Exam 4 Flashcards
What steps are involved in diagnosis of allergy?
- comprehensive history
- physical exam
- non-immunologic tests
- immunologic tests
What is the purpose of a physical exam when diagnosing allergy?
rule out other causes
examples of immunologic diagnostic tests for allergy
- in-vivo: allergy skin test
- in-vitro: IgE antibody
- provocative and elimination tests
types of skin tests
- cutaneous: prick, puncture, scratch
- intradermal
- in-vivo
skin test: cutaneous
- put a drop of allergen on pt’s skin
- scratch with needle
sensitivity of skin test
- depth of puncture
- amount of langerhans present
- presence of B and T cells in epidermis
risks of intradermal skin test
may hit a capillary with an allergen that pt is allergic to
What are positive results of skin tests?
- wheal
- flare
- happens within 15-30 minutes
How common is testing for immune complex disease done?
Not common; reactions don’t happen until after 2-4 hours and are similar to late phase reactions that occur following positive IgE-mediated reaction
Limitations to skin tests
- not good for food and drugs
- pt should not be on antihistamines or topical corticosteroids when taking skin test
skin test: in-vivo
- reaction may occur up to 48-72 hours
- for delayed hypersensitivity (associated with T cells)
What is an examples of skin tests done in-vivo?
- tuberculin: positive read out: erythema
- patch test: contact dermatitis
examples of in-vitro allergy tests
- IgE testing in blood
- eosinophil count
- blood differential
- serum ig electrophoresis
examples of tests of IgE testing in blood
- RAST (Radioallergosorbent)
- MAST (Multiple allergosorbent)
- FAST (Fluorescent Allergosorbent)
principle of IgE testing in blood
- allergen stuck to a solid phase
- pt’s IgE from serum is exposed to allergen
- anti-human IgE sticks on pt’s IgE
- imaging substrate attached to anti-human IgE
provocative allergen test
challenge with increased dose of allergen
elimination allergen test
get rid of antigen and see if allergic response goes away
Therapies to allergy
- eliminate exposure to allergen
- treat symptoms
- immunotherapy with allergy extracts
other names for immunotherapy
- desensitization
- hyposensitization
mechanism for immunotherapy
administering a small dose of allergen to induce an immune response against the allergen but not large enough of a dose to induce the allergic response itself
route of administration for immunotherapy
- subq
- sublingual
Examples of FDA approved sublingual therapy
- grass pollen: Oralair, Grastek
- ragweed pollen: Ragwitek
- dust mite: Odactra
What are standardized allergenic extracts?
- allergenic extracts that fall within FDA standards
- 19 available
quantity of allergenic extracts
- 900 diagnostic
- 600 therapeutic
Why would a panel of allergic extracts be useful?
because different geological areas are exposed to different allergens
With respect to the perspectives of infection, what are the emphasis on?
- parasite and parasite-drug interaction
- host and host-parasite interaction
opportunistic infections
- immunocompromised patients getting attacked by their normal flora
- happens when there is not enough CD4
virulence factors
- allow parasite to take advantage of host
- ex. capsule, LPS
causes of disease
when tissue damage is caused by pathogen directly or by the host response to the parasite
What are the top three infections that cause cancer?
- Hep B and C
- Human papillomavirus
- H. pylori
What are the general approaches to an ID?
- immune status of host
- characteristic of parasite
- type of host-parasite interaction
- management
What are the types of host-parasite interaction?
- toxigenic
- extracellular
- facultative intracellular
- obligate intracellular
What are the phases of the host immune response?
- innate immunity
- inflammation
- adaptive immunity
- protective response
- immunological memory
What are ideal goals to manage ID?
- prevent establishment of infection
- eradicate parasite
- prevent tissue damage; recover tissue
- establish lifelong immunity
toxigenic infection
- infectious agent produces toxins
- endo (LPS) or exo
exotoxins
- soluble protein excreted if infectious agent
- each is distinctive in their property
What are ways in which exotoxin can cause infection?
- intoxication
- toxigenic infetion
- toxin involvement + virulence factors
antitoxin
toxin neutralizing IgG
How can you protect against toxin?
- active immunization with toxoids
- passive immunixation with antitoxins
septic shock
- lipid A (toxin) induce release of pro-inflammatory cytokines (IL-1beta, TNFalpha)
- sepsis if live bacteria is present
What is the antibody for lipid A?
IgM
What is IgG’s role in toxin infection?
- toxin neutralization
- binds to toxin
- gets taken up in APC
- eliminated from body
examples of extracellular organisms that cause infections
- gram + / - bacteria
- spirochetes
- mycoplasma
Anti-infectives are most susceptible to which type of infection?
extracellular infection
What is an important virulence factor for bacteria?
- anti-phagocytic capsule
- without this, pathogen can be phagolysosomed
What are the phases of infection with respect to extracellular infections?
- attachment to epithelial receptors
- penetration of epithelium
- acute inflammatory response
- lymphatic spread
- efferent phase of immune response
What is present in the gut and lung that prevents infectious bacteria colonization?
sIgA
How does pathogens fight sIgA?
they have proteases that can cleave these IgA
What is a hallmark of bacterial infection? (per lecture)
presence of neutrophil
What are components of efferent phase of immune response (for extracelllar infection)?
- IgG, IgM
- Complement
- Neutrophil
- try to minimize amount of bacteria circulating
How does neutrophil kill microbial pathogens?
- neutrophils have cell surface receptors which help engulfs pathogen
- when pathogen is inside the cell, it is destroyed via neutrophil’s toxic contents (slides pg 31)
- release ROS to kill bacteria and phagolysosome (lec 4-13 @ 20:05)
What advantage does facultative intracellular organisms have?
they can survive best either intracellular or extracellular environment
examples of facultative intracellular organisms that cause infection
- mycobacteria (ex TB)
- actinomycetes
- fungi (ex Coccidioides)
phases of facultative intracellular infection
- attachment to epithelial receptors
- penetration of epithelium
- acute inflammatory response
- monocyte / macrophage involvement
- efferent phase of immune response
Which pathogen is neutrophil not efficient in killing?
- facultative intracellular organisms
- can be engulfed and live in neutrophil
What are components of efferent phase of immune response (for facultative intracellular infection)?
- cell mediated immunity
- IFNgamma works through its receptors on macrophages and facilitate phagocytosis
obligate intracellular organisms
survive best when they are withing our own cells
examples of obligate intracellular organisms
- viruses
- Chlamydia
- Rickettsia
tissue tropism (virus)
virus have a preferable site of infection
What does the body do to protect against viral infection?
- IFN - NK, T cells
- CD8 cytotoxic T cells
- sIgA and serum IgG to prevent reinfection
Why is CD8 the best to fight against viral infection?
will recognize infected host cell and kill it
What is best to fight off facultative intracellular infections?
- IFNgamma
- CD4
What is best to fight off extracellular infections?
- neutrophil
- antibody
What is best to fight off toxigenic infections?
- antibodies
- antitoxins
What is best to fight off obligate intracellular infections?
- CD8+ cytotoxic T cells
primary immunodeficiency
- hereditary / genetic
- gene missing that is not translating a protein
X-linked Agammaglobulinemia
body is deficient of anti-bodies
primary immunodeficiency consists of what being deficient?
- B cell
- T cell
- neutrophil
- macrophage
- complement
SCID
- person does not have B or T cells
- most susceptible to facultative and obligate
- RAG1 or RAG2 affected
What are factors that can lead to secondary immunodeficiency?
- poor lifestyle choices
- virus infections
- neoplasms
- trauma
- iatrogenic
How is immunodeficiency diagnosed? What are the steps taken to diagnose immunodeficiency?
- phagocytosis
- complement measurement
- NK cell #
- antibody-mediated immunity
- cell-mediated immunity
- evaluation of organ systems
In testing immunodeficiency, what consists of phagocytosis tests?
- CBC and differential; WBC and neutrophil count
- neutrophil function tests | chemotaxis
In testing immunodeficiency, what consists of antibody-mediated immunity tests?
- total serum Ig, IgG, IgA, IgM, IgE
- presence of specific antibody after immunization (titer)
- isohemagglutinins; IgM function
In testing immunodeficiency, what consists of cell-mediated immunity tests?
- CBC and differential; lymphocyte count
- T cell subsets | CD4:CD8 ratio
- delayed hypersensitivity tests
If you lack antibody, complement, neutrophil, what infection are you susceptible to?
common pyogenic bacteria
If you lack cell-mediated immunity, what infection are you susceptible to?
- virus
- parasite
- intracellular bacteria
If you lack antibody, what infection are you susceptible to?
- virus
- parasite
- intracellular bacteria
If you lack mucosal immunity, this may or may not lead to increased infections in mucous membrane. Why?
because other antibody types compensate for IgA deficiency
What is the main cause of immunodeficiency?
infection
If you lack IgA, what happens to suffice for it?
- IgG, IgM, and IgD will go up
- but since IgG goes up, lyses will go up because IgG induce phagocytosis
Therapy of immunodeficiency
- symptomatic and supportive therapy
- Ig (passive immunization)
- bone marrow transplant
- cytokines
- thymus derived factors
- gene therapy
What is the FDA and CDC’s role in vaccination?
- FDA oversees manufacturing process
- CDC published guidelines
What is the main goal of active immunization?
to have memory B and T cells stay in the body for a long period of time for protective response
passive immunization
preformed antibodies
Why do we need vaccines?
- serious enough
- contagious
- cannot control
- cost-risk-benefit
- where anti-infectives are useless
incubation period
time when person gets exposed to when infection manifests itself
Which immunization is most common? (pre or post exposure) And why?
- pre-exposure aka phophylactic
- because incubation period is short
What can post-exposure immunization be useful for?
- aka therapeutic
- pathogens with long incubation periods
- Rabies, Hep B
herd immunity
immunizing everyone in the region in which the pathogen will most likely strike
types of active immunizing agents
- toxoids
- live attenuated
- inactivated
- this list is not inconclusive
toxoid immunization
- modified toxin
- reduce toxicity without altering immunogenicity
live attenuated immunization
- modified pathogen with reduced pathogenicity but same immunogenecity
- must produce infection and proliferate to trigger immunity
inactivated immunization
pathogen killed and cannot proliferate but still immunogenic
subunit vaccine
contains purified or recombinant antigens of infectious organism
combined vaccine
consists of 2 or more immunogens physically combined into a separate product
conjugate vaccine
attaching poor immunogen to carrier protein
When you see a number at the end of a vaccine, what does that mean?
valency; how many strains it targets
storage of vaccines
most products are stored at 2-8°C and dated for about 2 years
Which vaccines are administered subq?
- most live virus vaccines
- fluid toxins
Which vaccines are administered IM?
killed vaccines
Why are vaccines never given IV?
- if you already have antibodies for that particular vaccine, it will bind to and clear it before it can be presented to T cell
- immune complex syndrom may occur
What are hazards of active immunization?
- direct toxicity
- allergy
- infectious
What can antibodies lead to with respect to immunization?
- no effect
- protective to host
- pathologic
- block pathogenesis of pathogen
What are potential risks of live virus vaccines?
- integrated infection
- oncogenic
- teratogenic
What are contraindications for active immunization?
- serious febrile illness
- pregnancy
- immunodeficiency
- passive immunization within past 6 weeks
- children under one year
Hep B
- should be given to baby before baby leaves hosptial
- if baby’s mom is hep +, baby should be given antibodies within 12 hours of birth and then give vaccine
influenza: quantity of doses
6 months to 6 years: two annual doses
poliomyelitis vaccine
- oral vaccine has live attenuated
- there is also an inactivated form
pneumococcus vaccine
13 valent
DTaP
initial 5 doses, boosters in the form of of TDap (@ 11 years) or Td (every 10 years)
Gardisil
- human papillomamvirus vaccine
- 4 and 9 valent
Vaccines for 0-2 year olds
- Hep B
- Rotavirus
- DTap
- Haemophilus influenzae type B (Hib)
- Pneumococcal conjugate
- Polio inactivated
- Influenza
- MMR
- Varicella
- Hep A
Vaccines for 3-18 year olds
- Tdap
- Polio inactivated
- Influenza
- MMR
- Varicella
- HPV
- Meninogococcal
Pneumococcal polysaccharide
administer to patients 2 years and older for high risk individuals
Vaccines for 19 years and older
- influenza
- Td / Tdap
- Varicella
- HPV
- HZV (zoster)
- MMR
- Pneumococcal
Vaccines for 19 years and older (high risk individuals)
- Meningococcal
- Hep A
- Hep B
- Haemophilus influenzae type B (Hib)
- Pneumococcal
heterologous immunoglobulin
comes from animals
homologous immunoglobulin
comes from humans
potential problems of homologous immunoglobulin
- presence of infectious organisms that causes latent infections
- blood clot formation
onset of action of IGIM, IGIV, IGSC
- IGIM: 2-5 days
- IGIV: almost immediately
- IGSC: 2.5 days
IgA content in IGIM, IGIV, IGSC
Relative to each other:
- IGIM: max
- IGIV: intermediate
- IGSC: low
IGIV most beneficial for which conditions?
- AIDS
- bone marrow transplant
- premature babies
- B cell insufficiency
What are disease for which we need hyperimmune immunoglobulins?
- Hep B
- rabies
- CMV
- small pox
- tetanus
- botulism
- anthrax
How are mab produced?
- mouse immunized against certain antigen
- spleen cells are isolated
- B cells from spleen are fused with myeloma cells
- hybridoma formed
- hybridoma produce antibodies specific to anigen used to immunize mouse
What is the solution to allergy sickness with respect to mabs?
- chimeric or humanized ab
- administer lower dose
forms of mab
- mostly IgG
- can be complete ig
- can be FAB fragment
administration of mab
- IV
- subQ
What are the ways in which mab interacts with cell receptor?
- agonist
- antagonist
- cell damage
How does mab cause cell damage?
- complement fixation
- ab-dependent cell cytotoxicity
- apoptosis
What is a side effect of targetting tumor cells via mab?
kidney obstruction trying to clear all the lysed cells
Define cytokine
Soluble intercellular mediators of immunity that regulate cell-cell interactions
How are cytokines categorized?
- interleukins
- interferon
- growth factors
characteristics of cytokines
- MW of 5k-75k
- weakly immunogenic
- produced by our own immune cells
- can be produced by non-immune epithelial cells
- can act as autocrine / paracrine manner
Pleiotropy
cytokine that can work on multiple types of cells
Redundancy
multiple cytokines that overlap in their action but binds to its own receptors
How can you lengthen half life of cytokine?
Pegylate it!
What are mechanisms of cytokines inhibitors?
- neutralizing antibodies
- cytokine antagonists
What are interferons used for?
- viral infection
- cancer
What are IL2 and IL11 used for?
- cancer
- thrombocytopenia
Hematopoietic Growth Factors
- G-CSF
- GM-CSF
- Epoetin
G-CSF
promotes neutrophil and granulocytes reconstitution from stem cells
GM-CSF
promotes myeloid (macrophages and dendritic) cells reconstitution from stem cells
Epoetin
stimulates erythropoiesis
Alpha interferon type I
- anti-viral
- anti-neoplastic
Beta interferon type I
MS
Gamma interferon type II
infections associated with chronic granulomatous disease (lack of NADPH oxidase)
