Immunopathology 2 Flashcards
HYPERSENSITIVITY REACTIONS
Here the organism responds to _____ with an antigen that it ______ and to which it is _____.
renewed contact
already knows
hypersensitive
Adverse reactions caused by immune mechanisms in which there is damage to the tissues/organs in the body.
Gell & Coombs classification
1) _______
2)_________
3)____________
4)__________ H.R
Anaphylactic
Cytotoxic/Cytolytic
Immune complex/Toxic complex rxn
Cell mediated
The first 3 in types of HR reactions requires ______. They are also (delayed or immediate?) H.R, ____hrs after exposure
The last is ____ mediated( ______ and ____)-(delayed or immediate?) H.R., _____hrs after exposure
antibodies(plasma cells); immediate; 2-6
cell ; Tcells & Macrophages; delayed ; 24-36
Hypersensitivity
Excessive pathogenic reaction of a ________ body to _______ contact with the ________
sensitized
renewed; sensitizing antigen.
H.R.- TYPE I
Common allergens in immediate- hypersensitivity reactions causing _____ symptoms include:
____,_____, and _____
Cat antigen and other ______ antigens
____ mite fecal pellet antigens
Mold spores
respiratory
Tree, grass, and weed pollens
animal dander
Dust
HR TYPE 1
Many allergens are environmental substances that are harmless for most individuals. Some individuals apparently inherit genes that make them susceptible to allergies. This susceptibility is manifested by the propensity of these individuals to make strong ____ responses and, subsequently, ____ antibody against the allergens.
TH2
IgE
HR TYPE 1
On first exposure,
____ gets implanted on ____ of ___ cells & ______
This causes ______ of the those cells
2nd exposure causes _________ Fc on surface of the mast cells
Mast cells becomes stimulated to __________
The process is called ______
IgE; FcR
mast; basophils
priming; cross linking of IgE
release all its products.
mast cell degranulation
In HR TYPE 1
Complement is involved
T/F
F
not
HR TYPE 1 PATHOGENESIS
Allergens may be introduced by inhalation, injection or ingestion
*____ cells are often recruited to the site of allergic reactions in response to chemokines that are produced locally; among these chemokines is _____, which also recruits ______ to the same site.
TH2
eotaxin
eosinophils
TYPE 1 PATHOGENESIS
IL-__ stimulates B cells specific for the allergen to undergo ______ to IgE and to secrete this isotype.
IL-___ activates _____ that are recruited to the reaction, and
IL- ___ acts on ____ cells and stimulates ______
4; heavy-chain class switching
5 ; eosinophils
13; epithelial; mucus secretion
Mast cells express a high-affinity receptor for the ___ portion of the __ (light or heavy?) chain of IgE, called _____.
Fc
ε
Heavy
FcεRI
______ are the circulating counterparts of mast cells.
Basophils
role of basophils in most immediate hypersensitivity reactions is not established
T/F
With reason
T
since these reactions occur in tissues and not in the circulation
Mention 3 cells that express the Fc3RI
Mast cell
Basophils
Eosinophils
The third cell type that expresses FcεRI are eosinophils, which are often present in these reactions and also have a role in IgE-mediated host defense against _______ infections
helminth
H.R.-TYPE I
Primary mediators (such as _____,______,____,____,_____,_____ )
cause vaso____, broncho______, etc.
and release of secondary mediators (such as _______,______,_____, and ______)
which lead to inflammatory cell infiltrates.
histamine, serotonin,NCF,ECF,proteases
dilation; constriction
leukotrienes, prostaglandin, PAF, cytokines
HR TYPE 1
CHEMOTAXIS- ____,_____,____
VASOACTIVITY- ______________
SMOOTH MUSCLE SPASMS- ______________
LTB4,ECF,NCF
histamine, PAF, LTC4, D4, E4, neutral protease,PGD2
LTC4,D4,E4,histamine,PG,PAF
HR TYPE 1
Consequences of the mediators
___ease vascular permeability
_____ of lining epithelium
___ease glandular secretion
Smooth muscle (relaxation or contraction?)
Inflammatory cell attraction( _______ and _______)
Incr
Edema
Incr
contraction
eosinophils & neutrophils
HR TYPE 1 Important medical conditions fall into this category
Systemic anaphylaxis: Classic examples are _________ and ______
In some individuals, a severe reaction occurs within minutes, leading to symptomatology such as acute _____, _____ edema, diarrhea, ______, and _____.
penicillin allergy and bee sting allergy.
asthma
laryngeal
urticaria
Shock
HR TYPE 1
Local anaphylaxis (_____)
Classic examples are food allergies and hay fever to ragweed pollen
atopy
About ____% of people have “atopy” and are easily sensitized to allergens that cause a _____ reaction when inhaled or ingested.
This can produce _____,_____,_____ , etc..
10
localized
hay fever, hives, asthma
H.R.-TYPE II
Type II hypersensitivity –cytotoxic
Definition
Ig_ or Ig__ against specific target in the body (cell or receptor)
Pathogenesis: once ____ is attached, the cell would be injured by either _______ or ______
M; G
Antibody; complement or cell mediated cytotoxicity
HR TYPE 2
•Complement-dependent cytotoxicity
-__________ anemia : Body is producing _____ against ______ & attaching to it
•Antibody-dependent cell-mediated cytotoxicity
_______ anemia
•Anti-receptor antibodies
Activate receptors- ______ disease Ab against a specific receptor
Autoimmune hemolytic; auto-ab
its own rbc
Pernicious
Grave’s
Complement dependent reactions:
Antibody is directed against antigen on cells (such as circulating ______) or extracellular materials (________).
The resulting Ag-Ab complexes activate _____ (via the ____ pathway), leading to _____ or extracellular tissue damage.
red blood cells; basement membrane
complement; classic
cell lysis
HR TYPE __
a red blood cell has _____ fixed on its surface to which _____ attaches.
The attached stuff sets off the ______, which ends with the formation of the “__________” of C_-__ which causes lysis of the cell. Other complement components may be generated, such as the opsonin ____.
2
antigen; antibody
complement cascade; membrane attack complex
C5-9 ; C3b
HR TYPE 2
Diseases in this complement dependent category include:
_______ reactions
__________ anemia.
____________: ______ crosses the placenta and attaches to fetal RBC’s.
___________
Transfusion
Autoimmune hemolytic
Erythroblastosis fetalis; maternal IgG
Good pasture syndrome
Goodpasture’s syndrome: _____ basement membrane antibody is present. Same type ___ ——- is also present in the ____
glomerular
IV collagen
lungs
Antibody-dependent cell-mediated cytotoxicity (ADCC):
(Low or High?) concentrations of IgG or IgE (in the case of parasites) coat target cells.
Inflammatory cells such as NK (natural killer) cells, monocytes, and granulocytes then bind to the _________ receptors and lyse, but __________, the target cells.
Low
immunoglobulin Fc
do not phagocytize
HR Type 2
A macrophage with Fc receptors on its surface is able to recognize a target cell coated with ____ via the ______ portion of the attached antibody.
The macrophage can then demolish the targeted cell by elaboration of _____.
_________ is not involved
antibody
Fc receptor
proteases
Complement
Examples of ADCC include:
_______
Immune reactions against _______
Immune reactions against ______
Transplant rejection
neoplasms
parasites
HR TYPE 2
Antireceptor antibodies: ____ antibody is directed against ____ in target cells, resulting in _____- mediated ______ of the receptors.
IgG; receptors
complement; destruction
HR TYPE 2
Antibodies can bind to cell surface receptors or essential molecules, and cause functional derangements (either _______ or _________) without cell injury.
The variant is sometimes classified as _____
inhibition or unregulated activation
TYPE V
HR TYPE 2
Antibody is directed against _____ receptors at the motor end plate of a muscle, ____ the receptors and diminishing the muscular response. This is the mechanism for muscle weakness in ____________
acetylcholine
blocking
myasthenia gravis
HR TYPE 2
Diseases caused by Antireceptor antibodies mechanism include:
____________: acetylcholine receptor antibody.
______ disease (thyrotoxicosis): _____ receptor antibody/TSI
______ anemia:_______ antibody.
Myasthenia gravis
Grave’s; anti-TSH
Pernicious; anti-parietal cell
H.R.-TYPE III
Type III hypersensitivity–immune complexes
Definition-
This reaction is mediated by _______ which promote tissue damage primarily through _______
immune (Ag-Ab) complexes
complement activation
HR TYPE 3
-_______ formation deposition in tissue inflammation + disease
____ as an opsonin attracts _____, which then release lysosomal enzymes.
____ as a chemoattractant brings in ____.
Immune complex
C3b; neutrophils
C5a; neutrophils
HR TYPE 3
Serum complement is ???
With reason
reduced
as it is used up in this process.
HR TYPE 3
Caused by (low or high?) levels of circulating, (soluble or insoluble ?) immune complexes containing _____ or ______ .
Circulating immune complexes overwhelm the ability of the _________ to __________ (eg. skin, glomeruli, blood vessels, synovium, lungs) and end up ______
High; soluble ; IgG or IgM antibody
mononuclear phagocyte system to remove them and deposit in various tissues
activate complement.
HR TYPE 3
_______ complexes are circulating and becoming trapped ______ of a small blood vessel, setting off the ______ and generating components that attract _____ to generate an ongoing inflammatory response.
antigen-antibody
beneath the basement membrane; complement cascade
PMN’s
HR TYPE 3
In contrast to type II, the ______ is not ___________
the Ag is not an intrinsic component of the target cells
In H.R.-TYPE III
Immune complexes can only be deposited locally
T/F
F
Both systemic and/or locally
H.R.-TYPE III
Complement is chemotactic for neutrophils with release of ____,____,_____
F.XII is activated causing _____ of nearby vessels
activation of the kinin system causes _____ and ——-
Platelet aggregation causes _____ formation and release of ______ from its ____ core granules
PG,kinin & free radicals
thrombosis; vasodilation & edema
microthrombi; vasoactive amines
dense
HR TYPE 3
Systemic immune complex disease:
Ag-Ab complexes form in the circulatory system and are deposited in tissues, typically near basement membranes in places such as __,_____,______ ,_____ .
blood vessels, glomeruli, skin, joints, pleura, and pericardium
HR TYPE 3
Larger immune complexes are _______ by ______ and _____, but small to intermediate complexes formed with antigen excess may escape removal leading to:
_________
____________
________
quickly phagocytized
macrophages and removed
Glomerulonephritis
Serum sickness
Vasculitis
HR TYPE 3
Local immune complex disease: Also called an “ ______ “ reaction,
it occurs with ______ of the antigen and leads to ________.
Arthus
local injection
focal vasculitis
HR TYPE 3
Local immune complex disease
This kind of immune reaction also plays a role in the development of hypersensitivity _____ (so-called “_________”).
pneumonitis
farmer’s lung
HR TYPE 3
Arthus reaction
-Local reaction which occurs when ________________ , In the presence of an excess of preformed Ab
-As the antigen diffuses into the vascular wall, it binds the ______, and (small or large?) immune complexes are formed locally.
These complexes precipitate in the vessel walls and cause _______, and super imposed ______ worsens the ischemic injury.
Ag is introduced- by injection/organ transplant
preformed antibody
Large ; fibrinoid necrosis
thrombosis
HR TYPE 3
Clinical examples:
Serum ______
_____
______ reaction
________
Immunecomplex mediated ______ dx
Rheumatoid arthritis
sickness
SLE; arthus
Polyarteritis nodosa
glomerular
In SLE(___vs our own dna)
In Rheumatoid arthritis(___ vs our own igg)
antibody
igm
HR TYPE 3
Serum sickness;
A systemic deposition of ag-ab complexes in multiple sites
Esply the _____,_____,____
kidneys,heart,joints
Before antibody containing foreign(horse) serum was used for ________ againts micro-orgs.and toxic products
Stopped because of __________
passive immunisation
the danger of S.S.
HR TYPE 3
The pathogenesis of systemic immune complex disease can be divided into three phases:
(1) formation of _________ in the circulation;
(2) ______ of the immune complexes in various tissues, thus initiating
(3)__________ at the sites of immune complex deposition
antigen-antibody complexes
deposition
an inflammatory reaction
SLE
Also an e.g.of multisystemic illness
Characterized by the _____ immune complex deposition
malar rash-
HR TYPE 3
PAN;
_________ complex dx
Especially involving the ___ sized arteries
Generalised immune
small & medium
HR TYPE 3
Immune-complex mediated glomerular diseases
Includes ________ glomerulonephritis , __________ glomerulonephritis & _______
post-streptococcal
membranous
lupus nephropathy
HR TYPE IV
Type IV hypersensitivity– _____/_____ type
Definition-no ____ is required
cell –mediated
delayed; antibody
HR TYPE IV
A disease mediated by sensitized _________
The cell-mediated type of hypersensitivity is initiated by antigen-activated (sensitized) __ lymphocytes, including ____________ T cells
Found in;______ formation Virus
Tumor
Th1 lymphocytes
T
CD4+ and CD8+
Granuloma
HR TYPE IV
Reactions of CD4+ T Cells: _____-Type Hypersensitivity and _______
Reactions of CD8+ T Cells: _____- mediated _______
Delayed; Immune Inflammation
Cell-Mediated Cytotoxicity
HR TYPE IV
Delayed-Type Hypersensitivity and Immune Inflammation
Both TH1 and TH17 cells contribute to organ- specific diseases in which inflammation is a prominent aspect of the pathology.
The inflammatory reaction associated with TH1 cells is dominated by _____, and that triggered by TH17 cells has a greater ______ component.
activated macrophages
neutrophil
The cellular events in T cell–mediated hypersensitivity consist of a series of reactions in which ______ play important roles.
cytokines
The reactions can be divided into the following stages:
_____________ of CD4+ T Cells.
_______________ T Cells.
Proliferation and Differentiation
Responses of Differentiated Effector
HR TYPE IV: delayed type hypersensitivity
Proliferation and Differentiation of CD4+ T Cells.
___ CD4+ T cells recognize peptides displayed by dendritic cells and secrete IL-__ , which functions as an autocrine growth factor to stimulate proliferation of the antigen-responsive T cells.
The subsequent differentiation of antigen-stimulated T cells to ____ or ____ cells is driven by the cytokines produced by _____ at the time of T-cell activation
In some situations the ___ produce IL- ____, which induces differentiation of CD4+ T cells to the ____ subset.
____ produced by these effector cells promotes _______ , thus amplifying the reaction.
Naive; 2
TH1 or TH17
APCs; APCs ; 12; TH1
IFN-γ; further TH1 development
HR TYPE IV: delayed hyper sensitivity
Proliferation and differentiation phase:
If the APCs produce inflammatory cytokines such as __,___ and a close relative of IL-12 called IL-___,
these work in collaboration with transforming growth factor-β (TGF-β) (made by many cell types) to stimulate differentiation of T cells to the ____ subset.
Some of the differentiated effector cells ________ and may remain in the ________ of T cells for long periods, sometimes years.
IL-1, IL-6, 23
TH17
Enter the circulation; memory pool
HR TYPE IV: Delayed-Type Hypersensitivity:Responses of Differentiated Effector T Cells.
Upon repeat exposure to an antigen, previously activated T cells recognize the antigen displayed by APCs and respond.
TH1 cells secrete cytokines, mainly ____, which are responsible for many of the manifestations of _______
IFN-γ; delayed- type hypersensitivity.
IFN-γ–activated macrophages are altered in several ways: their ability to _____ and ______ is markedly augmented; they express more class ___ MHC molecules on the surface, thus facilitating further antigen presentation; they secrete ___,____ and chemokines, which promote inflammation
phagocytose and kill microorganisms
II
TNF, IL-1,
HR TYPE IV: Delayed-Type Hypersensitivity: response of effector cells
TH17 cells are activated by some _______ and by ______ in autoimmune diseases.
Activated TH17 cells secrete IL- ___, IL-___, chemokines, and several other cytokines.
Collectively, these cytokines recruit _____ and —— to the reaction, thus promoting inflammation.
TH17 cells also produce IL- ____ , which amplifies the TH17 response.
microbial antigens ; self-antigens
17; 22; neutrophils and monocytes
21
Delayed-Type Hypersensitivity and Immune Inflammation
MORPHOLOGY
The classic example of DTH is the _____ reaction, which is produced by the intracutaneous injection of __________ (also called tuberculin), a protein-containing antigen of the tubercle bacillus.
In a previously sensitized individual, ______ of the site appear in 8 to 12 hours, reach a peak in 24 to 72 hours, and thereafter slowly subside
In fully developed lesions, the venules show marked _____, reflecting cytokine-mediated _______
With certain persistent or nondegradable antigens, such as tubercle bacilli colonizing the lungs or other tissues, the perivascular infiltrate is dominated by ______ over a period of 2 or 3 weeks.
tuberculin
purified protein derivative (PPD,
reddening and induration
endothelial hypertrophy; endothelial activation
macrophages
________ is a common example of tissue injury resulting from DTH reactions.
It may be evoked by contact with ______, the antigenic component of _____ or ______ , and presents as a ________
Contact dermatitis
urushiol; poison ivy or poison oak
vesicular dermatitis.
H.R.- TYPE IV
Reactions of CD8+ T Cells: Cell-Mediated Cytotoxicity
In this type of T cell–mediated reaction, __________ kill antigen- bearing target cells.
Tissue destruction by ____ may be an important component of many T cell–mediated diseases, such as ______,______
in reactions against viruses.
CD8+ CTLs
CTLs
type 1 diabetes, graft rejection
H.R.- TYPE IV
Reactions of CD8+ T Cells: Cell-Mediated Cytotoxicity
In a virus-infected cell, viral peptides are displayed by class I MHC molecules and the complex is recognized by the _____ of _________.
The killing of infected cells leads to the elimination of the infection, and is responsible for _______ (e.g., in viral hepatitis).
TCR of CD8+ T lymphocytes
cell damage that accompanies the infection
H.R.- TYPE IV
Reactions of CD8+ T Cells: Cell-Mediated Cytotoxicity
____-associated antigens are also presented on the cell surface
Tumor
CTLs are involved in tumor rejection
T/F
T
H.R.- TYPE IV
Reactions of CD8+ T Cells: Cell-Mediated Cytotoxicity
The principal mechanism of T cell–mediated killing of targets involves ______ and ______ , preformed mediators contained in the _______ granules of ____
CTLs that recognize the target cells secrete a complex consisting of _______, and a protein called _____, which enters target cells by _____.
In the target cell cytoplasm, perforin facilitates the release of the granzymes from the complex.
Granzymes are proteases that cleave and activate ______, which induce apoptosis of the target cells ..
perforins and granzymes,
lysosome-like ; CTLs.
perforin, granzymes; serglycin
endocytosis; caspases
Reactions of CD8+ T Cells: Cell-Mediated Cytotoxicity
Activated CTLs also express Fas ligand, a molecule with homology to ____, which can bind to Fas expressed on target cells and trigger apoptosis
CD8+ T cells also produce cytokines, notably IFN-γ, and are involved in inflammatory reactions resembling ____, especially following ____ infections and exposure to some contact sensitizing agents.
TNF
DTH; virus
Role of antibody in DTH
Antibody and complement play no role in DTH.
Role of complement in DTH
Antibody and complement play no role in DTH.
TYPE I – IMMEDIATE, _____, ANAPHYLACTIC
ATOPIC
Atopy is the term for the genetic trait to ___________________
Atopic individuals have higher levels of ______________
have a predisposition for localized anaphylaxis.
IgE and eosinophils.
Treatment of type 1 HR
DRUGS
________
______
______
Theophylline OR epinephrine -inhibits ______
Non-steroidal anti-inflammatories
Antihistamines
Steroids
degranulation
Treatment of type 1 HR
Immunotherapy
___sensitization (___sensitization) also known as ________
Repeated injections of allergen to ___________ and ________
De; hypo; allergy shots
reduce the IgE on Mast cells and produce IgG
Immediate (Type I) hypersensitivity ;
May be prevented by administration of disodium chromoglycate
T/F
T
Examples of type 2 hyper reactions
List 10!
Autoimmune hemolytic ananemia
Transfusion reactions
Immune thrombocytopenia
Erythroblastosis fetalis
Goodpasture syndrome
Hyperacute transplant rejection
Rheumatic fever
Grave’s disease
Myasthenia gravis
Pemphicus vulgaris
Goodpasture disease aka ________
Anti-GBM glomerulonephritis
Type 3 HR
Large amount of antigen and antibodies form complexes in blood.
If not eliminated can deposit in ______ or _____ and trigger inflammation.
capillaries or joints
IL__ activates eosinophils
IL__ does class switching to IgE
5
4
Type I hypersensitivity
The reaction may involve skin (____,_____), eyes (______), nasopharynx (____,_____), bronchopulmonary tissues (____) and gastrointestinal tract ( _______ ).
urticaria and eczema
conjunctivitis
rhinorrhea, rhinitis
asthma
gastroenteritis
Type 3 HR consists of 3 things
List them
antigen
Antibody
Complement
Examples of type 3 HR
LIST 4
SLE
Rheumatoid arthritis
Reactive arthritis
Polyarteritis nodosa
Post streptococcal glomerulonephritis
4Ts of HR type 4
Touching (contact dermatitis)
T cells
Transplant rejection
TB skin tests
Farmer’s lung disease
Type ___ HR
3
Poison ivy
Type ___ HR
4
