Clinical Medicine Flashcards
What are the 10 warning signs of primary immunodeficiency
- 4 or more new ear infections within 1 yr
- 2 or more serious sinus infections w/in 1 yr
- 2 or more mnths on abx with no effect
- 2 or more pneumonias w/in 1 yr
- Failure of an infant to gain weight
- Recurrent, deep skin/organ abscesses
- Persistent thrush in mouth or fungal infection on skin
- Need for IV ABX to clear infections
- 2 or more deep-seated infecting including septicemia
- A family hx of PI
Think Zebra campaign
The immune deficiency foundation started a campaign to promote awareness of PI. Meaning that although PI is less common, it is often not suspect. “when you hear hoofbeats, think of horses not zebras
According to the zebra campaign what are the signs that may point to primary immunodeficiency
- Persistent
- Unusual
- Recurrent
- Runs in family
What does SCID stand for
Severe Combined immunodeficiency. Not a single disease but is a group of diseases caused by different defects in genes
What are the cell deficiencies in SCID
- Absent or extremely low production of naive T cells from thymus
- Defects of T and B cells, # and function
- Sometimes absent NK cells
All 3 of these leads to infants who are severely compromised in fighting infection (which leads to many deaths)
How is SCID treated if recognized early
With hematopoietic cell transplantation (HCT) aka bone marrow transplant. This supplies B and T cells to system
When do infants typically show signs of SCID
At about 4-7mnths. The first few months they are protected by passive transfer of maternal antibodies
What are clinical presentations that suggest a presumptive diagnosis of HIV
- Pneumocystis pneumonia
- Esophageal candidiasis
- Kaposi sarcoma
- CNS lymphoma
- TB
- Toxoplasmosis
At what level of CD4 cells is it considered AIDS
Below 200 cells/mcL.
What is the epidemiology of HIV
- Modes of transmission include sex, parenteral and vertical transmission (needle sticks)
- Receptive anal has highest risk (1:30-100)
- If open wounds with sex higher risk
- Needle sticks (1:300)
- -increased risk in uncircumised
What is the risk of mom to baby transfer of HIV
13-40% risk of infection when mother has not received treatment or baby has not received perinatal HIV prophylaxis. Higher risk with vaginal delivery
What is the most common mode of transmission of AIDS for men and women world wide
Heterosexual spread. Highest in central/east africa
What co receptors are necessary for HIV entry into a cell
CCR5 - chemokine co receptors. These are located on the CD4 cells that the virus binds to
During HIV, B cells and macrophages are also infected, what effect does this have on the immune system
Because B cells need CD4 cells to induce proliferation, a lack of CD4 means a decrease in B cell antibody production. This can lead to hypergammaglobulinemia. This is a big reason why HIV patients are so susceptible to infection. Macrophages can disseminate to other organ system and carry the virus with it (i.e. CNS)
Orthotropic grafts
Tissue/organ that is placed in their normal anatomic location
Heterotopic grafts
Grafts that are placed into a site other than their normal one
Autografts
Grafts that are transferred from one part of an individual to another location on that same individual
Syngeneic grafts
Grafts transferred between 2 people who are almost identical (i.e. twins)
Allogeneic or allografts
Grafts transferred between 2 genetically disparate individuals of the same species (brother sister, parent child)
Xenogeneic grafts
Grafts that are exchanged between members of different species (i.e. primate heart into a human)
What is the major cause of host donor graft rejections
The MHC molecules differ between a host and a recipient which causes an immune attack against the foreign molecule. Can be the host cells that attack or the recipient cells that attack
How does graft rejection work (pathophysiology)
The genes of the graft tissue may encode “non self” molecules that will be detected by the recipient immune system. These become “antigens” to recipient and the CD8 cells (mostly) will bind to the MHC complex and kill new foreign graft cells
What are the 3 stages of rejection
- hyperacute
- acute
- chronic
2/3 establish blood flow. 1 does not
How do antibodies play a role in blood transfusion
natural antibodies (aka antibodies that are found in the body due to natural exposures) provide an attack on transferred blood. This is why the blood type has to match, other wise you get a reaction
How do antibodies play a role in graft transplant
Antibodies are made by B cells that attack against histocompatibility antigens on graft tissue. This is usually only seen in the hyper acute rejections
What is the main treatment for transplantation
Immunosuppression - involves blocking the general immune response (not specific)
What are 2 immunosuppressive techniques
- Irradiation
2. Toxic drugs that eliminate immune response
What are some risk factors associated with immunosuppression (long term)
- May be open to opportunistic infections
- Liver damage - extended use
- Secondary malignancy
- Increased risk of CV disease due to chronic inflammatory state
How does stem cell transplant work (hematopoietic)
Transplanting bone marrow from an immunocompetent person into an immunodeficient person
How does graft versus host disease occur (GVHD)
- Immunocompetent cells of donor recognize MHC antigens in the recipient as foreign and attack.
- Attack also stems from mature T cells. May be able to remove this before transplant in order to prevent
Host attacks recipient
What types of tissues is GVHD most commonly seen in
skin and GI tract
Once stem cells are transplanted what happens to them in order for the transfer to work
T cells generated by the stem cells undergo thymus education. Matching of host/recipient MHC genes occurs for selection events in the thymus. Once this occurs, the transplanted stem cells can function normally within the new body.
How does stem cell transplant happen
Patient is give lethal levels of immunosuppression (conditioning) to obliterate own bone marrow. They are then given donor stem cells.
What is the difference between transplant rejection and GVHD
In transplant rejection, the recipients T cells are attacking the tissue. Where as in GVHD the host T cells are attacking the recipient cells
What are the signs and symptoms of GVHD
- Fever
- Rash (81% of pts)
- Diarrhea
- lymphadenopathy
- hyperbilirubinemia (hepatitis)
What is the typical skin presentation of GVHD
Pruritic and maculopapular that spreads throughout the body but spares the scalp
What are the live donor requirements
- Consent
- No high BP, HIV, cancer, hepatitis
- No alcohol or drug abuse
- At least 18
- No psychological disease
Last 2x as long as deceased donors
What are the deceased donor requirements
- Consent prior to death
- Organ must still be viable and functioning
- Pt must be declared brain dead (different than CV death)
Indications for solid organ transplant
- Organ failure (i.e. ESRD)
- Cancer
- Autoimmune diseases
- Tissue damage
Risk of solid organ transplant
- Death
- opportunistic infections
- Rejection (hyperacute, acute, chronic)
- Organ failure, not rejection
Indications for bone marrow transplant
- Leukemia
- Lymphoma
- multiple myeloma
- aplastic anemia
- SCID
Risks of bone marrow transplant
- Death
- opportunistic infections
- secondary malignancy
- GVHD
- Rejection of stem cells
LONG TERM - Sterility, cataracts, musculoskeletal, secondary malignancies, organ failure
Pre-emptive kidney transplant
When a pt has a kidney transplant prior to going on dialysis. Kidney transplant is the preferred tx for ESRD when compared to dialysis
2 types of rejection
- Direct - Hosts immune system attack donor graft
2. Indirect - self attacking self
What are 2 remarkable features of HIV (diseases not seen and diseases seen)
- Low incidence of Listeriosis and aspergillosis
2. Frequent occurrence of neoplasms (lymphoma and Kaposi)
Immune system malfunction in systemic lupus erythematous
- Multisystem inflammatory disease
- Unknown cause, but may be due to antinuclear antibodies (which are auto self antibodies that bind to the cell nucleus)
What are some of the major autoimmune disorders
- Lupus
- Graves disease
- MS
- Psoriasis
- Crohns
- Type I
Clinical presentation of systemic lupus erythematosus
- Occurs in mainly young women
- FATIGUE-common, complaint, fever
- Butterfly rash
- Joint symptoms in 90% of pts
- Weight change
- Raynaud phenomenon
MULTI SYSTEM!!!!!
Immune system malfunction associated with Graves disease
Autoantibodies bind to TSH receptors which continually stimulates the release of TSH and thyroid growth hormone (causes goiters). Effects more women than men
Clinical presentation of Graves disease
- Exopthalamus
- Hyperactivity
- Anxiety
- Palpations/tachy
- Large goiter
- Enlarged thymus gland
- Weight loss - due to increased hyperactivity
- or weight gain due to increased appetite
Immune system malfunction of psoriasis
- Genetic
- Both innate and adaptive immunity disregulation that causes inflammation.
- Disregulation of immunity causes an inflammatory reaction with keratinocytes of the skin
Chronic inflammatory skin disease
Clinical presentation of psoriasis
- Silvery scales on bright red plaques
- Usually found on the extensor surfaces (elbows, knees, scalp)
- Can be systemic and spread all over
- Nail pitting/oncholysis
- Joint pain - some progress to psoriatic arthritis
Immune system malfunction of MS
- Still mostly unknown
- Breakdown of myelin sheaths
- Theory is that it begins as an inflammatory response mediated by auto reactive lymphocytes
Clinical presentation of MS
- Episodic neuro symptoms
- Pt usually under 55 yrs of age
- Muscle weakness, numbness, tingling
- Spastic paraparesis
- Vision loss
Immunes system malfunction of crohns disease
Chronic inflammatory malfunction of the GI tract, can affect entire (transmural) GI tract, but usually ileum and colon
Clinical presentation of crohns disease
- gradual onset
- Intermittent low grade fever, diarrhea
- RLQ pain
- Malabsorption
- Perianal disease with abscess/fistulas
Immune system malfunction of type I diabetes
Autoimmune destruction of the insulin-producing beta cells in the islets of langerhans (pancreas cells)
Clinical presentation of type I diabetes
- Affects young children
- More often boys
- Polyuria
- Polydipsia
- Weight loss
- High glucose levels
Acute cellular reaction is mediated by
T cells
Clinical presentation of rejection
Fever, pain over allograft, oliguria
Complications of immunosuppression
- infections
- Malignancy (kaposi, cervical, lymphomas)
- Medication specific complications
What types of immunosuppression drugs are used in the induction phase
Usually involves anti-lymphocyte antibodies
What types of immunosuppression drugs are used during the maintenance phase
Lifetime drugs, usually a combo of cytokine inhibitors, antimetabolites and steroids
3 sources of hematopoietic stem cells
- Bone marrow
- Cord blood
- Peripheral blood
Early opportunistic infections
- Herpes
- Oral candidiasis
- Donor infections
- Higher risk of bacterial infection from normal skin, GI flora
- Higher wound/catheter infection
Opportunistic infections post transplant 1-6mnts
- PCP
- Aspergillus
- Listeria
- Toxoplasmosis
- TB
- CMV!!!!! EXTREMELY COMMON IN TRANSPLANT PTS
- Herpes
Longer term risk for post transplant patients
GVHD, late viral infections, CMV, community acquired pneumonias
Why are immunosuppresents considered to have a narrow therapeutic window
- Too low = rejection
2. too high = nephrotoxicity
What is the number 1 cause of mortality in transplant patients
Cardiovascular disease
Must monitor BP, cholesterol, diabetes
Asplenia
Absence of a functioning spleen
What % of B cells are found in the spleen
50%
Why is the spleen important in B cell function
- Place where B cells opsonize bacteria
- Clearance of encapsulated organisms
- Eating old RBC
Effects of asplenia
- High risk of encapsulated bacterial infection - streptococcus pneumonia, neisseria
- High risk of uncommon gram - bacterial infections
Vaccination requirements in the immunocompromised patient
- Polysac vaccines for pneumococcus and meningococcus
- flu
- Influenze B
- Zoster/varicella
- Tdap
- MMR
- HPV
Direct rejection (or recognition)
Donor cell reacts with recipient T cells.
Indirect rejection (or recognition)
Recipient APC picks up antigen, then packages it as a peptide to present it to the T cell.
