Intro to disorders of immunity

Question 1

Type I hypersensitivity is mediated by __, and starts within a half hour

Types __ and __ are antibody (or Ab-Antigen complex) mediated HSRs that take about __

Type __ is __ mediated and starts within 2-3 days

Answer 1

Type I hypersensitivity is mediated by IgE, and starts within a half hour

Types II and III are antibody (or Ab-Antigen complex) mediated HSRs that take about 8 or less hours

Type IV is cell mediated and starts within 2-3 days

Question 2

Type I HSR is __ mediated and involves allergens. Describe the sequence of events involved in the Type I HSR.

Answer 2

IgE

(see image below)

Question 3

Describe the initial phase of the Type I HSR and the late phase of the Type I HSR

Answer 3

Initial: starts w/in 30 mins post exposure (ends w/in 60 mins); IgE-Antigen binding >> Mast cell activation >> Histamine release

Late: w/in 24 hrs and may last days; other symptoms follow (chemokines, leukotrienes released >> inflammation + tissue damage)

Question 4

The most severe Type I HSR is ___, which can be characterized by ___. Another reaction is __ (you have this)

Answer 4

Anaphylaxis

Laryngeal edema

Asthma

Question 5

Examples of localized Type I HSRs include ___ (hay fever) and __, which arises from cross-linking of IgE on GI mast cells

Answer 5

Examples of localized Type I HSRs include allergic rhinitis (hay fever) and food allergies, which arise from cross-linking of IgE on GI mast cells

Question 6

Describe the sequence of events resulting in asthma (Type I HSR)

Answer 6

(see image)

Question 7

The Type II HSR involves which type of cells? Describe the sequence of events that occurs in Type II HSR.

Which 2 disease processes are examples of Type II HSR?

Answer 7

Circulating B cells

The B cells release Ig that activates that binds antigen and leads to cellular destruction (phagocytosis/complement activation/NK cells), inflammation and cellular dysfunction

Graves Disease ad Myesthenia Gravis

Question 8

What events lead to autoimmune hemolytic anemia?

Answer 8

the Ig binds to a normal cell, which recruits neutrophils that end up destroying normal cells (result in autoimmune hemolytic anemia)

Question 9

What events lead to Graves disease/hyperthyroidism?

Answer 9

Thyroid TSH receptor is bound by the Ab in Graves disease even in the absence of TSH, resulting in unregulated release of T3/T4

Question 10

Describe the events that lead to Myesthenia Gravis

Answer 10

Ab binds and blocks Ach receptor, resulting in decreased ACh signaling >> neuromuscular problems

Question 11

In the Type 3 HSr, the antibodies bind to antigen that is ___ and form __ that recruit immune cells. The downstream effect involves recuritment of which cell type and activation of which system?

Answer 11

In the Type 3 HSR, the antibodies bind to antigen that is free-floating and form Antigen-Ab complexes that recruit immune cells. The downstream effect involves recruitment of neutrophils and activation of complement

Question 12

The downstream effects of Type III HSR include cytokine-mediated ___. Type III HSR is ass’d w/ ___ b/c these complexes like to form in blood vessels

Answer 12

The downstream effects of Type III HSR include cytokine mediated inflammation.

Type III HSR is ass’d w/ vasculitis b/c these complexes like to form in blood vessels

Question 13

In type 3 HSR, antigens can either be __ or __, and the resulting disease processes can be generalized, e.g. in __, or localized, e.g. in ___

Answer 13

In type 3 HSR, antigens can either be exogenous or endogenous, and the resulting disease processes can be generalized, e.g. in Systemic Lupus Erythematosus, or localized, e.g. in autoimmune thyroiditis

Question 14

The only HSR that doesn’t require antibody activity is Type ___. The type of immune cells involved here are __, __ and __.

Answer 14

The only HSR that doesn’t require antibody activity is Type IV. The type of immune cells involved here are CD4+ T cells, CD8+ T cells and macrophages.

Question 15

What are the downstream effects of the Type IV HSR?

Answer 15

Inflammatory reaction: T cells secrete IL2, which is an inflammatory mediator

Question 16

An example of a Type IV HSR is ___

Answer 16

Contact dermatitis

Question 17

What are the cell types ass’d with each HSR?

Answer 17

Type I - Mast cells

Type II - plasma cells mainly

Type III - plasma cells + neutrophils

Type IV - T cells

Question 18

Autoimmunity is defined a loss of __ and ___ tolerance

Where do either of these occur?

Answer 18

Central and/or peripheral tolerance

Central: Bone marrow + Thymus

Peripheral: in the periphery

Question 19

Describe the difference between central and peripheral tolerance

Answer 19

Central tolerance: tolerance that occurs in the organs where the lymphocytes develop

T cells undergo positive (recognition of MHC) and negative selection (avid binding to MHC + binding of self antigen)

B cells undergo negative selection (avid binding to self antigen)

Peripheral tolerance: when cells are activated in the periphery (after the B and T cells have been released);

the point is to ensure that those self-reactive B and T cells that escaped selection don’t cause trouble either through anergy or apoptosis via the FAS death receptor pathway

Question 20

Systemic Lupus Erythematosus is a Type ___ HSR

What are the events leading up to Lupus?

Answer 20

Type III

Antigen-antibody complexes deposit in multiple tissues, resulting in activation of complement

Decreased Ch50 (suggests complement components being used)

Antibodies are directed against host nuclear material

Early complement deficiency (deficit in C1q, C4 and C2**)

Question 21

What are the clinical features of SLE? (hint: DOPAMIN RASH)

What are the specifc features that’ll allow you to know that this is SLE and not something else?

Answer 21

D - Discoid Rash

O - Oral ulcers

P - Photosensitivity

A - Arthritis

M - Malar rash

I - Immune markers – anti-dsDNA or anti-smith or anti phospholipid antibodies

N - Neuro findings – psychosis, seizures

R - Renal involvement

A - Anti nuclear Abs (abs that attack something within a nucleus); not so specific for lupus

S – Serositis, Pleuritis, Pericarditis

H - Hematological – anemia, thrombocytopenia, leukopenia

Question 22

What are the types of antinuclear Abs that are seen in the following conditions?

SLE

Drug induced lupus (which drugs? HIP)

Sjogren syndrome

Systemic sclerosis

Answer 22

SLE - anti dsDNA and Smith (rhymes with dsd for ds-dna+ s is for smith)

Drug induced ( Hydralazine, Isoniazid, Procainamide) - anti histone (anti-HIPtone >> HIP drugs + histone)

Sjogren Syndrome: (SS = SS) anti-SS A and B (aas’d w/ neonatal lupus)

SysTemIc SCLerosis: anti Scl70 (anti-topoisomerase) or anti-centromere

Question 23

Define CREST syndrome. What disease is this ass’d with?

Answer 23

Calcinosis

Raynaud

Esophageal

Sclerodactyly

Telangectasia

Ass’d w/ limited type Systemic sclerosis

Question 24

Amyloidosis is a disorder in which ___ deposits accumulate in organs

You can tell amyloidosis on congo red staining and flourescence. What are the features that tell you you’re dealing with amyloidosis?

Answer 24

Proteins

Congo red - it’ll stain pinkish

Flourescence: apple-green brifringence

Question 25

Primary amyloidosis is ass’d w/ what type of malignancy?

Answer 25

Multiple myeloma

Question 26

Primary immunodeficiencies are ___ whereas secondary immunodeficiencies can arise from ___

Answer 26

Genetic

Infections e.g. HIV infection/ Immunosuppression/ Malnutrition (or pregnancy)

Question 27

Why do B cell deficiencies manifest at about 6 months? What’s one way to recognize that a pt has a B cell immunodeficiency?

4 examples of B cell immunodeficiencies are X-linked agammaglobulinemia, ___, X linked hyper IgM syndrome, and ___ (which is the most common)

Answer 27

Probably related to maternal antibodies going away and kid builds up her own system

Recurrent infections (esp w/Giardia and bacterial infections)

Congenital (Bruton) X-linked agammaglobulinemia

Common variable immunodeficiency

X linked hyper IgM syndrome

Selective IgA deficiency

Question 28

If you have a T cell deficiency, you’ll be more susceptible to infections with which 3 organisms?

Answer 28

Viruses, parasites and fungi

Question 29

___ syndrome is T cell deficiency resulting from a mutation in 22q11.

This diease results in t cell deficiency because there’s lack of ___ development, thus the pt has no thymus

The patient also has hypocalcemia because there are no __ due to developmental failure of the ___ pouch

Answer 29

DiGeorge syndrome is T cell deficiency resulting from a mutation in 22q11.

This disease results in T cell deficiency because there’s lack of 3rd pharyngeal pouch development, thus the pt has no thymus

The patient also has hypocalcemia because there are no parathyroids due to developmental failure of the 4th pharyngeal pouch

Question 30

What are the features of Di George syndrome?

Answer 30

CATCH 22

Cardiac defects

Abnormal faces

Thymic hypoplasia

Cleft palate

Hypocalcemia

22q11 deletion

Question 31

Severe Combined Immunodeficiency is called this because ___. SCID can arise because of __, ___

Answer 31

Combined B and T cell deficiency

Cytokine mutations or MHC II mutations

Question 32

___ ___ Syndrome is an X-linked combined B and T cell deficiency characterized by thrombocytopenia, eczema and recurrent infections. This disorder results from a defect in the ___ gene

Answer 32

Wiscott Aldrich Syndrome is an X-linked T cell deficiency characterized by thrombocytopenia, eczema and recurrent infections. This disorder results from a defect in the WASP gene

**remember WATER** (+ hypothyroidism)

Question 33

Complement deficiencies (esp in C5-C9) result in recurrent infections with which microbe?

Answer 33

Complement deficiencies (esp in C5-C9) result in recurrent infections with Neisseria