Inflammation and Immune response

H2

-stomach receptors -action on by histamine leads to increased gastric acid secretions

s/s of allergic rxts

-swelling -rash -itching -wheezing -SOB -elevated HR -N/V -fever -low BP -shock -anxious/impending sense of doom

self vs non self

-the ability of the body to recognize what belongs vs what doesn't Human leukocyte antigens (HLAs): -a barcode only the WBCs read off of all your cells -unique proteins on cell membrane and are cellular fingerprints for each individual -act as antigens only if they enter another person's body -keys for recognition and self-tolerance -WBCs patrol and mark bad cells for destruction via the HLA, triggering an immune response -inherited from parents: about 40 sets in body

congenital

-usually the result of a single gene defect -only about 25% hereditary -5 groups based on which principal component is defective >>B lymphocytes >>T lymphocytes >>both B and T lymphocytes >>phagocytes (neutrophils) >>complement

natural killer cells (NK cells)

-very important lymphocyte in providing CMI -direct cytotoxic effect on some non-self cells without first being sensitized -target viruses and tumor cells -"seek and destroy" missions to eliminate non-self cells -B cells create antibodies, T cells have cytotoxic cells, but NK cells do NEITHER - they kill chemically but are not sensitized -NK cells do what they want to do -look for signals by distressed cells (invaded by viruses or cancer) -cancer cells are so smart that they turn off those messages sent by the invaded cell and alter their DNA to not let them send out those messages for the NK cells to see

5 cardinal signs of inflammation

1. Heat 2. Redness 3. Swelling 4. Pain 5. Loss of function

Which of the following is a nonspecific barrier defense? 1. complement 2. NK cells 3. mucous membranes 4. macrophages 5. antibodies

3. mucous membranes

immunodeficiency

Age related: -thymus and bone marrow don't function well anymore Nutrition related: -contributes to bone marrow and body function in general Drug related: -corticosteroids -cytotoxic drugs Radiation related Congenital: -AM (antibody mediated) deficiency -CM (cell mediated) deficiency -combined deficiency

Type II hypersensitivites

Antibody -Own tissue is being attacked by antibodies - macrophages, NK, complement, etc. -Not usually in chains/complexes so easier for body to eliminate it Your own cells die

nutrition related immunodefiency

Degree of immune impairment is r/t severity of malnutrition: -immune systemic is built on nutrition CMI is most affected: -Thymus is heavily affected by nutrition (and it educates the T cells) -If not nourished as a child, thymus doesn't develop, so T cells can't develop, and thus immune system doesn't develop Adequacy of nutrition cannot be assessed by simply looking at client: -Just eating doesn't mean they're nourished - must be eating the right foods for nutrition There is a high incidence of malnutrition in acute care, sub-acute care, and long-term care!

Innate (nonspecific) immunity

First line of defense: -skin -mucous membranes (catch things, have cilia) -secretions -reflexes (cough, sneeze, blink, gag, vomit, pain) -normal microbiota Second line of defense: -inflammation -phagocytes -fever (part of systemic response; only treat if high) -complement (tags organism to phagocytize) -interferon (cytokine that send the body pro and anti inflammatory messages)

transplant rejection - 3 types

Hyperacute: -happens almost immediately (minutes to hours) -no treatment (organ must be removed) -thrombotic occlusion of graft vasculature -preexisting antibodies have some sort of memory to it for some reason Acute: -happens 1 wk to 3 months after receiving the donor organ -slower so the antibodies can be made (either AMI or CMI) Chronic: -happens over a long period of time, usually years -smooth muscle of blood vessels overgrows and occludes the vessels -thickened narrowed vessel wall due to fibrotic tissue leads to decreased organ function -occurs to some degree with all organ transplants -continual attacking-healing cycle leads to fibrosis/scar tissue and the organ eventually fails after years Inflammation and AMI are involved in the transplant rejection process but CMI responses are most significant

Type III

Immune Complex -Many antibodies form chains called complexes to attack your own tissue (not just a cell) -The neutrophil can't get rid of something this big and it gets deposited/lodged somewhere -How chronic autoimmune diseases often develop

_________________ always accompanies _________________ but _______________ does not always accompany _________________.

Inflammation; infection; infection; inflammation

management of transplant rejection

Maintenance therapy: -continuous immunosuppressant after solid organ transplant -includes combination of immunosuppressants and corticosteroids Rescue therapy: -used to treat acute rejection epidsodes -higher doses of maintenance therapy Anti-rejection therapy is very expensive. Drugs have many side effects (i.e. immunosuppression) and increases the risk of infection (including cancer).

WBCs involved in inflammation

Phagocytosis to destroy and eliminate invaders... -Neutrophils (largest # of; die once they phagocytize something) -Macrophage (clean up after neutrophils) Assist neutrophils and macrophages by releasing chemicals that act on blood vessels to cause tissue-level responses... -Mast cells (release histamine, live in tissues) -Basophils (heparin to balance out, come in when called) -Eosinophils (heparin to balance out, come in when called)

IgM

-1st antibody to respond to an infection -usually means an infection is acute

Type 1 hypersensitivites

-Allergic Anaphylaxis and Atopy (skin rxts) -Has to do with IgE antibodies -1st time produces the antibodies so only a small rxt which is not life-threatening -second time = anaphylaxis b/c army of antibodies is attached to mast cells already and ready to respond

What diseases do we use corticosteroids for?

-Autoimmune Disorders -Cancers -Inflammatory Disorders -Myasthenia Gravis -Psoriasis -Ulcerative Colitis -Endocrine Disorders -Pulmonary (i.e. COPD) -Allergic Reactions

Type IV

-Does NOT involve antibodies -ONLY involves T cells -T cells work alone, not together with everything so it is delayed (takes a few days) -i.e. poision ivy, latex, etc. (have to think back like what was I doing to cause this? - chemical rxt on skin)

Cytotoxic drugs

-Used for treatment of cancer (heavier doses) and autoimmune disorders (lighter doses) -Affects all rapidly dividing cells (cells coming from bone marrow) -Creates a decreased synthesis and release of lymphokines (cytokines) (b/c inside the cell the lysosome produces cytokines and if the cell is killed there's no lysosome to produce cytokines) and antibodies The challenge lies in finding the balance between therapeutic benefit and immune system suppression.

corticosteroids

-Utilized for both anti-inflammatory and immunosuppressive properties -Decreases inflammatory response by inhibiting lysosomes that control production of inflammatory cytokines -Decrease permeability of capillaries to the inflammatory cells (mast cells, histamine) decreased inflammation >>How they control inflammation -Decrease migration of white blood cells into inflamed areas -Lower fever by reducing the release of interleukin-1 (a cytokine) from WBC's >>Be very careful if pt is on steroids b/c infection can be masked due to fever suppression we don't see the fever to tip us off that an infection has started -Prolong survival of RBCs and platelets

immunity

-active internal protection -long term resistance to the effects of invaders -The body has to learn to generate specific immune response when it is infected by or exposed to specific organisms. -Lymphocytes develop actions and products that provide protection of true immunity. These cells develop specific actions in response to specific invasion.

purpose of the immune system

-adaptive internal protection that results in long-term resistance to the effects of invading microorganisms -protects against effects of injury and invasion -protects from anything on the outside trying to get in >>viruses, bacteria, fungi, parasites -protects from internal threats >>cancer, autoimmune, microflora

cell mediated immunity (CMI)

-adaptive or acquired true immunity -regulates the immune system by the production and activity of cytokines (messengers) -involves many WBC actions and interactions -must function optimally for total immunocompetence Cells involved are: -T lymphocytes -NK cells -WBCs

most common drug reactions

-antibiotics -anticonvulsants -insulin (animal source) -contrast dyes -sulfa drugs

loss of self tolerance

-autoimmune disorder -when the body can't remember how to read barcodes it gets scared and starts attacking everything in the body -destruction of body's own tissues

antibody mediated immunity

-body recognizes and reacts to the antigens on the invader (the barcode), not the bacteria itself -antigen-antibody interactions to neutralize, eliminate, or destroy foreign proteins -antibodies produced by sensitized B-lymphocytes (B Cells) -antibodies created only match a specific antigen/protein and only work on that specific one -one type off adaptive immunity (the other is cell mediated)

diseases that are inflammatory

-cancer -cardiovascular -Alzheimer's -arthritis -autoimmune disorders -neuro disorders -diabetes

IgG

-chronic situation or means you've developed immunity

adaptive/acquired/specific immunity

-destroys infectious microorganisms that are resistant to inflammation -provides long-term highly effective protection against future exposure to the same microorganism (builds a memory) -may be either active or passive depending on the host

helper T cell function

-doesn't kill anything -gives out orders and creates memory

hypersensitivites

-exaggerated or misdirected immune response to an allergen that results in tissue injury -may be immediate or delayed -most rapid and severe reaction is anaphylaxis

systemic response in inflammation

-fever and increased WBC count -used when the body needs help for a wider area to clean up -not always necessary

common s/s of organ transplant rejection

-flu like s/s -pain at site -swelling -decreased urine output -other s/s of those of the organ itself (HF, kidney failure, etc.)

non-specific/innate immunity

-general barrier to microbes and environmental hazards -response is the same regardless of particular pathogen -includes macrophages, neutrophils, and monocytes

corticosteroid interventions

-give lowest doses possible to achieve desired effect -local administration rarely produces systemic effects (eye drops, lotions, inhaler, ear drops) -every other day dosing to minimize adrenal atrophy/laziness - ***adrenal crisis*** GRADUAL WEANING

cytokines

-hormone-like proteins that regulate the intensity and duration of the immune response -transmit info between cells -monokines or lymphokines

Histamine

-key chemical mediator for inflammation -tells things in your body what to do and can be problematic if it goes over the top -stored within the mast cells (which reside in the tissues and are produced by bone marrow) -when released (when they recognize an injury), histamine dilates nearby blood vessels, causing capillaries to become more permeable -plasma, complement proteins, and phagocytes enter the area to neutralize microbes and prevent infection -H1 and H2

What does increased permeability do in the inflammatory response?

-lets the neutrophils leave capillary into tissue and clean up via phagocytosis -release of fluid out of capillaries leads to swelling

T cells

-lymphocytes -born in bone marrow, educated/grow up in thymus -if fail final test to mature, they should commit cell suicide, but sometimes flaws can let them through to the body -identified by marker proteins on the surface of cell membrane -Three subsets... 1. helper/inducer T cells (tell others what to do) 2. suppressor T cells (turn off rxt once it has done enough) 3. cytotoxic/cytolytic T cells (actually do the killing)

What causes vasodilation in inflammation?

-mast cell release release histamine for help when an injury occurs -basophils and neutrophils come and help -blood flow increases to the area and decreases to other areas -basophils release more histamine but then heparin to counter the response when necessary -heat and redness result

most common food triggers

-milk -eggs -peanuts -tree nuts -fish -shellfish -soy -wheat

inflammation

-natural immunity -provides IMMEDIATE protection against tissue injury or invading foreign proteins -part of our innate immunity -short-term protection (doesn't last very long) -may be acute or chronic -chronic goes on longer than it's supposed to and has the danger of becoming an autoimmune response

antibodies

-protective molecules that circulated throughout the body -classified by differences in size, location, amount, function, and timing -5 classifications

radiation related immunodeficiency

-radiation is cytotoxic to resting and proliferation cells -degree of immunodeficiency depends on location, dose, and duration of radiation exposure

H1

-smooth of muscle of the vascular system -action on by histamine leads to swelling there

Side effects of corticosteroids

Side effects alter depending on which steroid it is. But this is in general. Decreased growth in children: -accelerates growth plate and then stunts it later, leading to stunted growth Glaucoma: -aqueous humor builds up in the eye due to the hypertension Hypertension: -increased sodium and fluid retention Central distribution of body fat: -starts a fight or flight response (if heavy doses): gets mixed messages about body metabolism and fat content, so it keeps the fat incorrectly so it can easily get to it - around the abdomen; it also starts to break down muscle and redeposit it as fat when it runs out of fat Osteoporosis: -cytokine disruption interferes with osteoclasts & osteoblasts Increased risk of infection: -reduced inflammatory response decreases WBCs -masked fever response -high blood sugar High blood sugar: -fight or flight response wants sugar all the time Hirsutism: -excessive hair growth -altered hormones lead to sex hormone confusion Increased appetite: -fight or flight + increased metabolism leads to increased appetite Emotional disturbances: -hormone disturbances -hippocampal disturbances Peptic ulcer: -corticosteroid given with an NSAID decreases prostaglandins, which protect the gastric mucosa (give PPI when these are given together) Peripheral edema: -retention of sodium and water Hypokalemia: -increased renal excretion of potassium

anaphylaxis s/s

Skin: -hives -swelling -warmth -redness Respiratory: -coughing -wheezing -SOB -hay fever s/s GI: -nausea -stomach pain or cramps -vomiting -diarrhea Cardiovascular: -dizziness -weak pulse -fainting -shock -loss of consciousness Neurological: -anxiety -feeling of impending doom

stages of the inflammatory response

Stage I: Vascular -Injured tissues and leukocytes secrete histamine, serotonin, and kinins -Blood vessel changes cause redness and warmth of the tissues -Increased blood flow leads to edema at the site -Capillary leak leads to swelling and pain -Edema protects from further injury by creating cushion of fluid Stage II: Cellular Exudate -neutrophil count rises within 12 hours of inflammation initiation -neutrophils attack organisms and remove dead tissue -exudate/pus forms as a result of dead WBCs, necrotic tissue, and escaped fluid from damaged cells -main cells involved in this stage are neutrophils, mast cells and basophils that sustain the inflammatory response Stage III: Tissue Repair -WBC's replace/repair lost or damaged tissues by inducing healthy cells to divide (cytokine response) (i.e. in bone) -in cells that can't divide, WBC's trigger new vessel growth and scar tissue formation (i.e. in cardiac tissue( -scar tissue becomes a patch but does not function as the former tissue did -Wherever scar tissue is placed functional effectiveness is lost

acquired (specific) immunity

Third line of defense: -T cell lymphocytes -B cell lymphocytes -Antibodies Body makes a memory. Not born with this.

Histamine's effect on various receptor sites in the body...

Vascular site: -blood cells enter -risk for clotting H2 in stomach: -increased gastric secretion Lungs: -airways constrict -increased mucous production -possible bronchospasm Skin: -itchiness and pain from prostaglandin release -swelling and inflammation due to capillary leakage Adrenaline release: -increased HR Vasodilation: -weaker HR -lower BP

IgE

allergic responses

What happens when we have a delayed immune response or inability to activate an immune response?

called immunodeficiency

#1 effective txt for anaphylaxis

epinephrine could also give IV steroids some have biphasic rxt in 8-10 hrs which is repeat anaphylaxis so keep for observation

What happens when there is an exaggerated immune response to an allergen?

hypersensitivity

What happens when there is an insufficient reaction to an antigen?

immunodeficiency

purpose of pain and loss of function in inflammatory response

to prevent further damage to area