Passive Immunity Transfer and Hypersensitivity Reactions in Animals

Posted on Dec 8, 2024 in Biology

Passive Transfer of Immunity

A) Type of Placentation:

  • Humans and Primates: Hemochorial placentation, maternal blood is in contact with the fetal trophoblast. There are only 2 layers of cells separating the maternal and fetal blood circulation. This allows the passage of IgG. At the time of birth, the newborn has an IgG titer similar to the mother’s.
  • Dogs and Cats: Endotheliochorial placentation, the fetal chorionic epithelium is in contact with the endothelium of maternal capillaries. There are 3 cell layers between maternal and fetal circulation, allowing the newborn to have a small amount of circulating IgG that can pass through these layers.
  • Ruminants: Syndesmochorial placentation, the fetal chorionic epithelium is in contact with the tissues of the uterus. There are 4 layers of cells between the bloodstream of the maternal and fetal circulation. This does not allow the passage of Ig in any amount.
  • Equine and Swine: Epitheliochorial placentation, the fetal chorionic epithelium is in contact with the lining of the uterus. There are more than 6 cell layers separating the mother’s bloodstream from the fetus’s bloodstream. The transfer of immunity is totally helpless.

B) Colostrum: Composition and Absorption

Colostrum is the first secretion produced by the mammary gland after birth. It accumulates in the mammary gland in the last weeks before delivery. It contains proteins, including antibodies (Ac). These antibodies are transferred from maternal blood to the mammary gland under the influence of hormones like estrogen and progesterone. These hormones promote the expression of specific receptors on the mammary gland, known as FcRn. FcRn receptors are expressed as a result of the effects of sex hormones. These receptors allow circulating Igs in the blood to be trapped by the mammary gland cells, and then the antibodies pass from blood to milk (IgG).

IgG is the most abundant immunoglobulin in colostrum, comprising 65-90% of the total Ig. IgA makes up the rest. As lactation progresses, colostrum transitions to milk, and IgG decreases, but IgA persists. Ruminants gradually replace IgG1 with IgA.

Colostrum also contains many T helper cells (Th1 and Th2) and cytokines like IL-1, IL-6, TNF-alpha, and IFN-gamma, which promote the development of the neonate’s immune system.

Absorption:

Colostrum contains IgG and IgA. In ruminants, IgG1 replaces IgA. When the newborn suckles colostrum, it becomes alkaline in the stomach. The colostrum immunoglobulins pass through the stomach to the intestine. Colostrum neutralizes acidity in the newborn, and antitrypsin proteins allow immunoglobulins to pass intact into the intestine. Upon reaching the intestine, enterocytes of the newborn have FcRn receptors that bind to the immunoglobulins. These immunoglobulins are taken up by endocytosis, pass into the cell, and are secreted into the interstitial fluid, entering the thickness of the intestinal wall. From there, they are taken up by lacteal vessels or blood vessels in the intestinal wall and quickly pass into the blood.

Non-ruminants only absorb IgG, while IgA remains on the intestinal surface.

The newborn needs to suckle colostrum because:

  • The absorbed IgG defends the newborn against septicemic infections.
  • The absorbed IgA defends the newborn against enteric infections.

C) Failure of Passive Transfer

Failure can occur due to:

  1. Failures in the production or quality of colostrum:
  • The amount of colostrum absorbed depends on the number of offspring. There is no relationship between the number of offspring and colostrum production.
  • Loss of colostrum through dripping.
  • The quality of colostrum can be measured using a colostrometer to assess its density.
  1. Failure of ingestion:
  • Multiple births.
  • The mother delaying feeding a newborn.
  • Weakness in the newborn’s ability to suckle.
  • Nipple defects.
  • Defects in the mouth (cleft lip, sunken palate, prognathism).
  1. Failures in absorption:
  • Genetic factors.
  • Consanguinity.

Type I Hypersensitivity

A) Definition:

Acute inflammatory reactions mediated by IgE bound to mast cells and basophils. The inflammatory reaction is due to the release of vasoactive molecules by these cells.

B) Mechanism of IgE Action:

IgE is produced and released by plasma cells near the affected area. If an atopic individual is repeatedly exposed to an allergen, they respond by producing IgE instead of IgA or IgM. This allergen (antigen) will be recognized by an antigen-presenting cell (APC), such as a dendritic cell (DC). The DC engulfs the allergen, processes it, associates it with MHC-II, and presents it to a T helper 2 cell (Th2).

Additionally, a B cell (LB) must come into contact with the same allergen. The B cell, with its B cell receptor (BCR), receives an initial signal. Subsequently, the B cell receives a series of signals from the Th2 cell’s interleukins (ILs), allowing the B cell to differentiate into a plasma cell. These plasma cells then produce IgE.

The IgE binds to the surface of mast cells and basophils, which have high-affinity receptors for IgE (FcεRI) on their membranes. These receptors are composed of four chains: an alpha chain, a beta chain that spans the membrane, and two gamma chains that serve as signal transduction components.

When mast cells have IgE bound to their surface, the individual is considered sensitized. If the same antigen is reintroduced, it will be captured by the IgE antibodies on the mast cells.

The antigen-antibody reaction triggers a series of enzyme activations in the mast cell membrane, cytoplasm, and nucleus.

C) Mast Cell Response to Antigen-Antibody Reaction:

The antigen-antibody reaction signal product provokes a series of enzyme activations, both in the membrane of the mast cell and in the cytoplasm and nucleus. These changes occur very rapidly.

  1. Membrane: Methyltransferase is activated, leading to the activation of phospholipase A. This enzyme metabolizes membrane phospholipids, producing arachidonic acid. Arachidonic acid is then metabolized by:
  • Cyclooxygenase: Produces and releases prostaglandins, prostacyclin, and thromboxane.
  • Lipoxygenases: Produce leukotrienes, which are potent vasoactive factors released into the fluid surrounding the mast cell.
  1. Cytoplasm: Tyrosine kinases are activated, which in turn activate phospholipase C. This leads to the production of diacylglycerol and inositol, promoting increased intracellular calcium. Increased calcium activates protein kinases, inducing the phosphorylation of myosin in the cell’s cytoplasm. Myosin phosphorylation initiates the formation of microfibrils that move mast cell granules to the cell surface, resulting in degranulation.

These granules contain histamine, serotonin, chymase, tryptase, kallikrein, proteases, proteoglycans, heparin, and eosinophil chemotactic factor of anaphylaxis (ECF-A).

  1. Nucleus: Protein kinase activity promotes gene activation and transcription, resulting in the synthesis and release of cytokines such as IL-4, IL-5, IL-6, and IL-13.

D) Regulation of Mast Cell Response:

Mast cells have alpha and beta-adrenergic receptors, which regulate their activity and can also regulate mast cell degranulation. Some drugs stimulate or block these receptors.

Regulation of the Immune System

Tolerance: The immune system must differentiate between self and non-self. Our immune system responds only against foreign antigens. Tolerance is the loss of the ability to react against a specific antigen. It occurs as a result of the presentation of the antigen to immature T and B cells.

Antigen Factors:

  • To produce an immune response, the antigen must exist. When the antigen is exhausted or disappears, the immune response is suspended. B cells continue to grow and multiply, and upon suspension of the immune response, there is no cell proliferation, and therefore no memory B cells or plasma cells are formed. An adjuvant can be used to enhance the antigen’s effect.
  • Adjuvant: A group of substances that, when administered simultaneously with an antigen, promote, amplify, enhance, and accelerate the immune response. They are used in the preparation of killed vaccines, which are poor antigens, to improve their effectiveness (e.g., bacterins).
  • The immune response is regulated by the antigen depending on whether it is:
    • Endogenous antigen: Promotes a cell-mediated response (cytotoxicity).
    • Exogenous antigen: Promotes a humoral response (antibodies).
  • To produce an immune response, the antigen must be properly presented in MHC class I or II molecules.
  • The antigen response depends on the age of the individual:
    • Neonate (unborn): If administered, tolerance may develop.
    • Newborn: If administered parenterally, there may be no response because the newborn’s immune system is not yet capable of responding to antigens. During the first hours after birth, they have high levels of CD8+ T cells (suppressor/cytotoxic) and maternal antibodies (if they have suckled colostrum).
    • Young: There will be an appropriate response.
    • Old: If the same antigen is inoculated into an older individual, the immune response may be poor because CD8+ T suppressor cells inhibit an appropriate response.
  • The antigen response depends on the dose used:
    • Exaggerated dose: Will produce a temporary state of tolerance.
    • Adequate dose: Adequate immune response.
    • Low dose: Temporary state of tolerance.
  • Route of administration:
    • Parenteral route (IV, IM, SC, ID): The humoral immune response will involve IgM and IgG in serum.
    • Oral route: Expect an IgA response.

Antibody Factors:

Antibodies exert negative feedback on the immune response.

  • If an individual has enough IgM, they will not produce more IgM.
  • If an individual does not have enough IgM or IgG, they will produce more.

Erythroblastosis Fetalis:

An Rh-negative woman has a child with an Rh-positive man, and the child is Rh-positive. During delivery, there may be some hemorrhage, and Rh-positive erythrocytes can pass into the mother’s bloodstream. For her, the Rh-positive antigen is foreign, and she will develop antibodies against it, becoming sensitized. If this woman later conceives another Rh-positive child, these antibodies can cross the placenta into the child’s bloodstream. These antibodies react with the erythrocyte antigens, leading to the activation of complement and hemolysis of red blood cells. This condition is known as erythroblastosis fetalis.

To prevent this, the Rh-negative woman is administered anti-Rh antibodies during or after delivery. This prevents her immune system from producing antibodies against the Rh antigen. These administered antibodies disappear within weeks.

Why prevent the production of antibodies with antibodies?

Why don’t antibodies against antibodies occur?

A newborn individual has no immunity due to the type of placenta, and their immunity is at zero. In the next 24 hours, the newborn has a high level of complement and will suckle colostrum from the mother. When the level of maternal antibodies descends, it is the right time to implement the first vaccine. If there is a high level of maternal antibodies, vaccination should not be performed, as it could cause a negative phase.

Cellular Factors:

Among the cells capable of regulating the immune response, we have:

  • Helper T cells: Th1 and Th2.
  • Macrophages.
  • Dendritic cells (DCs).
  • Suppressor/cytotoxic T cells (CD8+ T cells).

The effects of helper T cells reflect antagonistic functions between Th1 and Th2.

Examples:

  • IFN-gamma produced by Th1 cells suppresses the production of IgE, which is driven by Th2 cells.
  • IL-10 produced by Th2 cells suppresses IL-12 production by DCs. IL-12 is a key cytokine for the development of Th1 cells.
  • IL-4 secreted by Th2 cells suppresses IL-2 production by Th1 cells. IL-2 is involved in the proliferation of B cells for IgG production.

Macrophages (especially M2):

Resting macrophages are activated when their receptors are stimulated, giving rise to innate activation and secretion of TNF-beta, IL-1, IL-6, and IL-12.

When a resting macrophage is stimulated by IFN-gamma and IL-2 from a Th1 cell, it becomes an activated macrophage known as M1. When a resting macrophage is stimulated by cytokines originating from Th2 cells, it becomes an activated macrophage known as M2. M2 macrophages are involved in healing and are immunosuppressive.

Dendritic Cells (DCs):

When DCs are stimulated by IL-10, they exert an inhibitory action on Th1 cells. These DCs are also involved in the maintenance of gestation to avoid rejection.

Suppressor/Cytotoxic T Cells (CD8+ T cells):

These cells are involved in all immune responses, determining their magnitude. They are responsible for:

  • Antigen competition: When several antigens are administered concurrently, the immune system only responds to some, not all, of the inoculated antigens.
  • Inability to respond to antigens in newborns and the elderly.
  • Immunosuppression after severe trauma, where the immune system does not respond (e.g., surgery, burns).
  • Prevention of autoimmune diseases.
  • Hypogammaglobulinemia.
  • Prevention of fetal rejection.
  • Anergy in tuberculosis: When tuberculin is applied to animals, and they do not respond.
  • Tolerance to food antigens: Suppressor T cells inhibit Th2 cells, preventing the production of antibodies against food antigens.
  • Blocking suppressor T cells can induce Th2 cells to produce IgE, leading to food allergies.

Central Nervous System (CNS):

There is mutual regulation between the CNS and the immune system.

The CNS modifies the immune response through two routes:

  • Hormones (catecholamines).
  • Nervous pathways (stress).

Lymph Nodes:

Lymph nodes are tiny organs that grow when stimulated by antigens. They are abundant throughout the body, especially in organs with mucous membranes, such as the intestines, respiratory tract, urogenital tract, and those associated with the intestines. They are spherical, kidney-shaped, and white-matte in color. They are part of the lymphatic system, so lymph produced in a region must pass through the regional lymph nodes. Lymph enters the lymph node through afferent lymphatic vessels, loses its walls, and flows through the lymph node parenchyma via channels called sinuses. Lymph then exits the lymph node through efferent lymphatic vessels.

The lymph node is made up of reticular cells, including T cells, B cells, DCs, and macrophages. A cross-section reveals a capsule of connective tissue. Between the capsule and the lymph node surface is a space called the subcapsular space.

There are three regions:

  • Cortex: Infiltrated with a large number of B cells, this region is known as thymus-independent. There are numerous B cells forming primary follicles, which, when stimulated by antigens, form germinal centers.
  • Paracortical region: Located under the cortex, this region is abundant in T cells, giving rise to tertiary follicles.
  • Medulla: Contains B cells, plasma cells, macrophages, and DCs.

Hypersensitivity Type II (Antibody-Mediated)

Blood Transfusion in Previously Sensitized Cattle:

If a blood transfusion is performed using blood from a genetically different individual (the transfused red blood cells have antigens on their surface), the recipient will develop antibodies against the donor’s red blood cell antigens. This leads to the destruction of the transfused red blood cells, either through complement-mediated hemolysis (intravascular hemolysis) or opsonization and phagocytosis by macrophages (extravascular hemolysis). This mechanism is known as hypersensitivity type II (HS-II).

Transfusions:

  1. If the donor’s red blood cells (RBCs) are antigenically identical to the recipient’s RBCs, no response will be triggered.
  2. If an initial transfusion of RBCs is performed using blood from a different individual, it will induce the development of antibodies in the recipient.
  3. If a second transfusion is performed using blood from the same donor in a previously sensitized individual, it will quickly lead to the destruction of the RBCs with complement activation, resulting in an HS-II reaction. This can cause a serious crisis, the severity of which depends on the amount of transfused RBCs (fever, potentially death).

Effects in a Previously Sensitized Individual Receiving a Large Amount of Incompatible Blood:

  1. Activation of complement with massive hemolysis of foreign RBCs.
  2. Release of a large amount of free hemoglobin, leading to hemoglobinemia and hemoglobinuria.
  3. A large amount of circulating RBC debris will trigger coagulation mechanisms and thrombus formation, potentially causing disseminated intravascular thrombosis.
  4. The significant activation of complement will produce sufficient quantities of C3a and C5a, which are anaphylatoxins. These substances cause mast cell degranulation, the release of vasoactive factors, and the development of HS-I, which can lead to vascular shock and death.

Test to Determine Transfusion Compatibility:

A blood sample from the donor is mixed with an anticoagulant to obtain RBCs. A blood sample from the recipient is allowed to clot to obtain serum, which will be tested for antibodies. The donor’s RBCs are mixed with the recipient’s serum on a glass plate. If no agglutination occurs after 4 minutes, it indicates that the recipient’s serum does not contain antibodies against the donor’s RBCs. If agglutination occurs, another donor should be sought.

Hemolytic Disease of the Newborn (HDN) or Isoerythrolysis:

The newborn receives maternal antibodies through colostrum that are directed against its own erythrocytes.

This occurs when a parent is homozygous for a genetic factor of erythrocytes (e.g., AA) and the mother is recessive for that factor (aa). Their offspring will be heterozygous (Aa), inheriting the dominant genetic factor from the father.

Sensitization of the mare occurs due to micro-hemorrhages in the placenta during gestation, allowing fetal erythrocytes (type A in this example) to enter the maternal circulation. The production of these antibodies may result from several matings with the same stallion. During previous pregnancies, these small hemorrhages may have allowed fetal erythrocytes to escape, leading to the production of antibodies in the mother. These antibodies (IgG) pass through the colostrum to the newborn’s gastrointestinal tract and are absorbed by the intestine. They reach the bloodstream, react with the newborn’s erythrocyte antigens, activate complement, and cause hemolysis of the RBCs, resulting in an HS-II reaction. The severity of the disease depends on the quantity of colostrum ingested.

Conditions for HDN:

  1. The offspring must inherit an erythrocyte antigen from the father that is not present in the mother.
  2. The mother must have antibodies against that antigen.
  3. The mother’s response to that antigen must be restimulated through several pregnancies.
  4. The newborn must ingest colostrum rich in maternal antibodies.

Drugs Causing RBC Destruction via HS-II and Other Mechanisms:

  1. The drug acts as an antigen, leading to the development of antibodies. These antibodies can activate complement, which, once bound to the erythrocyte surface, causes hemolysis and anemia.
  2. Some drugs (e.g., penicillin, quinine, L-dopa, aminosalicylic acid) bind to the surface of RBCs, modifying them and making them appear foreign. This triggers an immune response with antibody production against the modified RBCs. These antibodies react with the modified RBCs, activate complement, and lead to the development of hemolytic anemia via HS-II.
  3. Cephalosporins alter the RBC surface, allowing antibodies to bind and be absorbed. The RBCs are opsonized and removed by phagocytosis (neutrophils).

HS-II in Infectious Diseases: Hemolytic Anemia

Viral:

Equine Infectious Anemia: The virus causing this disease has a prolonged viremia (months to years). The virus is absorbed onto the surface of RBCs. Antibodies react against the virus, which is bound to the RBC surface. This activates complement, leading to RBC lysis and the development of anemia.

Bacterial:

Salmonellosis: Certain Gram-negative bacteria have lipopolysaccharide (LPS) in their cell walls. When released, LPS can bind to RBCs. Antibodies react with the LPS on the RBC surface, activating complement and causing RBC lysis and anemia.

Rickettsial:

Anaplasmosis: *Anaplasma marginale* invades RBCs. The bacteria live within the RBCs, and bacterial products are expressed on the RBC surface. Antibodies appear, react with the antigens, activate complement, and cause hemolysis and anemia.

Hypersensitivity Type III (Immune Complex-Mediated)

When a large amount of antigen is inoculated into an individual, it leads to an abundant antibody response. The reaction between antigens and antibodies forms immune complexes (ICs).

Immune complexes are activators of complement. Activated complement releases potent chemotactic factors, such as C5a, attracting neutrophils to the site in an attempt to phagocytose the ICs. Neutrophils phagocytose, die, and release proteases contained in their granules. These proteases cause tissue injury, hemorrhage, necrosis, and sloughing.

These injuries are identified as HS-III or immune complex-mediated reactions.

Factors Influencing HS-III Occurrence:

The occurrence of HS-III depends on the amount of immune complexes formed, the site of inoculation, and where the immune complexes are deposited.

Two types of HS-III are recognized:

  • Local: Occurs when immune complexes are deposited in a specific tissue.
  • Generalized: Occurs when a large amount of immune complexes circulate in the blood.

Immune complexes are formed by antigens and antibodies. They are capable of activating complement, attracting neutrophils that accumulate at the site (refer to outline 28-2, page 362, approximately minute 40 of recording v1003082).

HS-III Locations:

Blue Eye Disease (Anterior Uveitis): Results from corneal opacity following the deposition of immune complexes in the anterior chamber of the eye. It can occur in dogs that have received the canine adenovirus type I vaccine against canine hepatitis or have had the disease.

This is a temporary injury that affects one or both eyes of the dog. The cornea usually returns to its original appearance. It can also develop in dogs recovering from canine hepatitis.

It can develop in cattle during the dry season (dry-winter) when they are fed wet hay bales that promote the growth of thermophilic actinomycetes (fungi), such as *Micropolyspora*. These fungi produce many small spores.

Animals fed this wet hay containing the bacteria inhale the spores, which reach the pulmonary alveoli. Alveolar macrophages take up the bacteria, inducing an antibody response. Due to prolonged exposure to the antigen, a large antibody response occurs, leading to the formation of immune complexes. These complexes are deposited in the alveoli and surrounding tissues, activating complement and causing acute alveolitis with vasculitis, mucus exudation, coughing, difficulty breathing, and pneumonitis. Cowboys working with these hay bales can also develop pneumonitis. In poultry farms, it can occur in farmers who move the bedding and inhale the fungus due to a lack of protection.

Generalized HS-III:

Generalized HS-III occurs when a large number of immune complexes circulate in the blood or when the antigen is found systemically rather than localized in a tissue. These immune complexes activate complement and can be deposited anywhere in the body, such as the walls of arteries (vasculitis), joint surfaces (arthritis), or the glomeruli of the kidneys (glomerulonephritis).

Infectious Diseases Causing HS-III:

| Microorganism | Disease | Lesion |

|————————–|————————|———————|

| *Erysipelothrix rhusiopathiae* | Swine Erysipelas | Arthritis |

| *Mycobacterium avium* subsp. *paratuberculosis* | Johne’s Disease (Bovine Paratuberculosis) | Enteritis |

| *Streptococcus equi* | Strangles | Skin Lesions |

| *Staphylococcus aureus* | Dermatitis | |

| Adenovirus (Canine) | | Uveitis, Glomerulonephritis |

Serum Sickness (see notebook)

Note: See diagram in the book (page 362, schema 28.2).

Hypersensitivity Type IV (Delayed-Type or Cell-Mediated; No Antibody Involvement)

These reactions are the product of the involvement of antigen, antigen-presenting cells (APCs), and effector Th1 cells.

When certain antigens are injected intradermally into a previously sensitized individual, a slow inflammatory reaction develops at the inoculation site, which is called HS-IV.

These hypersensitivity reactions can only be transferred through the transfer of T cells, as they are mediated by cells and not antibodies.

HS-IV reactions have been used as a diagnostic method in campaigns for the control and eradication of bovine tuberculosis.

Robert Koch Reaction or Phenomenon:

A group of guinea pigs was inoculated with *Mycobacterium tuberculosis* (*M. tb*). These infected guinea pigs were then reinoculated with *M. tb*. It was observed that these guinea pigs developed an inflammatory nodule at the site of inoculation.

Purified Protein Derivative (PPD):


Prepared from an artificial tive Board of Mt, Mb, and Ma, this crop is put the autoclave to sterilize, filtered and precipitated using protein ac TRICHLOROA CETIC and finally suspended in a buffer solution. It’s a complete mixture of different proteins which the most important is the hsp65 and is a heat-shock proteins. The DPP is used to identify animals with tuberculosis or who have been.

As the individual becomes sensitive:
Cattle, cattle infected with a Mycobacterium is so ill, should be phagocytosed by Mac, but Macs are not able to stand to destroy the Mycobacterium, Mac must be activated and transformed into an M1, inmuitaria activation should occur and This is achieved through the participation of a LTh1. Moreover as the Mac has cannibalised the bact some bacterial products coming from the wall culminate with the activation of M1 and can kill, process, and present CMHII associate them to LT, the LTh1 multiplies and gives rise to CDM and also LTcd8 activated to be used against Mycobacterium infection.

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Because inflammatory reaction occurs:
• The PPD is injected intradermally.
· Forms a deposit of DPP in this part of the skin has a network of Langerhans cels (CD), take the DPP and migrate to NLR and present it to the CDM.
· These CDM are LT and when presented with the agno are activated and migrate to the site of inoculation and accumulate there (12hrs)
· These cells secrete cytokines and chemotactic factors that attract to the site of deposit to LT
· Other cells such as Mac and basophils secrete serotonin and local inflammation begins.
· Mast cells degranulate, inflammation, mast cells can release proteases tmb can cause necrosis in the inoculated skin site.
· Macrophages phagocytize and deplete the DPP.
• The reaction begins to regress and disappear in a couple of weeks.

Application of the DPP:
Intradermal test, inoculation is done in the caudal fold, from 05 ml of DPP and returned to make an observation about 72 hours later, Bernier is used to measure skin gruesor; more than 5mm of increase is positive.

Advantages:
1.facilidad of the completion and implementation, 5-6cm above the base of the tail, measured by the thickness of the skin.

Disadvantages:
Nonspecific 1.Reaccion: we know if it was infected with M. turculosis, M. bovis, M.avium.
2.falsos positive, if not infected with pathogens such as Mycobacterium M. phley, also in case of M. paratuberculosis and nocardia and who also have the hsp65 protein and therefore make us positive.
3.falsos negative: Individuals with advanced tuberculosis are negative or initially with incipient tuberculosis, older animals and animals that are newly birthed negative anergy.

examples:
brucellosis: applying brucellin filtering is growing 20 days of Brucella abortus.
Pseudolona Maley: mallein applies the ID, it reads from 48-72hrs and tmb oftalimica there is a test where you apply a drop in the eye and if ignition occurs POSITVE


VIRUS

Viruses cause disease because of their own life cycle, are organisms that lack enzymatic mechanism that allows them to synthesize their nucleic ac or proteins that make up the wrappings of the virus to replicate needs to invade a cell.
The viruses use segments of nucleic ac (DNA or RNA), can be found in the core part of the viral genome. Genome surrounded by proteins that form the capsid and that is where agnos receive. The capsids are composed of capsomeres.

Viral replication:
begins when a virus strikes on a cel and sup is fixed receptors that enable viral absorption. The virus proceeds to penetrarl and within the cell allowing the virus is stripped exibir wing cell genome and initiate the synthesis. When a virus genome exhibits the cell is unresponsive to its core and wings only obey orders viral encoded in the viral genome.
The viruses that cause disease mechanisms take over synthesis, the cell synthesizes its proteins no longer used to stay healthy, synthesize proteins and nucleic ac to synthesize the virus.

As we defend against viruses:
Defense mechanisms:
· Innate:
1.falta susceptibility: depends on type of genetic mechanisms or whether they have or not recipients, that has the animal condition, eg rabies, foot and mouth.
2.lisosima, bile, C, collectins (block the interaction between the virus and their receptors), premature apoptosis,
3.interferones: we use it to defend against viruses, such as: INF gamma.
· Are cytokines that pariticipan favoring processes that have to do with the humoral and cellular RI, INF gamma regulates cell multiplication.
· They mole of low weight glycoproteins. They can be of 2 types:
Type 1 Interferons: INFalfa, beta, omega, tau, delta and kappa receptors used CDW118
Interferons type 2 gamma. They use receptors
CDW119.
Everyone has antiviral action.
· Mechanisms antiviral INF (gamma) is a cytokine synthesized by a cell and acts on another cell,
· When LTh1 is invaded by a virus the viral nucleic ac is associated with the ribosome of the cell and gives a signal that triggers the guanidindifosfato that activates phosphorylation mechanisms that drive the signal to the nucleus and the activation is given d different INF rates.
• A property of the INF is to sum up very fast and are nonspecific,

· Acquired
1.humorales:
the virus will be recognized and phagocytosed by Mac and CD, they kill, they transform to peptides associated with MHC and the lon presented to LT. Moreover LB with the BCR of recognizing the virus, the LB are activated and stimulated by cytokines grows, multiplies and differentiates into CDM and plasma cells and these produce AC agnos against the capsid.
As the act vs Ac viruses (viral serum neutralization)
· The Ac react with the virus that block absorption can not use your receiver.
· The Ac oponizan facilitate phagocytosis and elimination of viral particles,
· The Ac + C would cause the destruction of the virus,
· Ac agglutinate the virus causes a reduction in the number of particles,
· The Ac + agnos viral sup on the infected cell involved in cytotoxicity mediated mec Ac.
2.celulares:
begins when the virus that has infected a cell and begins to synthesize proteins for the construction of the viral capsid. A small amount of these proteins are associated with ubiquitin, are brought to the proteasome for degradation, there are associated with carrier molecules, are driven to the ER and that are associated with MHC I mol and sup are taken wing in the same cell and presented a LTcd8 which initiates the extrinsic or intrinsic cytotoxicity wing causing the death of infected cells and viral replication is stopped.

Ways of Escape:
1.variación antigenic shift is the antigenic structure. Antigenic drift: antigenic variation is a product of small mutations acomulacion.
Recombination antigenic
Antigen Shift:
2.interferencia viral strains of viruses that induce cels mol synthesized chemically similar to IINF receptor, the virus induces synthesis of these mol-wing protein and these react with the INF, the INF reacts with receptors.
3.virus blocking cytotoxicity: they are capable of interfering CMHI wing expression in the sup of the cels, inhibit the expression of caspases, blocks the activity of granzymes and block the cytotoxicity
4.Inmunosupresion: Some viruses have the white cells lymphoid cells, the virus penetrates, and consequently destroys the immunosuppression occurs.
5.se stage have developed a pro-virus: herpes some retroviruses that enter the cell, but are in an inactive form and has no entoces epitopes LTcd8 not recognize the infected cells and infection of wing overlooked these. It is known as viral persistence.
6.se causes very slow immune response: that is poorly stimulate the immune system, therefore the response is very slow and when it appears the infection has passed or the individual has died or been infected for longer

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Viruses produce long-lasting RI


Bacteria

DIFFERENCE BETWEEN A BACTERIA GRAM + AND GRAM-A:
Gram +: produce exotoxins, the wall of gram + is very antigenic since it is made up of peptidoglycan acetilglucosamida as N-and N-acetylmuramic acid
Gram: the wall is not very antigenic since its wall is formed by polysaccharides, such produce endotoxins.

As the bacteria cause disease:
1.capacidad to produce toxins
· Exotoxin: products of cell metabolism that accumulate in the cytoplasm, are gram +
protoplasmic exotoxin: only released after death and lysis of bacteria
extracellular exotoxins: are released by the bacteria without having to die.
All exotoxins are complex mixtures of proteins and are highly antigenic.
· Endotoxin: found in the wall of gram-bact. are complex consisting of proteins, lipids, carbohydrates, which we call LPS LPS and these are part of the wall and gram-dela bact are toxic to the host.
Note: comparative table book review.

2.Capacity to invade tissues (multiply and damage)
Bact noninvasive Cl tetani.
Bact Invasive THROUGH enzymes that damage tissue: hialuronidazas, fibrinolytic, collagenases, elastases, proteases, cuagulasas.

3.capacidad to act as a facultative intracellular parasite:
are able to get into the cels and live in them; example
M. tuberculsis
B. abourtus
Listeria
Corynebacterium ovis
Campylobacter jejuni

As we defend vs. bacteria:
Defense mechanisms:
· Innate: they depend on the structure form and function.
1.resitencia on the surfaces of the body
Inespeficas antimicrobial 2.sustancias qumicas lysozyme (found in the serum), basic proteins and peptides such as the beta-lysin, fagocitina, leucine, insert, iron-binding protein;
3.celulas sentinels with its receptor TLR that recognize the PAMPs, there is an activation cd mac and that makes them secrete cytokines causing inflammation and changes in various organs.
4.inflamación
5.fagocitosis.


· Acquired:
Humoral (for AC):
1 .- Ac neutralize the wings toxins (exotoxins) neutralization of toxins by Ac.
How does the AC? The AC is linked to the chemical structure of the toxin by preventing the fixed wing d the target cell surface.

Gram +: produce exotoxins
Gram-: containing in its wall that constitute wings endotoxin LPS.


When bact gram – penetrate cause severe inflammation caused by LPS
The LPS consists of an oligosaccharide bound to a lupido A. The oligosaccharide consists of 2 parts: an internal (polysaccharides) and external (trisaccharides); when bacteria lose the external trisaccharides are 2 effects:
• The bacteria builds rough colonies
Loss of virulence.

Examples of rough strains TUBING PROCESSING vaccines:
Strain 45/20
Layer 19: used in mex. Smooth strain
RB51: rough, non-pathogenic, used to prevent brucellosis in cattle, sheep.

As endotoxins act?
Endotoxins are LPS and this is produced by gram-bact die (lyse and are free), the LPS is active as a result of the participation of a plasma proteases called CD14, activates macrophages (LPS) and produce IL 1 – 6-12, TNF, O2, leukotrienes, prostaglandins and the action of all these chemicals in animals causes what is known as septic shock and is characterized by depression, fever, acidosis, kidney damage, liver, lung and death .

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The addition of neutralizing Ac toxins are capable of neutralizing the action of enzymes preventing spread and cause widespread infection.


2 .- the Ac + C = will produce bacteriolysis, activation of C via classical
3 .- Ac opsonisan of the bacteria to promote phagocytosis
4 .- the different cells Ac + (Mac, CD, LB, NK) can cause the destruction of cels infected by bacteria that are facultative intracellular parasites
5 .- the AC + C can cause the destruction of cels infected by bacteria that are acting as facultative intracellular parasites.

Mobile:
Bacteria are PFI and hidden inside the cells are outside the reach of the AC, C, phagocytes, chemicals nonspecific allowing them to evade these defense mechanisms. These bacteria can invade other body cels multiply and destroy them, so finding them possess defense mechanisms cell type.
The bacteria to multiply inside a cell allows antigenic fractions are present in the surface and associated with MHC-I allowed to exert cytotoxicity mechanisms leading to the destruction of the cell allowing the bacteria that were inside and then go free them to act against the C, phagocytes, lysozyme and Ac.
In the cytotoxicity granulizina break apart and cause the cell lysis has wings own ability to kill bacteria and prevent them from invading other cells.

Bacteria are often phagocytosed by macrophages (activated) and can stand in east-destruct mechanisms that:
1.Some bacteria possess a wall very resistant to lysosomal enzymes.
2.secrecion of substances that inhibit the formation of the phagolysosome.
3.The bacteria fagososoma and pass out of the cytoplasm and there may not be attacked by enzymes.


Mechanisms of bacteria to evade the RI
1.mecanismo which warns recognition: Campylobacer fouetus
2.mecanismo resistance to effector organs. Some bact can block phagocytosis or cytotoxic cell activity or can inactivate the C, neutrophils, macrophages can destroy.
Some bacteria can manipulate the synthesis of cytokines of the host cell and to avoid LTh1 suppress the response and regulatory cytokines.

The immune Sintem is better against bacteria than viruses.


Helminths
A) NON-IMMUNE DEFENSE MECHANISMS, PARASITE FACTORS DERIVATIVES DERIVATIVES AND HOST FACTORS
1 .- Lack of susceptibility: the worms are sometimes marked by a guest host specificity in particular
2 .- parasite-derived factors: there must be some mechanisms of these parasites are intraspecies and interspecies there are others who are
4 Factors intraspecies: in which a parasite does not allow the development to the location of other individuals of the same species,
Interspecies 4: they impede the development of large populations of parasites.
3 .- host-derived factors: within these factors are some that are characteristic of a species, race, sex, are referred to parasites that can affect individuals of a species but not another.

Immune mechanisms against larval vineyards.
4 The larvae encuetra in adult tissues and cavities (bowel, stomach, breathing tubes, trachea, hepatic pathways, heart).
> 4 Antigens of helminths provoke a response characterized by IgE aparcicion (tmb may appear IgM and IgG) as the larvae are antigens on the surface, the AC are directed against surface antigens of the larvae.
4 It can recognize 2 types of antigens on the parasites, which are surface antigens and the antigens contained in the excretions and secretions.
4 against the surface antigens (agnos of the cuticle) is the IgE antibody response
4 against the agnos excreted or secreted by the larva’s response may be more IgM and IgG than IgE.

Larva:
4 The IgE binds to the surface of the larva, CD and macrophages have receptors for IgE, these cells then attach to the Ac travez of which have been deposited on the surface of the larva, are activated and release products with which injured the cuticle and cause the death of the larva.

As IgE is produced in response alos parasites?
IgE binds also on mast cells, the mast cell is senzibilizado and more contact between antigen is degranulate and resulting products are chemotactic factors for eosinophils (eosinophilia). These eosinophils also fixing surfaces of the larvae wings and participate in a fundamental way

4 shows another type of Ac (F and G) and react with antigens that are secreted or excreted by the larva form immune complexes with which the oral pore and excretory pore of the larva are covered and so the larva can not feed or remove products of metabolism.
4 The AC has also an undescribed mechanism that results in the difficulty that the larva to move, has to move from L1, L2, L3, etc and this move is hindered by the presence of Ac by an undescribed mechanism.
4 The larvae usually migrate to migrate travez of tissues that produce proteolytic enzymes with which the larvae can damage the tissues and migrating them to infiltrate and Ac of IgG, IgM neutralize these enzymes and prevent migration of the larvae.

self-healing:
worms and nematodes all live on the surface of the gut and must be fixed-grip the surface of the intestine, some are fixed and stuck into the surface epithelium that is nourished by blood or are hematophagous.
when embedded in the wall and reach a capillary fed blood, causing anemia in hosopedador if this is heavily infested.

self-healing is when parasitized animals removed from the parasite population, reduce the population, not eliminate it completely.
when the parasite nail tip into the bowel wall there is an ac response against antigens of the cuticle and therefore there is an IgE response and that is why animals are manifestations of intense Parrhasios hs-i. antigens of the cuticle of helminths produce IgE.
when the parasite is pushed into the surface of the gut cuticle of the parasite antigens and secreted by the same (the parasites have 2 types of agnos) provoke IgE response, the IgE binds to the surface of mast cells and mast cell degranulate causing inflammation. on the one hand there is an increase in output causing permeabildad capillary water, this stream passes through the intestinal epithelium and the parasite is clear and are carried by the motion of peristalsis, on the other side as a result of inflammation vasoactive factors are released that produce violent contractions in the bowel wall and shedding the parasite eliminated by peristalsis.

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Adults
4 In adults, it is against the self-healing:
Helminths reach the intestine and feed on blood, your cuticles are agno, on the surface or cuticle stimulates the LH2, produce IgE response and will have an answer from HS-I if the individual is highly infected.

4 In cattle: when the worms are nailed-embedded for responsiveness IgE binds to mast cells, this is degranulate and release vasoactive substances in intestinal smooth muscle contractions are causing an increased flow of liquids and the parasite is shed.
4 Moreover the AC have several effects on the adult parasite:
§ They take effect on posture, reduces the amount of eggs produced.
§ They distorting effect on the reproductive system of female and male.
4 also may be important cellular mechanisms, many parasites embedded in its front end wall of the intestine and cause cellular responses porke the parasite has different MHC molecules and may lead to mechanisms of cytotoxicity.

Artificial active immunity

Can be developed through the use of some metabolic products of bacteria toxodides, using vacuncas:
Live vaccines, attenuated or altered: they can be prepared with bacteria or viruses but with reduced virulecia. In this preceso of the reduction of virulence attenuation know him as.
If the attenuation is low, the virulence is high and its application can lead to infection, disease and death.
If atenuacuion is high, the vaccine will be ineffective.
Attenuation of bacteria.
The bacteria must adapt to losing the natural hospedadon; example: BSG used to prevent tuberculosis in humans.
Attenuation of viruses:
Advantages:
1.promueven humoral humoral and cellular resistance state as a result of the production of INF.
2.Proteccion long and fast
3.inespecifica
Application = less 4.menos HS
Cheap 5.mas
6.no need aids
disadvantages:

Residual virulence 1.tienen
2.requieren cold chain.
3.posibilidad the strain to revert to virulence.

Dead or inacivadas Vaccines: are produced by germs, bacteria (bacterins) or prepared with viruses (killed-virus vaccine inactivated.) Are prepared with viruses or bacteria that have been killed. An important condition for preparing this vaccine is that the inactivation (death of the bacteria or virus) must be performed so that the antigenic structure of the agent dead and not much different from the antigenic structure of the virus when he was alive, so do not be used to inactivate the heat, since it gives a change in the structure of the protein qumica. It has been used alcohol, formaldehyde, to Fenice, beta-propiolactone.
The substance used to inactivate the virus or bacteria should be a wing sustqumica not an undesirable effect on the individual who will receive the vaccine.
The inactivation results in the production of these vaccines dead or inactivdas

Advantages:
1.no pollution
2.no virulence
3.estables (no cold chain)
disadvantages:
RI 1.Only cause humoral
RI is 2.no cell
3.no INF: Not the best immune response against viruses
4.poco antigenic
Often 5.revacunacion
6.caras
7.utilizar adjuvant: can cause inflammation, necrosis, HS-I, tumors.

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Vaccines have been used to prevent disease and improve animal production.

Inactivated and modified:
What is the inactivation and is achieved?
· Is the method used to kill (disable) to microorganisms for use in a vaccine,
· Is important that they remain antigenically similar to living microorganisms.
· This is achieved using chemicals that should not alter the agnos that stimulate protective immunity.
· Example: formaldehyde, acetone or alcohol and agents such as ethylene oxide, etilenoimina, acetiletilenoimina and beta propiolactone.

That is the modification and how they can achieve?
· Is the set of techniques that have been used to reduce the virulence and that while they are alive capacez no longer produce disease.
· The methods of attenuation involves the adaptation of microorganisms to unusual conditions so that they lose their adaptation to regular guest.
Modern Technology of vaccines:

  • Agnos produced by genetic engineering. Category I

Are genetic engineering techniques to produce purified agnos first isolated DNA encoding a agno of interest then the DNA is inserted into bacteria, yeast or other cell which expresses the recombinant agno

  • Attenuated microorganisms by genetic means. CLASS II
    Attenuation is by culturing the desired outcome is to develop a strain of microorganism that for some reason lacks the ability to cause irreversible disease.
  • Microorganisms living recombiantes. Category III
    The genes encoding agnos can be cloned directly in various microorganisms and instead of being subsequently purified recombinant microorganisms are used as vaccines themselves.

Adjuvants Any qumicas substances that are not antigenic by themselves and when given concurrently with a agno extend, increase, magnify the RI.

Adjuvants act in 3 ways:
1.formando a deposit of agno, from which the agno is slowly released, prolonging the agno presnencia the vaccinated individual in prolonging the RI. Aluminum phosphite, alum, incomplete adjuvant freuds protect the agno d prlongado rapid degradation of RI
will form a granuloma at the site applied, the antigen escapes, promotes a prolonged antigenic stimulation.
These adjuvants stimulate only the RI bit to primary and secondary RI, RI no cellular form a granuloma, abscesses are sometimes deteriorate the quality of the channel.
2.adyuvantes immunostimulatory: increased synthesis of IL by the CPA or improves the presentation of agno promoting a better ROI. Example: fraccones of bacteria, ESR, moramildipeptido, bordetella of man, LPS, saponin, deterentes, dextran sulfate.
3.adyuvantes individuals: agno improve the presentation of the CPA as Mac and CD agno better recognized if presented in sizes similar to bacteria.

Adjuvant mixtures are used:
· Freuds incomplete adjuvant (water and oil)
· Freuds complete adjuvant (water and oil fractions of the wall most of the bacteria is the most powerful but produces an inflammatory reaction to deteriorate as the channel is used only for experimental work.

Aluminum hydroxide and saponin: best adjuvants for vaccine production.