Mechanisms of Defense & Alterations: Inflammation, Immune Function (RRD #3)

What is "innate resistance"?

The defense mechanisms we are born with.

AKA: "Natural resistance".

Innate resistance includes what lines of resistance?

The first and second lines of resistance.

What is the first line of resistance?

The first defense against invasion. It is comprised of the body's physical barriers: skin, membranes / glands of body openings, respiratory system defenses, etc.

The first line of resistance can be described as__________ and ___________.

immediate and non specific

What is the second line of resistance?

Inflammation. It is the secondary defense against against invasion.

What is acquired (adaptive ) immunity.

The third line of defense. It is the ability to resist certain diseases or conditions due to immunocyte involvement.

The third line of defense can be described as _____ and ______

delayed and specific.

What is Sjogren's Syndrome?

An autoimmune disease that dries up all lubricating fluids in the body (eyes, saliva, etc.)

What are some examples of respiratory system defenses (1st line defenses)

viscosity of mucus in nose, cilia of cells in bronchi, cough reflex

What is an example of a stressor that can breach the defenses of the GI system?

Sjogren's syndrome, anything that changes the bowel flora (invading microbes, use of antibiotics, etc).

What are typical symptoms of local inflammation?

swelling, redness (erythema), heat, pain

What are the two types of immunocytes (or lymphocytes)?

T-lymphocytes (T-cells)

B-lymphocytes (B-cells)

How do T-cells work?

They defend the body by direct attack against invading microbes.

How do B-cells work?

They defend the body using a more complicated method:

they differentiate into plasma cells

they plasma cells create antibodies to the microbe that has attacked the body

a particular set of antibodies (memory) now will always remember and lay in waiting for that specific microbe

What are antigens?

Proteins that can stimulate an immunocyte reaction against them.

What are the two broad types of acquired immunity (aka the 3rd line of defense)?

active acquired immunity (your own immune system developed the antibodies that established immunity)

passive acquired immunity ( you have been given someone else's antibodies-you did not develop these on your own).

What are the two types of active acquired immunity?

Natural active acquired immunity: when a person's plasma cells build up antibodies in response to a microbially-induced illness (like the meningitis example).

Artificial active acquired immunity: when a person's plasma cells build up antibodies in response to receiving innoculations of a much-weakened or inactive microbe (vaccines / boosters).

What are the two types of passive acquired immunity?

Natural passive acquired immunity: when there is a transfer of antibodies from mom to baby (placenta / breast milk).

Artificial passive acquired immunity: antibodies injected during treatment (TIG, immunoglobulin shot).

When is a normal inflammatory process considered to be a problem or disorder?

When it gets out of control, occurs inappropriately, and / or becomes chronic.

Example: many autoimmune diseases cause inappropriate, rampant, chronic infection.

What is the purpose of the inflammatory response?

To facilitate shifting of substances from blood into injured / irritated tissue to:

"clean up" the area, begin the clotting process, promote healing, and stimulate the 3rd line of defense if needed/

Why does irritation / injury of tissue lead to "leakinesss" and swelling?

Injured cells = disruption of cell's metabolic pathway / loss of cell membrane = leakage of fluid.

Irritation / injury causes local capillaries to vasodilate so they leak plasma containing neutrophils, clotting factors, and fibrin into the surrounding tissue.

Mast cells in the local tissue degranulate, leaking leukotrienes, histamine, and prostaglandins.

What is the role of neutrophils and macrophages in normal inflammation?

They phagocytize (eat and destroy) any dirt, debris, dying tissue, and / or microbes they might find in the tissue area.

What is exudate??

The combination of plasma, phagocytes, dead tissue cells, bacteria, fibrin, etc that is present in irritated / injured tissue. (It leaks from the injured area and is typically gold colored.)

What is serosanguinous exudate?

Exudate with some blood in it.

What is purulent exudate?

Exudate with microbe and WBC involvement (ie. infection or pus). It is usually thick, cloudy, and white / yellow / green colored depending on the microbe involved.

If bacteria or other microbes have caused irritation / injury to a cell, what is the role of the macrophage?

Macrophages phagocytize and process them. They will:

1. secrete chemotactic substances to "call" immunocytes (T and / or B cells) to the area).

2. present remnants of the microbes on their cell membranes as a guide to the lymphocytes to know who to attack.

How is granulating tissue produced?

Granulating tissue (pink, healthy, healing tissue) is produced by clotting factors, platelets, and fibrin.

Where are mast cells found?

They are WBCs that are found in tissue instead of the blood and they degranulate when local cells are irritated / injured (releasing the first set of inflammatory mediators - histamine, pro-inflammatory prostaglandins, leukotrienes).

What are two WBC's found in the tissue?

Mast cells and Macrophages

What is a granuloma?

A hunk of tissue that has been chronically inflamed & is now essentially just scar tissue.

What are acute phase reactants?

Circulating inflammatory mediators. They can increase / intensify a local response. They include: CRP, circulating prostaglandins, kinins, cytokines, the complement cascade and the clotting cascade.

What are the specific functions of acute phase reactants?

Enhance opsonization of bacteria.

Help with further lysis of bacteria.

Contribute to vasodilation and permeability of blood vessels.

Cause more pain (yikes)!

Help attract lymphocyte cells (esp neutrophils and CD4 cells).

Activate clotting cascade for clot / fibrin mesh formation at the site of injury.

What are signs and symptoms of a systemic inflammatory response?

malaise, aches, pains, fever (which has a beneficial effect of directly killing some microorganisms).

What are the deleterious effects of fever?

Fever can dilate blood vessels. Too much vasodilation = low blood pressure.

Fever increases metabolic rate and may cause decompensation in very ill, debilitated, and / or elderly patients.

What is leukocytosis?

An increase beyond the normal number of WBC's. (Normal: 5,000 - 10,000 K/ul)

What is leukopenia?

a decrease in WBC numbers (below 5000 K/u)

What is neutropenia?

a decrease in neutrophils

Describe two qualitative defects in phagocytes.

1.) "chemotactic defects" - they won't respond appropriately when summoned.

2.) impaired function: phagocytes damaged by diabetes mellitus have decreased ability to fight microbes.

What happens when patients have complement deficiencies?

They have problems similar to patients with antibody deficiencies, they will be extra susceptible to infections.

Give four examples of abnormal inflammation.

SIRS

sepsis

septic shock

chronic inflammation disorders (there are lots of these)

SIRS is usually present when two or more of the following signs and symptoms are present:

1.) unexplained change in mental status (confusion, not as awake and alert as normal)

2.) fever of more than 100.4 F

3.) increased heart rate

4.) increased respiratory rate

5.) abnormal white blood cell (WBC) count.

What is the difference between SIRS and sepsis?

The person has at least two symptoms of SIRS and a suspected or known site of infection (then it becomes sepsis).

When does SIRS and / or sepsis become septic shock?

When the person has at least two symptoms of SIRS and a suspected or known site of infection (then it becomes sepsis) and they also have a low blood pressure (at or below 90/60).

Why does low blood pressure occur in septic shock?

High levels of systemic inflammatory mediators trigger widespread extreme vasodilatation. This allows blood to pool in the periphery instead of being part of circulation and resuces the amount of O2 being brought to the tissues / organs (hypoxia / ischemia).

Identify therapeutic actions for inflammation.

1.) protected ice

2.) using antiinflammatory medications (NSAIDS and steroids) to suppress the effects of prostaglandins.

What are the two main groups of prostaglandins?

Protective and proinflammatory prostaglandins.

Where do steroids work?

Steroids work in the cell membranes of most cells where both protective and proinflammatory prostaglandins and leukotrienes are created. They are used for major inflammatory conditions.

What are potential side effects of steroids?

Stomach ulcers, easier bleeding, dimished kidney function, diminshed capacity to combat infection, increased skin fragility, hypertension.

Where do NSAIDS work?

NSAIDS work lower in the arachidonic pathway, are not as powerful as steroids, and are used for problems such as headaches, general aches and pains, etc.

What part of the immune system is in charge of developing "cell-mediated" immunity?

T-cells

What part of the immune system is in charge of developing "humoral" immunity?

B-cells

What are some ways that antibodies defeat microbes?

neutralization (neutralizing bacterial toxins by binding to the toxins of bacteria renddering them unable to bind to the host tissues)

opsonization (coating bacteria which promotes phagocytosis by optimizing recognition and "digestibility" of the antigen for phagocytes).

What is the definition of a hypersensitivity?

When the response from our immunocytes (which is supposed to help us) goes too far and harms us.

Name three subcategories of hypersensitivity responses:

allergic responses

alloimmune responses

autoimmune responses

What types of s/sx might you see in an allergic reaction?

local reactions (dermatitis, itching, swelling)

systemic reactions (angioedema, anaphylaxis, urticaria, laryngeal edema, wheezing, NVD, hypotension / shock).

Why do our own T-cells sometimes attack our own antigens?

Sometimes after fighting off an infection, our own immune system stays primed, and instead of standing down it begins attacking antigens on our own cells. (Example: rheumatic heart disease)

Also: there may be genetic factors and gender differences that predispose individuals to be more likely for this to happen.

List the tissue specific auto-immune diseases:

multiple sclerosis, graves disease, goodpasture's syndrome, myasthenia gravis, type-1 diabetes, celiac disease, and autoimmune hemolytic anemia

What is multiple sclerosis?

A disease where T-cells destroy random patches of the myelin sheath that insulates the fibers of the neurons of the brain. This results in asymmetric weakness and / or malfunction of various area of the body.

What is Graves Disease?

A disease that causes most cases of hyperthyroidism. An autoantibody stimulates the thyroid gland cells to oversecrete thyroid hormone, causing S/sx of hyperthyroidism.

What is Goodpasture's syndrome?

A disease in which autoantibodies attack the connective tissue in the basement membranes of the glomerulous and in the lungs. It results in pulmonary hemmorage and glomerulonephritis.

What is myasthenia gravis?

A disease in which autoantibodies attack the acetylcholine receptors on cells of muscles, resulting in poor conduction of nerve impulses to the muscle tissue (weak muscle response).

What is type 1 diabetes?

A disease in which the T-cells destroy the insulin producing cells within the pancreas. With no insulin, glucoose accumulates in the blood and can't be transported to the cells for energy.

What is celiac disease?

Gluten triggers an attack by the T cells on the patient's intestinal lining, causing abdominal discomfort and diarrhea.

What is autoimmune hemolytic anemia?

A trigger (such as a medication) causes autiantibodies to attach a patient's RBC's/ The result is abnormally high hemolysis of RBC's and anemia.

What is an immune complex?

An auto-immune reaction in which an antibody and a self-antigen pair up into a molecule called an immune-complex. They are found in systemic auto immune diseases and can be detected in the patient's blood. They are also deposited into the walls of blood vessels in varoius locations and can cause irritation to the surrounding tissue.

What are the s/sx of systemic lupus erythematosus (SLE)?

A great variety of exists in the presentation of this disease, and the pattern is one of exacerbations and remissions. Symptoms include: skin rashes, nonerosive arthritis of at least two joints, serositis, kidneys, seizures, fatigue, and serum lab tests: elevated CRP, positive ANA (antibody + nucleic acid).

What are the s/sx of rheumatoid arthritis (RA)?

Inflammation develops anywhere there is collagen, but most commonly in synovial membranes / lining of joints. Symptoms include: fatigue, joint pain / swelling / deformation, and any inflammatory s/sx of the eyes, heart, lungs or other tissue and serum lab tests: elevated CRP, positive RF. RA begins at any age, and pain tends to be worse on awakening and better as the day progresses.

What are the s/sx of osteoarthritis (OA)?

OA is age-related and/or overuse-related wear and tear to joints...not an inflammatory process, and no other body parts are involved except the joints. Pain in OA tends to get worse as the day goes on.

What is the target antigen in alloimmune hypersensitivity?

Someone else's cells / tissue. In nursing, alloimmune concerns are thought of as compatibility issues.

What are HLAs and where are they most likely to be found?

Human leukocyte antigens (HLAs) are found on the cell membrane of most body cells except RBCs and are important in certain patient situations such as transplants. The closer the match between the donor and recipient HLAs, the less likely the transplanted tissue will be seen as foreign and attacked.

What are ABO compatibility issues?

RBCs have ABO blood group antigens and Rh blood group antigens on their surfaces. Nurses need to know which type of blood is ok to give to a patient to avoid a transfusion reaction.

What will happen when a person receives a blood type that is incompatible with theirs? Example: B+ patient receives A+ blood?

The anti-A immunoglobulins in the patient with B+ blood will attack the newly transfused A+ blood and hemolyze it. The symptoms that result are known as a transfusion reaction: rash, fever, low BP, body aches, blocked vessels in kidneys or other areas leading to ischemia.

What is erythroblastosis fetalis?

A situation which occurs when an Rh- mom begins to develop antibodies to an Rh+ fetus / pregnancy. These antibodies MAY cross over to attack the Rh factor present on the fetus' RBC membranes, resulting in hemolysis.

What helps to prevent erythroblastosis fetalis?

A Rhogam shot is given to the Rh- motherjust after the birth of that first Rh+ child and after every Rh+ child thereafter.

What are immunodeficiencies?

An abnormality in one or more of the branches of the immune system that renders a person susceptible to diseases normally prevented by an intact immune system.

Immunodeficiences can be congenital or acquired .

The etiology of immunodeficiences can be B-cell problems, T- cell problems, or both.

An example of a congenital combined B and T cell immunodeficiency is ________________.

Severe combined immunodeficiency syndrome (SCIDS).

Examples of causes of acquired combined B and T cell immunodeficiencies would be:

radiation and cytotoxic drugs used to treat cancer

immunosuppresant drugs used post transplant

aging

An example of a congenital humoral (B-cell) immunodeficiency is:

x-linked hypogammaglobulinemia (IgG is missing or lessed in amount)

An example of a congenital cell-mediated (T-cell) immunodeficiency is:

DiGeorge's Syndrome

An example of an acquired cell-mediated (T-cell) immunodeficiency is:

HIV (an RNA retrovirus) and AIDS

Which groups are at highest rist for HIV infection?

anyone engaging in unprotected sex (sex without a latex barrier)

homosexual / bisexual men and their partners (whther male or female)

IV drug users / anyone with bloood to blood contact

children born to HIV+ mothers

breast milk from HIV+ mothers

When is an individual diagnosed with AIDS?

HIV+ (+ELISA, +Western Blot)

serum CD4 count less than 200

presence of an opportunistic infection (OI): thrush, pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV) retinitis, Kaposi's sarcoma

The patient may also have cachexia, weakness, and even dementia.