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Identify two situations in which the direct antiglobulin test would be of value in diagnosis.

1. To ID whether a patient has hemolytic anemia or some other autoimmune disease.
2. To ID whether a newborn’s high bilirubin count is due to hemolytic disease of the newborn or something else.


describe Brutons (X linked hypogammaglobulinemia)

-block btwn pre B cells and B cells
-normal T and low B and Ab
-defective btk (tyrosine kinase gene)
-why we dont use live polio


Describe the immediate allergic reaction and the late-phase reaction in terms of time course of the reaction and mediators involved.

immediate rxn: secreted IgE immediately binds to mast cells, when 2 adjacent IgE are cross-linked by antigen for which they are both specific - preformed granules in mast cell released including: histamine, heparin, enzymes, TNF,
- v. rapid w/i 15 min. of exposure

Late phase: phospholipase PLA2 cleaves arachidonic acid from membrane phospholipids --> converted by cyclooxygenase to **prostaglandins or by lipooxygenase to **leukotrienes --> these initiate inflammation, constrict bronchioles = "eosinophilic chemotactic factor of anaphylaxis" ECF-A; mast cells also release cytokines;
- begins 4-10 hrs after exposure

** antihistamines effective for immediate rxn but anti-inflammatory needed for late phase rxn


Define heterophile antibody, and identify a common disease in which one type is increased enough to be useful diagnostically

-Ab to one antigen which bind, fortuitously, to another; a fancy name for cross-reactive antibodies

-Ex. EBV (mono) cross reacts w/ sheep blood (mono-spot test)
-Cardiolipin (from syphilis) cross reacts w/ beef heart


how can cell mediated and humoral immunity cause immunopathology?

humoral- serum Ab can cause serum sickness (type III- complexes)

cell mediated: Viruses that don’t have to appear in the blood or lymph, or go latent and express few proteins, are very hard for the immune system to deal with. Such a virus is herpes simplex type


A Antiglobulin (COOMBS) test uses antibody against human Ig to detect human Ig on the surface of ____ (direct test) or ___ (indirect)

red blood cells- direct

in plasma- indirect


Explain how red cells are destroyed following a mismatched transfusion, and why this may be devastating to the recipient.

This is important so that patients don’t create an immune response to the donated blood, activate complement-mediated hemolysis, get renal failure from free hemoglobin deposition in kidneys, die etc. You can also get high levels of bilirubinemia from hemolysis in neonates, jaundice, and damage to the basal ganglia from bilirubin crossing through the BBB and leading to cerebral palsy or death


Outline the Hygiene or Old Friends Hypothesis

exposure to harmless microorganisms e.g. non-tuberculosis Mycobacteria, lactobacilli, helminth worms, helps to develop a balance between Th1 and Th2 + right number of Tregs

-w/o exposure at critical development 0-2 yrs, you may be too ready to make a strong Th1 or Th2 response to gut flora or pollen


Explain the difference between ‘HIV-seropositive’ and ‘AIDS’

HIV-seropositive: if have antibody to HIV; most common way in which infection is first detected

- AIDS: when they get symptoms of opportunistic infections; or Kaposi's sarcoma; or Th (CD4⁺) fall to less than 200/ µL


Discuss the types of infections seen in AIDS patients, and provide an immunological basis for this spectrum

1. seropositive- asymptomatic

2. minor opportunistic infection (Candida albican of mouth, esophagus or rectum),
night sweats, wt. loss

3. major opportunisitc infections (TB, Kaposi sarcoma, Burkitt lymphoma, CD4 below 200)

4. Late AIDS dementia complex

*The infections seen in AIDS are primarily of types that require T cell-mediated immunity, as might be expected given the virus’ primary target
*Infections with opportunistic intracellular bacteria, usually Mycobacterium avium complex or MAC, and more and more commonly, M. tuberculosis, are frequent


define immediate hypersensitivity

aka Type I hypersensitivity

is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Type I immunopathology involves IgE and mast cells and can lead to anaphylaxis in severe cases.


Describe intradermal skin tests with reference to safety and specificity

- drop of allergen placed on skin --> fine hypodermic needle or lancet used to prick skin through drop --> observed for 15-20 minutes --> record diam of central raised wheal/diam. of flare e.g. 5/15 mm

--- (+)skin test does not necessarily mean that your symptoms due to that allergen;
-your level of sensitivity may be subclinical even w/ (+) test
- symptoms may be from something that cross-reacts w/ test extract


what are adjuvants

substances added to vaccines to make more immunogenic.
-They all seem to work by causing an innate immune response, which then leads to a more effective adaptive response.


Identify those organisms against which humoral immunity is most effective

"high-grade" Extracellular bacteria (most of the high-grade pathogens) are combated by Ab (Strep, Staph, H. flu)--> can be blocked from attachment to mucous membranes by IgA, once in the body opsonized by plasma Ab and complement--> some susceptible to lysis by MAC

ex. Neisseria gonorrhoeae
Staph. aureus
H. influenza
Strep. pneumoniae


Group O
describe the RC antigen, ABO antibody in plasma, who they can donate to and who they can receive from?

-RC antigen: none
-Ab in plasma: anti-A and anti-B
-Can donate to: ALL
-Can receive from: O

*most common (universal donor- except bom)


In hemolytic anemia of the newborn, explain:
The consequences of severe hemolysis in the newborn

mom's IgG crosses placenta and destroys fetus' RBCs --> fetus born jaundiced, dangerous b/c increased levels of bilirubin can cross BBB and damage basal ganglia --> CP, fetal death, kenicterus


describe CVID

-B cells are difficult to trigger to make specific Ab
-normal pre B and B but low Ab
-presents in 20-40y/o


give an example of a live virus vaccine and a possible associated hazard

-Sabin (attenuated, live) oral polio

-Can be shed and immunize others (good!)
-Arthus rxn (Type III because immune complex forms at injection site--> complement activation and attraction of neutrophils
-Harm Bruton hypogammaglobunemia patients

*IgA response


Identify those organisms against which cell-mediated immunity is most effective

Intracellular pathogens (mycobacteria, listeria, Brucella, TB)

*viruses, certain bacteria, yeasts, fungi (Candida albicans and Pneumocystis jirovecii


what is the only approved adjuvant in the US

alum, a hydrated potassium aluminum sulfate


Describe the contents of commercial gamma globulin and indicate the conditions in which it can be useful replacement therapy. Compare and contrast intramuscular and intravenous therapy

-pooled IgG from many donors; half-life of 3 weeks

- IM: painful, compliance problems
- IVIg: effective but expensive, in short supply

*if pt.. has IgA def, the infusion may provoke an allergic or immune complex rxn


Discuss transplantation therapy in immunodeficiency diseases. Include a consideration of side effects

- DiGeorge: fetal thymus w/ good partial MHC I and II match; or cultured thymic stromal cells to minimize GVH dz

- SCID: bone marrow transplantation has 50% success rate, GVH dz risk (type IV immunopathology)
* better to transplant stem cells than whole bone marrow; sibling donors are best; good MHC II match imperative

- ADA-deficiency get transfusions of irradiated RBCs or purified ADA


define hives, wheals and flare reaction

an allergic disorder marked by raised edematous red patches of skin or mucous membrane and usually by intense itching and caused by contact with a specific precipitating factor (as a food, drug, or inhalant) either externally or internally—called also urticaria

-"hive" occurs w/i 15 min of intradermal injection of an allergen; histamine granule most important causes itch, blood, vessel dilation, leakiness but ½ life 1 min. therefore rxn is transient


presents w/ viral infections and fungal infections
-abnormal pouches, heart, cleft palate




Explain the situation in which ABO hemolytic disease of the newborn can occur

-occasionally people make IgG isohemagglutinins (usu. IgM only b/c it is a carb antigen); especially true of type O women therefore A or B fetus at some risk of ABO hemolytic dz

- no RhoGam b/c in this case the issue isn't the crossing of baby blood out into the mother's circulation but rather the IgG crossing placenta to baby


Major crossmatch answers the question of

whether there are antibodies in the recipient’s plasma that will react with antigens on the donor’s RBCs


Given a child with recurrent infections, describe in principle tests which could be done to determine if there is a:

- Complement: CH₅₀; assay for C1inhibitor; indiv. complement component levels


___ test detects cells that were coated with antibody in vivo. Useful in questions of autoimmunity (hemolytic anemia). The antiglobulin will lead to crosslinking and agglutination

The direct test


and discuss the rate of change in HIV incidences

-heterosexual HIV half of new cases; half of that women, girls
- w/ new treatments decreased death rates significantly; 28-40% of HIV+ patients survive at least 10 year

- link btw HLA and susceptibility: LTS are either homogenous for CCR5 (delta32) or elite controllers w/ HLA-B57 and don't progress to AIDS bc they make effective CTL to HIV peptides


Given a child with recurrent infections, describe in principle tests which could be done to determine if there is a:
B cell deficiency

- B cells: IgG, IgA, IgM levels; Abs to prev. immunizations; ABO isohemagglutinins; Ab response to novel Ags; gene sequencing