Activated B-cell: Plasma cell: Antibody -Bacteria & Viruses: outside of cells -Cell-mediated -Virus-infected cells -Cancers -Transplants -Fungi -Helminths (worms)

TH2 cells

-Activate B cells to produce IgE; activate eosinophils

Macrophages

-Activated by cytokines or the ingestion of antigenic material -Migrate to the lymph tissue, presenting antigen to T cells

Third-Line Defenses

-Adaptive -Lymphocytes that target specific pathogens for destruction when the second-line defenses aren't effective. It includes memory component that allows body to more effectively respond to that same pathogen in the future

Adaptive Immune System

-Adaptive immunity: defenses that target a specific pathogen -Specific Mechanisms: Third Line of Defense -Acquired through infection or vaccination -Primary response: first time the immune system combats a particular foreign substance -Secondary response: later interactions with the same foreign substance; faster and more effective due to "memory"

Agglutination

-Ag binding sites can bind to two separate foreign Ags. -Cause clumping --> easier to phagocytize -Reduces number of infectious units to be dealt with

Primary Adaptive Response

-Ag is recognized for the first time -7 days-14 days -Producing Ab (IgM, IgG)

T-dependent antigen

-An antigen that requires a T-helper cell to produce antibodies

Antibody-dependent cell-mediated cytotoxicity (CCDC)

-Antibodies attach to target cell -Cause destruction by macrophages, eosinophils, and NK cells

Antigens

-Antigens are Macromolecules, usually of molecular weights greater than 10,000 such as proteins and polysaccharides that cause the production of antibodies; components of cell wall -Usually components of invading microbes or foreign substances -Antibodies interact with epitopes, or antigenic determinants, on the antigen -They are recognized by the immune system as Foreign

Haptens

-Antigens too small to provoke immune responses; attach to carrier molecules ->Hapten & Carrier can stimulate an Immune Response -Penicillin is not antigenic by itself -In combination with the host, an immune response occurs

Antigens

-Antigens: substances that cause the production of antibodies -Usually components of invading microbes or foreign substances -Antibodies interact with epitopes, or antigenic determinants, on the antigen

Endogenous Antigen

-Are produced by intracellular microbes and integrated into host cell's cytoplasmic membrane -Protozoa, fungi, bacteria, viruses...

Anatomical Barriers

1) Skin 2) Mucous membranes 3) Lacrimal glands 4) Saliva 5) Ciliary escalator

Monocytes

-Become phagocytic when they leave the blood, enter into body tissues and mature into macrophages -Lymph node swelling due to proliferation of macrophages there

Neutralization

-Blocks binding of pathogen to host cell -Blocks adhesion of bacteria and viruses to mucosa -Blocks attachment to toxin

Antiserum

-Blood-derived fluids containing antibodies

Histamine

-Causes Vasodilation

Dual Nature of the Adaptive System

-Cellular immunity attacks antigens found inside cells -Viruses; some fungi and parasites -Humoral immunity fights invaders outside cells -Bacteria and toxins

Action of the Complement System Against a Bacterium

-Complement proteins form holes in the bacteria cell wall and membrane -->holes allow fluids and salts to enter the bacterium -->bacterium expands until it bursts

Cytokines: Chemical Messengers of Immune Cells

-Cytokines are chemical messengers produced in response to a stimulus -Interleukins -Chemokines -Interferons -Tumor necrosis factor -Hematopoietic cytokines -Overproduction of cytokines leads to a cytokine storm

Interleukins

-Cytokines between leukocytes

Fever

-Cytokines released by macrophages that encounter invading microbes -Act on hypothalamus to raise body temperature above 98.6 degrees F. -Phagocytic cells are more active -Reduce iron availability --> some bacteria grow slower

CD8+

-Cytoxic T-lymphocytes (CTL) -Clusters of Differentiation (CD) -Bind MHC class 1 molecules

Cerumen

-Earwax -Fatty acid composition (low pH) -Lysozyme: can break down cell walls, especially of Gram (+) bacteria -> attacks Peptidoglycan bonds (in earwax and saliva)

Dendritic cells (DCs)

-Engulf and degrade microbes & display them to T cells -Found in the skin, genital tract, lymph nodes, spleen, thymus, and blood

Antigen-Antibody Complex

-Forms when antibodies bind to antigens -Strength of the bond is the affinity -Protects the host by tagging foreign molecules or cells for destruction 1. Agglutination 2. Opsonization 3. Antibody-dependent cell-mediated cytotoxicity 4. Neutralization 5. Activation of the complement system

Major Histocompatibility Complex (MHC)

-Genes encode molecules on the cell surface -Class 1 MHC are on the membrane of nucleated animal cells -Identify "self" -Class 2 MHC are on the surface of antigen-presenting cells (APCs), including B cells -Inactive B cells contain surface Ig that bind to antigen -B cells internalize and processes antigen -Antigen fragments are displayed on MHC class 2 molecules

Antibodies (Figure 17.4)

-Globular proteins called immunoglobulins (Ig) -Plasma proteins -Produced by Activated B Lymphocyte -In response to antigen -Valence is the number of antigen -binding sites on an antibody

Inflammation Mediators

-Histamine -Prostaglandin -Kinins -Leukotrienes -Complement

Alleries

-Hypersensitivity -Immune Response to Non-pathogenic Agent

Complement Activation

-IgG or IgM Abs -Microbes in infected area are coated with antibody-complement complex -> lysis of microbe -> invasion of phagocytes to area -Causes inflammation and cell lysis

Antigenic Determinant Epitope

-Individual antibodies are not made against entire antigen molecules by rather to particular chemical group on the molecule known as Antigenic Determinant or Epitope -Many different antibodies can be made against a single antigen -Each antibody reacting with a different epitope -Complex structures such as bacterial cell may have many different epitopes and each different antibody binds only to the correct epitope

Chemokines

-Induce migration of leukocytes

Artificially acquired PASSIVE immunity

-Injection of antibodies -Preformed antibodies in immune serum are introduced by injection from an animal or person who is already immune to the disease -Monoclonal antibodies -Short-lived: antibodies will be degrades over time

Artificially acquired ACTIVE immunity

-Injection of vaccination (immunization) -Attenuated or killed agent -Antigens are introduced in vaccines/body produces antibodies and specialized lymphocytes

First-Line Defenses

-Innate -Keep pathogens on the outside or neutralize them before infections begins

Second-Line Defenses

-Innate -Slow or contain infections when first-line defenses fail. Include proteins that produce inflammation, fever, that enhance cytokine activity, phagocyte cells and NK cells

Interferons (IFNs)

-Interfere with viral infections of host cells

Tumor necrosis factor (TNF)

-Involved in the inflammation of autoimmune diseases

Secondary (Memory or Anamnestic) Response

-Occurs after the second exposure to an antigen -More rapid, lasts many days, greater in magnitude -Memory cells produced in response to the initial exposure are activated by the secondary exposure -Immunological memory

Lacrimal Apparatus

-Lacrimal glands (tears) -> under upper eyelid -> lacrimal canals -> nose -Microbes prevented from settling on eye surface -More tears may be produced in response to invasion by large amounts of microbes -Lysozyme in tears; effects the cell wall and peptidoglycan of gram positive bacteria

Skin

-Largest organ of the body -Two layers: epidermis and dermis -Keratin overlying dermis (protective) -Keeps moisture out (inhibits microbe growth) -Sloughed off periodically to remove surface dwelling microbes -If moisture available microbes may be able to get in and thrive --> fungi can hydrolyze keratin when water is around Skin is also very salty. Most bacteria do not like salty environments.

IgE

-Monomer -0.002% of serum antibodies -Attached to surface of mast cells and basophils in the blood -Bind to antigens such as pollen cause release of histamine (cause the release of histamines when bound to antigen) -Lysis of parasitic worms (In helment/worm infections, this monomer increases in number)

IgD

-Monomer -0.02% of serum antibodies -Structure similar to IgG -In blood, lymph, and on B cells -No well-defined function / assists in the immune response on B cells

MHC Class II

-More advanced compared to cytotoxic because it has the ability to deal with humoral and cellular mediated cells) -Receptor for Helper T Lymphocyte (HTL)- Th cells or CD4 cells -Proteins produced inside Antigen Presenting Cells (APCs) -Macrophages, B cells, Dendritic Cells -Cell first ingests and digest pathogen -Antigenic parts of pathogen bound to MHC II -MHC II presents antigen on surface of APC -T Helper cells bind to MHCCII-Ag -T Helper cells can signal to -B cells make antibodies against this pathogen -T cytotoxic cells Kill infected body cells that present with this antigen -NK cells

Mucous Membranes

-Mucous: glycoprotein produced by the cells of the mucous membrane -Prevent from drying out -Cilia line the epithelium of the lower respiratory tract -Mucous coated hairs in respiratory tract --> filter air and trap microbes, dust, pollutants -Coughing or sneezing speeds the process up -Mucociliary Escalator: move mucous and any trapped particles UPWARD

Extracellular Killing by the Immune System via Natural Killer Cells

-Natural Killer Cells (NK) = large, granular leukocytes destroying cells that don't express MHC class 1 self-antigens -Kill virus-infected and tumor cells -Attack parasites -Not always stimulated by an antigen -Form pores in the target cell, leading to lysis or apoptosis

Types of Adaptive Immunity

-Naturally acquired ACTIVE Immunity -Naturally acquired PASSIVE Immunity -Artificially acquired ACTIVE Immunity -Artificially acquired PASSIVE Immunity -Antiserum -Serology -Globulins

Innate System (Front Line)

-Non-specific mechanisms -First Line: Anatomical barriers; secretory chemicals -Second Line: Cellular mechanisms (T cells) -Surface barriers: Skin, mucous membranes -Internal defenses: Phagocytes, fever, NK cells, Antimicrobial proteins, inflammation

Secondary (Memory or Anamnestic) Response

-Occurs after the second exposure to an antigen -More rapid, lasts many days, greater in magnitude -Memory cells produced in response to the initial exposure are activated by the secondary phase -Faster (experiencing and B memory cell) -Binding memory cells to Ag -IgG (more of this & faster) -IgM

Neutrophils

-Polymerphonuclear leukocytes (PMNs): nuclei contain two to five lobes -Highly phagocytic -Active during the 1st stages on infection -Leave blood, enter infected tissue, destroy microbes

Kinins

-Present in blood plasma -Vasodilation, increase BV permeability, chemokine for phagocytic cells

TH1 cells

-Produce IFN-delta, which activates macrophages, enhances complement, and stimulates antibody production that promotes phagocytosis

TH17 cells

-Produce IL-17 and contribute to inflammation

Leukotrienes

-Produced by mast cells and basophils. Help phagocytes attach to pathogens, increase BV permeability

Interferon

-Produced by virally infected cells -Bind to surface receptors on un-infected neighboring cells and induce production of anti-viral proteins: -Stop protein synthesis -Break down nucleic acids

Apoptosis

-Programmed cell death

Antibody-Dependent Cell-Mediated Cytotoxicity

-Protozoans and helminths are too large to be phagocytized -Both of their target cells are coated with antibodies -Immune system cells attach to the Fc regions of antibodies -Target cell is lysed by chemicals secreted by the immune system cell

MHC Class I

-Receptor for Cytotoxic T Lymphocyte (CTL): Tc cell or CD8 cell -Proteins produced inside Body Cells!!! -Body cells that have been infected by a virus or bacteria or even cancer cells: -Take antigens from inside of it -Bind them to the MHC I -MHC I present antigen on surface of sick cell -Says "IM SICK!!! KILL ME!!!" (to prevent damage to rest of tissue) -CTLs recognize and kill self-cells altered by infection -CTL releases perforin (create pores on target cell for granzymes to enter) and granzymes (enter the virus infected cell for apoptosis) that induce apoptosis in the infected cell -The cytotoxic proteins only affect those cells to which the Tc cell has specifically interacted -Apoptosis: programmed cell death -Prevents the spread of infectious viruses into other cells

Inflammation 4 Cardinal Signs

-Redness (erythema) -Heat -Swelling (edema) -Pain -Additional Signs of Inflammation: -Pus: dead bacteria and dead PMNs -Abscess: accumulation of pus within tissue -Granuloma: longtime infection (chronic) inflammation with a wall -Leprosy, Tuberculosis, Syphilis

Prostaglandins

-Released by damaged cells -Intensify histamine's effects

Naturally acquired ACTIVE immunity

-Resulting from infection; exposure to antigen and make antibody -Antigens enter the body naturally / body induces antibodies & specialized lymphocytes -illness; recovery

Gamma globulin

-Serum fraction containing antibodies

Globulins

-Serum proteins

Basophils

-Stain blue-purple with basic dye (methylene blue) -Release histamine: -Dilate blood vessels -Capillaries more permeable -Recruit other WBCs to come in to sites of injury

Eosinophils

-Stain red or orange with acidic dye eosin -Enzymes that degrade proteins, nucleic acids, carbohydrates, etc... -Play a role in allergic response -Fight Helminths!!! -May also fight viral infections with the RNases and DNases

T-independent antigen

-Stimulates the B cell without the help of T cells -Provokes a weak immune response, usually producing IgM -No memory cells generated

T Regulatory Cells (Treg)

-Subset of CD4+ cells / carry an additional CD25 molecule -Suppress T cells against self -Protect intestinal bacteria required for digestion -Protect fetus

Complement System

-System of 30 proteins: C1-C9 with various activated fragments -They are activated through -a cascade type mechanism -Present in the blood -Made by liver -Some are made by macrophages -It has two pathways: -Classical pathway: can be activated by binding to antigen-antibody complexes OR -Alternate pathway: by combing with the pathogen itself

Cellular Immunity Response Process

-T cells combat intracellular pathogens: -Mature in the thymus -Thymic selection eliminates immature T cells -Migrates from the thymus to lymphoid tissues -Attach to antigens via T-cell receptors (TCRs) -Pathogens entering the GI tract pass through microfold cells (M cells) located over Peyer's patches: -Transfer antigens to lymphocytes & antigen-presenting cells (APCs)

CD4+

-T-helper cells -Clusters of Differentiation (CD) -Cytokine signaling with B cells / interact directly with antigens -Bind MHC class 2 molecules on B cells and APCs

T-Helper Cells (CD4+ T cells)

-TCR on the T-helper cell recognize and bind to the antigen fragment and MHC class 2 on APC -APC or T-helper cells secrete a costimulatory molecule, activating the T-helper cell -T-helper cells produce cytokines and differentiate into: TH1 cells, TH2 cells, TH17 cells, and Memory cells

IgA

-The monomer is serum; dimer in secretions -10-15% of circulating Abs (13% of serum antibodies) -Common in mucous membranes and secretions (saliva, mucus, tears, and breast milk) -Prevent Microbial attachment of pathogens to mucous membranes

IgG

-The most prevalent Monomer that is one unit we have in our blood circulation -80% of serum antibodies -In the blood, lymph, and intestine -Long-term protection -Can cross the placenta -Trigger complement system -Bind to Ag and enhance phagocytosis -Neutralize toxins and viruses -Protect the fetus

Antibody titer

-The relative amount of antibody in the serum -Reflects intensity of the humoral response -IgM is produced first, followed later by IgG -Immunological memory

Serology

-The study of reactions between antibodies and antigens

Naturally acquired PASSIVE immunity

-Trans-placental or via colostrum -Antibodies pass from mother to fetus via placenta or to infant by mother's milk

Exocytosis

-Undigested materials (residual bodies) are removed via movement of the phagolysosome to the membrane of the cell and --> exocytosis

Vaccines

-Vaccine: suspension of organisms or fractions of organisms that induce immunity -Variolation: inoculation of smallpox into the skin -Jenner inoculated cowpox to prevent smallpox -Termed vaccination by Pasteur -Vacca= cow -Safety of Vaccines: -On rare occasions, vaccines can cause the disease -Safest and most effective means of preventing infectious disease in children

Antibody Structure

-Variable Region: -Binds to the antigen -Antigen specific -Constant Region: (Fc) -Activation of complement -Serves as a Flag for pathogens opsonized by antibody. This is what the macrophage needs to see!!! -Four protein chains form a Y-Shape: -2 Identical light chains and 2 identical heavy chains joined by disulfide links -Variable (v) regions are at the end of the arms; bind epitopes -Constant (Fc) region is the stem, which is identical for a particular Ig class -Five classes of Ig (IgG, IgM, IgA, IgD, IgE)- know this order because it goes from most prevalent to least prevalent; don't need to know specific percentages)

Attenuated (live) Vaccine

-Weakened pathogen -Closely mimic an actual infection -Confers lifelong cellular and humoral immunity -Pathogenic virus raised in lab for several generations -Eventually it loses its pathogenicity -Inject this into patient -Advantage -Antigens on virus not modified thus, strong immune response generated against virus -Contact immunity: vaccinated individuals can infect those around them and provide them with immunity as well -Disadvantage & Problem -Sometimes virus can revert back to pathogenic form -Examples of attenuated (LIVE) vaccines -MMR (Measles, Mumps, Rubella) -Varicella -Smallpox

Lymphocytes

-White cells that are crucial to our immune systems -There are three main types -Clusters of differentiation- CD4 and CD8 i. T cells (has surface markers) -T helper (Th cells: CD4 cells- has CD4 on the surface of T helper cells so can be considered as a CD4 cell)-Humoral & Cellular Responses -T cytotoxic (Tc cells: CD8 cells)-Cellular Responses ii. B cells -15% of lymphocytes -Plasma cell: antibody -Memory cell iii. Natural Killer cells -Lymphocyte but are involved in Innate Immunity iv. -Antigen Presenting Cells (APCs): Macrophages

Hypersensitivity (Table 19.1 Types of Hypersensitivity)

1) Anaphylactic (type I)-less than one day to have reaction with the help on antibody 2) Cytotoxic (type II)-less than one day to have reaction 3) Immune complex (type III)- less than one day to have reaction 4) Delayed type hypersensitivity (type IV)-takes more than one day to have reaction with the help of cellular

Secretory Chemicals

1) Lysozyme 2) Interferon 3) Complement

T-Cytotoxic Cells (CD8+)

Activated into cytotoxic T lymphocyte (CTL) with the help of T-helper cell and costimulatory signals -Cytotoxic T-cells recognize & kill self-cells altered by infection -Self-cells carry endogenous antigens on a surface presented with MHC class 1 molecules -Cytotoxic T-cells release perforin and granzymes that induce apoptosis in the infected cell -Apoptosis = programmed cell death -Prevents the spread of infectious viruses into other cells -Cells cut their genome into fragments, causing the membranes to buldge outward via blebbing

Opzinization

Coat Ag with Ab -Its phagocytosis is enhanced -> Antibody mediated cell-mediated cytotoxicity -Coating antigen with antibody enhances phagocytosis

Which cells are the Antigen-Presenting Cells (APCs)?

Dendritic cells and Macrophages

What Can Complement Do?

Form a: -Membrane Attack Complex (MAC) (C5bC6789) -Make holes/pores into microorganism and lyse it -Formation of MAC created pores in cell membranes, disrupting the integrity of the cell (lysis of foreign cells) -Opsonization -C3b binds to microbial cells, functioning as an opsinin -Opsonize pathogens (C3b) -By attaching to microorganisms, as a flag for phagocyte -Inflammatory Response (C3a, C5a) -C3a and C5a induce changes that contribute to local vascular permeability and attract phagocytes -To attract immune system cells to an infected area

Inactivated (killed) vaccine

Safer than live vaccines -Require repeated booster doses -Induce mostly humoral immunity -Active microbe treated with a chemical agent that inactivates them -Antigens remain ->generate immune response by patient -Response may be weak -> Booster shots may be required -Examples: Hep B, Haemohphilus influenza type B (meningitis), Hep A, Influenza (Flu Shot)

Phagocytosis

The engulfing and usually the destruction of the particulate matter by phagocytes -Steps: Chemotaxis -->Adherence --> Ingestion --> Digestion -->Exocytosis 1) Chemotaxis: -Chemical attraction of phagocytic cells to infected area -Recruitment of phagocytic cells to infected area -Released by infected or damaged cells or even macrophages in the area --> tries to get more macrophages into the site 2) Adherence (attachment) -Attachment of the phagocyte's plasma membrane to the surface of the microbe -Sometimes this readily occurs -Sometimes this is required if the microorganism is first coated with attachment promoting proteins: Opsonins (antibody or complement) -This coating process is called opsonization (coating antigen with antibody enhances phagocytosis) 3) Ingestion: -Extension of pseudopods ("false feet") by the phagocyte -Microorganism is surrounded and engulfed -Contained within a sac called a phagosome -Enzymes within the phagosome are activated by the pumping of protons (H+) into the sac to make the inside more acidic (pH 4). -Low pH activated hydrolytic enzymes 4) Digestion -Phagosome fuses with lysosomes phagolysosome -Lysosomes contain lysozyme, lipases, proteases, ribonucleases, deoxyribonucleases -Also contain superoxide radicals, hydrogen peroxide, etc.... -Result = microbe is killed and broken down

Why could the oral (Sabin) polio vaccine sometimes cause polio, but the injected (Salk) vaccine does not?

The oral one has live diseases, and the injected one is dead diseases