Unit 8-10 Flashcards
(122 cards)
1
Q
Identify two situations in which the direct antiglobulin test would be of value in diagnosis.
A
- To ID whether a patient has hemolytic anemia or some other autoimmune disease.
- To ID whether a newborn’s high bilirubin count is due to hemolytic disease of the newborn or something else.
2
Q
describe Brutons (X linked hypogammaglobulinemia)
A
- 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
3
Q
Describe the immediate allergic reaction and the late-phase reaction in terms of time course of the reaction and mediators involved.
A
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
4
Q
Define heterophile antibody, and identify a common disease in which one type is increased enough to be useful diagnostically
A
-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
5
Q
how can cell mediated and humoral immunity cause immunopathology?
A
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
6
Q
A Antiglobulin (COOMBS) test uses antibody against human Ig to detect human Ig on the surface of ____ (direct test) or ___ (indirect)
A
red blood cells- direct
in plasma- indirect
7
Q
Explain how red cells are destroyed following a mismatched transfusion, and why this may be devastating to the recipient.
A
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
8
Q
Outline the Hygiene or Old Friends Hypothesis
A
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
9
Q
Explain the difference between ‘HIV-seropositive’ and ‘AIDS’
A
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
10
Q
Discuss the types of infections seen in AIDS patients, and provide an immunological basis for this spectrum
A
- seropositive- asymptomatic
- minor opportunistic infection (Candida albican of mouth, esophagus or rectum),
night sweats, wt. loss - major opportunisitc infections (TB, Kaposi sarcoma, Burkitt lymphoma, CD4 below 200)
- 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
11
Q
define immediate hypersensitivity
A
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.
12
Q
Describe intradermal skin tests with reference to safety and specificity
A
- 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
13
Q
what are adjuvants
A
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.
14
Q
Identify those organisms against which humoral immunity is most effective
A
“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
15
Q
Group O
describe the RC antigen, ABO antibody in plasma, who they can donate to and who they can receive from?
A
- 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)
16
Q
In hemolytic anemia of the newborn, explain:
The consequences of severe hemolysis in the newborn
A
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
17
Q
describe CVID
A
- B cells are difficult to trigger to make specific Ab
- normal pre B and B but low Ab
- presents in 20-40y/o
18
Q
give an example of a live virus vaccine and a possible associated hazard
A
-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
19
Q
Identify those organisms against which cell-mediated immunity is most effective
A
Intracellular pathogens (mycobacteria, listeria, Brucella, TB)
*viruses, certain bacteria, yeasts, fungi (Candida albicans and Pneumocystis jirovecii
20
Q
what is the only approved adjuvant in the US
A
alum, a hydrated potassium aluminum sulfate
21
Q
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
A
-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
22
Q
Discuss transplantation therapy in immunodeficiency diseases. Include a consideration of side effects
A
- 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
23
Q
define hives, wheals and flare reaction
A
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
24
Q
presents w/ viral infections and fungal infections
- convulsions
- abnormal pouches, heart, cleft palate
A
CATCH22
DiGeorge
25
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
26
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
27
Given a child with recurrent infections, describe in principle tests which could be done to determine if there is a:
complement
- Complement: CH₅₀; assay for C1inhibitor; indiv. complement component levels
28
___ 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
29
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
30
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
31
give an example of a toxoid and a possible associated hazard
- Tetanus, diphtheria, botulinum
| - Good for 10-20 years, need booster
32
Explain the ABO antigen situation in a person of Bombay blood type, and the consequences of a transfusion of non-Bombay blood into such a patient
- lacking transferase gene that puts final sugar on core therefore, do not express even the H antigen like in type O
- v. rare but all blood, even type O, is foreign
33
give an example of a human anti-toxin and a possible associated hazard
- Tetanus, rabies, hepatitis, chicken pox, rattlesnake
| - Cannot use IV because IgG aggregates, activates complement, reaction to IgA
34
Discuss the reasons for using glucocorticoids in asthma treatment.
- untreated chronic inflammation leads to fibrosis, irreversible therefore glucocorticoids used w/o serious side effects to decrease inflammation
- excellent when effects kept local; e.g. inhaler or ointment; risky w/ mult. side effects when used systemically b/c inhibit production of arachidonic acid from phospholipds and thus block both PG and LT synthesis; also induce apoptosis in eosinophils
35
In hemolytic anemia of the newborn, explain:
| The way in which the mother becomes sensitized
in last trimester and at birth some of baby's Rh(D)⁺ cells cross into Rh(D)⁻ mom's circulation; also can occur in abortion, fetal manipulations,
*But in a subsequent pregnancy with another Rh(D)+ fetus, the mother’s antibodies (IgG), formed after the first pregnancy, can cross the placenta and destroy the fetus’ red blood cells. In addition, each subsequent pregnancy with an Rh(D)+ fetus boosts her response.
36
explain the difference between type and screen and cross match and explain why they are important
- type and screen: all donor units of blood typed for ABO and Rh; tested for presence of unexpected Ab; tested for syphilis, hep B and C, HIV, WNV Ab
- crossmatch: are there unexpected Abs in this recipient's plasma which react w/ antigens on this donor's RBCs? --> test by mixing plasma from recipient w/ RBCs of donor
37
define asthma
- both bronchoconstrictive and inflammatory, and not considered a mild disease. The late inflammatory changes require specific treatment, with the aim of maintaining good control now, to avoid fibrosis in the future.
- a chronic lung disorder that is marked by recurring episodes of airway obstruction (as from bronchospasm) manifested by labored breathing accompanied especially by wheezing and coughing and by a sense of constriction in the chest, and that is triggered by hyperreactivity to various stimuli (as allergens or rapid change in air temperature)
38
Group AB
| describe the RC antigen, ABO antibody in plasma, who they can donate to and who they can receive from?
- RC antigen: A and B
- Ab in plasma: none
- Can donate to: AB
- Can receive from: ALL
*least common (universal recipient)
39
what type of immunity controls spreading of the virus in the body
IgG, phagocytes
40
what produces the longest lasting immunity
- Natural, active immunity is most long-lasting
| - Live vaccine- good because can spread immunity by shedding and because IgA prevent colonization
41
where are T and B cell areas in a lymph node?
Cortex: B and Tfh cells
Deep (para) cortex: T cells
Germinal center in lymphoid follicle: dividing B cells
42
Characterize the infections you would expect in a pure T cell deficiency
T cell def: severe infxns w/ intracellular pathogens incl viruses, certain bacteria, yeasts, fungi, esp. Candida, Pneumocyctis; viruses b/c need CTL to destroy infected cells, Tfh to force class switch for protein antigens;
* abnormal gut organisms w/ either type of dz therefore diarrhea and malabsorption frequent complaints, and failure to grow
43
when do children get immunized for diptheria, pertussis, tetanus, polio and measles
DaPT: 2-4-6 months (blanket onset of IgG production)
IPV: 2-4-6 months and booster at 4-6y/o
MMR: 12-15 months
44
describe HyperIgM
- defective CD40 or CD40L so IgM can't class swithc
| - high IgM, low IgA, IgG
45
define herd immunity
Proportion of given population that has immunity to a given infection
46
describe SCID
-blocked lymphoid stem cell development
-no T or B cells
-poor prognosis- maternal IgG is somehwat protective
-50% X linked recessive- gene for gamma chain
50% auto. recessive-lack ADA- adenosine accumulates
47
Describe the mechanism of IgE-mediated hypersensitivity in terms of: IgE attachment to basophils or mast cells; reaction with allergens; mediator release; effects of mediators on target tissues and cells
IgE binds strongly to FcɛR1 receptors on the surface of mast cells. When 2 adjacent IgE molecules so bound are cross-linked by a specific allergen, the mast cell is signaled to release the contents of its characteristic granules, including histamine, which causes local or systemic vasodilation and increased permeability, and gut and bronchial smooth muscle contraction.
- IgE production is Th2 and IL-4 dependent; development of symptomatic levels slow, boosted by multiple exposures
- propensity to make excessive IgE genetic, some due to early postnatal development
48
Given a child with recurrent infections, describe in principle tests which could be done to determine if there is a:
phagocyte
- Phagocytes: WBC count w/ diff & morphology; NBT test, oxidative burst; assay for phagocytosis chemotaxis; genetics
49
Describe the immunological problem of the Nude Mouse, and name the human immunodeficiency condition it resembles
similar to Di George: fail to make thymic stroma and hair, no T cells
50
what type of immunity controls recovery from viral disease
T-cell mediated,
| CTL-MHCI-CD8
51
Group A
| describe the RC antigen, ABO antibody in plasma, who they can donate to and who they can receive from?
- RC antigen: A
- Ab in plasma: anti-B
- Can donate to: A, AB
- Can receive from: A, O
52
Characterize the infections you would expect in a pure B cell deficiency
B cell def: "high-grade" infxns extracellular, pyogenic bacterial pathogens e.g. Staph aureus, H. flu, Strep pneumo; enteroviruses get in b/c not enough IgA; susceptible to bacterial infxn b/c lack of IgM to carb antigens
53
Identify the oral and parenteral polio vaccines by the names of their developers. Discuss their relative advantages and disadvantages, and note which is currently used in the USA
Salk:
- Killed, injected polio vaccine
- Currently used in USA
- (-) lack of IgA
- IgG response
- Herd immunity only with high vaccine rate not shed
Sabin:
- Attenuated, live oral polio vaccine
- IgA development
- Shed virus for herd immunity
- Risk for vaccine-associated paralytic poliomyelitis (rare)
54
Name the antibody class of most ABO isohemagglutinins
IgM
*because these carbohydrates are naturally occurring in the environment and you have likely made antibodies to them in response to these common antigen exposures
55
give an example of a killed virus vaccine and a possible associated hazard
- Salk (killed, injected) polio
- Doesn’t work for immunocompromised
* IgG response
56
Name two viruses, which are immunosuppressive in humans. Discuss a possible mechanism for the immunosuppression caused by one of these viruses.
AIDS
CMV
Measles
EBV/mono
*HIV infects helper T cells, macrophages, dendritic cells, leading to impaired cell-mediated immunity and severe immunosuppression.
57
Discuss reasons for the apparent ineffectiveness of antibody in HIV infection
- when host cell is replicating HIV gp120 made first → inserts in host plasma → fuses cell with other uninfected CD4 cells → forms syncytium;
- method for spread w/o extracellular phase where Ab would be effective
- people do make HIV Ab but not effective in protection
- people w/ HIV infection have Th2/Tfh dominated helper T cell response vs. those with more Th1 ↔ CTL against HIV antigens have better prognosis
58
isohemagglutinins are ___
| Anti-Rh antibodies are ___
IgM
| IgG
59
presents recurrent bacterial infection, increased risk for lymphoma, enteropathy, and autoimmune
CVID
60
define local immunity and give an example
- Local immunity is on the surface that is being invaded (nasopharynx, GU, GI tract) with secretory IgA
- Ex. W/ Sabin (attenuated, live) OPV people have high levels of IgA and therefore do not get colonized
61
Positive IgM antibody titers before day 14 indicates
prior infection
*the rash appears 14 days after exposure. IgM rises shortly after the rash, peaks 10 days later, and falls to undetectable at about 50 days
62
Name the virus that causes AIDS, and its classification
Human Immunodeficiency Virus-1 (HIV-2 is isolated in West Africa)
RNA virus; nontransforming retrovirus; carries no oncogene; RNA --> DNA by reverse transcriptase
- most antigenically variable pathogenic virus b/c reverse transcriptase error prone
63
Identify the approximate number of cases in the U.S. and in the world
- World: 36.7 million (1.8 million under 15 y/o)
- USA: 1,100,000 people and 16% dont know it
- CO: 12,7000
64
Discuss the pathogenesis of AIDS, including target cell types, mode of entry of the virus into a cell and mode of exit
- virus enters body → adheres to lectin on DC → carried to lymph nodes
- target cell types: binds gp120 to CD4 on Th cells
- mode of entry of virus into cell: gp120 binds CD4 → conf.∆ → binds chemokine co-receptor CCR5 or CXCR4 → conf.∆ of HIV gp41 → exposes hydrophobic region → melts Th membrane → Th + virus fuse → HIV injects core → activates reverse transcriptase RNA → DNA → moves into nucleus → viral integrase inserts into host's DNA → latent virus
- mode of exit: virus buds from cell tearing holes in membrane killing cell;
65
```
In hemolytic anemia of the newborn, explain:
The class of antibody to Rh(D) the mother makes
```
Anti-Rh antibodies are IgG (being anti-proteins), and do cross the placenta
66
What does it mean if there is agglutination or no agglutination w/ cross matching?
agglutination: probably by complement activating IgM
No agglutination: RBCs still can be opsonized
if poor match: decreased survival of RBCs, and decreased pt survival
67
Discuss the prospects and problems of AIDS vaccine development
1. HIV exhibits tremendous global genetic diversity.
2. Its immense mutational capacity allows evasion of both T and B cell immunity.
3. HIV goes latent in the host genome, from which it cannot be eliminated by conventional antiretroviral drugs.
4. There has been no known example of spontaneous immune clearance, to use as the basis for data-driven vaccine design (one person after a BMT but likely due to CCR5 Delta 32 mutation from donor blocking HIV virus from binding gp120 to CCR5).
5. Although bnAbs have been found, they are rare, only found in a subgroup, take years to develop, and are extensively hypermutated; no method exists now for induction of these Abs by immunization.
6. But a lot of smart people think that they can figure out a way to make these epitopes immunogenic in everybody.
68
Describe the laboratory diagnosis of AIDS.
most common is HIV Ab measured w/ ELISA
--> if (+) must be confirmed w/ Western blot
- (Oraquick) saliva test --> if (+) --> must be confirmed by lab
- CD4 < 200 cells /µL
69
High-grade, extracellular bacterial pathogens are less of a problem with AIDS, possibly because
the ability to make Tfh-independent antibody responses to capsular polysaccharides is preserved.
70
give an example of a animal anti-toxin and a possible associated hazard
- anti-snake venom, horse antiserum against streptococcus pneumoniae, diphtheria
- Risk of serum sickness
71
Discuss the incidence of selective IgA deficiency, and the associated syndromes
- most common immunodeficiency dz (1 in 500 persons), most people fine b/c replaced by IgM
- usually asymptomatic, pt. might have diarrhea and sinopulmonary infxn or increased freq. and severity of allergies; repeated infxns in mucosa? --> DDx should include IgA def
72
Discuss the origin of the AIDS virus and the origins of the current epidemic
-most closely related to Simian Immuno deficiency Virus (SIV)
- evolved as recently as 1940s in Zaire (D. R. Congo)
- seroepidemiology: Africa --> Caribbean mid-1960s --> Europe --> USA (NY, LA, SF) probably by homosexual men vacationing in Haiti
- first sera w/ HIV-1 in D.R. Congo 1959; 1978 USA
73
Define and discuss “elite controllers"
maintain undetectable amounts of HIV in the blood without treatment--> dont progress to AIDS
*bc of HLA-B57
They make effective CTL to HIV peptides presented in HLA-B57. There is a good correlation between HIV-specific CTL numbers and prognosis (because ab doesn’t really help).
74
Discuss possible reasons for which the total number of CD4 cells in AIDS patients decline
b/c targets of HIV by gp120 binding and infecting and eventually destroying and forming syncytium; bone marrow burn out
75
In hemolytic anemia of the newborn, explain:
| The role of Rh-immune globulin.
given at delivery of first Rh(D)⁺ baby b/c it can opsonize any fetal RBCs and they will be destroyed by phagocytes before mom can become immunized, also given at 28 weeks to prevent immunization by small transplacental bleeds,
--> RhoGAM is IgG to Rh(D) and it binds it up before it can be detected
76
define anaphylaxis
severe IgE reaction to an antigen after re-exposure. Leads to dyspnea, diarrhea, shock, and sometimes death
77
herd effect decreases infection rate in non-immune part of herd/community due to 2 probabilities:
1. Chance that a susceptible, non-immune member will contact an infectious member (decreases w/ more immunized people)
2. If contact does occur, probably of transmission (infectivity of disease organism)
*If pathogen is highly infective need you need increased herd immunity % to get herd effect
78
State the approximate incidence of atopic diseases in the general population, and in individuals with allergic parents
- Allergic disease is among the most common conditions suffered by human
- 15-20% of people have it
- risk ≈ 35% if have one allergic parent
- risk ≈ 65% w/ two allergic parents
79
Discuss the features that the various atopic diseases have in common which justify lumping them together
begin life as infant w/ eczema (atopic dermatitis) --> allergies to milk, fish, eggs --> develop asthma in middle school or hay fever in college
*It is an atypical immune response to environmental antigens, and is also characterized by increased reactivity or hypersensitivity of the end-organs to inflammatory mediators and irritants.
80
Discuss the use of IgG and IgM antibody titers in the diagnosis of intrauterine and neonatal infections
- IgM indicates recent infection
- Newborns will have increased IgG anti-rubella too, but this is from mom
- IgG can be from past infection, from mom or if rising indicates active infection
81
define atopic
a genetic disposition to develop an allergic reaction (as allergic rhinitis, asthma, or atopic dermatitis) and produce elevated levels of IgE upon exposure to an environmental antigen and especially one inhaled or ingested
82
Discuss why live viral vaccines tend to be ineffective in the very young
- Children in the first year or two of life are poor at T-independent antibody --> couple w/ carrier protein to help Tfh cells respond and get Ab response
- Before 1 yr. mothers IgG partially neutralizes live virus vaccines so they don't grow into a fully immunogenic dose
83
Discuss the possible roles of Th1 and CTL in recovery from virus infection
DCs pick up debris from free virus--> process to peptides--> present on MHC II to Th1 and on MHC I to CTL--> CTL w/ Th1 help can activate
84
Name the enzyme which is absent in some cases of SCID. Discuss approaches to replacing this enzyme that are currently used
-adenosine deaminase (ADA)
- easy to transfuse RBCs or synthesized ADA
- transfusions of irradiated RBCs
- gene replacement therapy
85
In hemolytic anemia of the newborn, explain:
| The consequences of sensitization to subsequent fetuses
if mom making anti Rh(D) Ab, it is IgG and can cross placenta and destroy fetus' RBCs --> kenicterus; HDN
86
Distinguish between the roles of Th1 and Th2/Tfh in the progression of HIV infections
- HIV targets Th cells
- perhaps the way HIV loads into DC polarizes it so that it favors Th2/Tfh over Th1 therefore not as aggressive of a response
- HIV+ pts w/ good CTL against HIV have a better prognosis, perhaps more Th1
87
measuring titer of isohemagglutinins can be of use in Dx of ___ bc __
B cell immunodeficiency b/c should appear btw 3-6 mo of age
88
define allergy, allergen
the antigens identified in allergy studies that bind to IgE/mast cells
89
what type of immunity prevents viral infection
humoral Ab, IgA, IgG
90
discuss the pathogenesis of AIDs from Latency vs productive infection
- latency versus productive infection: viral DNA can be latent lysogenic cycle; when replicating gp120 made first, inserts in host plasma, fuses cell with uninfected CD4 forms syncytium;
- if viral load down to 50 particles/mL slows/halts dz progression
* *people w/ two CCR5 alleles w/32 bp deletions do not express surface CCR5 ∴ can be chronically infected in DCs and marcrophages but not Th cells
91
Describe DiGeorges
- deletion on chrom. 22
| - pharyngeal pouches develop abnormally so fail to make thymic stroma
92
Identify two situations in which the indirect antiglobulin test would be of value in diagnosis.
1. To ID whether a donor’s blood is a good match for a recipient or if there will be an antibody/complement response.
2. To ID whether an Rh(D)- woman is already immunized to Rh(D)+ cells from a previous pregnancy, perhaps leading to frequent miscarriages.
93
presents w/ bacterial infections (pneumonia, chronic diarrhea), enterovirus and polio
Brutons (X linked hypogammaglobulinemia)
94
Given a child with recurrent infections, describe in principle tests which could be done to determine if there is a:
T cell deficiency
- FamHx, PMH, PE: growth, tonsils visible?, lymph nodes palpable, DiGeorge abnormalities
- T cells: skin test w/ recall Ag pane; total lymphocyte count; CD3, CD4, CD8 counts;
95
Describe the clinical features which, although not immunological, are associated with DiGeorge syndrome
- hypocalcemia --> convulsion
- heart defects, e.g. Tetralogy of Fallot
- hypertelorism, down-slanting eyes, fishmouth, micrognathia, low-set ears
- cleft palate
96
Discuss the roles of IgG and IgE in helminth immunity
worm infestation --> make IgG and IgE --> IgG binds worm or ova -->activates complement (worms impervious) --> C3a + C5a attract neutrophils --> neutrophils arrive, seize opsonized worm --> nothing --> worm sheds antigens --> diffuse to mast cells loaded w/ anti-helminth IgE
IgE: IgE cross-linked by antigen --> mast cells degranulate --> histamine causes gut smooth muscle contraction--> violent peristalsis--> worm expulsion --> late phase PGs and LTs elaborated --> attract eosinophils w/ Fc receptors --> binds to IgG coating worm --> eosinophil engaged w/ opsonized worm -->release of granules incl. Major Basic Protein (MBP) which is highly toxic to helminths -->Th2 attracts eosinophils & macrophages --> Th2 released IL-4, IL-5, IL-13 turn macrophages into M2 --> wall off parasite infection
97
Group B
| describe the RC antigen, ABO antibody in plasma, who they can donate to and who they can receive from?
- RC antigen: B
- Ab in plasma: anti-A
- Can donate to: A, AB
- Can receive from: B, O
98
Compare and contrast the techniques of the direct and indirect antiglobulin tests and the questions they are designed to answer
Direct Antiglobulin Test: is there Ab already on these cells I am interested in? rinse cells, add antiglobulin --> detects cells already coated w/ Ab
take RBC and wash them--> add antibody agasint human IgG--> if they had some human IgG sticking ot their surface this "antiglobulin" could cross link it
- Indirect Antiglobulin Test: is there unexpected Ab to RBC antigens (donor) in this plasma (of recipient)? take red cells, add plasma, rinse cells (we assume they haven't agglutinated them) --> add antiglobulin--> if cells now agglutinate there must have been Ab to them in the plasma (bc antiglobulin alone won't react w/ red cells)
* agglutination from cross-linkage w/ Ab
99
the molecular and cellular details of the immunologic mechanisms by which tissue damage can occur in a Type II autoantibody-mediated reaction
1. complement mediated damage
| 2. Stimulatory hypersensitivity
100
Describe the molecular and cellular details of the immunologic mechanism COMPLEMENT MEDIATED DAMAGE in a Type II autoantibody-mediated reaction
- Tissues against Ab are made and can be damaged by:
1. lysis (ex. RBC in AI hemolytic anemia)
2. phagocytosis (ex. platelets in AI thrombocytopenia purpura)
3. Release of phagocytes lysozomal enzymes and reactive oxygen species (ex. Goodpasture and myastheia gravis)
101
Describe the molecular and cellular details of the immunologic mechanism STIMLUATORY HYPERSENSITIVITY DAMAGE in a Type II autoantibody-mediated reaction
- Auto-Ab against a cell surface receptor-- may behave like an agonist mimicking a HR
- Ex. LATS (aka IgG) binds to TSH receptor and stimulates TH release --> results in hyperthyroidism/Graves
102
Give an example of a Type II mechanism disease of muscle, kidney, heart, red cells, and thyroid
Muscle- Myasthenia Gravis against myosin and ACh receptors
Lung and Kidney- Goodpasture’s Disease against lung and kidney basement membrane Type IV collagen
Heart- rheumatic fever post Group A Streptococcus infx, Dressler’s Syndrome post MI
Red cells- autoimmune hemolytic anemia induced by viral infx, cancer, autoimmune syndromes, drugs like PCN, and cold temperature rarely
Thyroid- Grave’s disease against TSH receptor
103
Distinguish between the “lumpy-bumpy” and “linear” immunofluorescent patterns in terms of the most probable immunopathologies they represent.
Lumps: probably clusters of antigen-antibody complexes stuck in the basement membrane (ie type III immunopathology).
Linear: probably antibodies that directly attack the basement membrane, all lined up in a row on the membrane (ie type II immunopathology-- Goodpasture
104
Describe how antibody-mediated tissue damage could result from:
-Cross-reaction of a foreign antigen with self
- Structural similarities between foreign antigen epitope with self, that leads to antibody binding and destruction
ex. rheumatic fever between Group A strep and valves of heart muscle and thrombocytopenia purpura-platelets
105
Describe how antibody-mediated tissue damage could result from:
-Coupling self antigen with a foreign antigenic "carrier"
- Hybrid (foreign + self) antigen formation
- a foreign antigen were to couple to the self-antigen. The anti-self B cell could bind to the self part and ingest it, carrying along the coupled foreign antigen. Then foreign epitopes might be presented to a Tfh cell on the B cell’s Class II MHC. The B cell would have received all necessary signals and become activated. Then it would make its antibody, against self → tissue damage. It would also be instructed by the Tfh to class-switch.
- This process has been called “illicit help.”
ex. Celiac Disease- tissue transglutaminase II + gliadin
106
Describe how antibody-mediated tissue damage could result from:
-Exposure of a sequestered antigen
- There are self-antigens that the immune system don't generally see (brain stuff, testicular stuff) so are not normally immunogenic. If they get out into the bloodstream, for whatever reason, they can trigger immune responses because there's been no negative selection against those self antigens.
ex. mumps breaks down the blood/testis barrier, allowing immunization to sperm antigen causing infertility
107
Describe how antibody-mediated tissue damage could result from:
-Inadequacy of regulatory T cells
A proper balance between Th1, Th2, and Treg activity usually assures that immune responses are appropriate. Does this balance get perturbed in some way, so that some responses are exaggerated, and eventually self/non-self discrimination breaks down?
108
Identify “Rheumatoid Factor” and describe its molecular nature
the stuff that shows up in the joints of patients with rheumatoid arthritis.
-Molecular nature: it's IgM antibodies made against IgG antibodies. Etiology unknown
109
Name a condition in which antibody stimulates rather than inhibits or harms its target cell.
Graves Disease
‘long-acting thyroid stimulator’ found in the blood of most patients with hyperthyroidism. LATS, as it was called for a long time, is simply an IgG antibody to the TSH (thyroid-stimulating hormone) receptor on thyroid cells; when it binds to these receptors, it mimics TSH and causes the cell to secrete thyroid hormones. Of course, the normal feedback controls won’t work in this case, so the result is hyperthyroidism, or Graves disease.
110
Discuss the idea that switching from Th1 and Th2 to Treg responses may be a way to treat autoimmune disease
-changing the binding affinity of ligands for MHC can alter the type of T-cell that responds and may ultimately be able to prevent or treat autoimmune diseases.
- linked to IBS
- there is normally abudnatn TGFB int eh submucosal Peyer's Patches, and that favors the differentiation of Th0 into Treg. Thus these sites are rich in Treg cells, which is desirable considering the constant bombardment w/ bacteria- and food- derived potential immunogens coming through the gut-lining
- TGFB and IL-6 together downregulates Treg and up regulates Th17
111
Describe the mechanism involved in Type III immune complex disease
- complexes + complement can accumulate in capillary beds (where there is net outflow of fluid) including: joints, pleura, peritoneum, skin, choroid plexus, kidney
- too large to pass through basement membranes and small blood vessels →vasculitis - stuck in BM → removal delayed, inefficient, or impossible, then prolonged or chronic inflammation can result b/c activate complement
- C3a and C5a attract neutrophils that arrive and release inflammatory factors includeing proteases and H₂O₂ → degrade BM
- release of histamine → ↑inflammation
112
Discuss the types of tissues in which damage is most likely to occur from deposition of immune complexes
- Anywhere were there is net outflow of fluid
- number one is kidney!
- in capillary beds → vasculites
- joints, lung pleura, peritoneum, skin (esp. on shins/lower legs where BP is high), choroid plexus, kidney
113
Define rheumatoid factor and discuss its components
- RF is a Type III w/ elements of Type II and Type IV b/c it is an IgM antibody to the patient's own IgG → forms complexes
- also Th1 cells against joint antigens ∴ Type IV
- b/c it is an autoantibody, Type II
114
Discuss the pathogenesis of post-streptococcal glomerulonephritis
- GA β hemolytic Strep pyogenes infxn that also causes type II immunopathology w/ rheumatic fever heart disease can lead to → lumpy-bumpy immune complex deposition in the kidney
- Sx begin 10-14 days after infection (strep throat, scarlet fever, impetigo of skin) and are typical of Type III (antibody/strep antigen complexes forming), with the kidney being the most affected site.
115
Discuss the pathogenesis of Farmer’s Lung
HYPERSENSITIVITY PNEUMONITIS
- exposure tho thermophilic actinomycetes a filamentous bacteria in moldy hay and silage → serum IgG Ab to the Actinomycetes builds up over time from chronic exposure→ inhale antigen → formation of antigen-Ab complexes in lungs that diffuse through alveoli into capillaries → complement and neutrophils arrive and cause sx--> acute attack will start 4 to 8 hours after the exposure--> As time goes on, the antibodies become less important, and Th1 immunity starts to predominate.
- often considered allergic Type I dz but actually Type II b/c of complexes
116
Define Type IV immunopathology
- T-cell mediated and delayed hypersensitivity
- immunization and effector phases: initiation exposure DC binds antigen on MHC → lymph node → Th1 cells activated → elicitation w/ 2nd exposure → memory T activated in area of antigen contact → release of IFNγ → ↑M1 macrophages → ↑inflammation in 6-12 hrs w/ peak at 24-48 hrs → ↑Memory T cells
* * e.g. poison ivy, contact dermatitis (latex, nickle, neomycin, detergents, chemicals, etc.)
- Tx: avoidance, topical steroid creams
117
Describe the cellular and molecular events following intradermal injection of tuberculin antigen into a person who have cell-mediated immunity to it. Justify calling the process ‘delayed hypersensitivity’. Characterize the cells that would be seen in a 48-hour biopsy of the site with regard to whether T cells or macrophages predominate
- Mantoux skin test is 0.1 mL of Purified Protein Derivative → injected intradermally → antigen taken up by local macrophages and DCs → presented on MHC II → if have anti-Tb Th1 → induration wheal full of macrophages
- this does is v. small so cannot immunize patient, but can elicit rxn in person w/ anti-Tb
- The induration is significant, since it represents a cellular infiltrate. You may remember that one activated Th1 can attract 1000 macrophages, so these macrophages, not Th1, would be the predominant cell you’d see if you biopsied the site at 48 hours
118
Explain why a person usually has no observed symptoms when first exposed to poison ivy
by time the activated T cells launched, antigen is gone
- The first exposure leads to sensitization that decreases the threshold for subsequent response due to memory cells. Thus, the second reaction occurs much more quickly and aggressively, creating the classic blistering rash in poison ivy
- contains a compound which can penetrate intact skin and become associated with MHC on dendritic cells. The dendritic cell leaves the skin and travels to the draining lymph nodes, where it presents its MHC to the appropriate precursors, which develop primarily into Th1 cells. These begin to divide in the usual way, but by the time increased numbers of them are in the circulation, the antigen has been washed or worn off the skin, and there is no reaction
119
Explain why TB skin tests can be administered repeatedly to the same subject
Memory cells decrease level of antigen needed to create a measurable response if previous sensitization (via exposure or vaccination) has occurred.
*Thus, the levels is sufficient to generate an induration if person has TB, but not enough to immunize the recipient if they do not have the disease.
120
Differentiate between a first-set and second-set graft rejection
- grafts recognized b/c T cell receptors look at MHC → T cell probably interprets this as it's own MHC + foreign antigen → activate → swift rxn that includes allograft memory
- first set rxn: graft → 5-10% of T cells react to foreign MHC → 10-20 days for response → ↑↑anti-MHC Th1 and CTL
- second set rxn: another graft from same donor placed → rejected w/in 5-10 days b/c of T cell memory
121
Discuss how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.
brain is antigenic but not immunogenic, meaning that immune cells have not seen brain tissue ∴ cannot launch immune response b/c require professional antigen-presenting cells, innate response, cell damage → however, if similar enough brain is introduced into the human body (e.g. meat-packing plant story, neurology resident blender accident story), recognized as foreign, picked up by DCs → brought to lymph nodes → T cell activation → activated T cells can then cross BBB and cause encephalitis
122
Discuss the requirements for graft-versus-host disease to occur
graft w/ T cells will recognize HLA antigens of recipient/host as foreign → graft will try to reject the host →→ the host will usually reject the grafted lymphocytes first
-These 3 conditions must be met:
→ graft must contain immunocompetent T cells
→ must be at least 1 antigen in host which graft's T cells recognize
→ host must be immunoincompetent or unable to recognize graft's MHC
