Module 2: Mechanisms of Defense (MOD) PART 3

- Our immunocyte system stays "primed"

- Instead of "standing down (sending post-attack immunocytes back to lymph tissue appropriate), our immunocyte system begins attacking self antigens

Sometimes after we "fight off" an infection, what can happen to our immunocyte system that may lead to Autoimmune Hypersensitivity?

1. Person gets strep and it resolves b/c their antibodies kill strep bacteria

2. Instead of antibodies standing down, they "look around" for anything that "resembles" strep antigen

3. Heart valve cells appear to be close enough match b/c autoantibodies begin attacking them --> heart valve can malfunction --> become floppy & leaky instead of opening & closing tightly

4. Possible sequela of strep --> bad heart valves via autoimmune attack

5. NOTE—post strep sequelae like this don't usually occur if strep was treated thoroughly by antibiotics

Explain the Etiology of Rheumatic Heart Disease, which is an autoimmune hyper-inflammatory reaction.

(5 bulletpoints in this flashcard)

HLA (human leukocyte antigen)

A presence of certain ___ in people with certain autoimmune diseases is statistically significant.

- Present on cell membranes of most tissues & are a "declaration" of "I am self."

- Which HLA antigens you have depends on genetic inheritance

What are HLA antigens?

ankylosing spondylitis or psoriasis

A positive HLAB27 test has a correlation with having what autoimmune diseases?

10:1

Females are way more likely to get autoimmune diseases!

Gender can affect autoimmune diseases. What is the ratio of female to males having autoimmune diseases?

1. Autoantibody attack (humoral)

2. AutoT-cell response (cell-mediated)

What are the 2 ways that Autoimmune diseases are often categorized?

a pathologic antibody because it attacks self antigens

What does Autoantibody mean?

1. Autoantibody attacks tissue cells, opsonizing them & causing them to be phagocytized by macrophages as if they were a bacteria

2. This triggers an inflammatory response which usually causes damage to target tissues + usual S&S of inflammation in those organs/tissues—these are the S&S of the disease

Describe the Humoral Autoimmune Response.

- Instead of autoantibody, the "attacker" is our own T-cells which attack our tissue & trigger damaging inflammation & usual S&S in organs/tissues

Describe the Cell-Mediated Autoimmune Response.

tissue specific vs systemic

HOWEVER, instead of thinking humoral vs cell mediated, we'll categorize disease according to what 2 categories?

Tissue specific autoimmune dz

1. T lymphocytes destroy random patches of myelin sheath that insulates fibers of neurons in brain

2. Results in asymmetric weakness and/or malfunction of various areas of body

What kind of autoimmune disease is Multiple Sclerosis? Describe it.

Tissue specific autoimmune dz

1. Disease that causes most cases of HYPERthyroidism

2. Autoantibody stimulates thyroid gland cells to oversecrete thyroid hormone (TH), causing S&S of hyperthyroidism

What kind of Autoimmune dz is Graves Disease? Describe it.

Tissue specific autoimmune dz

1. Autoantibody attacks connective tissue in pulmonary & glomerular basement membrane

2. Results in pulmonary hemorrhage & glomerulonephritis

What kind of Autoimmune dz is Goodpasture's Syndrome? Describe it.

Tissue specific autoimmune dz

1. Autoantibody attacks acetylcholine receptors on cells of muscles

2. This means that acetylcholine wouldn't have enough effective post-synaptic gap receptor....S&S of muscle weakness

What kind of Autoimmune dz is Myasthenia Gravis? Describe it.

Tissue specific autoimmune dz

1. T-cells destroy insulin producing cells

2. Without insulin, glucose accumulates in blood + no energy source for cells

What kind of Autoimmune dz is Type 1 Diabetes? Describe it.

Tissue specific autoimmune dz

1. Caused by individual's intolerance of a protein called gluten found in wheat and other foods

2. Gluten triggers attack by T-cells on own intestinal lining & causes diarrhea

What kind of Autoimmune dz is Celiac Disease (aka "Sprue")? Describe it.

Tissue specific autoimmune dz

1. Trigger such as a drug causes autoantibodies to attack RBCs

2. Result is abnormally high hemolysis (destroying RBCs) thus low # of RBCs (anemia

NOTE: this one is on the borderline of being a SYSTEMIC dz but in this case, the blood is considered one tissue

What kind of Autoimmune dz is Autoimmune Hemolytic Anemia? Describe it.

1. These are autoimmune rxns where antibody & circulatin SELF antigen pair up into a molecule called an immune-complex

2. Immune complexes are circulated via bloodstream and damage is done all over b/c the complex gets deposited in walls of various blood vessels that supply tissues throughout body

3. Immune complex irritates blood vessels & cause inflammation of them (vasculitis)...causing surrounding tissue to be inflamed

4. Damage itself & S&S occur in similar fashion to that of tissue specific dz, but more widespread since immune complexes can be deposited in blood vessels of many tissues

Give an overview of Systemic Autoimmune Dz.

Lupus and Rheumatoid Arthritis

What are 2 examples of Systemic Autoimmune Dz?

a systemic autoimmune dz that's mostly seen in women who are genetically predisposed

What is Systemic Lupus Erythematosus (SLE) or just "Lupus"?

1. Everyone normally always has bits of degraded cells & nucleic acids like DNA circulating in blood otw to being disposed of in spleen/liver/etc.

2. B/c of not well-understood mechanism, some antibodies circulating in blood too become autoantibodies when they encounter these person's own nucleic acids

3. They attach themselves to DNA & together they become immune complexes

What are the first 3 of 6 steps/bulletpoints to the pathogenesis of Lupus?

4. Immune complexes circulate and deposited in tiny blood vessels of mostly connective tissues in variety of areas—kidneys/lungs/joints/skin—causing vascular inflammation in the tissues (vasculitis)

5. In whichever tissues involved, process is same...inflammation begins--causing S&S related to tissues

What are the last 2 of 5 steps/bulletpoints to the pathogenesis of Lupus?

- A great variety exists in presentation & degree of the disease...plus the pattern is one of flare ups and remissions

- It's often mistaken for other diseases

Why is SLE/Lupus known as one of the "great imitators"?

1. Skin rashes like "butterfly" malar rash (across cheeks)....creates a wolf-like facial appearance hence Latin "lupus" = "wolf"

2. Joints: nonerosive arthritis of at least 2 peripheral joints

3. Serositis—inflammation of serous (sacs in body like pleura and pericardial sac...causing pleurisy and pericarditis)

What are the 6 common S&S of Lupus? (part 1 of 2)

4. Kidneys—proteinuria

5. Neurons of brain—seizures

6. Fatigue (almost always found in all autoimmune dz of all types)

What are the 6 common S&S of Lupus? (part 2 of 2)

- Lab test for elevated CRP (acute phase reactants in blood)—non specific inflammatory test (indicates inflammation but not specific to lupus)

- Specific test for lupus called ANA (antinuclear antibody)—test looks for immune complexes made of antibody + nucleic acid (DNA)

- 95 to 98% of SLE patients have positive ANA test

Aside from S&S, how do we diagnose SLE/Lupus?

- Similar to SLE but RA immune complex is autoantibody attached to collagen

- Inflammation develops anywhere collagen is but most commonly in synovial membranes of small joints like hands (synovial = lining of joints)

What is the etiology of Rheumatoid Arthritis (RA)?

1. Fatigue

2. Joint pain, swelling, & deformation

3. Can also have inflammatory S&S of eyes (iritis), heart, lungs, almost any tissue

What are the 3 S&S of Rheumatoid Arthritis (RA)?

1. Elevated CRP lab test...again, non specific inflammatory test

2. Lab test specific for RA—rheumatoid factor...looks for antibody + collagen immune complexes

Besides the S&S of Rheumatoid Arthritis, how do we diagnose?

1. Begins at any age & due to inflammation that damages joints

2. Other areas of body become inflamed & painful too

3. Pain tends to be worse in morning and lessens throughout day

RA differs from osteoarthritis! Describe RA in the way that differs it from osteoarthritis.

1. Age related and/or overuse related wear & tear to joints

2. NOT due to widespread inflammatory process, and no other parts of body involved

3. Pain in joints tends to get worse throughout day

RA differs from osteoarthritis! Describe osteoarthritis in the way that differs it from RA.

1. Someone else's cells

2...

- In essence, body is just doing what it's supposed to aka attack foreign antigens

- But traditionally alloimmune rxns are placed amongst hypersensitivities b/c they're unwanted and unhelpful—they cause problems for the person instead of helping like a normal antibody/antigen rxn does

1. What is the target antigen in Alloimmune Hypersensitivity

2. Describe why this type of hypersensitivity in some respects not a "true" hypersensitivity.

1. Compatibility = "what treatment may cause an untoward immune reaction" due to introducing a foreign antigen and having body attack it

2. Types of compatibility issues are HISTOcompatibility and ABO/Rh compatibility

In nursing, why are Alloimmune Concerns thought of as compatibility issues?

1. To be able to distinguish self from foreign, almost all body cell membranes have self antigens composed of protein

2. These are called Histocompatibility Antigens (histo = tissue) and are commonly known as HLAs—human leukocyte antigens (bc they're first discovered on leukocytes)

Explain what a Histocompatibility issue is.

1. except RBCs

2. transplants

1. HLAs are found on the cell membrane of most body cells except for...?

2. What kind of certain patient situation would HLAs be super important?

1. Histocompatibility testing done on tissue cells of both donors & recipients to see if HLA cells match

2. Closer the match, less likely transplanted tissue will be attacked by immunocytes that see it as foreign

3. If immunocytes attack, this is called rejection and patient may have S&S like pain over the area, fever, etc.

4. To minimize this, transplant patients usually on immunosuppressant drugs to make immune system lethargic and not attack transplanted tissue

Describe Histocompatibility testing and organ transplant processes (4 bulletpoints in this).

ALWAYS foreign

Will a person's immune system detect a transplanted kidney as self or ALWAYS consider the kidney as "foreign"?

1. HLA not found on RBCS—instead, RBCs have ABO blood group antigens and Rh blood group antigens

2. Ppl w/ certain blood types have specific antigens & antibodies; nurses need to know which type is ok to give in a transfusion to avoid reactions

Describe ABO compatibility issues.

Donor cells clump b/c body's antibodies hemolyze donor blood, leading to...

1. Donor cells burst --> kidney damage

2. Small vessels blocked --> reduced blood supply (ischemia)

In a transfusion reaction where the wrong blood is given, what happens?

rash, fever, low BP, and/or body aches

Sometimes instead of OR in addition to hemolytic clumping, a transfusion reaction involves what?

positive and negative (ABO leads to A/B/O/AB)

Rh leads to what part of ur blood type?

1. Person either born with/without Rh factor on their RBC cell membrane

2. Person not genetically programmed to develop anti-Rh antibodies in the same way with ABO process

3. Person w/o Rh factor given Rh+ blood will be ok the FIRST time since they dont have antibodies yet

4. If they receive Rh+ blood a second time, they may have a transfusion reaction

Describe Rh factor compatibility issues.

1. Normally mom & fetus blood don't mix during pregnancy but during birth, some fetal blood may enter mom's system

2. If mom is Rh- negative, her immune system may see the baby's Rh factor as foreign and developing antibodies

3. If fetus of a SUBSEQUENT pregnancy is Rh+, mom's antibodies may cross over and attack baby...resulting in hemolysis—this is erythroblastosis fetalis aka hemolytic disease of the newborn

4. To prevent hemolytic problems in future pregnancies, mom gets Rhogam shot just after birth of Rh+ child and Rh+ child thereafter

Describe Hemolytic Disease/Anemia of the Newborn.

medication killing Rh antibodies

What's a Rhogam shot?

- Abnormality in 1+ branches of immune system that renders person susceptible to diseases normally prevented by an intact immune system

What's the definition of Immunodeficiency?

1. Cause much higher susceptibility to dz that immunocompetent ppl get (we ALL get colds/flus/infections but these ppl get them way easier)

2. Greatly increase chance of immunocompromised person getting OPPORTUNISTIC dz

No matter etiology/type, ALL immunodeficient dz have in common that they...

an opportunistic infection

If you're immunoCOMPETENT, you'll RARELY get what?

1. Diseases caused by increased susceptibility to dz that immunocompetent ppl DON'T get (ex. normally harmless microbes)

2. Immunocompetent ppl don't usually get severely ill from harmless flora like yeast/fungi/protozoa...we live in harmony w/ them

3. In immunocompromised ppl, harmonious balance tips in favor of normal flora's natural opportunistic nature & they'll invade

4. Thus, flora becomes opportunistic invaders and are now PATHOGENs...organisms causing harm

Describe Opportunistic Diseases.

1. Subcategories of mechanism of action

2. Congential or acquired

Immunodeficient disorders can be subcategorized into what 2 things?

1. Humoral (B-cell) immunodeficiency

2. Cell mediated (T-cell) immunodeficiency

3. Combined B-cell and T-cell immunodeficiency

What are the 3 subcategories of mechanism of action for Immunodeficient disorders?

Congenital = present at birth, Acquired = develop after birth

Congenital vs Acquired immunodeficiency?

- CONGENITAL severe combined immunodeficiency syndrome—caused by diverse genetic mutations that lead to complete absence of all immune function "bubble boy"

What is SCIDS?

1. Irradiation & cytotoxic drugs for cancer --> wipe out bone marrow, so don't have enough T & B lymphocytes

2. Immunosuppressant drugs post-transplant

3. Aging

What are the 3 ways that you can get ACQUIRED combined B-cell & T-cell immunodeficiency?

Congenital—ex. is X-linked hypogammaglobulinemia

Humoral (b cell) immunodeficiency is most commonly what kind of problem? Give an example.

1. IgG missing or lessened in amount

2. Less antibodies = can't fight dz

Describe X-linked Hypogammaglobulinemia.

DiGeorge's Syndrome

- Genetic defect on chromosome 22 that causes failure of development of thymus—immature T cells leading to lower ability to fight certain infection

What's an example of CONGENITAL Cell-Mediated (t cell) immunodeficiency? Describe it.

AIDS—acquired immunodeficiency syndrome

- Caused by human immunodeficiency virus (HIV)

- Virus invades CD4 cells & begin killing them --> decreased ability to mount immune responses b/c CD4 cell is so important as "intro" component to development of various immunities

What's an example of ACQUIRED Cell-Mediated (t cell) immunodeficiency? Describe it.

- Caused by HIV and is now worldwide BUT originated in Africa as a cross species jump

- Chimpanzee meat infected with SIV (simian immunodeficiency virus) was eaten by humans

Describe the origin of AIDS.

1. Certain infected bodily fluids like semen or vaginal fluids

2. Breast milk

3. Direct blood-to-blood contact like sharing IV drug implements or receiving tainted blood transfusion (rare now)

How does HIV spread?

1. ANYONE having unprotected sex

2. Gay/bi/other men who fck men

3. Trans women who fck men

4. Injection drug users

5. Children of women who are HIV+ or children who drink breast milk of HIV+ women

Who are the 5 groups at highest risk of HIV infection?

1. HIV is an RNA retrovirus

2. A regular RNA virus inserts its RNA into cytoplasm of host cell & takes over ribosomal protein-building for its own propagation

3. A RETROVIRUS inserts its RNA into a host cell cytoplasm, converts its own RNA into DNA, then back into RNA

Describe the Pathogenesis of HIV infection.

1. HIV introduced to blood --> virus finds CD4 cells, uses its protein coating (capsid) to bind membrane receptors on CD4 cell & insert its RNA into CD4 cytoplasm

2. Once inside, it uses enzyme reverses transcriptase to convert its RNA to DNA

3. DNA goes to nucleus of CD4 cell --> uses enzyme integrase to insert its new viral DNA into host cell's DNA

4. In nucleus, it can remain dormant for years

(At this point, person is HIV+ but doesn't have AIDS b/c minimal destruction of CD4 cells....more destruction will lead to AIDS)

Describe the 4 steps of the invasion process of HIV.

less CD4 = increased susceptibility to infections in general and opportunistic infections in particular

Why does more CD4 cell destruction lead to AIDS from HIV?

1. Tests for presence of antibodies to HIV (usually detectable by 2 weeks)

2. 96% of infected individuals will be positive within 2-12 weeks

3. If ELISA negative, recommendations for further testing depends on patient risk status and timing of testing

How does ELISA detect HIV?

- If ELISA positive, Western blot is used as a second/confirmatory test

- More expensive but more specific and very few false positives

How does Western Blot help with HIV detection/diganosis?

1. Someone can be HIV+ and live many years w/o AIDS....until they meet certain other criteria

2. Person usually diagnosed with AIDS when CD4 count drops

How do we diagnose AIDS?

1. Yeast infection of mouth & throat

2. Type of fungus that invades lungs

1. Thrush is an opportunistic infection (OI). What is it?

2. Pneumocystsis Jiroveci Pneumonia (PCP) is an OI. What is it?

1. Virus normally harmless invades eyes

2. Malignant skin tumor that invades immunocompromised people

1. Cytomegalovirus (CMV) Retinitis is an OI. What is it?

2. Kaposi's Sarcoma is an OI. What is it?

due to OIs & atrophy of tissue

- Weight loss, anorexia, general cachexia (weakness and body wasting), and dementia

S&S of AIDS are....

1. Use of LATEX condoms for prevention

2. Understand HIV can affect anyone

How do we educate about HIV/AIDS?

Drugs targeted at...

1. Different phases of viral invasion & replication

2. Treating OIs—oral & nebulized sulfonamides for PCP, antifungals for yeast, etc.

What are the treatments for HIV/AIDS?

ANY person w/ ANY immunodeficient dz

Who's susceptible to OIs like thrush, PCP, CMV, and Kaposi Sarcoma?