patho: alterations in immune function

antibodies

proteins that specifically bind a particular antigen

IgG, IgM, IgA, IgD, IgE

IgG

most prevalent antibody class (75%)

IgM

first kind to be produced on antigen exposure

IgA

primarily found in body secretions

IgD

present on the B-cell membrane and functions in signal transduction

IgE

binds to basophil and mast cell membranes and mediates inflammation and allergy

passive immunity

transfer of plasma containing preformed antibodies against a specific antigen from a protected or immunized person to an unprotected or non-immunized person

active immunity

confers a protected state attribute to the body’s immune response

requires maturation and maintenance of memory B cells

second exposure: antibody response is much greater and more rapid

what does the immune system do?

DEFENDS body against invasion/infection and PATROLS for/destroys abnormal/damaged cells

immune system disorders

excessive immune responses

deficient immune response

excessive immune responses

increase in immune system activity

* autoimmunity
* hypersensitivity

autoimmunity

immune system attacks own tissues

hypersensitivity

describes the mechanism of injury

theories of autoimmunity

antigenic mimicry

sequester antigens

abnormal production of subclasses of T lymphocytes

development of abnormal B cells that do not respond to suppressor T-cell signals

genetic factors of autoimmunity

female gender

MHC genes (multiple sclerosis, rheumatoid arthritis disease, DM1, lupus)

environmental triggers to autoimmunity

chronic or multiple viral/bacterial infections

variety of noninfectious environmental factors have been associated with autoimmunity

environmental stress and occupational stress

autoantibodies injure body tissues through type II and III hypersensitivity reactions

pharmacotherapies

immunosuppressive therapy (corticosteroids, biological agents, immunomodulators, cytotoxins)

purine analogs

therapeutic plasmaphresis

intravenous immunoglobin (IV Ig)

hypersensitivity

normal immune response that is either

* inappropriately triggered
* excessive
* produces undesirable effects on the body

reactions are specific to particular antigen

FOUR TYPES

type I, II, and III are mediated by….

antibodies

type IV is mediated by…

T-cells

type I hypersensitivity

atopic, anaphylactic

mediated by IgE

mast cell degranulation: release histamin, kinin, prostglandins, interleukins, leukotrienes, increased vascular permeability, vasodilation, hypotension, urtcaria, brochoconstriction

bee sting reaction, allergic reaction, rhinitis

clinical manifestations of type I hypersensitivity

medications, biological agents, insect venom, foods, inorganic chemical and irritants

* hives, allergic rhinitis, eczema
* mild bronchoconstriction
* localized edema, tightening of the throat, wheezing, and tachycardia
* angioedema or severe airway restriction
* anaphylaxis (life threatening) caused by bee stings, seafood, or peanut ingestion

type IIa hypersensitivity

tissue-specific/cytotoxic

mediated by IgM or IgG

activated by complement

surface antigen and antibody leading to killer cell cytotoxic action or complement-mediated lysis

transfusion reactions, hemolytic disease of newborn, GRAFT infection

transfusion reaction

acute hemolytic blood transfusion reaction

* symptoms: fever, chills, flushing, tachycardia, hypotension, low back pain, pleuritic chest pain, nausea, vomiting, restlessness, anxiety, oliguria, and headache

Labs

* CBC
* bilirubin

Treatment

* fluids
* symptoms management

hemolytic disease of newborn

erythroblastosis fetalis

rhesys (Rh) incompatibility

Rh negative mother

Rh positive father

RhoGAM contains antibodies against Rh antigens on fetal blood cells

type IIb hypersensitivity

graves disease occurs as a result of an immune attack on the thyroid gland

infection, diet, iodine, stress, and smoking are contributing factors

circulating IgG antibodies attack thyroid-stimulating hormone receptor

type III hypersensitivity

immune complex (arthus reaction)

IgG and complement

Ag-Ab complex deposited in tissues; complement activates and polymorphonuclear leukocytes

systemic lupus erythematosus

chronic multisystem inflammatory disease

autoantibodies against

* nucleic acids
* erythrocytes
* coagulation proteins
* phospholipids, lymphocytes, platelets, etc.

circulating immune complexes containing antibody against host DNA are deposited in organs

type IV hypersensitivity

delayed hypersensitivity

CD4 TH1 or TH2 cells, CD8 cells

no complement activation

Ag-sensitized T cells release cytokines, leading inflammatory reaction and recruitment of macrophages, eosinophils, neutrophils

IVa, IVb, IVc, IVd

deficient immune responses

result from decrease in one or more components of immune system or failure of immune/inflammatory response

primary and secondary

primary immunodeficiency disorders (PIDs)

predisposed to multiple deficiencies (AIDs)

congenital, genetic, or acquired defects

B and T cells disorders

T-cell disorders

B-cell disorders

B and T cell disorders of PIDs

severe combined immunodeficiency disorders (SCID); sepsis and opportunistic infections

Wiskott-Aldrich Syndrome

T cell disorders of PIDs

22q11.2 Deletion Syndrome (DiGeorge Syndrome)

chronic mucocutaneous candidiasis disease

B cell disorders of PIDs

IgA deficiency

x-linked agammaglobulinemia

transient hypoammaglobulinemia

common variable immunodeficiency disease

secondary immunodeficiency disorders

cause is problems in neuroendocrine and immune system interactions and excessive neuroendocrine response to stress with increased corticosteroid

medications

* cytotoxins and other cancer pharmacotherapeutic drugs
* anesthetics, alcohol, antibodies, steroids