type 3-4 HS

both are antibody-mediated but Type 3 is against soluble antigen in the blood vs antigen bind to basement membrane or non-blood area

opsonization (complement dependent)

• Fc-mediated on the leukocyte --> initiate inflammation (fix tissue, basement membrane) 
• Inc production of C3a-C5a --> inc vasodilation and recruitment of PMN and immune cells 

AB-mediated by binding to the receptor --> can both activate and inactivate the receptor (Myasthenia gravis and Grave disease)

1.Deposition of Immune Complexes

• Antigen-antibody complexes produce tissue
• damage by eliciting inflammation at site of deposition

• Antigens:  exogenous (foreign protein)
•             endogenous (self-component)
• -get circulating immune complexes
• that can be deposited in many organs or localized to one.

2.Complement Activation

3.Neutrophil Accumulation

• 1.Introduction of antigen triggers an immune response that produces antibodies.  (Takes about a week)
•      Antibodies are secreted into blood where
• they react with antigen still present in circulation, forming an antibody-antigen complex.

2.Next phase:  Deposition of immune complex

Circulating Ab-Ag complexes are deposited in various tissue. 

• What determines whether complex formation will lead to tissue deposition and
• disease?

1.Complexes that are medium size

2.Formed in slight antigen excess

• 3.Tissue Injury caused by immune
• complex:  Once in tissue, complexes
• initiate acute inflammatory response.

Fever

Rash/Urticaria (hives)

Arthritis

glomerulonnephritis

Small blood vessels

Joints

Kidney

Heart

•Intense neutrophilic infiltration

• •Necrotic tissue will have deposits of
• immune complexes (called fibrinoid necrosis)

•Acute necrotizing vascularitis (necrosis of the vessel wall)

• I.Single large exposure to antigen 
• Usually resolves
• •acute serum sickness
• •Streptococcal glomerulonephritis

• II. Chronic exposure to antigen
• •Systemic lupus erythematosus
• •Streptococcal glomerulonephritis

• III. Local immune complex disease (Arthus
• reaction)
• •Usually in skin
• •Reproduced by injecting antigen in
• an immunized animal

take time to form complex --> deposit lead to fever vasculitis arthritis and nephritis 

delayed in response of inflammation

•Most common in children 6-10 years old after a streptococcal infection

•Antibody to streptococcal ag form compounds that deposit in glomeruli.

vasculitis and intense neutrophil reponse 

repeat and prolong exposure --> lupus

local immune complex disease 

Localize area of tissue necrosis resulting from acute immune complex vasculitis

 take 1-2 hours

• 1.Macrophage activation by TH1 cells, which
• results in an inflammatory response.

• 2.Damage is caused by activation of TH2
• cells.  Inflammatory response is predominated by eosinophils

• 3.Damage is caused directly by cytotoxic T
• cells (CTL).

Th2 mediated

•Reactions are mediated by T cells

•All take some time to develop (delayed 

• •3 syndromes, grouped according to
• the route by which antigen passes into body. 
• Injected into the skin
• abosorbed into skin
• Aborbed by gut

Take 24-72 hours

• 1st phase: uptake, processing and presentation of the antigen by local antigen
• presenting cells

• 2nd phase: TH1 cells that were primed by a previous exposure to the antigen migrate
• into the site of injection and become activated.  Because these specific cells are rare, and
• because there is little inflammation to attract cells into the site, it can
• take several hours for a T cell of the correct specificity to arrive.

• 3.  These cells release mediators that activate local endothelial cells, recruiting an inflammatory cell infiltrate dominated
• by macrophages and causing the accumulation of fluid and protein.  At this point, the lesion is apparent.

• 1.A contact sensitizing agent is a small
• highly reactive molecule that can easily penetrate intact skin.  It binds to a variety of endogenous proteins, which are taken up and processed by Langerhan cells (major antigen presenting cell of the skin)

• 2.These APCs present the peptides to
• effector (and previously primed) TH1 cells

3.Activated TH1 cells secrete IFN-g that then activate kerintocytes to secrete more cytokines and chemokines.

• 4.These products recruit and activate
• macrophages resulting in an inflammatory lesion.

macrophage

• Delayed type HS and immune inflammation:
• Th1 (macrophage) and Th17 (neutrophil)
• --> depend mostly on cytokine secreted. TH17 at the lesser extense
• Tcell-mediate: CLT --> kill

1.Injection of tuberculin in sensitized individual

2.Local T cell inflammatory reaction

3.Peaks at 24-72 hrs

• Perivasular cuffing
• Driven by T-cell secreted cytokines:IFNg, IL-12, IL-2, TNFa & lymphotoxin

• granuloma 
• lymphocyte on theh outside
• epitheliod cell on the inside w/ giant cell

cell-mediated cytotoicity --> graft rejection and

direct and indirect recognition

Host T cells (transplant recipient) are activated by APC within the transplanted tissue (graft).

Host T cell activated by Graft APC

APC from the host present graft antigens to host T lymphocytes --> chronic rejection to graft

• mediated by CD4 Tcell --> macrophage
• and AB mediated

direct pathway

hyperacute rejection

acute rejection

chronic rejection

when immunologically competent cells are transplanted into immunologically criplled recipient