5. Introduction to Immunopathology Flashcards
SKIPPED ALL REVIEW OF IMMUNE SYSTEM - MAKE SURE YOU REVIEW!
YAS
Hypersensitivity disease classification
• Classification based on principle immune mechanism responsible for injury (3-Ab, 1 T-cells)
• Mechanism of injury often good predictor of ____ and ____ changes
• Type I hypersensitivity:
– Etiology: allergens activate ____ cells and
promote hyper ____ production
– Pathogenesis: allergen-IgE-mediated ____ activation
– Risk factors:
• ____ predisposition
• Route of allergen ____; dose; chronicity of exposure
• Exposure to environmental ____
• Decreased infections ____ in life
Perturbation of a host response designed to respond to ____
• Hypersensitivity - how immune system in response to foreign antigen creates tissue disease, etc. ○ AID - immune reaction to an autoantigen that causes disease, additional requirements are needed ○ Do not apply autoimmunity answers to hypersensitivity questions! • Classification is based on underlying immune mechanisms that contribtues to pathogenesis ○ I-III - \_\_\_\_ mediated; IV mediated by \_\_\_\_ cells • \_\_\_\_ hypersensitivity = Type I • It's due to antigens - referred to as allergens (only time used) - activate T cells after processed, and activate Th2 cells • When exposed to allergens, overproduce IgE - \_\_\_\_ individuals: ○ This example is truly a hyperresponse • IgE - can bind to mast cells > sensitizes the mast cells, and activated but in an abnormal way (same result, but expolsive) • May have \_\_\_\_ involvement • \_\_\_\_ hypothesis - contributed to higher incidence of atopic disease
morphologic (histopathology)
functional (clinical manifestations)
Th2
IgE
mast cell
genetic
entry
pollutants
early
parasites
ab
T
anaphylactic
atopic
MHC
hygiene
Overview of Type I hypersensitivity
• Left: normal immune response • \_\_\_\_-fold higher levels of IgE • IgE have Fc that allow it to bind to a receptor on mast cells - \_\_\_\_ ○ When produce IgE > blood column > tissue > sensitizes mast cells in tissues, and basophils • Most hypersensitivity happens in two steps: \_\_\_\_ and \_\_\_\_ • At end of sensi > overproduce IgE > mast cells sensi, not damaged > however, the binding of Ab makes it \_\_\_\_ specific; in non-atopic, perhaps 10,000 are occupied in IgE, in atopic 1-20,0000 receptors are occupied; IgE can be replaced and fall off, and all the receptors don't contain the same IgE > contain the IgE you're currently producing at that time (\_\_\_\_ allergies, etc), and the mast cells contain an array of \_\_\_\_ • Atopic disease occurs upon \_\_\_\_ exposure, as a result of sensitization • Requires that multiple IgE molecules are \_\_\_\_ - if atopic, you have lots of receptors clustered - more likely to be \_\_\_\_ > signal transduction > signals to mast cell that causes it to degranulate ○ IgE not involved in acute inflammation [???] ○ Much greater degranulation - more histamine • \_\_\_\_, PG are also all created following degranulation • Late phase where \_\_\_\_ may be produced - most of the pathologic reactions that occur are due to the immediate release of \_\_\_\_ and \_\_\_\_
1,000-10,000
FcERI
sensitization
reactive
antigen
seasonal
specificities
repeat
crosslinked
activated
leukotriene
cytokine
histamine
PG
Overview of Type I hypersensitivity- continued
• Consequence of release depends on what tissue it occurs in: ○ Bronchial, intestine - \_\_\_\_ contraction ○ Lung, mucus producing cells - activated, more \_\_\_\_ ○ Platelets activated - produce \_\_\_\_ ○ Sensory nerve endings may be stimulated, along with kinins - \_\_\_\_ with these reactions ○ Do not see the presence of inflammatory cells - only see the \_\_\_\_ in the acute phase
smooth muscle mucous serotonin itching (peritis) eosinophil
Primary Mediators Produced by Mast Cells and Basophils
- Biogenic amines (histamine)
- ____ contraction
- Increased ____ permeability
- Increased secretion by nasal, bronchial and gastric ____
- Enzymes (proteases, hydrolases)
- Cause tissue damage
- Generate ____ and activate complement
- Proteoglycans (____)
- Serve to package and store other mediators
Secondary Mediators Produced by Mast Cells and Basophils
• Lipid-derived mediators:
• ____- increase vascular permeability and bronchial smooth muscle contraction; also chemotactic for eosinophils
• Prostaglandin- ____ and increased mucus secretion
• ____- platelet agregation, release of serotinin, chemotactic for eosinophils
- Cytokines:
- Participate in late phase response
- Tissue damage is not a hallmark of type I reactions
- Lipid mediators - minutes to hours
- PAF - serotonin > vasodilation
smooth muscle vascular glands kinins heparin
leukotrienes
bronchospasms
PAF
Type I hypersensitivity
• Immune mechanism: ____ production > mast cells > ____ release
- Lesion/Clinical manfestations:
- Route of exposure determines nature of reaction/lesion
- vascular ____
- Vascular permeability— ____
- smooth muscle contraction
- mucus production• Sensitized mast cell > upon exposure to antigen, activated resulting signal transduction > increase intra ____> cell degranulates, releasing histamine, heparin and enzymes; later: LT, PG; hours: cytokines
• Clinical manifestations depend on where you encounter ____ in secondary response and the subsequent reaction
○ No consequence to the production of IgE
○ Edema is due to ____, but low in protein cxn (more serous)
IgE mediator dilation edema Ca++ antigen exudate
Kinetics of Type I hypersensitivity
• Immediate: \_\_\_\_, and AA metabolites • Hours-days: can be recycling of early events, but involves \_\_\_\_ • B: dilated \_\_\_\_, edema (in skin - clear spaces bt collagen bundles); cells are \_\_\_\_ ○ Eosinophils - \_\_\_\_ response, IgE in highly contaminated areas - parasites induce IgE response > eosinophils play a role that facilitate killing of parasite ○ Where parasites are endemic, it's protective; but in atopic individuals, they're mounting and resulting… [NOTES]
histmine cytokines BV eosinophils vestige
Clinical examples of Type I hypersensitivity disease
• Pathogenesis:
– antigen-IgE mediated mast cell ____
• Morphologic and functional changes:
– Result of action of mediators; depends on ____,
i.e., route of exposure to allergen
• Local disease: (local antigen) challenge
– Atopic ____: hives, urticaria, ____
– Allergic ____ (hay fever) and conjunctivitis
– Allergic gastroenteritis
– ____
• Systemic disease: ____
• Penicillin - 100-500 deaths/year from prescribed medications • \_\_\_\_ - hay fever • \_\_\_\_ - GI tract • \_\_\_\_ - involving lower respiratory tract - asthma ○ Type I not only cause, but prominent
degranulation
location
dermatitis
angioedema
rhinitis
asthma
anaphylaxis
inhalation
ingestion
inhalation
Urticaria and Angioedema
• Common disorder
• Antigens: ____, foods, drugs, insect venom
• Pruritic slightly elevated areas on the skin which are redder or paler than the surrounding skin (____; hives)
– Edema of ____ dermis
• Lesions appear rapidly and fade with in hrs
– Episodes may last for ____
• Angioedema: closely related; deeper edema of both ____ and ____ (lips, tongue and eyes)
– Don’t confuse with hereditary angioneurotic edema (____ deficiency)
* ATOPIC DERMATITIS * Pruiritic - itch * Develops bc of mediators (vasodilation, permeability) > edema formation > occurs in superficial dermis (right below the epidermis) * HAE has nothing to do with angioedema, has to do with a deficiency in a complement inhibitor
pollens wheals superficial days dermis subcutaneous fat
C1 inhibitor
- Can be ____
* More ____
small
ring-like
• Left: ____ - first thing you want to know what thing you’re allergic to (usually multiple things); can block, but one antigen at a time
○ Injected ____ - reaction = ____ (erethymetous)
• Right: dilated BV (sensitized ____ cells > IgE > degranulate); edema (collagen bundles are pushed apart)
○ Taken early in lesion; if gone on longer > would only see ____
skin test subcutaneously hives mast eosinohpils
- Left: hives, urticaria
- Middle: LP, dots are mostly ____
- Right: eosinophils - taking up a lot of eosin in cytoplasm bc of granules
- Hallmark of Type I: ____, presence of ____, presence of ____
eosinohpils
vasodilation
edema
eosinophils
- Related disorder - how we’re exposed to antigen
- Same reaction - involves deeper ____ (lips); transient, but can last a while - occurs in ____ individuals (____)
- ____ are a potent inducer of this reaction
- Life threatening when it affects the ____ - deeper ____
cutaneous tissue
sensitized
ingestion
nuts
tongue
submucosa
Allergic Rhinitis/allergic conjunctivitis (hay fever)
• Affects ____ of population
• Antigens: ____, fungi, animal allergens, dust mites
• Morphologic changes:
– ____ edema, redness and ____ secretion
– Secretions and mucosa contain numerous ____
* Can develop atopy later in life, or can \_\_\_\_ out of it * \_\_\_\_ and \_\_\_\_ component to this - never know when you received the first dose * Doesn't matter how the primary exposure to antigen takes place > how it gets \_\_\_\_ * The manifestations are a result of \_\_\_\_ infection
20% pollen mucosal mucous eosinohpils
grow environmental familial sensitized secondary
- Increased ____ duct secretion, increased ____ secretion
* Histo: from ocular area > many ____ and evidence of edema
tear
mucous
eosinophils
