Physiology: Immune System Part 2

B lymphocytes

Antigen binding to a B cell receptor activates cloning. Form 2 types of clones after about 5 days: Memory cells - formed during a primary immune response (first time being exposed to pathogen), essential for a secondary immune response. Long lived, inactive clones which respond rapidly to a subsequent attack, may survive for a lifetime. Plasma cells - produce and release antibodies, 3000 secreted per second. Initial immune response lifespan is 3-4 days. Following affinity (process of being exposed to pathogen over and over again) maturation lifespan is years, cells continue to secrete high levels of antibodies. Antibody recognizes just that molecule. Cell starts growing and dividing.

Memory Cells: Long Term Immunity

B and T cells persist long term. Secondary exposure to SAME pathogen triggers fast response. If you've had chicken pox then you'll get shingles, but you can't get chicken pox again. These memory cells are what causes vaccines to work. Primary response takes about 14 days for them to proliferate and release antibodies. Secondary response has the same immune response by day 1 and becomes 100x higher/better immune response with secondary exposure. What happens when you get vaccinated. Flu has different strains so you could get flu again in same year.

B cell

B cell has an antibody, antigen, mitochondrion, and endoplasmic reticulum. B cell starts growing and dividing. It is released into the extracellular environment. It can become a plasma cell or a memory cell. Memory cell is just like original, but there's a lot more of them. Likelihood that it will come into contact with a cell at a later date increases.

Effectiveness of Immune System

B cells, T cells, Memory B cells, and Memory T cells are all effective against viruses. T cells and Memory T cells are effective against intracellular bacteria (living and replicating inside cells). B cells' antibodies can't bind to bacteria inside the cell, because it's not on the surface. B cells and Memory B cells are effective against extracellular bacteria. B cells and T cells provide minimal defense against fungi and parasites. Memory cells provide no defense against fungi and parasites. Memory and viruses: lifelong immunity typically Memory and bacteria: variable effectiveness Tetanus: no immunity (need booster shots) Diptheria: lifelong immunity Mutates enough and vaccine is no longer effective for viruses. Ex: HIV (surface proteins change fast).

Major Histocompatibility Markers

Complex (MHC). Recognition of normal "self" tissues. On leukocytes (easily tested) = human leukocyte antigens (HLA molecules). Class I MHC - on about every cell in the body with the exception of RBCs. Activation of cytotoxic T cells (and ONLY means of activation). Class II MHC on B cells and antigen-presenting cells (macrophages, dendritic cells). Presents antigens to lymphocytes causing the activation of Helper T cells (and ONLY means of activation). T cell receptor and MHC molecule/antigen particle identifies whether it's normal or not. Antigen presenting cell activates a Helper T cell which is on the Class II MHC for C4. Target cell activates killer T cell which is on the Class I MHC for C8. Cell produces abnormal antibodies then killer T cell pops in and does its job.

HAART

Highly Active Anti-Retroviral Therapy: use of at least 3 drugs to attack different stages of HIV replication "drug cocktails". Combination of drugs trying to prevent multiplication and escape of virus. Life expectancy has gone up tremendously. More living, less dying, less being diagnosed but rising recently.

IgD

IgD makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes, usually coexpressed with IgM. Secreted IgD is produced as a monomeric antibody (one single antibody released and functions all on its own). Signals activation of the young B cells in the spleen. Structure: monomer with a tail piece.

IgE

IgE is capable of triggering the most powerful immune reactions (well-known for function in allergies), monomeric immunoglobulin, typically the least abundant. Elicits an immune response by binding to Fc receptors on the surface of mast cells and basophils. Also found on eosinophils, monocytes, macrophages, and platelets. Plays an important role in allergies, especially associated with type 1 hypersensitivity. Binds to receptors on surface of cell. Internalization and then degranulation and release.

IgG

IgG is the most abundant, monomeric (monomer) immunoglobulin. Approximately equally distributed in blood and in tissue liquids. Predominantly involved in the secondary immune response (now circulating at high volume in bloodstream). Only isotype that can cross the placenta, providing protection to the fetus in utero (passive immunity): directly give someone an antibody - also in breast milk. It has two foreign particle binding sites.

The order of the heavy chain exons are as follows:

IgM, IgD, IgG3, IgA1, IgG2, IgG4, IgE, IgA2. Classes (isotypes) in "switch order" before encountered antigen. IgM is on surface of antibody prior to antigen encounter. Primary antibody against A and B antigens on RBCs. Physically largest antibody in the circulatory system, a pentamer of antibodies so little gets into tissues; 5 subunits looped together. Predominant antibody.

Classes of Antibodies

IgM: 5-10%, first antibody produced, membrane bound, allow Th cell recognition. (Immunoglobulin) IgG: 80%, target antigen tagged cell for destruction (most abundant). IgA: 10-15%, external secretion, prevents pathogen entry across mucous membranes (snot). IgE: <1%, allergic response (elevated then allergic response). IgD: <1%, signals B cell activation. IgE and IgD have the lowest numbers.

Autoimmunity

Immune system kills normal tissues. Immune system dysfunction where "self" recognizing T cells or B cells making "self" recognizing IgG cause the destruction of "self" tissues. Genetic influence + Environment + Immune regulation = Autoimmune disease. Identical twins may not suffer from disease! Women will sometimes produce autoimmune response after having a baby. NOT 1 determining factor.

Specific Immunity

Lymphocyte comes from the bone marrow. It matures in the thymus into either CD4 or CD8. Antigen-presenting cell causes activation in the lymph or lymph nodes causing some to become memory cells. When they reach the plasma, the CD4 cells will become helper T cells and release cytokines. The CD8 cells will become Cytotoxic T cells or Suppressor T cells.

Lymphokines

Lymphokines are cytokines (chemical signal stimulates other cells) specific for subsets of lymphocytes. Interleukin-1 (IL-1) induces fever, induces proliferation and activation of lymphocytes, increases the number of bone marrow cells and causes degeneration of bone joints (don't want in excess). Interleukin-2 (IL-2) produced by helper T cells, activate cytotoxic T cells, especially during microbial infection. Used in cancer treatments as the drug Proleukin. Interleukin-4 (IL-4) produced by helper T cells (cytokines released), activates B-cell and T-cell proliferation, differentiation of CD4+ T-cells into helper T cells (that can make more IL-4), induces B-cell class switching to IgE, and up-regulates MHC class II production. Stimulate themselves and others.

IgA

Main immunoglobulin found in mucous secretions (snot), dimeric immunoglobulin. Found in tears, saliva, colostrum, intestinal juice, vaginal fluid and secretions from the prostate and respiratory epithelium. Resistant to degradation by enzymes to survive in harsh environments (digestive and respiratory tracts) to provide protection against microbes that multiply (replicate in mucous membrane) in secretions. Constant regions are linked with variable regions on outside.

Opportunistic Infections

Opportunistic Infections: PCP pneumonia (fungal), R. equi (bacteria - severe diarrhea), Toxoplasma gondii (parasite), recurrent yeast infections. Typically don't cause problems in normal immune systems. Measure of viral particles present. Primary infection, Acute HIV syndrome with wide dissemination of virus and seeding of lymphoid organs, clinical latency with a gap of years in time, Constitutional symptoms where T cell count drops, Opportunisitic Infections, Death. <200 (AIDS) instead of HIV positive.

Acquired Immune Deficiency Syndrome

Proteins brought inside cell. CD4 on surface of virus. Makes viral RNA and proteins and put into next cell.

Antibody Generation

Recognize millions of different antigens from handful of genes. V(D)J recombination of the variable region - mechanism of genetic recombination which randomly assembles segments of genes (DNA in cell). The first recombination event is between one D and one J gene segment of the heavy chain locus (DNA in between is deleted/gone). This D-J recombination is followed by joining one V segment to the newly formed DJ complex. All sequences between V and D segments are deleted/lost. Genetic recombination - cut and paste DNA to make a difference at genetic level.

HIV

Retrovirus has RNA (viral) genome, must: 1. convert the RNA into DNA (reverse transcriptase) 2. Integrate its DNA copy into the host genome (integrase). Then the cells own DNA synthesis machinery (proteins, RNA) makes viral components. Enveloped virus - uses host cell membrane to leave cell. Deplete T-helper cells and can't fight off other pathogens. Retrovirus binds to receptor. Single-stranded DNA made from RNA template.

Somatic Hypermutation

SHM is a programmed process of mutation in variable regions of genome. In this case there is a tremendous amount of variation usually leading to cancer. Affects only individual immune cells (not widespread). Involves deamination of cytosine to uracil in DNA (CG = GU mismatch). A CG pair is mutated to a UG mismatch. Mutations repaired by DNA mismatch repair enzyme. Error-prone DNA polymerases are then recruited to fill in the gap and create mutations (just put in a base that's not U - not specific).

Delayed hypersensitivity (type IV hypersensitivity) reactions

Secondary cellular response, appears 48-72 hours after antigen exposure. Mediated by T cells and monocytes/macrophages rather than by antibodies. Reaction occurs several days after exposure. Major mechanism of defense against various intracellular pathogens (mycobacteria, fungi, certain parasites, transplant rejection and tumor immunity). Examples: contact dermatitis (poison ivy rash) does not occur within minutes but the next days. Tuberculin skin test reactions (TB). Granulomatous inflammation (sarcoidosis, Crohn disease - allergic response, autoimmune). Allograft rejection, graft versus host disease, autoimmune hypersensitivity reactions. Spreads from delayed response.

Immune System Overview

Stem cells in bone marrow become either B lymphocytes or T lymphocytes. If a pathogen with an antigen initiates it then it will be a B lymphocyte. If an antigen-presenting cell initiates it then it will be a T lymphocyte. B lymphocytes start proliferating to create both memory cells and plasma cells. Plasma cells secrete antibodies that bind to pathogen and kill pathogen. T lymphocytes proliferate and become both CD4 cells and CD8 cells. CD4 cells differentiate into Th (helper) cells and Memory T cells. Helper cells stimulate other defense cells. CD8 cells differentiate into Tc (cytotoxic) cells and Suppressor T cells. Cytotoxic cells kill abnormal cells. Suppressor T cells suppresses defense cells.

Active Immunity - Vaccinations

Stimulate a primary immune response in order to build up a supply of memory cells to fight real pathogen. Triggers rapid secondary response to a subsequent infection. Uses dead or inactivated pathogen (pieces of pathogen). Hand of Sarah Nelmes - milkmaid, didn't get smallpox as bad as everyone else because exposed to cowpox. Vaccine introduces antigen into body in some way and antigen produces antibody. Edward Jenner vaccinating James Phipps with cowpox virus to protect against smallpox. First developed against smallpox, smallpox left face scars. Rub cowpox into scab and don't get smallpox. Allow for mutation from vaccine. Some can't be vaccinated due to allergy.

CD4 cells

T lymphocytes - CD4 cells. Activated by MHC class II molecules. Produce memory cells (remember infection). T Helper cells stimulate other immune cells to secrete cytokines and activate CD8 T cells. CD8 T cells, macrophages, phagocytes, NK (natural killer) cells, B cells, and non-specific WBCs. Stimulate a host of other cells to do their jobs. MHC molecule is on an antigen-presenting cell (APC). CD4 receptor is on an inactive helper T cell. Activation occurs upon binding. Memory T cells form. Clonal expansion occurs resulting in Cytokine production.

CD8 cells

T lymphocytes - CD8 cells. Activated by MHC class I molecules. Produce memory cells. Cytotoxic - kills abnormal cells. Vesicles contain perforin which creates holes in the target cell. Granzymes activate caspases, signaling apoptosis. 1. Intact target cell membrane 2. Perforin pore partially assembled 3. Completed pore; granzyme passing through

Natural Killer T cells

T lymphocytes - Natural Killer T cells (NK-T cells). Recognize glycolipid antigen presented by CD1d. Can perform functions of either helper or cytotoxic T cells. Innate - respond in non-specific way.

Suppressor (Regulatory) T cells

T lymphocytes - Suppressor (Regulatory) T cells. CD4+/CD25+/FoxP3+ Inhibit excessive immune response (keep immune response in check). Reduce inflammation (anti-inflammatory). Exact mechanisms unknown.

Allergy Testing

Testing the skin for responses to known allergens, analyzing blood for allergen-specific IgE. Skin Allergy Tests. Little irritation from being hit. Jam plastic thing in back. The point of contact is designed to apply the test without breaking the skin.

A cure for HIV?

Adult had bone marrow transplant for an HIV patient with leukemia that happened to have the CCR mutation in bone marrow donor. CCR is a gene making them resistant to infections (harder for virus to get in, producing T cells resistant to infection). Virus showed up in blood again. Child had infant born to HIV+ mother, aggressive treatment (antiretroviral therapy) started hours after birth. HIV+ still. Newest research: HIV reservoir is larger than we first thought. Other tissues where HIV will hide (liver) - not cured. Want damaged receptor, using same receptor, plague from Europe.

Immunoglobulins, gamma globulins

4 protein chains (2 heavy; 2 light), each with constant and variable regions. Heavy chains are joined together by disulfide bonds. "Y" shaped molecule, with the variable regions at the top. Light chains are the two topmost sections of the Y. Viable regions are the topmost inside and outside of the Y. The variable region determines what type of antigen binds to it. These are very important regions that recognize specific antigens.

Specific Immunity

AKA Adaptive Immunity (Cell-mediated Immunity) Ability to recognize and remember specific pathogens. Ability to mount stronger attacks each time the pathogen is encountered. Only purpose is to identify one specific pathogen. Macrophage does pathogen uptake and elimination. Inflammatory cytokine does inflammatory reaction and shock. Interferon attacks on virus authoimmunity. These 3 are innate immunity. Cytotoxic T cells attack on virus/bacteria/tumor. B cells attack by antibody release allergic reactions. These last 2 were adaptive.

Antibodies

AKA immunoglobulins, gamma globulins. Formed during the maturation of B cells and are found as B cell receptors and secreted into plasma (gamma globulin fraction). Antibody is bound to the plasma membrane.

Breakdown of complement cascade

Ab goes to infected cell which binds to natural killer cell and then the infected cell lysis with ADCC. Ab portion binds and causes either opsonization or complement activation and virolysis. Opsonization leads to phagocyte and C3b receptor which binds with complement cascade and phagocytosis occurs.

AIDS

Acquired Immune Deficiency Syndrome develops from HIV (Human Immunodeficiency Virus) which replicates in and kills Helper T cells. Has CD4 on its surface, which binds to receptors on T cells. Transmitted via body fluids: blood, semen, vaginal secretions, milk. Not saliva, unless large quantity of blood (vampire) into open wound. Ex: Rheumatoid Arthritis - attacks joint capsules and deteriorates protective layer.

The Allergic Response

Allergy is also called type I (or immediate) hypersensitivity. Hypersensitivity is undesirable (damaging, discomfort-producing and sometimes fatal - anaphylactic shock) reactions produced by the normal immune system, there are four forms. They require a pre-sensitized (immune) state of the host. It is characterized by excessive activation of mast cells and basophils by IgE, resulting in an extreme inflammatory response. Common allergic reactions: eczema, hives, hay fever (sinuses), asthma (constriction of airways), food allergies, and reactions to the venom of stinging insects. Localized (mosquito bites) vs. Systemic (whole body). Treatments: allergen avoidance (released by mast cells and basophils, don't eat foods), use of antihistamines, steroids or other oral medications, immunotherapy to desensitize the response. Food tastes good when you smell it. 1st time exposed to allergen, you may have no response. Next time, you'll get a response. 1. Exposure to allergen causes B cells to produce specific IgE antibodies. 2. The IgE antibodies bind to mast cells and basophils, sensitizing them to future exposures to the same allergen. 3. The next exposure to the allergen causes mast cells and basophils to release histamine. 4. Histamine causes a localized or systemic inflammatory response.

Anaphylaxis

An acute systemic (multi-system) and severe Type I Hypersensitivity allergic reaction. Treatment - epinephrine (adrenaline). Prevents worsening of the airway constriction by acting on Beta-2 adrenergic receptors in the lung as a bronchodilator. Stimulates the heart to continue beating. May be life-saving. Follow-up with hospital visit. Keep them all over the place. Short-term relief. Not in allergy reaction then epi-pen (speed) crazy. Blood pressure increases, breathing rapidly, loss of appetite, and very awake. Keep it at school (backpack and school office), In transit (purse, briefcase, and luggage), Work (office and briefcase), Gym (locker and gym bag), Daycare (backpack and daycare office), and Home (on every floor).

Anaphylaxis Reaction

Full body. Can be caused by minute amounts of allergens and be life-threatening. May occur after ingestion, skin contact, injection, or inhalation (rarely - incense, husks of peanuts, brush burned). Anaphylactic shock is when an allergic response triggers rapid release of large quantities of imunological mediators leading to: systemic vasodilation (sudden drop in blood pressure), edema (swelling) of bronchial mucosa - bronchoconstriction and difficulty breathing, can be fatal within minutes if left untreated. Epi-Pen affects the sympathetic nervous system by increasing blood pressure and dilating airways.

Recombination Process

Genes in heavy chain locus with multiple V's, D's, and J's. Middle is cut out and degraded. Removal of unwanted D and J gene segment. Recombination of D and J exons - DJ recombination. Removal of unwanted V and D gene segment. Recombination of V and DJ exons - VDJ recombination. Exon. Constant region (lower portion of chain) gives you response. Antibody transcript will also include constant domain gene. Number of heavy chains you can make starts to expand.

Isotype Switching in words

Genes in heavy locus of an IgM expressing B cell. Transcript for IgM. Removal of DNA segment by enzyme activity between switch regions (switching occurs). Everything in between is lost then you gotta go down in order and can't reverse it. Non-homologous end joining of DNA at switch regions. Excised DNA segment. Genes in heavy chain locus of an IgG expressing B cell with transcript for IgG1.

Antibodies

Light chains held to heavy chains via disulfide bonds. Variable portions (Fab fragment) create the antigen binding sites (say you've been binded, this is how we should respond). The "stand" consists of the constant portions of both chains (Fc fragment). Fab2 fragments are created when the lower constant portion is removed.

Transplantation

Donor and recipient should have as many MHC molecules in common as possible, so it's not recognized as abnormal by recipient body. Transplantation could be of tissues or bone marrow. Say an organ is transplanted tissue. The organ could have a non-self MHC pattern or recipient B and T cells could be stimulated causing rejection of the organ (heart, lungs). Immune suppressive drugs (cyclosporin) may minimize. Need to be on drugs forever to prevent immuno-compromised response. Transplanted tissue could also give it's donor T cells which make the recipient immune system suppressed and see the recipient tissue as foreign to the donor T cells. Bone marrow. This is known as graft vs. host disease. Cyclosporin and steroids may help alleviate. Reject whole body because transplanted T cells reject body and attack everything as abnormal. Transplant patients will forever be "immune-suppressed."

Role of Antigens

Foreign molecules from pathogens. Usually proteins or polysaccharides. Stimulate the immune system directly OR processed and "presented" to immune system by antigen presenting cells. APCs are like dendritic cells.

Lymphocytes are the key cells

Innate and Specific occur simultaneously. Lymphocytes are defined by the type of immunity they confer and/or their tissue/organs in which they become immunocompetent. B lymphocytes mature in the bone marrow, produce and release antibodies into the plasma (humor) to act at a distance, and they confer humoral immunity. Humoral immunity is cell memory - respond much faster and more aggressively the second time. T lymphocytes mature in the thymus, antibodies remain bound to cell, must destroy pathogens upon contact, and confer cell-mediated immunity to an individual.

Interleukin-5 through 12

Interleukin-5 (IL-5) is produced by T helper cells and mast cells, stimulates B cell growth and increases immunoglobulin (antibodies) secretion, key mediator in eosinophil activation. It is associated with several allergic diseases including allergic rhinitis and asthma with a large increase in the number of circulating, airway tissue, and induced sputum eosinophils. Interleukin-10 (IL-10) aka human cytokine synthesis inhibitory factor (CSIF) is produced primarily by monocytes, lymphocytes and by mast cells, an anti-inflammatory that counteracts the inflammatory effect that these cells have in an allergic reaction. Interleukin-12 (IL-12) aka T cell stimulating factor is produced by dendritic cells, macrophages, and human B-lymphoblastoid cells in response to antigenic stimulation, involved in differentiation of naive T cells into helper T cells. Naive = CD4+; not stimulated by antigen-presenting cells.

Class Switching

Isotype Switching: constant region of the heavy chain changes allowing different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (IgG1, IgG2). Different constant regions on heavy chain. Example: Naiive mature B cells produce both IgM and IgD, after activation by antigen, these B cells proliferate and begin to produce high levels of these antibodies. If these activated B cells are also activated by CD40 and IL-4 receptors they undergo antibody class switching to produce IgG, IgA, or IgE antibodies (not membrane-bound). Requires another genetic recombination event to trigger class switching.

Antibody Function

Mark pathogens for destruction by other immune cells or through compliment activation (cascade). Antibody opsonization = the process by which an antibody binds to a receptor on the pathogen cell membrane and triggers: Phagocytes - after Ab binding to antigen, phagocytes are attracted to the pathogen. The Fab portion binds to the antigen, the Fc (constant) portion binds to an Fc receptor on the phagocyte. Complement activation - the receptor-Ab complex creates byproducts like C3b and C4b (triggered by antibody complex), important components of the complement system. Deposited on the pathogen cell surface of to aid in its destruction. Antibody-dependent cellular cytotoxicity - destruction of the pathogen without phagocytosis. Opsonization (coating of pathogen with antibodies) triggers a release of lysis products from cells like monocytes, neutrophils, eosinophils, and natural killer cells. How response works together.

Isotype Switching

Mature B cell has Cf region which is used for production of antibody. Same antigen - new response based on constant region used. Looping out then cut out other antibody classes and go to I3 instead. Switch-region recombination where a new class is produced. Different antibodies.

T lymphocytes

Mature in thymus. Memory cells are mature active cells. Cell-mediated Defense against bacteria, viruses, parasites, fungi, and abnormal cells. T cells are subdivided into CD4 and CD8 cells; these are the receptors on the surface of cell and recognizes antigen presented to them. Activated by antigen bound to an MHC molecule. Antigen presenting cells. Can not respond to antigen directly. Takes coordinated effort to get immune response.

"Off Switch" for T cells

Not in regulatory T cell sense. After the infection has been removed. Producing and secreting FAS ligand, which binds back in an autocrine (T cell produces FAS ligand and binds to receptor on its own surface) manner to the FAS receptor on T cells leading to apoptosis. Cascade 8 is important.

Immunotherapy

Pills, injections, under tongue drops. Desensitization used to reduce or eliminate the reaction to an allergen. Administration of small doses produces an IgG response (want IgG?) eventually overrides the hypersenstitive IgE response. Plasma cells help with reduced IgE production. Mast cells help with the production of blocking antibodies.

Thymic Selection

Positive selection ensures immune response. Cells that bind the MHC/antigen complex with adequate affinity receive vital survival signal. Cells with inadequate affinity die via apoptosis (don't react then die). Must bind, not ignore MHC molecules. Negative selection (next stage) prevents autoimmune (cells attack normal tissue) response. Cells interact strongly with self-antigen receive an apoptosis signal. Testing them, shouldn't kill/destroy self-antigen. MHC and abnormal antigen reactions. Need to bind to MHC appropriately and recognize antibodies that do NOT belong. Positive selection of cells whose receptor binds MHC molecules OR Death by apoptosis of cells that do not interact with MHC molecules. Negative selection and death of cells with high-affinity receptors for self-MHC or self-MHC + self-antigen.

Stages of AIDS

Primary HIV infection - lasts for a few weeks, often accompanied by a short flu-like illness (symptoms). In up to 20% of people the symptoms are serious enough to consult a doctor, diagnosis of HIV is frequently missed at this stage. Clinically Asymptomatic Stage - lasts for an average of ten years, can vary greatly depending on how robust immune system is. Free from major symptoms, level of HIV in the peripheral blood at very low levels, patient remains infectious, HIV antibodies are detectable in the blood, antibody tests show a positive result. Symptomatic HIV infection - immune system becomes severely damaged by HIV, no longer able to fight infections. Primary reasons: the lymph nodes and tissues become damaged or 'burnt out' because of the years of activity, HIV mutates and becomes more pathogenic (stronger, more varied, better at causing disease) and able to kill more T cells, The body fails to keep up with replacing lost T cells. As the immune system fails, symptoms develop and continually worsen. More illnesses, more severe, longer recovery. T cell count decreases.

Immunizations - Passive

Transfer of antibodies, not long lasting. Naturally, maternal antibodies via the placenta and breast milk (infant saliva may stimulate mom's immune system). Artificially, antibodies specific for a pathogen or toxin are injected in non-immune individuals. Rhogam, anti-venoms (from sheep who are injected with snake). Tetanus (tetanus antitoxin - passive pathogens OR toxoid vaccine will give long-term active immunity), diptheria. Indications: high risk of infection and insufficient time for the body to develop its own immune response (so give passive immunity), reduce the symptoms of ongoing or immunosuppressive diseases (antiserum or antitoxin). Mom's immune system sends antibodies to baby because baby don't have any in saliva. Tetanus in horses - massive doses of antibody (3rd eyelid). Immunizations are ways of conferring immunity to a particular pathogen. 1. Mouse, or other animal, injected with antigen. 2. IgG antibodies removed from the blood. 3. Product freeze-dried and comercially available.

Somatic Hypermutation Explanation

V region and S region with AID. Base-excision repair (C->U specific in mutations). Error-prone repair leads to somatic hypermutation. Double-strand break leads to class switch recombination. Machinery puts whatever base/nucleotide in there. Usually get a mutation unless puts in a C.