WCU PATHO FINAL PARK CH 10,13,14,15

What are the three functions of the immune system

1. Defends body against invasion or infection by pathogens (antigens)

2. Removes dead or damaged cells

3. Attempts to recognize/remove abnormal cells (cancer cells)

What are the three lines of defense of the immune system

1. Physical and chemical barriers to infection (skin, mucous membranes)

2. Inflammatory response

3. Immune response (innate and adaptive)

What is innate immunity

Always present, requires no previous exposure to respond to antigens

Non-specific: does not distinguish between different microbes

Immediate response

Inflammation

What cells does innate immunity involve

Natural killer (NK) and phagocytic (neutrophils and macrophages)

What is the most important aspect of innate immunity and why

Inflammation because it increases vascular permeability, vasodilation, emigration of leukocytes (neutrophils, macrophage) phagocytosis, chronic inflammation

What are the manifestations of inflammation

Redness, swelling, heat, pain, and loss of function

What is the purpose of inflammation

Neutralize and destroy invading agents, limit spread and prepare damaged tissue for repair

What is adaptive immunity

Attacks specific antigens (bacteria,toxins)

Slower response but more effective to 2nd exposure

What does adaptive immunity involve

B and T lymphocytes

What are the mechanisms that adaptive immunity uses

Cell mediated (T)

Humoral (B)

Where do lymphocytes come from and where do they mature

Stem cells are made in the bone marrow (all WBC come from bone marrow)

B cells mature in the bone marrow

T cells born in bone marrow but mature in thymus

Describe cell mediated immunity

Involves phagocytic cells that attack the specific antigen, mediated by T lymphocytes

What do cytotoxic T cells do

Bind to the surface of infected cell (MHC I), disrupt the membrane, and destroy it before it can infect other cells

What do helper T cells do

Stimulated by phagocytic cells (macrophage)

Macrophage will take virus and present it in MHC 2 and when it is present the helper T cells will bind and recognize virus and helper T call for more help by activating other B cells

What do suppressor T cells do

Reduce the humoral response

Describe humoral immunity

Antibody proteins in the blood that attack the specific antigen mediated by B lymphocytes

B lymphocytes become plasma cells which secrete antibodies

Antibodies destroy bacteria and viruses preventing them from invading cells

B lymphocytes can also become memory B cells which remain to fight future infection without needing a T helper cell telling them to do so

What is a vaccination

Produces a primary immune response because B cells also become memory cells (don't have to wait for helper T cells just stimulate and make antibodies)

What is a booster shot

Cause a secondary immune response so antibody levels will be high before the disease is encountered

What happens during primary immune response

Macrophages eat the antigen then present it to the T helper cells.

T helper cells activate B cells

B cells become plasma cells and produce antibodies

Plasma antibody levels rise

Takes 2-3 weeks

What happens during secondary immune response

B memory cells respond to the antigen immediately

Plasma antibody levels rise within days (make more antibodies)

IgM initially then IgG

What are the 5 classes of antibodies

IgG

IgA

IgM

IgE

IgD

What is antibody IgG

Makes up 80% of plasma antibodies

Is a major antibacterial and antiviral antibody, crosses placenta, smallest.

Easily leaves bloodstream into interstitial fluid

What is antibody IgA

Found in body secretions (saliva,sweat, tears,mucus, bile) protect against respiratory and Gi infections

What is antibody IgM

First antibody produced during an immune response (primary immune response) major antibody on B-cell surfaces

What is antibody IgE

Initiates inflammatory and allergic reactions

What is antibody IgD

Primarily found in surface of B cells (with IgM) (mainly acts as an antigen receptor to stimulate B cell)

What is one factor contributing to the immune system in the elderly

Decline in immune responsiveness

(Aging is characterized by a declining ability to adapt to environmental stressors)

What are some common immune disorders

Autoimmunity

Hypersensitivity

Deficient

What are two excessive immune responses

Autoimmunity

Hypersensitivity

What is autoimmunity

Occur when the immune system recognizes an individual own cells as foreign and mounts an immune response that injures self tissues

What are some theories of autoimmunity

Antigenic mimicry

Release if sequestered self antigen

T cell

B cell

Mast cell theory

What is antigenic mimicry theory

Self and foreign antigens made of the same material so small alterations in self lead to attack

(When a small change in our own cells makes it look foreign therefore lead to attack)

What is release if sequestered self antigens

Self antigens not in direct contact with lymphocyte during fetal development are released

(Any antigen escape then it returns)

What is T cell theory

Thymus gland detect, decreased suppressor T-cell function, altered T helper cell function

What is B cell theory

B cells lose responsiveness to suppressor T-cell signals, over activation of B cells

What is mast cell theory

Cytokines are released causing activation of other cells

What are the triggers of autoimmunity

Gender -females are higher risk

Chronic or multiple viral or bacterial infections

Environmental and/or occupational stress, especially in genetically susceptible individuals

Stress

What are some treatments of autoimmunity

Individualized immunosuppressive therapy

Corticosteriods, tumor necrosis factor inhibitors (cytokines that cause cell death) and immunomodulators, therapeutic plasmapheresis (components of plasma thought to cause disease are removed and remaining blood returned to the circulation)

What is hypersensitivity

Normal immune response that is either inappropriately triggered, excessive, produces undesirable effects on the body

Usually does not occur on first exposure

4 types

All involved IgE

1,2,3 are mediated by antibodies produced by B lymphocytes

4 mediated by T cells and do not require antibody production

What is the cause of hypersensitivity type I

Strong genetic or hereditary linkage regarding IgE response to antigens (allergens)

What is the pathogenesis of hypersensitivity type I

Immediate hypersensitivity (reaction occurs 15-30 min after exposure)

Immediate allergic or anaphylactic type of reaction mediated primarily by sensitized mast cells

Mast cells and basophils are the principle effector cells

IgE is the principle mediating antibody

What are the clinical manifestations of hypersensitivity type I

Mild (hives, seasonal allergic rhinitis, eczema)

More problematic (localized edema, throat constriction, wheezing, tachycardia)

Anaphylaxis (most threatening reaction occurs in very small number of highly allergic individuals, Epi pen right away)

What are some treatments for hypersensitivity type I

Antihistamine = block the effects of histamines

Beta-adrenergics = decrease bronchoconstriction (causes SNS which is a bronchodilator)

Corticosteroids = decrease inflammatory response (suppressed immune system)

Anticholinergics = block PNS (blocking PNS no longer bronchoconstrict)

IgE therapy = inhibits binding of IgE to mast cells

Epinephrine = adrenergic agent given subQ or IV during acute allergic reactions. Causes bronchodilation and vasoconstriction to help breath and BP doesn't fall far and put you into shock

What is hypersensitivity type 2

Tissue-specific, cytotoxic, or cytolytic hypersensitivity

When does hypersensitivity type 2 occur

Occurs when antibodies attack antigens on surface of specific cells or tissues causing lysis which may be mediated by activated complement fragments (membrane attack complex) and phagocytic cells

What is an example of hypersensitivity type 2

Transfusion reaction: individual receives blood from someone with a different blood type. Recipient antibodies attach to the donors RBC antigens

What is hemolytic disease of the newborn? (Hypersensitivity type 2)

Aka erythroblastosis fetalis

Occurs during pregnancy

Rh-neg mother is sensitized to her fetus's Rh-pos RBC when fetal and maternal blood are mixed

Mother's IgG Rh-pos antibodies cross the placental barrier and attach the fetus RBCs

Mother's Rh status is monitored and if Rh-neg, RhoGAM is administered

What is hypersensitivity type 3

Aka immune complex reaction

Immune and phagocytic systems fail to effectively remove antigen-antibody immune complexes

Not tissue specific

Why does hypersensitivity type 3 occur and what does it result in

Occurs when antigen-antibody complexes that precipitate out of the blood are deposited in tissue and results in activation of complement and inflammation causing tissue damage

What are example of hypersensitivity type 3

Immune complex glomerulinephritis

Systemic lupus erythematosus

What is immune complex glomerulinephritis (hypersensitivity type 3)

Inflammatory renal disorder

Typically occurs 10 days to 2 weeks after streptococcus or straphylococcal infection

Complex is deposited in glomerular capillary wall

What is systemic lupus ertgematosus (hypersensitivity type 3)

Occurs frequently in women

Individual develops antibodies against nuclear antigens such as DNA and RNA

What results from deficient immune responses and what can it affect

Results from functional decrease increases opponents of the immune system and it affects lymphocytes, antibodies, phagocytes, complement proteins

What is primary immunodeficiency disorder

May be congenital (present at birth, not necessarily linked to genes) genetic (linked to genes) or acquired defects that directly affect immune cell function

Rare and often sex linked (X chromosome) ex. HIV/AIDS

First clinical indicators: S&S of infection

Suspected with: severe recurrent, unusual or unmanageable infections

What is secondary immunodeficiency disorder

May be cause by excessive or defective neuroendoceine responses

Excessive: increased corticosteroid increases susceptibility to infection

Defective: low corticosteroid increases susceptibility to autoimmunity

Poor nutrition, stress, drugs, cancer treatments

What is the total blood volume in men and women

75.5 ml/kg in men

66.5 ml/kg in women

What is the composition of blood in body weight

7% to 8%

What is the composition of blood in liters

5-6 L

How much blood cells make up blood volume

45%

How much does plasma make up of blood volume and what is it composed of

55%

92% water

7% plasma proteins

What are some organic and inorganic components of the plasma

Plasma proteins are formed in the liver and contribute to colloid osmotic pressure

Regulatory proteins (hormones,enzymes)

Organic constituents (products of tissue metabolism, nutritive organic materials)

Inorganic constituents (electrolytes, iron)

What are the three general types of plasma protein

Serum albumin

Serum globulin

Fibrinogen

What are the cellular components of blood cells

Erythrocytes (RBC)

Leukocytes (WBC)

Platelets

What do erythrocytes do

Transport oxygen to tissues from lungs

Remove carbon dioxide from the tissues

Buffer blood pH (bind H ions)

What do leukocytes do

Act primarily in tissues but circulate in blood an lymphatic system

Protect the body by phagocytosis of microorganisms

Form immune antibodies

What do platelets do

Circulating fragments of megakaryocytic

Form blood clots and control bleeding

1/3 of body's platelets are in reserve (in the spleen)

Why does adult hemoglobin consist of and what what does it do

Two alpha chains

Two beta chains

Each protein chain holds one iron containing heme group (carries oxygen)

Oxygen binds to the heme groups

Average person has ~15g of hemoglobin per 100ml or 1dl of blood

1ml=0.1 dl

What is erythropoiesis?

Process of making RBC

stimulated to make RBC when oxygen levels are low

Where do most RBC break

Spleen

What is the process of RBCs breaking in the spleen

Break in capillaries of the spleen which is eaten by WBC in the spleen, liver, bone marrow, or lymph nodes which hemoglobin processed into unconjugated bilirubin

What can unconjugated bilirubin in blood turn into

1. Bilirubinemia which turns to jaundice

And

2. Liver links it to glucuronic acid which turns to conjugated bilirubin which turns to bile and bile is stored in the gallbladder then releases to help digest fat in your GI tract

What happens when RBCs are destroyed outside the spleen

Break in capillaries outside the spleen which hemoglobin released into the blood turns to hemoglobinemia that turns to hemoglobinuria

What is hemoglobinemia

Build up of hemoglobin in the blood

Makes the plasma turn red

What is hemoglobinuria

Build up of hemoglobin In urine

Makes the urine cola-colored

What is anemia

An abnormally low hemoglobin level, number of circulating RBCs or both resulting in low oxygen carrying capacity of the blood

Tissue hypoxia

Anemia is not a disease

It is an indication of some disease process or alteration in body function

What are some compensatory mechanisms to restore oxygen for anemia

Increased HR, Cardiac output, circulatory rate, flow to vital organs, increase in 2,3-DPG in erythrocytes and decreased oxygen affinity of hemoglobin in tissues

What are causes of anemia

Blood loss (bleeding)

Hemolysis (breakdown of RBCs)

Impaired RBC production (because of a lack of nutritional elements or bone marrow failure ) iron, folate and vitamin B12 (required for DNA synthesis)

What are the manifestations of anemia

Mild (hemoglobin above 8g/dl of blood): mild symptoms

Moderate/severe (below 8g/dl of blood): hypotension, pallor, tachypnea(rapid breathing) headache,lightheaded, fainting, tachycardia and palpitations (compensatory mechanisms to increase oxygen delivery to tissues) angina, heart failure, nighttime leg cramps, fatigue, weakness

What are the types of anemia of deficient RBC production

Iron-deficiency

Megaloblastic

Aplastic

Chronic disease

What is hemolytic anemia

Due to abnormal breakdown of RBCs

What is thalassemias

Genetic defect results in reduced rate of synthesis of one of the globing chains as well as increased RBC destruction (hemolysis) resulting in decreased survival rates

How is the alpha gene effected in thalassemias

Defective gene for alpha-chain synthesis

May have 1-4 defective genes

Affects both fetal and adult Hb

I'm fetus, gamma4 Hb May form; in adult beta4 Hb May form

How is the beta gene effected in thalassemias

Defective gene for beta-chain synthesis

May have 1-2 defective genes

Affects only adult Hb

Alpha4 Hb May form

What is sickle cell disease

Point mutation in beta chains of Hb, substitution of glutamate, the 6th a.a. In the 146 -a.a. Chain is replaced with valine

What happens when Hb is deoxygenated with sickle cell

Beta chains link together forming long protein rods that make the cell "sickle"

What do sickle cells cause

Vascular occlusion, acute pain

Severe anemia, RBCs of different shape and size

Sickled cells block capillaries

Sickled cells more likely to be destroyed = causing jaundice

What are treatments for sickle cell

Stem cell transplant

What happens when sickle cells block capillaries

Infarctions (tissue death due to low blood supply) cause chronic damage to liver, spleen, heart, kidneys, eyes, bones

Pulmonary infarction which is acute chest syndrome

Cerebral infarction which is stroke

What is polycythemia

An excess of RBCs ( increases blood viscosity and volume which leads to clinical symptoms such as hypertension)

What are the types of polycythemia

Polycythemia Vera

Secondary polycythemia

Relative polycythemia

What is polycythemia Vera

Bone marrow is the issue

Neoplastic transformation of bone marrow stem cells

What is secondary polycythemia

Issue with lungs

Due to chronic hypoxemia with resultant increase in erythropoietin production

What is relative polycythemia

Due to dehydration

What does fetal hemoglobin not have

Beta chains

What does fetal hemoglobin have

Alpha and gamma

Can fetal hemoglobin sickle

No

What is hemostasis

Blood clotting

The arrest of bleeding or prevention of blood loss after blood vessel injury

What does hemostasis involve

The vessel wall, circulating platelets, and plasma coagulation proteins

What is inadequate hemostasis

Bleeding

Not enough clotting which will lead to bleeding out or don't stop bleeding

What is excessive hemostasis

Clotting/thrombosis

Clotting too much