Animal Health Midterm 1

what is immunity defined as?

the ability of the body to defend against foreign micro-organisms

innate immunity

• an animal can be born with this type of immunity

• may develop & strengthen overtime (hair, skin, mucus membranes)

• no prior exposure needed

• non-specific and does not have memory

adaptive immunity

• develops due to exposure of the host to an infectious agent

• specific and has memory

name the non-specific defenses of the innate immune system and give examples

• physiologic barriers - pH (acid in the stomach or bile in small intestines) and temperature of the body

• anatomic barriers - epithelial surfaces (skin and hair, mucosa, cilia in the respiratory tract)

• mechanical barriers - urinary pH and flushing action

• microbiome - “good bacteria” in the large intestine

• phagocytic barriers - macrophages and neutrophils

• inflammatory barriers - dilated leaking blood vessels deliver inflammatory cells and proteins to the site of injury and infection

examples of anatomical barriers

the skin, hair, hooves, nails, and mucous membranes are all anatomical barriers given these factors:

• rapid cell turnover

• pH protects and prevents attachment of pathogens

• proteins and lipids in sweat and oils produced by the skin

anatomical and physiological barriers in the upper respiratory tract

nasal hairs, cilia, mucus blanket, cough reflex, and the alveolar macrophages all help to protect against pathogens by trapping particles and cleaning them out of the lungs

the human flora

• bacterial normal flora population present in the gut, dermal skin, and vagina

• they occupy attachment sites and produce by-products that prevent attachment required for invasion of pathogenic bacteria

body secretions

work to prevent pathogenic agents from attaching and flush them away. examples include: urine in the urinary tract, mucous in the gastrointestinal tract, respiratory, and repro tract, as well as milk in the mammary glands, and tears in the eyes

pH secretions

help to deter bacteria mainly in the mouth, urine, and the stomach

other secretory products

help deter and counteract pathogens: mucous traps bacteria, enzymes neutralize bacteria, anti-toxins bind and neutralize toxins, and iron chelators make iron unavailable for bacterial growth (found in colostrum)

tissue damage

will trigger an innate inflammatory response —> damaged cells will release chemicals called chemokines which will work to attract inflammatory cells to the site of injury in a process called chemotaxis

• the inflammatory response will cause blood vessels to dilate and become leaky allowing white blood cells to escape from the blood vessels into the damages tissue causing heat, redness, swelling, and pain

• the inflammatory cells in turn release more cytokines

interferons & intracellular organisms (viruses)

polypeptides produced and secreted by cells containing viruses - helps prevent spread by protecting other cells

natural killer (NK) cells & intracellular organisms (viruses)

a type of white blood cell that can recognize and destroy virus infected cells, involved in the acquired immune response

what is the main difference between an infectious and a non-infectious agent?

infectious agents are living and non-infectious agents are nonliving

examples of non-infectious disease

nutritional, metabolic, trauma, toxic materials, congenital defects

causes of infectious disease

• caused by an infectious disease agent such as: bacteria, virus, prions, protozoa, fungi, parasites

• can be either contagious by animal to animal transfer or non-contagious by environmental to animal transfer

what is the overall process of infectious disease

1. enter host 2. multiply 3. evade host defenses 4. harm host

determinants of disease

the existence, severity, and consequences of disease are determines by these three factors:

host - genotype, species, breed, age, sex, social, occupational (layer vs broiler chickens)

agent - pathogenicity (ability to cause disease) and virulence (severity of disease)

environment - location, climate, housing, management, feeding, stress

portals of disease entry

ingestion, inhalation, cutaneous penetration, ascending infection

direct disease transmission

spread by cough, touch, bites, grooming, licking, ingestion

indirect disease transmission

spread by vectors or fomites

what are vectors

organisms that transmit an infectious agent from one animal to another

what are fomites

inanimate objects that transmit a particular disease or parasite from one animal to another

what is an epidemic

the rate of new cases of disease within a population is greater than expected

what is an endemic

the disease is being maintained at a relatively constant rate in the population without the need for external input

what is a pandemic

an epidemic of worldwide (large geographical area) distribution is also called a pandemic

commensalism

neither party is harmed, one benefits - ex: barnacles attach themselves to the skin of whales and sea turtles, barnacles get a free ride through nutrient-rich waters to feed on passing plankton, the whale is normally unaffected by their presence

mutualism

both party benefits - ex: clownfish live safely inside the stinging tentacles of sea anemones, protected from predators, the clownfish clean the anemone, chase away polyp-eating fish, and provide nutrients via their waste

parasitism

one lives at the expense of other, these are infectious agents that cause disease

infectious agents vary in their ability to infect and induce disease in animals

virulence: the degree of harm the organism causes, a pathogen may cause varying degrees of harm

pathogenicity: the ability of a microorganism or agent to cause disease in a host

both determined by host, environmental, and agent characteristics

infectious dose

the number of organisms required to cause infection, variable depending on host factors such as; age, sex, immune status, pregnancy status

obligate pathogens

associated only with disease

opportunistic or potential pathogens

mannheimia haemolytica is frequently found in the nasal cavity of healthy cattle, but this bacteria causes “shipping fever” if the host is immunocompromised due to stress or other infections

pathogenic microbes - frontal assault (acute)

short incubation period, rapid clinical signs, intimate transmission. examples include childhood diseases, parvovirus, and salmonella.

pathogenic microbes - stealth assault (insidious)

lengthy incubation, slow onset of signs, may have environmental transmission. examples include tuberculosis or bovine johnes disease.

definitive host

this is the host in which the infectious agent reaches sexual maturity or replicates

intermediate host

essential part of the parasite lifecycle, temporary environment for development

reservoir host

harbors pathogens that infect others, the reservoir does not demonstrate clinical signs of the disease

dead end host

this host can get infected but is unlikely to pass the agent to another host. cattle are dead end host for rabies, and people are dead end hosts for lots of zoonotic diseases as they are unlikely to bite and the viruses do not reach high enough concentrations to be spread.

acquired immunity

• specific and has memory

• a form of adaptive immunity

• healthy animals are able to actively acquire immunity via exposure to foreign antigens

antigen

any substance that stimulates the immune system (either innate or acquired)

antibody

made by an activated B lymphocyte in response to a specific antigen

differences between innate and adaptive immune response

• adaptive immune response is specific - the response is directed at a specific antigen and has memory - the response to the antigen is rapid as long as the animal has been exposed to the antigen before (vaccines)

• innate immune responses lack specificity and memory

naturally acquired active immunity

the animal develops immunity to an antigen following natural exposure to the antigen

artificially acquired active immunity

• can be induced by vaccinating an animal

• vaccination (immunization) stimulates the adaptive immune system by artificially exposing the animal to an antigen

• examples: Tetanus vaccine, intranasal Bordetella vaccine, BVD vaccine for cattle

natural passive immunity

• healthy adult female is naturally & artificially exposed to many antigens in her lifetime and has acquired adaptive immunity to diseases

• mom’s B lymphocytes produce antibodies that are passively transferred to the baby via the placenta or colostrum, these antibodies protect the baby in the first few weeks of life until they have time to produce their own active immunity

• this immunity is transient and there is no immunological memory

artificial passive immunity

• provides immediate immune defense, but does not have immunological memory

• injection of ready-made antibodies from another person or an animal, own immune system does not make these antibodies, anti-serums such as anti-venom are an example of this

bone marrow

• the primary site of blood cell production in adults

• red blood cells- erythrocytes, carry oxygen and are important in cellular respiration

• white blood cells- leukocytes, are important mediators and participants of both the innate and adaptive immune response

B & T lymphocytes

• adaptive immune response relies on the activity of B and T lymphocytes

• mature lymphocytes migrate to the secondary lymphoid tissues such as the lymph nodes, spleen, and mucosal associated lymphoid tissues for surveillance and responding to antigenic stimuli

thymus

• structure is usually only present in young animals & is located cranial to the heart

• undergoes involution around the time of puberty

• T-cells mature and differentiate here

bursa of fabricius

• structure is only found in birds

• B-cells mature and differentiate here in birds ONLY, in mammals B-cell maturation occurs in the bone marrow

lymphatic system

• consists of the lymph nodes, spleen, and lymph vessels

• unidirectional flow

• main functions: augments the circulatory system, drains extracellular fluid (lymph), movement of lymph brings micro-organisms and other foreign substances into contact with the immune cells

lymph

• refers to the fluid in the lymphatic vessels

• the lymphatic vessels run in parallel with the blood vessels

• lymph is returned to blood vessels via the lymphatic duct and the thoracic duct

• has no form of a pump, relies on movement and muscles (passive), upon return to the heart lymph is filtered at the lymph nodes

damaged or blocked lymphatics

• leads to edema or a build up of fluid because it builds up faster than it can be drained

• fluid can also cause edema by leaking out of the lymphatics faster than it moves in

causes of edema:

• parasites like filariaisis can block lymphatic vessels and cause severe swelling

• traumatic lymphatic damage can occur post surgery example - mastectomy for breast cancer

• removal of lymph nodes as part of cancer treatment disrupts drainage and causes swelling in the area

• eating too much salt followed by inactivity, promotes fluid retention and reduced circulation

endothelial cells

• lymph vessels have overlapping endothelial cells that allow large substances like cells and bacteria to enter and leave the lumen of the cell

• lymph carries there substances back to the lymph nodes where lymph is filtered and comes into contact with the immune cells such as: macrophages, lymphocytes, plasma cells, dendritic cells

location of lymph nodes

• found throughout the body & are full of lymphocytes and some other immune cells, surrounded by fibrous capsule

• lymph nodes are involved in immune system activation

• enlarge in response to foreign substances

spleen

• very vascular lymphoid organ attached to the stomach

• microscopically the spleen is made up of red pulp and white pulp

  • red pulp consists of splenic cords and vascular spaces filled with RBC and macrophages, macrophages remove old and sick red blood cells

  • white pulp or splenic follicles are filled with B cells and are surrounded by T-cells

tonsils

• un-encapsulated aggregations of lymphoid tissue in the pharynx

• no afferent vessels (connection to the CNS)

• has direct contact with the foreign substances that enter the body

mucosa-associated lymph tissues (MALT)

• the first line of defense at the mucosal barrier, sentinel stations for the immune system

• found in these locations: BALT- bronchial associated, GALT- gastro-intestinal tract, also found in the urogenital tract

• many pathogenic agents are adapted to use these lymphoid aggregates as a way of the body via the M-cells

M-cells

• specialized epithelial cells that are located over the peyers patches (small clusters of lymphatic tissue located in the mucous membrane lining the ileum) in the intestine

• M stands for microfold cell

• help to deliver antigens across the epithelium to the peyers patches

• also serves as site of entry for some pathogens such as salmonella and rhodococcus

mononuclear phagocyte system

• cells of this system initiate the immune response

• originate in the bone marrow, derived from monocytes

• play and important role in both innate and adaptive immune response in inflammation & tissue remodeling + repair

tissue macrophages & related cells

• derived from monocytes - monocytes float around in the blood and when needed move from the blood vessels to the tissues

• macrophages and related cells in the skin, lungs, and liver conduct surveillance and if pathogens are detected or sources of antigen, they will initiate the immune response by releasing chemokines that attract other inflammatory cells to the site (chemotaxis)

phagocytosis

• the process in which macrophages engulf damaged cells, bacteria, virus infected cells, and other foreign material

• engulfed material in a phagosome joins with a lysosome to become a phagolysosome, where the material is then degraded into smaller pieces for antigen processing

• they present the smaller pieces or antigens to cells of the adaptive immune system (usually a T-cell)

osteoclasts

part of the mononuclear phagocyte system and help remodel bone, macrophages can form giant cells to help remodel bone

dendritic cells

• conduct surveillance in tissues that contact the environment, originate in the bone marrow

• are important antigen presenting cells (migrate to lymph nodes to do this), and are the most important cell for initiating the primary immune response to protein antigen

• found in the: nose, lungs, stomach, intestines, and skin where they are called langerhans cells

neutrophils

• first cells to arrive at the site of injury

• important in the innate response but work even better if activated by the adaptive immune response

• phagocytic, short lived in tissue, arrive in large numbers, commonly associated with bacterial infections

granular leucocytes

• neutrophils are classified as this, they are polymorphonuclear cells

• the granules of the neutrophil are filled with enzymes, antimicrobial peptides, and proteins & they do not stain

extravasation

neutrophils are attracted to the site of injury from chemicals released by damaged cells and macrophages (chemokines) and move out of the blood vessels and into the tissues by this process

neutrophils & phagocytosis

• neutrophils kill microbes and tumor cells and eliminate foreign material by phagocytosis

• foreign material is digested in phagolysosome

• neutrophils release the contents of their granules into the tissues surrounding the injury-sometimes this can cause damage to healthy tissue too

eosinophils

• a form of polymorphonuclear granular leucocytes

• eosinophils increase in the blood in parasitic and allergic diseases & are attracted to the site of inflammation by histamine

• release of inflammatory granules can cause extensive tissue damage

basophils

• a form of polymorphonuclear granular leucocytes

• very important in allergic reactions

• granules in basophils take up hematoxylin and stain dark purple, rarely seen in blood films

mast cells

• reside in the tissues and are not normally found in the blood

• release histamine and other (preformed) key mediators of inflammation

• larger then basophils

• many chemical mediators activate mast cells and many chemicals are produced by mast cells to activate more cells

natural killer (NK) cells

• mononuclear but have granules, smaller than monocytes but larger than lymphocytes

• important in innate immune response and have a non-specific response

• they are also important in early response to tumor cells and viral infections, and other intracellular pathogens

• does not require specific antigen

NK cells & MHC

• unlike cytotoxic T lymphocytes, NK cells attack cells that do not express MHC (name tag system, identifies self vs non self cells)

• virus infected cells and neoplastic cells may not express MHC and this makes them susceptible to NK attack

what does the adaptive immune response rely on

activity of the B and T lymphocytes

what are T - lymphocytes responsible for

• cell mediated immunity (does not use antibodies)

• originate in the bone marrow and mature and differentiate in the thymus

• reside in the peripheral lymph nodes

• are specific and have memory

T lymphocytes: Cytotoxic T cells (CD8+)

• kill infected or damaged host cells

• CD8+ and CD4+ refer to the surface proteins on the T-lymphocyte that mediate their function and help immunologist to identify them

T lymphocytes: T-helper cells (CD4+)

• Th1 cells stimulate cytotoxic T lymphocytes and macrophages

• Th2 cells stimulate B lymphocytes to make more antibody

HIV & FIV

• both retroviruses that infect CD4+ T helper cells

• gain entry to the cell via the CD4 receptor on the cell surface

• causes an immunodeficiency very specific to TT_HH inactivity

• higher risk for developing opportunistic infections and certain types of cancers

regulatory T lymphocytes (T_reg)

• produce immunosuppressive and anti-inflammatory cytokines

• down regulate antibody production

Major Histocompatibility Complex (MHC)

• complex of genes that code for specialized molecules on the cell surface involved in intracellular recognition and distinguishing of self from non-self

• most T cells only recognize antigen when it is bound to MHC = MHC restriction

antigen processing

in phagocytic cells like macrophages, the antigen is degraded into peptide fragments which are complexed with the MHC molecule

antigen presentation

the MHC-antigen complex is transported to the cell membrane surface and displayed to show foreign invaders to T cells to trigger an immune response

what is an antigen

any molecule that stimulates the immune system (either innate or adaptive)

intracellular antigens

• processed inside the cell and are presented with MHC1 molecules

• MHC1 molecules are present on all nucleated cells and stimulate cytotoxic T cells (CD8+) to kill the infected or neoplastic cells

MHC ll molecules

• only present on antigen presenting cells such as macrophages and dendritic cells

• class ll MHC stimulates T-helper cells, and T-helper cells stimulate B-lymphocytes to make antibody

• extracellular antigens are degraded inside a phagocytic cell, bind with MHC ll molecules, and are then presented on the cell surface

T-cell differentiation

T cells originate in the bone marrow but undergo differentiation, selection, and maturation in the thymus

B-cell differentiation

B cells originate in the bone marrow and undergo differentiation in both the bone marrow and lymph nodes in mammals, but in birds B cells differentiate in the Bursa of Fabricius

what does cell differentiation mean in the immune system

when exposed to an antigen the immune system may be responsive and develop a state of immune response or it can be non-responsive and develop a state of tolerance

auto-immune disease

an inappropriate immune response to self antigens

clonal deletion of self-reactive T lymphocytes

• the process where immature T cells that strongly bind to the body's own proteins are destroyed by apoptosis

• occurs when the T cells are developing in the thymus (central tolerance) AND when the T cells are mature and out in the lymph nodes (peripheral tolerance)

• MHC is integral to development of tolerance

mechanisms of tolerance

• very effective but not perfect

• self reactive T & B lymphocytes may be found in normal individuals

sequestered antigens

• hidden from the immune system when the T cells and B cells are developing

• examples are myelin protein, lens protein, sperm protein

• release of these proteins due to infection or trauma may lead to an immunological response by lymphocytes that react against these proteins which leads to failure of self tolerance

Natural Killer (NK) cells

• mononuclear but have granules smaller than monocytes but are larger than lymphocytes

• NK cells are important in the innate immune response and have a non-specific response

• they are important in early response to tumor cells and viral infections and other intracellular pathogens

• does not require specific antigen

NK cells attack method

• unlike cytotoxic T lymphocytes, NK cells attack cells that do not express MHC

• virus infected cells and neoplastic cells may not express MHC and this makes them susceptible to NK cells

B-lymphocytes

• make antibodies = humoral immunity (part of the adaptive immune system driven by antibodies that circulate in body fluids to neutralize pathogens)

• reside in the peripheral lymph nodes

• are specific and have memory

B cell selection

• are selected for, and self-reactive B cells are eliminated in a process like T-cell selection

• during development B cells that react to self antigens are deleted from further development

• each B cell is specialized to recognize a certain antigen, after being presented with its specific antigen the specialist B cell in the lymph node becomes activated, replicates, and makes antibodies

activated B cells

can become plasma cells (pump out large amounts of targeted antibodies to neutralize invaders) or memory cells (stick around for a long time to spot the same germs quickly if it returns later)

B lymphocytes & antigens

• there is a different B lymphocyte for every antigen

• a specific B cell recognizes a specific antigen

immunoglobulins

• serum glycoproteins produced by plasma cells in response to antigenic challenge (specialized Y-shaped proteins produced by white blood cells that help your body fight off harmful germs like bacteria and viruses)

• antibodies are immunoglobulins that are specific for a certain antigen

• the terms antibody and immunoglobulin are used interchangeably