Exam 3 Flashcards
Anatomy of GALT
- Waldeyer’s Ring
- Peyer’s patches- T and B cells and follicular dendritic cells- small intestine
- Isolated lymphoid follicles – in small and large intestines
- Lamina propria- many IgA-producing B cells
- Intraepithelial lymphocytes- lymphocytes reside between lumenal epithelial cells beneath the tight junctions.
What is claudin and occludin?
proteins whose strands band the epithelial plasma membranes together
examples of diseases caused by oral tolerance
- Crohn’s disease
- Ulcerative coliltis
How does IgG gets passed onto the fetus?
FcRn binds to maternal IgG and transcytoses to the fetal circulation
How does IgA gets passed in breast milk?
sIgA secreting B cells migrate to breast in response to hormones; sIgA is transported to milk via the SC transport process.
Characteristic of gut at birth
- little to no bacterial colonization
- little to no mucus secretion
- no IgA producing plasma cells
Composition of immune cells in human breast milk
- Macrophages (55-60%)
- Neutrophils (30-40%)
- Lymphocytes (5-10%)
Other protective components in breast milk
- lysozyme
- lactoferrin
- oligosaccharides
- antiviral lipids
- glycosylated proteins
When you’re clearing a bacterial infection, the termination of the response happens when bacteria is cleared. How do you terminate an autoimmune, alloimmune, or allergic [AAA] response?
You can’t terminate the response because you cannot get rid of the antigen
How does diversity / heterogeneity happen in the AAA response?
breakdown of tolerance at a primary level that didn’t keep cells in circulation
What is the major cause of damage in the actual immune response (most of the time)?
inflammation or immune response to etiologic agent
What can happen if you have a pathogen antigen that look like auto-antigens?
- pathogen will be more effective
- once your body find the pathogen as a foreign substance, it will try to get rid of it and your self-antigens that looks like the pathogen
Can you distinguish between protective immunity and immunologically-mediated diseases?
No because they are often part of the same process; immune response work like abnormal ones
How can you classify the immunologically-mediated responses?
by source of antigen or mechanism
How can you classify immunologically-mediated responses via source of antigen?
- autoimmune - your own cells
- alloimmune - within a species
- allergy - environment
How can you classify immunologically-mediated responses via mechanism?
Coombs and Gell type I-IV (CaG)
Define tolerance as it relates to immunology
you don’t reject yourself
Properties of tolerance
- acquired
- active process
- developed during fetal life
- required continued presence of immunogen
How can you lose tolerance?
if you stop becoming exposed to it or if you stop expressing it
Define central tolerance
tolerance that occurs in a central area where cells are going through development; ex. negative selection
Give an example of peripheral tolerance
- immunogen-induced anergy in absence of co-stimulation
- suppressive cells
What is responsible for oral tolerance to proteins?
- Treg
- CD103+ dendritic cells in the gut
Describe how tolerance can happen in the gut
- M cells process antigen (ex. food)
- taken up by dendritic cells
- travel to mesenteric lymph nodes to make IL-10
- favors Treg development
What are anti-idiotypic antibodies?
- Ab against antigen binding portion of another Ab
- neutralize the antigen binding portion of auto Ab
What is Galluci’s definition of “disease”?
when rate of damage exceeds rate of healing
Explain TH1 and TH2 type persons
- kids - middle age tend to lean towards TH1
- passed middle age tend to lean towards TH2
- TH1 -> TH2 => antiviral -> anti-parasitic
What are the ways in which you can have a loss of tolerance?
- failure to delete autoreactive clone by thymus
- breakdown of peripheral tolerance
- nonspecific activation; eg superantigens
- molecular mimicry
- abnormal lymphocyte interaction
What is molecular mimicry?
pathogens pick up the surfaces of cell membranes and stick it on their own surface so that body recognizes them as self
What are examples of autoimmune diseases involving T cells?
- DMI
- RA
- MS
What is the key to autoimmunity?
TH17
What are the three main alloantigen systems?
- ABO blood types
- Rh factor
- HLA
Why does alloimmunity happen?
the genome between each person is different; even though there are conserved proteins between people, HLA change with each person because it accommodates each person’s T cell/receptors
What are other terms for alloantigens?
- isoantigens
- isoimmunity
Why is the first baby most likely not affected by erythroblastosis fetalis?
because the barrier has never been broken before; it CAN happen if the placenta tears
RhoGAM
- drug used to prevent erythroblastosis fetalis
- antibodies against Rh factor
What are drugs that have reduced the need for transfusions and how do they work?
- epogen
- oprelvekin
- stimulates your bone marrow to make more erythrocytes
If you’ve never had a transfusion before, what is one possible way in which you can get a reaction to that?
a bacterial infection via molecular mimicry which has an antigen similar to the blood that you’re getting a transfusion from
What are reasons that you may need transfusion (either blood or derivatives of)?
- replacement
- passive immunization
- immunosuppression
- diagnostic products
If the organ is perfused before transplant, why does the blood type matter?
because blood grouping antigens can be expressed on capillary endothelial cells
Acute organ rejection
- T cell mediated
- even if peptide is the same, sees MHC as foreign
Describe the mechanism of acute organ rejection
- patient’s CD4/8 sees the donor’s DC MHC classes as foreign
- patient’s DC processes donor’s dead cells and expresses donor’s MHC classes on their surface
Mechanism of chronic transplant rejection
- antibodies against MHC on the capillary endothelium
- leads to thickening -> substances no longer able to diffuse through capillary
- will kill the organ over time
Graft-vs-host disease
when transplanted immune cells attacks the recipient
If immune cells are transplanted into you an go through your thymic education and go through your negative selection, why is it not 100% effective against inducing tolerance?
because some cells will/can escape the thymus
Define sensitization
like immunization with respect to allergy
T/F: Symptoms of allergies depend on the allergen.
FALSE; they depend on the immunologic mechanism involved
If you’ve never been exposed to a drug before, how can you amount an immune response to that drug?
you’ve been exposed to something similar and therefor you may have T or B cells that recognize that antigen
CaG I
- IgE mediated
- allergen crosslinks two IgE molecules on mast cells -> degranulation
- mediators released (ex. histamine, leukotrienes)
- inflammation
CaG III
- complement mediated
- allergen + IgG -> immune complex -> complement -> toxins -> inflammation
CaG IV
- cell mediated
- t cells pick up allergen -> produce cytokines -> inflammation
CaG II
- cytotoxic
- allergen sticks to surface of target cell
- target cell looks foreign
- complement or ADCC -> cell death or anti-receptor antibodies
What does anti-receptor antibodies do?
reduce or alter function of cell
What are other names for IgE-mediated allergy?
immediate or anaphylactic hypersensitivity
Besides allergy, what else is IgE mediated?
atopy; rhinitis
What are the ways in which CaG I cannot happen even if you are exposed to the allergen?
- insufficient antibodies for crosslinking
- too much antibodies that they bind up the allergen, keeping it away from the mast cells
- small monovalent antigen that cannot crosslink
Mast cell degran. in GI
- ↑ fluid secretion, ↑ peristalsis
- expulsion of GI content via N/V/D
Mast cell degran. in airways
- ⇩↓ diameter, ↑ mucus secretion
- expulsion of airway content via cough, sneeze
Mast cell degran. in blood vessels
- ↑ blood flow, ↑ permeability
- edema, inflammation, ↑ antigen to lymph nodes
Besides mast cells, what else can bind to IgE?
- eosinophils and basophils
- also have Fcε receptors
- important in allergic asthma
- populate lungs in asthma patients
- more toxic than mast cells
Cell destruction in spleen is associated with which CaG classification?
CaG II
What are examples of diseases that CaG lead to?
- Grave’s disease
- Masthenia Gravis
- via anti-receptor antibodies
What is the time course of CaG II?
- within hours
- varies on how sensitive a person is ex. more Ab = more severe, how much allergen patient is exposed to
Which CaG classification is vasculitis, arthus reaction, and serum sickness associated with?
CaG III
What are conditions for CaG to occur?
highly immune person expose to high level of immunogen
What is the time course of CaG II?
within 2-12 hours
What does DTH refer to?
- delayed type hypersensitivity
- CaG IV
What are the immune effectors for CaG IV?
- CD4 Tcells promote inflam. reponse via TH1 and TH17
- CD8 Tcells cause tissue rejection
What is the time course of CaG IV?
- 8-12 hours to 48-72
- vary with allergen
- can wear nickel for months before response developed
Define atopy
inherited tendency for IgE mediated allergy to common environmental allergens
T/F; Not all IgE-mediated diseases are atopic
True
What are your probability of having atopy with respect to inheritance from your parents?
- 50% = one parent
- 75% = both parents
Describe the mechanism of allergy
- allergen exposure
- allergen extracted, passes mucous membrane to an APC
- APC processes it on the surface of their cell
- shown to T cell -> TH2 response
- IL4 production -> IgE -> mast cells
What is another name for allergic rhinitis?
hay fever
What are the differences between extrinsic vs. intrinsic
- extrinsic: TH2
- intrinsic: does not know initial cause but usually follows infection
What are nonspecific triggers of atopic diseases?
- exercise
- stress
- cold
- irritants
- drugs
What are the differences in FEV1 values between non-asthmatics and asthmatics?
- non-asthmatics’ lungs will expand with max. inspiratory -> bigger FEV1
- asthmatics will not have that expansion; albuterol will help with that
atopic diseases
- allergic rhinitis
- allergic asthma
- atopic dermatitis
- allergic gastroenteropathy
Non-atopic allergens
- ingestants
- injectants
What happens during sensitization?
when you’re exposed to the allergen for the first time, instead of making neutralizing antibodies (IgG), you start to make IgE
What are the symptoms associated with anaphylaxis?
- tongue swelling
- constricted airways
- wheezing
- hypovolemia
- vascular collapse
- urticaria / angioedema
anaphylactoid reactions
mast cells mediated; no IgE or T cells involved
What are ways in which you can get mast cells to degran. to produce an anaphylactoid reaction?
- receptor or drug interaction with mast cells
- radiocontrast dyes changing osmotic pressure
- drying out of bronchial tissues by breathing hard
Which cells are involved in early phase inflammation?
- mast cells
- basophils
Which cells are involved in late phase inflammation?
- these aren’t really involved in an acute response
- eosinophil (usually traffic into place of prolonged inflammation)
- neutrophil
What are conditions that need to be met in order for CaG III to occur?
- patient must have high levels of IgG
- patient must be exposed to high dose of antigen
Explain why you need a perfect ratio for CaG III to happen
- not enough antibodies or antigen -> complexes aren’t big enough
- big complexes get cleared
- need slight antigen excess
Describe the events that occur in serum sickness
- primary happens within 1 week after exposure of foreign protein; resolves in 4 weeks
- secondary happens within 2-4 days after exposure
What symptoms can serum sickness lead to?
- at site on injection: rash, swelling, pain
- fever
- headache
- nausea
- vomiting
- malaise
- arthralgia
- myalgia
What results if the site of immune-complex deposition is in the joint spaces?
arthritis
Injected serum can lead to immune complex disease. What else can cause it?
- any disease that results in a circulating antigen ex. RA, lupus, etc.
- infectious diseases ex. viremia
- Farmer’s lung
- Aspergillosis mold
Which CaG is allograft rejection?
CaG IV
Which CaG is graft-vs-host disease?
CaG IV
chemokine functions
recruit immune cells into area of interest
