BMS 310 Test 2

Define Innate Resistance

Born with it does not need any priming. Born with, don’t change/ adapt, die with it, acts the same way. Non-specific. Injury results in activation of inflammation.

Primary Immunity

Physical and chemical protection. Skin-has lysosome on it. Mucosal tissue (Respiratory, GI) Mucocilliary escalator. Sweat saliva and tears- lysozyme- causes lysis of bacterial cell walls. Nasal Hairs. Ear wax. Low pH: urine, gastric juices, vaginal secretions. Antibacterial and antifungal fatty acids.

Secondary Immunity

Non-specific. Proteins and cells.

Complement system- MAC (membrane attack complex) Bradykinin- activate free nerve endings for pain sensation. Coagulation cascade- forming membrane around things so it doesn’t interact with the rest of the body. Forms a granuloma- seen in TB.

Antimicrobial peptides- cathelicidins and defensins disrupt bacterial cell membranes. Collectins- facilitate macrophage binding. Mannose binding lectins- activate complement system

Cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor

Neutrophils, monocytes/macrophages, eosinophils, basophils. All are phagocytes. Have enzymatic mechanisms of destruction. Cytokines- anything released by inflammatory of immune cells.

Cytokine storm

Overactive inflammatory response mostly responsible mostly responsible for significant symptoms of COVID-19

Tertiary immunity

Adaptive immunity- very specific. B and T cells. Maturing B and T cells react to specific antigens. Take 7-10 days to be active. Memory some of the population cells will be left for memory. When exposed to it again instantly so don’t get sick.

Pathogen Associated molecular patterns (PAMPs)

Microbial in nature. DNA and RNA in viruses. Glycoproteins, lipoproteins, and membrane compounds in bacteria.

Damage associated molecular patterns

Mitochondrial DNA- should never be seen recognized by neutrophils will destroy it increases inflammation. Heat shock protein, high levels of uric acid, fibrinogen- activation of fibrinogen seen in clotting and recognized by it. defensins and cathalacedins.

Pattern Recognition Receptors (PRR)

PAMPs and DAMPs

Can be membrane bound and cytosolic

Time-immediate. Inflammatory cell receptors. These can be found inside the cell or on cell surface. DAMPs are found on cell surface. Toll-like receptors recognize cell wall/ viral proteins, stressed cells. Bridge between innate and adaptive. Intracellular receptors recognize if viral RNA or DNA are in cell.

Complement receptors- recognize compliment fragments

Scavenger receptors (macrophages)- facilitate phagocytosis

Chronic Inflammation

Want to prevent this pathway. Lasts over 10 days. Causes tissue damage.

Mast Cells

Found in all connective tissue. Kinda like a blood cell. Secrete several different types of cytokines, vasoactive mediators and other things that are pro-inflammatory.

Recruitment of other these allows you to amplify inflammation in the area. Cytokines- dumped locally into tissue.

What does activation of complement, clotting, and kinin do

Vasodilation- redness and heat. Endothelial retraction. Every endothelial cell pulls in puts space between cells. Histamine.

Vascular Permeability, Cellular infiltration (pus), thrombosis (clots), and stimulation of nerve endings (pain)

Opsonin

Facilitate macrophage phagocytosis

Chemotactic Factors Anaphylatoxins

Activate mass cell degranulation

Membrane Attack Complex

Cell lysis

Cylindrical protein system that pops hole in bacterial wall. Loses membrane potential or water rushes in and cell blows into a million pieces.

Chemotaxis

Process of using chemicals to call leukocytes over. Move toward greater concentration of these C5a and C3a.

Complement System Activation

1. Mannose binding lectin

2. Immune system. Antibody two conserved portions get close together and activate this.

3. Alternate pathway

Primary Cells in inflammation

1. Mast cell degranulation- first cell. Hematopoietic in lineage, but are in all connective tissue. Excrete vesicles full of cytokines. Leads to endothelial retraction. Diapedesis occurs.

Histamine released- endothelial cells pull in and create gaps

Transudate- fluid and protein- complement clotting and kinin.

2. Neutrophils- once activated in tissue last 24 hours. Neutrophil second cell fast and aggressive.

Monocytes- bigger- called macrophage when leave tissue. More like a amoeba. Increase at 24 hours after infection. Much longer lived produced ROS not as much as neutrophils though.

Exudate- fancy name for pus

Short term effects mast cell degranulation

Tryptase → heparin → chondroitin sulfate

Cytokine → IL-4 → B cell proliferation and antibody production. Naive B-cells not sensitized to specific antigen yet.

Cytokine→ TNF-alpha → vascular effects→ increased permeability and leukocyte emigration. Histamine like effects.

Histamine→ vascular effects→ dilation increased permeability→ exudation

Neutrophil chemotactic factors→ neutrophils attracted to site→ phagocytosis- increased ROS production and lysosomal enzyme release.

Eosinophil chemotactic factor- eosinophils attracted to the site. Leads to phagocytosis- number 1 factor in parasitic infection. Also leads to inhibition of vascular effects of histamine outside local space anti-histamine effects.

Long term response mast cell degranulation

Leukotrienes (phospholipid bilayer)→vascular effects →dilation increased permeability →exudation

Prostaglandins→ vascular effects→ dilation increased permeability → exudation. Prostaglandins also cause pain.

Cytokine → TNF-alpha → vascular effects → increased permeability and leukocyte emigration

Cytokine → IL-13 → chemotaxis B cell proliferation and antibody production. Makes B-cells receptive to antibodies.

Growth factor → VEGF → endothelial cell proliferation

Growth factor → PDGF → connective tissue and smooth muscle proliferation

H1 Receptors (target cell and effects of histamine)

Smooth muscle cell → contraction

Endothelial cell → contraction (retraction at endothelial junctions)

Neutrophil → increased chemotaxis

Mast cell → prostaglandin synthesis

Some cells have both receptors. Initial release this is activated. When less histamine is present H2 is activated

H2 Receptors (target cell and effect of histamine)

Parietal cell of stomach mucosa → secretion of gastric acid

lymphocyte → decreased activity

Eosinophil → decreased activity

Neutrophil → decreased chemotaxis

Mast cell → decreased degranulation

Platelet activating factor

Enhanced inflammation: eosinophil chemotaxis, vasoconstriction, bronchoconstriction, platelet activation (vasodilation increased capillary permeability at low this concentrations). Pro-inflammatory stimulus.

Prostaglandins

Enhanced inflammation: smooth muscle contraction (bronchoconstriction), increased capillary permeability, increased vasodilation.

COX-1 and COX-2

Leukotrienes results

Enhanced inflammation: smooth muscle contraction (bronchoconstriction), increased capillary permeability, increased vasodilation.

Enhanced inflammation neutrophil chemotaxis

Identify role white blood cells

1. Lymphocyte- have memory B and T cells. Natural killer cells.

2. Neutrophils- ROS phagocytes lysosomal enzymes last 24 hours. Form greatest amount of exudate.

3. Eosinophils- parasites and anti-histamine effect.

4. Basophil- blood infections phagocytes

5. Macrophage- main job phagocytosis long live through whole period acute inflammation.

phagocyte migration

Colony stimulating factor- make macrophages stay still stimulates colony to form

Phagocytosis process

1. Recognition and adherence (binding)

2. Engulfment and formation of phagosome

3. Fusion with lysosome to form phagolysosome

4. Destruction (killing) and digestion

Phagocyte migration process

Adherence margination and diapedesis. Neutrophil adhesion and then diapedesis. Chemotactic factors are then released. Colony stimulating factor make macrophages stay still stimulates a colony to occur.

NADPH Oxidases

High number in neutrophils with lower numbers in macrophages. Increase oxidative stress and lower pH around neutrophil. make it hard for bacterial cells to live. Creates a lot of damage in host cells.

NADH from krebs cycle becomes NADPH

superoxide is made the gets converted to hydrogen peroxide and then makes hypochlorous acid.

Chart cellular injury

Cellular injury or infection → acute inflammation 7-10 days (healing can occur) → chronic inflammation (10 days or more) can lead to healing too → granuloma formation (hallmark sign contained or prolonged inflammation) → healing

Mediators (cytokines) of inflammatory processes

Vasodilation

Vascular permeability

pain

Pyrogens- go up to hypothalamus to increase body temperature. Low grade fever good- slow down bacterial replication. Speed up body’s enzymatic reactions. Too high of a fever leads to protein denaturation

Leukocytosis

Acute phase reactants- mechanism we can use to measure inflammation. Comes off of complement activation C-reactive protein good measure is done a lot but too expensive.

Limit inflammation

Immune response

Repair and healing

Adherence and diapedesis and chemotaxis

Cardinal Signs of (acute) inflammation

Rubor = redness histamine, bradykinin, TNF- alpha, prostaglandins and leukotrienes

Tumor=swelling

Calor = heat

dolor = pain

Functio laesa = loss of function. Twist knee doesn’t bend as well.

Acute phase reactants

Stimulus macrophages (IL-6), trauma (IL-6), DAMPs and PAMPs (IL-1), Mast cells (TNF-alpha), viral (interferons)

All go to liver, which makes these. Can be positive or negative.

Positive increase affect increase concentration

Negative down regulate effect

Proteins- are normally found in blood at low concentrations, but following hepatic stimulation by IL-6 their concentration increases. Detection of elevated levels of acute phase proteins in an indication of an inflammatory response.

Interferons

Block healthy cells from getting infected with virus.

Positve Acute Phase Reactants

1. Procalcitonin-marker or diagnostic for bacterial infection. Main marker for infection.

2. C-Reactive protein- indicative of bacterial infections. Opsonin, activates complement system, activate adaptive immunity

3. Ferritin- binds iron to keep it away from pathogens

4. Fibrinogen- affects RBC sedimentation rate

5. Hepcidin→ blocks iron absorption keep it away from pathogens. Chronic inflammation anemia of chronic disease.

6. Serum Amyloid A- decrease inflammation, decrease platelet activation, decrease monocyte activation, increase B and T cell chemotaxis, decrease respiratory burst. Chronic state responsible for amyloidosis.

Negative Acute Phase Reactants

Decrease albumin

Decrease liver protein synthesis Decrease oncotic pressure of albumin. Saving amino acids for proteins of inflammation

Granuloma Formation

1. pre-exudative in blood

2. Exudative -tissue

3. Caseation Encagement surround what you can’t get rid of.

TST conversion tubercle forms sclerotic. Softening also can occur. Mediated by TNF-alpha and other proinflammatory cytokines where some differentiate into large epithelioid cells, which specialize in taking up debris and other small particles. Other macrophages fuse into multinucleated giant cells, which are active phagocytes, which can engulf particles larger than those can be engulfed by a single macrophage. These two types of cell form the center of this and lymphocytes surround it.

Chronic inflammation pathway

1. Persistence of infection antigen or forigen body.

2. persistent acute inflammation, neutrophil degranulation and death lymphocyte activation (B and T cells) and fibroblast activation (helps form scars)

3. Lymphocyte and monocyte/ macrophage infiltration (pus). Tissue repair (scar)

Tissue Resolution

Minimal scar return to normal function proper healing. Clincially this is the goal.

Tissue Repair

Usually due to larger wound, greater disruption. More scar tissue leads to greater loss of function. This scar formation is like putting a patch on it.

Keloid Scar

Raised mad looking scar. Over proliferation of keratinocyte. Stimulated by EGF. EMT occurs leads to myofibroblast count to increased. This leads to Keloid myofibroblast. Decreased P53 expression, decrease in apoptosis- associated genes, increased proliferation. Leads to reduced rate of ECM degradation, hyperfibrosis excessive synthesis of ECM and increased scar contraction. Leads to abnormal hyperfibrotic scar expansion and chronic contraction.

Acute Inflammation characteristics

Pathogens irritant damage

Neutrophils, basophils, eosinophils, macrophages, monocytes

0-7 days Immediate

Lasts a few days

Resolution, abscess formation, chronic inflammation.

Chronic Inflammation

Persistent acute inflammation due to non-degradable pathogens, persistent foreign bodies or autoimmune reactions.

Monocytes, macrophages, lymphocytes, plasma cells, fibroblasts

Delayed 10+ days starts

lasts Up to many months or years

Tissue destruction fibrosis

General Characteristics Adaptive Immunity

Recognizes foreign or non-self substances, Provides long term protection (memory cells). It is slower than innate but more specific. 7-10 days. End products include lymphocytes: B and T cells and Antibodies: immunoglobulins. Antibodies coat it to inactivate pathogen and tag it for phagocytosis.

T cells produced in the red marrow and travel to the thymus. B cells hang out in the lymph nodes.

Generation of clonal diversity

Antigen Example

Anything we can recognize. Pathogens, noninfectious environmental agents, drugs, vaccines, transfusions, and transplants.

Clonal Diversity

Each individual T or B cell specifically recognizes only one particular antigen. Sum of the population of lymphocyte specificities may represent millions of foreign antigens. Primary lymphoid organs: is the thymus for T cells and bone marrow for B cells.

Immunocompetent T cell- naive T-cell ability to recognize pathogen

Macrophage- antigen presenting cell

Humoral Response

Fluids and blood. B cells and circulating antibodies. Causes direct inactivation of a microorganism or the activation of inflammatory mediators. Protect against bacteria and viruses.

Cell Mediated Response

Direct attachment. T cells. T-cell differentiation. kills targets directly or stimulates the activity of other leukocytes. Protects against viruses and cancer. Immune surveillance cancer cells.

Active immunity

Antibodies or T cells are produced after either a natural exposure to an antigen or after immunization. Is long lived.

Passive Immunity

Preformed antibodies or T lymphocytes are transferred from a donor to a recipient. Occurs naturally or artificially. Is temporary or short lived. Examples include maternal antibodies through breast milk or monoclonal antibodies.

Monoclonal antibodies

Used also with cancer in immunotherapy of T-cells. Different with passive immunity no memory passive immunity functional 2-4 weeks.

Takes virus out of solution can’t bind the virus.

Antigens

Not all are immunogenic. Transplants need to match blood types and cell surface proteins as close as possible because not perfect match need immunosuppressive drugs.

Is molecule that can react with antibodies or receptors on B and T cells. Is mostly protein but can be other molecules as well. Immunogenic antigen: an antigen that can trigger an immune response. Sites for binding to antibodies and lymphocytes. This binding site: antigenic determinant (epitope). Antibody or lymphocyte’s binding site: antigen-binding site (paratope).

Degree to which this has immunogenic capability. Degree of foreignness to a host. Pathogens extremally antigen or immunogenetic. Size- if large is extremely immunogenic. Small-molecular weight antigens called haptens: cannot trigger the immune response themselves but can when bound to a carrier protein. Chemical complexity and amount. Concentration- greater dose more immunogenic. Repeated doses make it worse.

Haptens

Poison ivy plant has urishol which is harmless on its own. Oil mixing with skin proteins are very immunogenic. Dendritic cell phagocytosis complex activates t cells activate t helper cells. First exposure minimal. Now sensitized helper T cells. Move subsequent poison ivy infections greater and worse response to poison ivy.

These bind with something else to be antigen. Penicillin is an example.

IgG

Most prevalent. Used primarily through monoclonal antibody treatment. Most of protective activity against infection. Crosses the placenta. Passive immunity breast feeding.

IgA

Mostly in secretions. Most of protective activity in body secretions. Can be thought to be in first line of defense.

IgE

Most Rare. Mediator of many common allergic responses. Activate mast cells leads to mast cell degranulation causes anaphylaxis, This activates the anaphylactic pathway. Dangerous bee venom, peanut allergies- sends people into ampholytic shock. Systemic response.

Defends against parasitic infections.

IgD

Not well known. Functions as one type of B-cell antigen receptor.

IgM

Largest. First antibody produced during the initial, or primary response to an antigen. IgG takes over in the long term after this has been expressed

Antibody Molecular Structure

Antigen binding fragments (Fab)- acts as recognition sites (receptors) for antigenic determinants; binds antigens. Amino acids sequences of the variable regions of the heavy and light chains. Over 15,000,000 combinations of variable, diversity, and joining gene segments are possible. Imprecise recombination and mutation increase the variability of billions of possible combinations.

Crystalline fragment (Fc)-conserved. Is responsible for biological function. Activates complement and opsonization. Two conserved regions next together activate complement.

Major Histocompatibility Complex

Glycoproteins on the surface of all human cells (except red blood cells)

Human leukocyte antigen (HLA) alleles: inherited in a codominant fashion to enable both maternal and paternal antigens to be expressed.

1. A bacterium is engulfed by phagocytosis into a dendritic cell and is encased in a phagosome.

2. Lysosome fuse with the phagosome and digest the bacterium.

3. Immunodominant epitopes are associated with this II and presented on the cell surface.

MHC Class I

Expressed on all nucleated cells, present normal self antigens.

MHC Class II

On antigen presenting cells (macrophage, B cells, dendritic cells)

MHC Class III

Other genes that control the quality and quantity of an immune response.

B-cell maturation

Occurs in the bone marrow. Develops surface cell markers. Interleukin (IL)-7 receptor. IL-7: Is produced by stromal cells; is critical in diving the further differentiation and proliferation of the B cell.

Changes in characteristic surface markers. CD21: complement receptor. CD40: adhesion molecule required for later interactions with T-helper cells.

T-cell maturation

Thymus and spleen is the central lymphoid organ of T-cell development. Produces changes in characteristic surface markers. Initiates the expression of CD2 on the cell surface. CD2 is a marker of T cells. Developing T cells make surface proteins CD4 and CD8. CD4 cells recognize antigens on MHC class II molecules and develop into T-helper cells. CD8 cells recognize antigens presented by MHC class I molecules and become mediators of cell-mediated immunity and directly kill other cells. (T-cytotoxic cells)

CD4 and CD8 t-cells host cell of HIV virus. Lower t-cell further you are in progression of AIDS

Central Lymphoid Organs

Thymus and bone marrow

Peripheral Lymphoid organs

Peyer patches (ileum only), adenoid, tonsils, lymph nodes, spleen

Antigen Processing and Presentation

Require this by antigen presenting cells

B lymphocytes: Present antigen to T-helper cells that facilitate humoral immune response.

Macrophages: present antigen to memory Th cells to initiate a rapid response to antigens (secondary immune responses)

Dendritic cells: process antigen from a site of inflammation to T-cell rich areas of lymph nodes.

Pathways of antigen processing

Class I MHC molecules: generally present endogenous (inside cells) antigens. 1. Antigen uptake. 2. Antigen processing through proteasomes. 3. peptide MHC association.

Class II MHC Molecules: prefer exogenous (outside cells) antigen.

T-Helper Lymphocytes

Cells help the antigen-driven maturation of B and T cells.

Facilitate and magnify interaction between antigen presenting cells and immunocompetent lymphocytes. Plasma cell. Th → cytotoxic (Tc). Differences are based on cytokine production.

Th1

Cells provide help in developing cell-mediated immunity. Activate macrophages (colony stimulating factors) and Tc cells

Th2

Cells provide help in developing humoral immunity. Activate B cells.

Th17

Help the inflammatory response

Treg

Cells limit the immune response.

B-cell clonal selection

Results from the recognition of soluble antigen by B-cell receptors, processing of antigen, and presentation by MHC class II antigens to Th2 cells. When an immunocompetent B cell encounters an antigen for the first time, B cells with specific B-cell receptors are stimulated to differentiate and proliferate. A differentiated B cell becomes a plasma cell. A plasma cell is a factory for antibody production. Single class or subclass of antibodies. Plasma cell commited to make one single antibody.

B cell differentiation in secondary exposure

B cells differentiate into antibody-producing plasma cells and into long lived memory cells. On re-exposure, memory cells do not require much further differentiation and will rapidly differentiate into new plasma cells. Memory cells hang out in case second infection comes around.

T-Cell Activation in secondary exposure

Bind antigens to T-cell receptors.

Allows: direct killing of foreign or abnormal cells (Tc cells or cytotoxic T lymphocytes). Assistance or activation of other cells.

T-regulatory cells- regulate the immune response to avoid attacking self.

T-memory cells

Antibody Function

1. Shuts down its metabolism. 2. Blocks binding to its receptors.

Neutralization: Inactivates (pathogen) or blocks the binding of an antigen to a receptor.

Agglutination: Clumps insoluble particles in suspension.

Precipitation: Makes a soluble antigen into insoluble precipitate.

Complement and phagocytes: anything tagged by antibody will be phagocytized.

Indirect effects antibody

Is mediated by the Fc portion of the antibody molecule. Includes opsonic activity leading to enhanced phagocytosis. Activates the complement system, which may lead to complement-mediated destruction of the pathogen.

Chronic Inflammation: T cells that activate macrophages

T cells produce cytokines that activate macrophages. IFN-y → Acute phase reactants (APR) → Inflammation

Stimulate a macrophage to become a more efficient phagocyte.

Increase production of proteolytic enzymes and other antimicrobial substances.

Retain macrophages at the inflammatory site. CSF- colony stimulating factor.

Increase adhesion between Th1 and macrophages

Allergy

Hypersensitivity reaction. Is an exaggerated response against an environmental antigen.

Autoimmunity

Is a misdirected response against the host’s own cells. Selection of cells those who are self reaction go through apoptosis. Loss of self-tolerance lead to autoimmune adaptive immune system attacks self-antigen.

Alloimmunity

Is directed against beneficial foreign tissues (ex: transfusions and transplants). Organ rejection, graft rejection, etc….

Three variables hypersensitivity

1. Original insult. Alters immunologic homeostasis which is the steady state of tolerance to self-antigens or the lack of immune reaction against environmental antigens. Story about making himself to rats. Initial exposure rat dander loss of steady state tolerance became sensitized.

2. Individual’s genetic makeup: Determines the degree of the resultant immune response from the effects of the insult. If family line allergic to rag weed you are likely to also be allergic.

3. Immunologic process: causes disease symptoms.

Hypersensitivity

Is an altered immunologic response to an antigen that results in disease or damage to the host. Anaphylactic reaction activation of mast cells by antigens. Annoying. Dangerous if systemic. Patient goes into critical hypotension.

Sensitization: adequate amount of antibodies or T cells is available to cause noticeable reaction on reexposure to antigen.

Immediate reaction. Reaction that occurs within minutes to a few hours. Anaphylaxis: systemic or cutaneous. Histamine also causes smooth muscle contraction.

Delayed reaction: reaction that takes several hours to appear. Maximum severity occurs days after reexposure to the antigen.

Type I hypersensitivity

IgE mediated

Is against environmental antigens (allergens). IgE binds to crystalline fragment (Fc) receptors on the surface of mast cells. Cross linking causes the release of histamine from mast cell degranulation. H1 and H2 receptors, Increases the chemotactic activity. Daily allergy medications are leukotriene inhibitors.

Type II hypersensitivity

Tissue specific reactions. Specific cell or tissue (tissue-specific antigens) is the target of an immune response.

1. Most common: cell is destroyed by antibodies and complement.

2. Cell destruction occurs through phagocytosis.

3. Neutrophils release granules

4. Antibody dependent (T- cell activity) cell mediated cytotoxicity (Tc) is present.

5. Causes target cell malfunction

Type III hypersensitivity

Immune complex mediated. Primary infection have resolution but leave behind circulating complex. When not cleared get deposited in tissues leads to a secondary adaptive immune response.

Is immune (antigen-antibody) complex mediated. Complexes are formed in the circulation and deposited later in vessel walls or extravascular tissues. Is not organ specific. Damage results from complement activation and neutrophil lysosomal enzymes.

Immune complex clearance. Large: macrophages → phagocytized. Small Renal clearance → goes into urine. Intermediate: deposited in tissues. Causes problems. Stimulate inflammation. Strep throat can cause this. Becomes a problem at the glomerulus of the kidney. Glomerular nephritis- post-streptococcal type. Day 21-24 low back pain urinating small amounts. Rare not everyone gets it. Most common cause after diabetes to cause renal failure. Circulating complexes can also cause endocarditis wherever they get stuck can have three types of reactions.

1. Intermediate-sized immune complexes deposited in the tissue. 2. Complement activated 3. Neutrophil chemotaxis 4. Neutrophil adherence and degranulation.

Type IV Hypersensitivity

Cell mediated delayed

T-cytotoxic → colony stimulating factors → macrophages

Classic example poison ivy. Is mediated by T lymphocytes or is cell mediated. Destruction of the tissue is usually caused by direct killing by toxins from cytotoxic T (Tc) cell. Helper T (Th) 1 and Th 17 produce cytokines (colony stimulating factor) that recruit phagocytes especially macrophages. T-cells responsible for tissue breakdown. Breakdown and liquification of tissue.

Clinical Symptoms Type I sensitivity

Conjunctivitis Rhinitis, Laryngeal edema (swelling around neck), urticaria (hives), bronchospasm (asthma)= bronchoconstriction → increase resistance to breathing. Harder time getting gases out of the lungs. Increase CO2 retention. Dysrhythmias usually increase heart rate to try and counter vasodilation.

Itching scalp, angioedema (swelling around nose and eyes), hypotension (from vascular dilation). Gastrointestinal cramps and malabsorption. Epi-pen. Rescue inhaler has albuterol-does that same thing as epinephrine but is more stable.

Anaphylaxis

The more asthma attacks, the airway get thicker and thicker and thicker until patient has trouble breathing all the time leads to pulmonary dysfunction and can lead to death.

Anaphylactic shock- constriction causes airway changes can become permanent if not treated,

Blood Transfusion Reactions

Anucleated cells have antigens A, B, and O (no antigen). If get different blood type, RBC lysis: no longer have RBC you need and hemoglobin goes into circulation changes oncotic pressure.

Antibody binds to antigen. Activates the complement system. Leads to a cytotoxic reaction and hemolysis.

Potential Causes of autoimmunity

Do not know mechanism and cause overall loss of self-tolerance. Exposure to a previously sequestered antigen.

Complications of an infectious disease. Target antigen on pathogen. If self antigen looks a lot like it. Close enough that it starts to grab onto self antigen. Molecular mimicry.

Development of neoantigen- haptens that become immunogenic after binding self proteins.

Ineffective peripheral tolerance- probally number one cause. Inability to tolerate self antigens.

Systemic lupus erythematosus (SLE)

Through all organ systems. Autoantibodies against: nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets and many others.

Deposition of circulating immune complexes containing antibody against the host’s cells deoxyribonucleic acid (DNA).

Clinical manifestations: arthritis, vasculitis and rash, renal disease, hematologic changes especially anemia, cardiovascular disease. Targeting tons of different things. Patients are put on immunosuppressive drugs. Happens in waves.

Presence of at least four findings indicates this. Facial (malar) rash, discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis, renal disorders, neurologic disorders, hematologic disorders, immunologic disorders, and presence of antinuclear antibodies (ANAs)

Diabetes Mellites Type I

Cytotoxic t cell → beta cells. less than 10% of normal beta cells. Leads to decreased insulin. Most show signs and symptoms around 8-12 years of age.

Neonatal alloimmunity

Thrombocytopenia- occurs when you have less than 150,000 platelets per cm³ blood.

1. Fetal platelets carrying HPA-1a antigen enters maternal circulation. amino acid switch

2. The mother develops HPA-1a antibodies that traverse the placenta.

3. Fetal HPA-1a positive platelets are destroyed. The baby becomes a temporary bleeder.

4. Bleeding in neural tissue causes disability or death.

Usually resolves with spontaneous abortion.

Alloimmune Graft Rejection

Response results in this. Deterioration or complete loss of graft function. Tissue stress with different MHC protein cause rejection.

Relate arousal and awareness to consciousness

Consciousness base point we look at. Time affects neurological healing.

Awareness- ability to interact with the environment.

Arousal- wakefulness of consciousness base level neurological functioning idea you can be woken up. Base line homeostasis.

Neural network mechanism model that makes sense for memories. Dysfunction occurs when interrupt pathways. Neural cells don’t regenerate. Cerebral function when test how aware you are. Processing takes place on cerebral cortex, Grey matter lacks myelination processing. White matter myelinated used for communication. Eye open- eyes stuck open but can’t see you. Groaning- make noise can’t form words. Flexion extension- kinda like a seizure

Cranial nerve tests: frontal-orbicular, V oculovestibular, pupillaty light, H oculovestibular, oculocardiac.

Structural Alterations

Supratentorial affect cerebral cortex and underlying white matter (Focal Effects). Extra cerebral- outside brain tissue. Tumor, closed head injury → take hit to skull inflammation inside skull not inside brain. Infection → pus. Intracerebral. Tumors (glial) or stroke. Subdural- Subdural hematoma- most common in elderly patients. Brain atrophies as we age. Veins hang out fall can cause veins to burst. Eventually stops but chunk of blood puts pressure.

Infratentorial. RAS- reticular activating system series of neurons involved in regulating sleep wake cycles. Brain stem- loss of homeostatic mechanisms. Life threatening changes.

Metabolic Alteration

Hypoxia, electrolytes (hypo/hyper natremia), hypoglycemia. Decrease glucose brain susceptible because brain has no glucose.