L24- Hypersensitivity Reactions Flashcards
definitions:
- Antigen
- Immunogen
Ag- substance that evokes production of one or more Abs
Immunogen- substance that evokes adaptive immunity response if injected alone
**not all Ags are immunogens
definitions:
- Antigenicity
- Immunogenicity
Immunogenicity- ability to induce humoral and or cell-mediated immune response
Antigenicity- ability to combine specifically with the final products of the immune response
Note- not all Ags are immunogens
Innate / (1) immunity:
- (non-/specific)
- (slow/rapid) action
- (4) main components
1- natural
2- non-specific (no Ag required)
3- rapid / immediate response
4:
-tissue barriers: skin, mucosa (respiratory, GI)
-cells: neutrophils, macrophages, NK cells
-plasma proteins: complement (no memory)
Adaptive / (1) immunity:
- (non-/specific)
- (slow/rapid) action
- (4) main components
1- acquired 2- specific: in response to Ag --> **memory 3- slow response 4: -cells: B and T lymphcytes -lymphocyte products: Abs, CKs
list the results of activating complement, include specific factors (hint- 3 results)
Inflammatory response; C3a, C5a
Opsonization, C3b –> phagocytosis
MAC formation (C5b-C9) –> lysis of microbe
briefly compare humoral vs cell-mediated immunity
Humoral:
-mediated by soluble Abs via plasma cells (B lymphocytes)
Cell-mediated:
- mediated by T lymphocytes
- mechanisms: direct cytotoxicity, CK production
At the introduction of a microbe to the body, (1) are the cells that initially respond and take action. (2) is required for the stimulation of adaptive immunity.
1- **neutrophils, macrophages, NK cells
2- capture and display of microbial Ags via APCs, mostly *dendritic cells
CD4+ lymphocytes:
- (1) subset will stimulate macrophages via (2)
- (3) subset will stimulate (4) cells
CD8+ lymphocytes = (5) and functions destroy and target (6)
1- Th1 2- IFN-γ 3- Th2 4- plasma cells, eosinophils, mucus secreting epitheliam Th cells --> phagocytosis
5- Tc cells (cytotoxic)
6- intracytoplasmic microbes via apoptosis
list the general categories for diseases of the immune system
Overactive:
- hypersensitivity
- transplant rejection
- autoimmune diseases
Underactive:
- primary immune deficiency diseases
- acquired immune deficiency diseases
Hypersensitivity diseases:
- (1) definition
- (2) list the three basic characteristics of these reactions
- (3) causes
1- reaction of Ag with Ab or sensitized lymphocyte that is harmful to the host
2:
- prior Ag sensitization (sensitizing dose)
- re-exposure to Ag (challenge dose)
- additional exposures => inc reaction severity
3: -microbial Ags -environmental Ags: organic, inorganic -self-Ags (= autoimmunity) Note- Ags are difficult to eliminate and or avoid (common in environment / in host)
Type I hypersensitivty:
- (immediate/delayed) type
- (2) is the main mediator –> it is normally in (3) location and activation by (2) binding Ag => (4)
- (5) are the effector cells that carry out this response
1- immediate 2- IgE 3- surface of mast cell 4- mast cell degranulation 5- mast cells, eosinophils, basophils
In type I hypersensitivity, (1) is the first step which includes (1) presentation to (2) via (3). This process allows for the development of (4). The second step is (5) causing (6) progression.
1- sensitization — exposure to Ag
2- Th2 cells
3- APCs
4- IgE (via B-cell) –> binds to mast cell
5- re-exposure to Ag / allergen
6- Ag binds IgE –> mast cell degranulation
Type I hypersensitivity, first phase = (1):
- (2) time-frame
- (3) mediators
- (4) physiological changes
1- immediate response
2- minutes
3- histamine (+ other vasoactive amines), proteases, PG-D2
4:
- vasodilation (flushing)
- inc vascular permeability (angioedema)
- bronchoconstriction
- inc mucus secretion
describe the mast cell contents released in type I hypersensitivity
Immediate Phase:
- Histamine
- Proteases
- PG-D2
Late-Phase:
- LT B4, C4, D4
- CKs and chemokines
Type I hypersensitivity, second phase = (1):
- (2) time-frame
- (3) mediators
- (4) physiological changes
1- late phase response
2- 2-8hrs
3- LT-B4/C4/D4, chemotactic cytokines
4:
- inflammatory response –> neutrophils, eosinophils, lymphocytes (leukocyte infiltration + tissue destruction)
- epithelial injury via inflammation (tissue destruction)
- bronchospasm
- hypoxic Sxs
Localized type I hypersensitivity:
- (1) definition and common affected sites
- (2) is the main predisposition with (3) and (4) as signs and symptoms
1- Ag confined to particular site —> lungs, GIT, skin
2- Atopy, familial predisposition
3- hay fever, urticaria, some form of asthma
4- inc IgE levels
Note- atopy allows for quicker and stronger type I hypersensivity responses
Systemic type I hypersensitivity:
- (1) definition
- usually in response to (2)
- (3) is the main dangerous effect
- (4) are the initial and other effects
1- involves 2 or more organ systems
2- IV administration of Antisera (foreign Abs), hormones, penicillin products
3- anaphylaxis –> hypotension
4- (w/in minutes) itching, hives, skin erythema —- angioedema, laryngeal edema
list some histological features of each Acute and Late phase type I hypersensivity
Acute:
- masts cell currently degranulating
- vascular congestion (dilated)
- edema surrounding vessel
Late:
- little mast cells – most fully degranulated
- many eosinophils
Type II hypersensitivity:
- (1) binding occurs in (2) location
- (3) are the possible progressions after (1) occurs
1- Ag-Ab interactions
2- cell surface (plasma membranes)
3:
- complement / Fc mediated inflammation (+ tissue injury)
- opsonization –> phagocytosis
- altered cell function
Autoimmune hemolytic anemia:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- RBC membrane protein
2- type II
3- opsonization, phagocytosis
4- hemolytic anemia
Hemolytic transfusion reaction:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- RBC membrane protein
2- type II
3- opsonization, phagocytosis
4- hemolytic anemia, ARF
Goodpasture syndrome:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- basement membrane protein (part of type IV collagen – kidneys, lungs)
2- type II
3- complement / Fc mediated inflammation
4- nephritis, lung hemorrhage
Graves disease:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- TSH receptor
2- type II
3- Ab stimulation of TSH receptor
4- hyperthyroidism
Myasthenia gravis:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- AChR
2- type II
3- Ab blockade of AChR – dec number of receptors
4- muscle weakness, paralysis
Pemphigus vulgaris:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- intercellular proteins in keratinocytes – desmosomes
2- type II
3- disruptions of intercellar adhesions
4- skin vesicles – easily rupturing blisters
Type III hypersensitivity:
- (1) is the main mediator binding (endo/exo)-genous Ags
- (3) is the common location of (1)/(2) binding followed by (4)
- (5) is an additional location/mechanism of (1)/(2) binding
- both (3)/(4) and (5) are mediated by (6) process
1- IgM, IgG 2- both endogenous and exogenous Ags 3- plasma / serum 4- tissue deposition of Ab-Ag complex 5- tissue deposition of Ag followed by binding of Ab 6- complement activation
list the favored sites of type III hypersensitivity reactions and the associated disease process (hint- 6)
- renal glomeruli –> glomerulonephritis
- joints –> arthritis
- skin
- heart –> carditis
- serosal surfaces (serositis)
- small BVs (vasculitis)
In type III hypersensitivity, Ab-Ag complex within tissue will initiate (1). (2) will mediate (3) progression; (4) will mediate (5) progression where (3) and (5) both result in injury of the local tissue.
1- complement activation
2- C3a, C5a
3- anaphylactoid rxn + chemotactic rxn –> neutrophil infiltration (+ inc vascular permeability) –> CKs + other mediators –> tissue destruction
4- C3b
5- opsonization –> phagocytosis –> tissue destruction
SLE:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- nuclear Ags
2- type III
3- immune complex deposition
4- nephritis, arthritis, skin and other lesions
Post-Streptococcal Glomerulonephritis:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- streptococcal wall Ag
2- type III
3- immune complex deposition
4- nephritis
Polyartheritis nodosa:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- HepBs Ags + others
2- type III
3- immune complex deposition
4- necrotizing vasculitis
Reactive arthritis:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- bacterial Ags
2- type III
3- immune complex deposition
4- arthritis
Serum sickness:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- foreign Ag like xenobiotic serum used in therapy
2- type III
3- immune complex deposition
4- necrotizing vasculitis, nephritis, arthritis
discuss Dx of a type III hypersensitivity reaction
1) demonstration of immune complexes in target organ (microscopy) — immunofluorescence, SEM/TEM
2) immune complex blood assays
Type IV hypersensitivity:
- (1) mediated
- (2) are the two mechanisms
- (3) are the possible Ags
1- sensitized T cells (Th or Tc)
2- DTH (delayed type hypersensitivity), direct cytotoxicity (autoimmune diseases, viral infections)
3- broad range: mycobacterium/bacteria, fungi/protozoa/helminths/viruses, chemical agents, tissue grafts, self-Ags
DTH, type IV hypersensitivity:
- (1) mediated, reaction to Ag presented by (2)
- (1) will secrete (3) and (4), include functions
1- Th1, Th17 (mostly fungi)
2- MHC-II, APCs (Ag presenting cells)
3- IFN-γ –> activated macrophages
4- TNF, IL-17 –> recruit neutrophils, macrophages
Note- possible granuloma formation
Direct cytotoxicity, type IV hypersensitivity:
- (1) mediated, reaction to Ag presented by (2)
- (1) will secrete (3) and (4), include functions
1- Tc
2- MHC-I from targeted cells
3- Porforin –> promotes entry of granzymes
4- Granzymes (proteases) –> initiates apoptosis
describe the development of a granuloma (indicate hypersensitivity type)
Type IV, DHC subtype:
- Th1 cells release IFN-γ –> macrophage recruitment
- macrophages surround indigestable microscopic aggregation
- macrophages differentiate into epthelioid (–> possible giant cell formation via fusion)
- architecture => granuloma
Tuberculosis:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- mycobacterium components
2- type IV
3- delayed type hypersensitivity, Th1
4- caseating granuloma w/ inflammation + tissue destruction
DM, type I:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- β-cell Ags, pancreatic islets
2- type IV
3- direct cytotoxic, Tc
4- β-cell destruction –> no insulin –> hyperglycemia
MS:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- proteins in CNS myelin
2- type IV
3- direct cytotoxic, Tc
4- range of sensory and motor deficits
RA:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- unknown Ag in synovium
2- type IV
3- direct cytotoxic, Tc
4- chronic arthritis –> destruction of articular cartilage and bone
Contact Dermatitis:
- (1) target Ag
- type (2) hypersensitvity
- (3) mechanism
- (4) clinical manifestations
1- various environmental Ags
2- type IV
3- delayed type hypersensitivity, Th1
4- skin inflammation with blisters
