L47, L49- Hypersensitivity, Immune Tolerance, Autoimmunity Flashcards by Connor Patrick

Type I hypersensitivity reactions have (1) as the immune reactant and Ag in the (2) form. (1)-(2) complex binds to (3) on (4) cells inducing (5).

1- IgE
2- soluble
3- FcεRI
4- mast cells (basophils, eosinophils)
5- degranulation of mast cells

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Type II hypersensitivity reactions have (1) as the immune reactant and Ag in the (2) form. (1) binds to (3) leading to (4) activation and (5) of target cell.

1- IgG or IgM
2- cell-bound
3- cellular Ag
4- complement (classical pathway)
5- lysis
(Note- IgG can lead to ADCC w/ Tc / NK cells, macrophages, neutrophils)

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Type III hypersensitivity reactions have (1) as the immune reactant and Ag in the (2) form. (1)-(2) complexes are deposited in tissues which activates (3) resulting in (4) and recruitment of (5) which will cause local tissue damage.

1- IgG &amp; IgM
2- soluble (SERUM)
3- complement
4- inflammation (C3a, C5a)
5- neutrophils (release enzymes => tissue damage)

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Type IV hypersensitivity reactions have (1) as the immune reactant and Ag in the (2) form. (1) secretes (3) to activate (4) cells.

1- T cells (Th1)
2- soluble or cell-bound
3- CKs
4- macrophages & Tc cells

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hypersensitivities take place in response to… (hint- 3 things)

infection that can’t be cleared
normally harmless exogenous substance (allergen)
auto-antigen

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define hypersensitivity

exaggerated or inappropriate immune response => tissue damage

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Type _ hypersensitivity(ies) is(are) Ab mediated (humoral)

Type _ hypersensitivity(ies) is(are) cell mediated

I, II, III –> Ab mediated

IV –> cell mediated

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(T/F) hypersensitivities occur upon first contact with Ag

F- never, sensitization occurs on 1st contact, hypersensitivity always upon re-exposure

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define atopy

genetic predisposition to produce IgE in response to many common, naturally occuring Ag/allergens (~20% individuals in US)

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IgE is the usual response against (1), where it binds (2) after binding Ag on (3) cells

1- metazoal parasites (too large to be phagocytized)
2- FcεRI (high-affinity)
3- mast cells, basophils (+ eosinophils)

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Type I hypersensitivities are (immediate/delayed) reactions

immediate-type hypersensitivity

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describe development of IgE against (harmless) Ags in upon first contact

IgM on B cell binds Ag
Th2 cell binds B cell via CD4 and releases IL-4 / IL-13
ILs stimulate class switching to IgE
results in memory B cell + plasma cell producing Allergen specific IgE

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list the primary mediators in mast cell granules

(made before and stored)

histamine, proteases, eosinophil chemotactic factor, heparin

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list the secondary mediators in mast cells

(2-4 hrs after immediate response)

platelet-activating factor, LTs, PGs, bradykinins, some CKs + chemokines

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compare atopic to immune allergy response

(based on genetic + environmental factors)
-Atopic: Th2, IgE; not exposed to pathogens regularly (urban enviro., western diet, widespread Antibiotic use)

-Immune: Th1, IgG, exposed to pathogens regularly (hygiene hypothesis)

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examples of localized and systemic Type I hypersensitivity

Local: allergic rhinitis, asthma, food allergies, wheals, atopic eczema

Systemic: anaphylaxis

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explains desensitization using Abs

for type I hypersensitivity in people with mild to moderate allergies (not for extreme- must have some tolerance)
development of IgG as ‘blocking Abs’ preventing IgE binding and rxn with mast cell

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Type II hypersensitivity can involve cytotoxic process where (1) is activated, phagocytosis occurs via (2) receptor, and (3) occurs via NK cells and eosinophils. Non-cytotoxic process involves (4).

1- classical complement pathway (IgG, IgM)
2- FcR and complement receptors
3- ADCC (Ab-dep. cellular cytotoxicity)
4- interference with receptors (anti-receptor Abs)

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Autoimmune hemlytic anemia (HDNB) is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type II (cytotoxic)
2- RBC membrane proteins (Rh, ABO)
3- opsonization, phagocytosis, complement-mediated destruction of RBCs
4- hemolysis, anemia

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Acute rheumatic fever is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type II (cytotoxic)
2- streptococcal cell-wall Ag (cross-reaction with myocardial Ag)
3- inflammation + macrophage activation
4- myocarditis, arthritis

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Goodpasture syndrome is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type II (cytotoxic)
2- type IV collagen (BM of kidney glomeruli + lung alveoli)
3- complement + Fc-receptor-mediated inflammation (IgG accumulation in tissue)
4- nephritis, lung hemorrhage, linear Ab deposits

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Myasthenia Gravis is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type II (non-cytotoxic)
2- AChR
3- blocks ACh binding
4- muscle weakness, paralysis

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Graves disease is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations)

Study These Flashcards

1- type II (non-cytotoxic)
2- TSH receptor
3- stimulates TSH receptor
4- hyperthyroidism (followed by hypothyroidism)

describe Erythroblastosis fetalis

Study These Flashcards

Rh+ fetus, Rh- mother
upon 1st vaginal birth, mother exposed to Rh –> develops IgG against
upon 2nd pregnancy –> IgGs can cross placenta and damage fetus
RhoGAM administered to block Rh from being exposed to mother

describe Arthrus reaction

(type III hypersensitivity) - individual sensitized to Ag - Ag administered locally (SQ, ID) - rxn occurs locally - mast cell mediated

what is serum sickness

(type III hypersensitivity) - response to foreign protein after receiving anti-serum, which is usually from another animal containing anti-toxin - deposition of serum immune complex (Ag-IgG/IgM) systemically - fever, vasculitis, arthitis, nephritis

Type IV hypersensitivities are (immediate/delayed) reactions

delayed-type hypersensitivity (48-72 hrs after second exposure)

Type I hypersensitivities are important for the clearance of...

- intracellular pathogens (ex. M. tuberculosis, Leishmania major) - if Ag persists --> lytic products of macrophages can damage healthy tissue

describe sensitization phase of Type IV hypersensitivity

upon first exposure, APCs (macrophages, Langerhans cells) present Ag to naive T cells generating Th1 (generally)

describe effector phase of Type IV hypersensitivity

- Th1 cells secrete CKs and chemokines to effect macrophages | - macrophages inc MHC-II, TNF receptors, O2 radicals + NO

prolonged DTH can lead to formation of....

(delayed-type hypersensitivity) | granuloma (surrounding resistant intracellular microbe)

define central tolerance

- deleting T or B clones before maturity if they have receptors that recognize self-Ags with great affinity - 'negative selection' - occurs in primary lymphoid tissues

define peripheral tolerance

- killing lymphocytes that bind self-Ag (high dose) in secondary lymphoid tissue - regulated by apoptosis or anergy (no proliferation)

(T/F) B cells can escape anergy or deletion in peripheral tolerance

T- Receptor Editing can occur; further rearrangement of their immunoglobulin genes

in peripheral tolerance (1) cells may be responsible for controlling this process, as they recognize (2) and then will (3)

1- Treg cells (CD4+) 2- self-Ag (intermediate affinity) 3- suppress T cells (non-reg) that bind with low affinity to self-Ag

list the 5 ways immunogens can become tolerogens

- high doses of Ag - persistent Ag - IV / oral introduction - absent adjuvants - low levels of co-stimulators: CD28/B7 low => CTLA-4 binding B7 to inhibit

(T/F) CD28 has higher affinity for B7 than CTLA-4

F- CTLA-4 (inhibitory) has higher affinity than CD28 (activator)

tolerogens induce ______ in mature lymphocytes

apoptosis or anergy

how does the body prevent autoimmunity

- central tolerance - peripheral tolerance - immune regulation (Treg cells)

list the immunologically privileged sites and what occurs there (include the CK that might be most responsible)

- brain, eyes, testis, placenta (only exposed to immune system in trauma) - T cells enter => undergo apoptosis - foreign Ags (+ tissue grafts) don't elicit immune responses - tolerance >> destructive reponse - TGF-β may be key CK responsible

list the 4 ways peripheral tolerance prevents autoimmunity

- lack of co-stimulatory - lack of Ag presentation - negative feedback prevents overstimulation - T cells entering immune-privileged sites undergo apoptosis

list the 6 discussed causes of autoimmunity

- Tolerance => thymic breakdown (genetic) OR in periphery (enviroment) - HLA (human leukocyte Ag) = genetic predisposition - release of sequestered Ags (tissue traumas) - Infection => mimicry of self-Ags (short-lived and reversible) - some viruses activate B cells non-specifically - inappropriate MHC expression

(T/F) autoimmune diseases affect women more than men

which hypersensitivity mechanisms can result in autoimmunity

- Type II, Ab mediates, immediate rxn - Type III, immune complex mediated - Type IV, cell-mediated, delayed rxn

Autoimmune thrombocytopenia purpura is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading

1- type II (cytotoxic) 2- platelets' integrin or glycoprotein 3- Abs destroy platelets => thrombocytopenia

list the 3 autoimmune anemias (include Ags and through what hypersensitivity mechanism)

[type II cytotoxic mechanism] - hemolytic anemia: Abs for Rh or AB(O) RBCs - drug induced anemia - pernicious anemia: Ab against intestinal protein responsible for B12 uptake

Pernicious anemia is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type II (cytotoxic) 2- intestinal B12 protein responsible for uptake 3- no B12 absorption from intestine 4- anemia (+ neurological symptoms)

systemic autoimmunities are usually due to type ___ hypersensitivity mechanisms

type III (immune complex mediated)

Systemic Lupus Erythematous is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type III 2- antinuclear Ags (ANA): dsDNA (mainly), histones, platelets, leukocytes, clotting factors 3- excessive complement activation (systemically) 4- fever, weakness, arthritis, rash, kidney issues (note typically affects middle aged women most)

what is an ANA and how is it detected

- antinuclear Ag: dsDNA, histone, ect. | - detected via indirect immunoflorescent Ags

Polymyositis is considered a type (1) hypersensitivity. It involves (2) as target Ag.

1- type IV | 2- muscle cells

Hasimoto's Thyroiditis is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type IV 2- thyroid Ags- mainly TPO (thyroid peroxidase) 3- destruction of thyroid tissue + accumulation of incomplete thyroid hormone 4- hypothyroidism, goiter (mainly affects middle aged women)

Insulin dependent DM (type I) is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type IV 2- β-cell (pancreas) elements 3- Abs / T cells destroy insulin producing β-cells 4- diabetes

Multiple sclerosis is considered a type (1) hypersensitivity. It involves (2) as a mechanism leading to (3) as clinical manifestations.

1- type IV 2- inflammatory lesions in myelin sheath caused by T cells 3- numbness, paralysis, vision loss

Rheumatoid arthritis is considered a type (1) hypersensitivity. It involves (2) Ag, has (3) as a mechanism leading to (4) as clinical manifestations.

1- type IV 2- Fc region of IgG 3- immune complexes (T cells + IgG) depositing systemically in tissue 4- chronic inflammation of joints

CTLA-4 is expressed on (1) cells in (2) fashion and (3) cells in (4) fashion. CTLA-4 binds to (5). Variants of CTLA-4 has been associated with the following autoimmune diseases: (6).

1/2- Treg cells, constitutively 3/4- activated T cells, only when activated 5- B7-1/CD80, B7-2/CD86 6- type I DM, Grave's, Hashimoto's. Celiac's, SLE, others

L47, L49- Hypersensitivity, Immune Tolerance, Autoimmunity Flashcards

(56 cards)