7 Hypersensitivity Type II, III, IV

True or False: Hypersensitivity reactions are normal mechanisms and they are only more harmful than good b/c exaggerated into something inappropriate

True

True or False: Only Type I Hypersensitivity requires sensitization

False ==> all hypersensitivity reactions (II, III, IV) require sensitization b/c hypersensitivity is an effector memory rxn

Type II Hypersensitivity Reactions

hypersensitivity rxn due antibodies (IgG or IgM) binding cells resulting in complement activation, ADCC, or receptor dysfunction (symptoms based on what antibody is used)

*target antigens are on cells & tissues

What are the 3 mechanisms of antibody-mediated injury in type II hypersensitivity?

-complement-mediated --> leads to cell lysis or render them susceptible to phagocytosis

-ADCC --> IgG-coated cells are killed by NK cells

-Anti-receptor antibodies --> blocking or stimulating

Describe the mechanism of ADCP or ADCC antibody-mediated injury in type II hypersensitivity

antibody binds to targeted self-cell & the cell goes down the complement MAC pathway to cell lysis or opsonization pathway via binding of NK/T cells to Fc of antibody

Describe how anti-receptor antibodies are blocking or stimulating in type II hypersensitivity

-blocking ==> bind receptor on self cell & prevent its ligand from binding (block a process from taking place)

-stimulating ==> binds receptor on self cell & stimulates it like its ligand would (falsely signals a process)

What kind of hypersensitivity causes transfusion reactions?

type II hypersensitivity to ABO blood group antigens

What kind of hypersensitivity causes autoimmune hemolytic anemia?

type II hypersensitivity to RBC membrane proteins

What kind of hypersensitivity causes autoimmune thrombocytopenia?

type II hypersensitivity to platelet membrane proteins

what kind of hypersensitivity causes goodpastures syndrome?

type II hypersensitivity to renal & lung basement membranes

what kind of hypersensitivity if hyperacute graft rejection?

type II hypersensitivity to allogenic MHC on transplant

autoimmune hemolytic anemia

type II hypersensitivity that produces anti-red cell antibodies ==> IgM binds RBCs --> activates complement --> RBC lysis

True or False: Autoimmune hemolytiv anemia is due to ADCC type II hypersensitivity

False ==> anti-red cell antibodies; IgM binds RBCs --> activates complement --> RBC lysis

autoimmune thrombocytopenia

type II hypersensitivity that produces antiplatelet antibodies

*symptoms

-easy bruising & bleeding

-pinpoint sized reddish-purple spots on the lower legs

Myasthenia Gravis

type II hypersensitivity disease that produce anti-ACh recpetor antibodies ==> block the ACh receptor in neuromuscular junctions --> weaker movements (not complete loss of muscles b/c some ACh still able to bind receptors, just way less than normal)

Grave's Disease

type II hypersensitivity disease that produces anti-TSH receptor antibodies ==> binds TSH receptor & stimulates the release of thyroid hormones -->>>overproduction b/c antibodies block thyroid cell from negative feedback

Type III Hypersensitivity Reactions

immune complex diseases ==> antigen-antibody complexes become trapped in small vessels, esp in the joints, skin, & kidneys --> makes classical pathway of complement become activated --> C3a & C5a attract neutrophils--> migrate into vessel walls --> die & release lysosomal granules --> damages vessel wall --> vasculitis & glomerulonephritis

*target antigens are small molecules (soluble antigen)

If Type II and III Hypersensitivity reactions both use IgG then what is the difference bwtn them?

-Type II --> IgG binds soluble antigen (small targets)

-Type III--> all rxns have similar symptoms (immune complexes trapped in blood vessels --> activates complement --> attraction of neutrophils --> neut death & lysosomal granule released --> damage to vessel wall = vasculitis or glomerulonephritis

vasculitis

vessel wall damage

-thickening of vessel wall

- narrowing of blood vessels

-reduced blood flow

True or False: Type III hypersensitivities are always local to the certain sites

False ==> type II hyp can be systemic or local

Systemic Type III Hypersensitivity

complexes are trapped in skin, kidneys, & joints causing vasculitis

-systemic lupus erythematosus (SLE) --> complexes of IgG & nuclear antigens (DNA)

-post-streprococcal glomerulonephritis--> circulating anti-strep antibodies combined w/ strep antigen

-serum sickness --> due to non-human antibody

-drug reactioms (ex: penicillins)

Local Type III Hypersensitivity

local anthus reaction; appears when antigen is introduced into an individual who already has antibodies ==> immune complexes at the sit attract neutrophils & produce inflammation

ex: Delayed complexes of IgG & tetanus toxoid due to tetanus vaccination (person already has tetanus antibodies)

systemic lupus erythematosus (SLE)

systemic type III hypersensitivity due to complexes of IgG + nuclear antigens that get trapped in skin, kidneys, & joints

post-streptococcal glomerulonephritis

systemic type III hypersensitivity due to circulating anti-strep antibodies combined w/ strep antigen

*complexes get trapped in the glomeruli

Anytime you suspect type III hypersensitivity you should _____________________.

monitor kidney fxn ==> type III leads to glomerulonephritis

serum sickness

systemic type III hypersensitivity in response to antibody therapy with non-human antibodies

-onset of fever

-development of skin rash similar to urticaria

-joint pain & swelling

Type III Hypersensitivity Drug Reactions

for example, rash that appears 8 days following the start of pencillin Tx

*get serum sickness-like disease

Delayed Hypersensitivity (Type IV Hypersensitivity)

hypersensitivity reactions that take us the same mechanisms as cell-mediated immunity, except the end result is tissue damage in autoimmunity & chronic inflammation

*rxn peaks at 48-72 hrs after exposure to antigen

True or False: Type IV Hypersensitivity may require sensitization

True ==> Type IV uses cell-mediated immunity (T cells) --> T cells need to recognize the self-antigen, clonally expanded, etc

Describe the 2 types of cell-mediated immunity utilized by delayed hypersensitivity

-cytokine-mediated inflammation ==> APC presents antigen to CD4 cell --> release cytokines --> inflammation & release of proteolytic enzymes & ROS-->> tissue injury

-T cel mediated cytotoxicity ==> CD8 cells bind targets on self cells & cause cell death & tissue injury (ex: Type I diabetes)

*sensitization required

What kind of hypersensitivity reaction is contact dermatitis?

type IV/delayed hypersensitivity

ex: -poison ivy

-cosmetics

-chemicals

-latex (can also cause type I)

-metals (ex: nickel & zinc)

After poison ivy exposure, why does it take approx 48hrs before a rash appears?

delay due to T cell activation & recruitment (poision ivy causes cell mediated hyp rxn)

erythema induration

sign/symptom of hypersensitivity rxn in the skin that appears 48-96 hrs after exposure==> skin pataches are hard to the touch (contain macrophages & CD4 cells)

*not same thing as edema

Patch Test

test for Type IV Hypersensitivity

Tuberculin Skin Test

test for T-cell memory of TB

*PPD (purfied protein derivative of M. tuberculosis) injected into the skin & evalusted 48-72 hrs after

**positive result = bubbling of injection site = pt has T cell memory of TB = pt has or had TB infection

Will the tuberculin skin test or the QuantiFERON test be the most accurate in patients who have received the BCG vaccine against TB?

QuantiFERON ==> distinguished memory T cells developed from the BCG vaccine from memory T cells developed due to past or present TB infection (skin test can;t distinguish)

What is the etiology of insulin dependent diabetes mellitus (IDDM)?

cytotoxic CD8 T cell killing of insulin producing beta cells via type IV hypersensitivity

What is the etiology of rheumatoid arthritis?

activation of osteoclasts by CD4 cells via type IV hypersensitivity -->>> bone loss & joint damage

-observe elevated levels of TNF

-anti-TNF therapy is a game changer

what is the etiology of multiple sclerosis?

killing of oligodendrocytes due to type IV hypersensitivity that leads to damaged myelin-->>> slowed neuron signaling

*done mainly by CD4, but some CD8s are activated as well

crohn's disease

type IV hypersensitivity caused by antigen from the normal gut micorbiota being targeted--> kills epithelial cells

celiac disease

type IV hypersensitivity caused by type IV hypersensitivity to gluten from wheat, barley, & rye --> kills epithelial cells

*not autoimmune

Humira

anti-TNF therapy that can be used to treat rheumatoid arthritis

Which auto-antibodies are important in the diagnosis of rheumatoid arthritis?

-anti-citrullinated peptides

-rheumatoid factor (anti-IgG)