Immunopathology 2 Flashcards by Iseoluwa Ojo

HYPERSENSITIVITY REACTIONS

Here the organism responds to _____ with an antigen that it ______ and to which it is _____.

renewed contact

already knows

hypersensitive

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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

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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

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Hypersensitivity

Excessive pathogenic reaction of a ________ body to _______ contact with the ________

sensitized

renewed; sensitizing antigen.

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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

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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

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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

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In HR TYPE 1

Complement is involved

T/F

not

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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

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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

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Mast cells express a high-affinity receptor for the ___ portion of the __ (light or heavy?) chain of IgE, called _____.

Heavy

FcεRI

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______ are the circulating counterparts of mast cells.

Basophils

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role of basophils in most immediate hypersensitivity reactions is not established

T/F

With reason

since these reactions occur in tissues and not in the circulation

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Mention 3 cells that express the Fc3RI

Mast cell
Basophils
Eosinophils

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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

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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

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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

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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

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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

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HR TYPE 1

Local anaphylaxis (_____)

Classic examples are food allergies and hay fever to ragweed pollen

atopy

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About ____% of people have “atopy” and are easily sensitized to allergens that cause a _____ reaction when inhaled or ingested.
This can produce _____,_____,_____ , etc..

localized

hay fever, hives, asthma

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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

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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

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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

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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

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

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

Poison ivy Type ___ HR

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Immunopathology 2 Flashcards

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