Clin Med II exam 1

gbalsam

HLA-B27 disease association

- ankylosing spondylitis

- reiter (reactive arthritis)

- acute anterior uveitis

HLA-DR4 disease association

rheumatoid arthritis

HLA-DR3 disease association

SLE in caucasians

HLA-B*57:01 disease association

abacavir hypersensitivity

what are the 4 cardinal signs of inflammation?

- rubor (redness)

- tumor (swelling)

- calor (heat)

- dolor (pain)

what is sometimes considered a 5th cardinal sign of inflammation?

functio lassae (loss of function)

PG12, PGD2, and PGE2 in acute inflammation

vasodilation and vascular permeability

PGE2 in acute inflammation

mediates pain and fever

LTB4 in acute inflammation

attract and activate neutrophils

LTC4, LTD4, and LTE4 in acute inflammation

slow-reacting substances of anaphylaxis (i.e., vasoconstriction, bronchospasm, and increased vascular permeability)

CD4+ T-cells

MHC class II molecules

CD8+ T-cells

MHC class I molecules

how is pain caused during inflammation?

bradykinin and PGE2 sensitizes sensory nerve endings

deficiency in terminal components of complement

recurrent neisseria infections

deficiency in complement C3

susceptibility to encapsulated bacteria (pyogenic infection)

deficiency in complement C6,7

Raynauds phenomena

deficiency in complement C1 esterase inhibitor

hereditary angioedema

hypersensitivity reaction

allergy to drugs, pollens, foods, bacteria, or any other substance may induce a protective reaction

how are hypersensitivity reactions classified?

on the basis of the principal immunologic mechanism that is responsible for tissue injury and disease

variations of hypersensitivity reaction

mild itching to severe bronchial asthma

Gell-Coombs classification

the mechanisms of immune responses to antigen grouped into 4 distinct types of reactions

type I hypersensitivity reaction

immediate hypersensitivity

associated diseases with type I hypersensitivity reaction

atopy, anaphylaxis, and asthma

mediators of type I hypersensitivity reaction

IgE

type II hypersensitivity reaction

antibody-mediated hypersensitivity

associated diseases with type II hypersensitivity reaction

autoimmune, hemolytic anemia, Goodpasture's disease, and erythroblastosis fetalis

mediators of type II hypersensitivity reaction

IgG or IgM and complement

type III hypersensitivity reaction

immune complex-mediated hypersensitivity

associated diseases with type III hypersensitivity reaction

serum sickness, Arthus' reaction, and lupus nephritis

mediators of type III hypersensitivity reaction

IgG and complement

type IV hypersensitivity reaction

delayed hypersensitivity

associated diseases with type IV hypersensitivity reaction

transplant rejection, contact dermatitis, and tuberculosis

mediators of type IV hypersensitivity reaction

T-cells, macrophages, and histiocytes

pathological lesions of type I hypersensitivity reactions

- vascular changes (vasodilation)

- edema

- contraction of smooth muscle

- production of mucous

- inflammation

effects of type I hypersensitivity reactions

- IgE is produced

- vasoactive amines released from mast cells

- inflammatory cells accumulate later at the site

when do type I hypersensitivity reactions occur?

within minutes after the combination of antigen with antibody bound to mast cells

in what people do type I hypersensitivity reactions occur?

those who have been previously sensitized to the antigen

what are the chief cells in type I hypersensitivity reactions?

mast cells

immediate phase of type I hypersensitivity reaction

seen within 5-30 minutes

late phase of type I hypersensitivity reaction

sets in after 2-24 hours (seen in allergic rhinitis or bronchial asthma)

what can activate mast cells?

- IgE

- anaphylatoxins (C3a and C5a)

- IL-8, drugs, and mellitin (found in bee venom)

histamine

a biogenic amine that causes smooth muscle contraction, increased vascular permeability, and secretions

chymase and tryptase

enzymes that cause tissue damage

heparin and chondroitin sulfate

proteoglycans of type I hypersensitivity that help to store mediators in granules

lipid mediators of type I hypersensitivity reactions

leads to the activation of phospholipase A2 and then to the activation of arachidonic acid metabolism

cytokine mediators of type I hypersensitivity reactions

play in a role in the "late phase" reaction

- TNF

- IL-1, 3, 4, 5, and 6

- GM-CSF

leukotrienes

LTB4 is chemotactic for eosinophils, neutrophils, and monocytes

prostaglandin D2

causes intense bronchospasm

platelet-activating factor (PAF)

platelet aggregation, release histamine, and bronchospasm

local immediate hypersensitivity reaction

known as "atopic allergy;" often caused by pollen, house dust, animal dander, food, etc.

features of local immediate hypersensitivity reaction

- urticaria

- angioedema

- allergic rhinitis

- asthma

local lesion

wheal-and-flare reaction confined to one region of the body

urticaria

disseminated form of a wheal-and-flare reaction

angioedema

localized areas of swelling beneath the skin, often around the eyes and lips, but it can also involve other body areas as well

hereditary angioedema

autosomal dominant deficiency or malfunction of C1 esterase inhibitor (C1-INH)

symptoms of hereditary angioedema

- recurrent episodes of severe non-pruritic swelling of the face, limbs, GI tracts, and airways

- recurrent abdominal pain

- no urticaria

- begins in childhood and worsens during puberty

- death from laryngeal edema may occur

prevalence of family history in hereditary angioedema

positive in 80% of patients

diagnosis of hereditary angioedema

- low C4 level (due to exaggerated cleavage of C4 by C1 complex)

- low C2 level

- low C1 inhibitor protein or function

acute treatment of hereditary angioedema

FFP or C1-INH concentrate

chronic treatment of hereditary angioedema

ecallantide and androgens (i.e., danazol or stanazol)

commonly understood patho of acquired angioedema

ACE inhibitors

anaphylaxis

a life-threatening manifestation of immediate hypersensitivity

when do symptoms of anaphylaxis develop?

within 30 minutes of exposure to the inciting agent

symptoms of anaphylaxis

- urticaria or severe upper airway obstruction resulting from edema of the larynx, epiglottis, and surrounding structures

- hypotension, secondary to profound vasodilation

- possible seizures

management of anaphylaxis

maintenance of airway and oxygenation (i.e., attach a pulse oximeter and cardiac monitor)

pharmacologic management of anaphylaxis

epinephrine 1:1000 solution (0.01 mL/kg with max of 0.5 mL IM repeated every 15 minutes as needed)

other pharmacologic management of anaphylaxis

- for bronchospasm, administer albuterol by metered-dose inhaler (MDI) with spacer device or nebulizer

- rapid IV fluid if patient is hypotensive

- diphenhydramine 50mg IV/IM/PO

- corticosteroids (such as prednisone 60 mg IV/IM/PO) to reduce late-phase recurrence of symptoms 4-8 hours later

- consider glucagon and/or atropine for patients on beta blockers whose symptoms are refractory to therapy

- injectable epinephrine and antihistamine on discharge

how long should children be monitored following anaphylaxis with airway involvement?

at least 24 hours

effects of type II hypersensitivity reactions

IgG and IgM produced are bound to the target cells that are then lysed by activated complements

two major changes observed in tissues during a type II hypersensitivity reaction

cell lysis and inflammation

mechanism of type III hypersensitivity reactions

deposition of antigen-antibody complexes leading to activation of complements

pathological changes observed in type III hypersensitivity reaction

necrotizing vasculitis and inflammation

examples of type III hypersensitivity reactions

SLE, polyarteritis nodosa, poststreptococcal glomerulonephritis, acute glomerulonephritis, Arthus reaction, and serum sickness

serum sickness

reaction to certain medications or antiserum (snake) that develops 7-10 days after initial exposure

symptoms of serum sickness

- redness & itching at injection site

- fever

- joint pain

- adenopathy

- wheezing

- diarrhea & nausea

causes of serum sickness

- PCN (most common cause)

- Prozac

- barbiturates

Arthus reaction

acute immune complex vasculitis causes a localized area of tissue necrosis in the skin developing 4-10 hours after the injection

patho of Arthus reaction

as the antigen diffuses into the vascular wall in a previously sensitized person, large immune complexes are formed producing an inflammatory response

mechanism of type IV hypersensitivity reactions

- activation of T-lymphocytes and macrophages

- T-cell mediated cytotoxicity

pathological changes seen in type IV hypersensitivity reactions

- granuloma formation

- edema

- perivascular inflammation

- cell destruction

delayed type hypersensitivity

mediated by CD4+ T-cells as seen in tuberculosis, fungal, viral, and parasitic diseases as well as some autoimmune diseases

T-cell mediated cytotoxicity

sensitized CD8+ T-cells kill antigen bearing target cells

what is the classic example of delayed type hypersensitivity?

tuberculin reaction (TB skin test)

positive tuberculin reaction

reddening and induration appear within 8-12 hours

what happens to lymphocytes with long-standing infections?

they are replaced by macrophages that are then transformed to look like epithelial cells

granuloma

collection of macrophages (epithelioid cells)

primary immunodeficiency disorders

genetic defects that can lead to abnormalities in immunocompetence

effects of any immunopathogenic mechanism that impairs T-lymphocyte function or cell-mediated immunity

predisposes the host to the development of serious chronic and potentially life-threatening opportunistic infections with viruses, mycobacteria, fungi, or protozoa involving any or all organ systems

effects of immunopathogenic dysfunction of B-lymphocytes

results in antibody deficiency that can predispose the host to the pyogenic sinopulmonary and mucosal infections

clinical features of adaptive primary immunodeficiency disorders (B-cell defects)

- recurrent bacterial sinopulmonary infections or sepsis, particularly with polysaccharide encapsulated organisms

- unexplained bronchiectasis

- chronic or recurrent gastroenteritis (often with Giardia or enterovirus)

- failure to thrive

- chronic enteroviral meningoencephalitis

- arthritis

clinical features of adaptive primary immunodeficiency disorders (T-cell defects)

- recurrent, severe, or unusual viral infections (VZV, CMV, HSV)

- failure to thrive

- chronic candidiasis

- chronic diarrhea

- lymphopenia during the neonatal period or in infancy

- pneumocystis pneumonia

- graft-versus-host disease

- severe/neonatal eczematoid or seborrheic rashes

symptoms of graft-versus-host disease

maculopapular and/or desquamating skin, abnormal liver function tests, and/or chronic diarrhea

clinical features of innate primary immunodeficiency disorders (phagocytic defects)

- poor wound healing

- delayed separation of the umbilical cord

- lymphadenitis or soft tissue abscesses

- hepatosplenomegaly

- chronic gingivitis and periodontal disease/oral mucosal ulcerations

- infection with catalase positive bacteria and fungi

- recurrent GI and GU tract obstruction

clinical features of innate primary immunodeficiency disorders (complement defects)

- angioedema of face, hands, feet, and GI tract

- autoimmune disease or lupus-like symptoms

- pyogenic bacterial infections (i.e., Neisseria meningitidis)

- history suggestive of autosomal dominant inheritance (should have an affected parent)

clinical features of innate primary immunodeficiency disorders (other defects)

- herpes simplex meningoencephalitis in infancy

- papilloma virus infections of skin, including extensive warts

- ectodermal dysplasia

- pyogenic infections (i.e., sepsis, meningitis)

ataxia-telangiectasia syndrome

autosomal recessive disorder due to a defect in DNA damage repair leading to defective B- and T-cell functions

symptoms of ataxia-telangiectasia syndrome

- delay in walking due to atrophy of the cerebellum

- uncoordinated head and eye movements

- speech failure

- characteristic ocular and cutaneous telangiectasias

- decreased IgE and IgA levels

- increased serum alpha-fetoprotein

prognosis of ataxia-telangiectasia syndrome

increased risk for lymphomas and leukemias

treatment of ataxia-telangiectasia syndrome

none specific but is directed at specific symptoms

severe combined immunodeficiency diseases (SCID)

- genetic defect in stem cells resulting in the absence of the thymus, T- and B- cells

- half autosomal recessive; half X-linked leading to prevention of DNA synthesis and problems with interleukin signaling