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General pathology 
Lec: 11 
Dr. Hind Zuhair 
 
Diseases of the Immune System     
  
I. Hypersensitivity reaction (Allergy)  
  
II. Transplantation immunopathology:  
    Transplantation of solid organs (e.g., liver, kidney, 
heart) and bone marrow become nearly routine with the 
greater understanding of humoral and cellular immune 
response, the development of immunosuppressive drugs 
such as cyclosporine, and understanding of the role of 
the major histocompatibility complex (MHC), antigens 
(human leukocyte antigen =HLA) which is cell surface 
antigens that determine whether transplanted tissue is 
recognized as foreign or not.  
  
Transplanted tissue can be categorized as:  
1- 
Allogeneic if the donor and recipient are related or 
unrelated but share similar HLA types.  
2- 
Syngeneic if the donor and recipient are identical 
twins.  
3- 
Autologous if donor and recipient are the same 
person.  
  
Immune Recognition of Allografts   
  
Rejection of allografts is a response to MHC molecules, 
which are so polymorphic that no two individuals are 
likely to express exactly the same set of MHC 
molecules (except twins). There are two main 
mechanisms by which the host immune system 
recognizes and responds to the MHC molecules on the 
graft:  
  
Direct recognition. Host T cells directly recognize the 
allogeneic (foreign) MHC molecules that are expressed 
on graft cells. Because DCs in the graft express high 
levels of MHC, they are the most likely APCs in direct 
recognition.  1-Host CD4+ helper T cells are triggered 
into proliferation by recognition of foreign MHC 
molecules and produce cytokine causing delay type 
hypersensitivity (DTH).   
 
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2-CD8+ T cells recognize foreign MHC and 
differentiate into cytotoxcic T cells (TCLs) which kill 
the cells in the graft.  
  
Indirect recognition.  
1-Host CD4+ T cells recognize donor MHC molecules 
after these molecules are picked up, processed, and 
presented by the host's own APCs activating DTH 
reaction.  
2-Production of antibodies by host B cells against 
graft alloantigens. Helper T cells, stimulate antibody 
responses.  
  
 
 
 
Host-Versus-Graft Disease: (HVGD)  
  
     If the transplanted graft bearing foreign MHC antigens, the 
recipient’s immune system, attack the donor cells of the transplanted 
organ. Rejection involves T cell-mediated and circulating antibodies. 
The initial target of the recipient antibodies is graft vasculature.   
 
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There are three basic patterns of transplant rejection: 
  1-Hyperacute reaction occurs immediately after transplantation; in kidney transplants, as 
soon as blood flow from the recipient to the donor organ begins, it takes on a cyanotic, 
mottled appearance.   
  
2-Acute rejection usually occurs within the first few months after 
transplantation and it is evidenced by signs of organ failure.   
  
3-Chronic HVGD occurs over a prolonged period. It is manifest by 
dense fibrosis of the intimal layer of blood vessels in the transplanted 
organ.   
  
Graft-Versus-Host Disease(GVHD):  
  
      In GVHD, the cellular immune system of the transplanted graft 
(donor T cells) recognizes and attacks the unrelated recipient HLA. 
Occurs mainly in:  
1- Bone marrow transplant.  
2- Severely immuno-compromised patients, who have received 
blood products containing HLA-incompatible lymphocytes.    
3- After transplantation of solid organs rich in lymphoid cells (e.g., 
the liver).   
  
  
III. Autoimmune disorders  
  
        They are caused by a breakdown in the ability of the immune 
system to differentiate between self and non-self-antigens. Normally, 
there is a high degree of immunologic tolerance to self-antigens, 
which prevents the immune system from destroying the host. 
Autoimmune diseases can affect almost any cell or tissue in the body. 
Some autoimmune disorders are tissue specific; others affect multiple 
organs and systems.   
 
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Mechanisms of Antibody-Mediated Diseases (Type II)  
  
Opsonization and phagocytosis.   
 
When circulating cells, such as erythrocytes or platelets, are coated 
(opsonized) with autoantibodies, with or without complement proteins, 
the cells become targets for phagocytosis by neutrophils and 
macrophages. Opsonized cells are usually eliminated in the spleen, and 
this is why splenectomy is of some benefit in autoimmune 
thrombocytopenia and hemolytic anemia.  
  
Inflammation. Antibodies bound to cellular or tissue antigens activate 
the complement system, recruiting neutrophils and monocytes, 
triggering inflammation in tissues, opsonize cells for phagocytosis, and 
lyse cells, especially erythrocytes.   
  
Antibody-mediated cellular dysfunction. In some cases, antibodies 
directed against cell surface receptors impair or dysregulate cellular 
function without causing cell injury or inflammation. In myasthenia 
gravis, antibodies against acetylcholine receptors in the motor end 
plates of skeletal muscles inhibit neuromuscular transmission, with 
resultant muscle weakness.   
Antibodies can also stimulate cell function inappropriately. In Graves' 
disease, antibodies against the thyroid stimulating hormone receptor 
stimulate thyroid epithelial cells to secrete thyroid hormones, resulting 
in hyperthyroidism.   
  
 
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Immunologic Tolerance: Self-tolerance  
The ability of the immune system to differentiate self from Non self-
antigens by the presence of HLA antigens which serve as recognition 
markers. Autoimmune diseases results from loss of immune tolerance.  
  
Central tolerance: It is the elimination (deletion or death) of 
autoreactive T cells in the thymus and B cells in the bone marrow. 
Clonal deletion of autoreactive lymphocytes is not perfect because 
many self-antigens may not present in the thymus so these 
lymphocytes bearing receptors for those auto- antigens may escape 
into the periphery causing autoimmune diseases.  
  
Peripheral tolerance: It is the deletion or inactivation of autoreactive 
T cells or B cells that escaped elimination in the central lymphoid 
organs. Autoreactive B cells are deleted in the spleen and lymph 
nodes. Autoreactive T cells may undergo activation, induced cell 
death, or be rendered inactive so that they cannot recognize self-
antigens.  
  
Several mechanisms in the peripheral tissues that silence such autoreactive T cells 
have been identified:  
  
1-Anergy: It is functional inactivation (rather than death) of   lymphocytes.  
2-Suppression of the response of T lymphocytes by regulatory T cells  
3-Activation-induced cell death: It involves apoptosis of mature 
lymphocytes as a result of self-antigen recognition.   
  
4- 
Antigen sequestration: Some antigens are hidden from the immune 
system because the tissues, in which these antigens are located, do not 
communicate with blood and lymph; these organs are also called immune 
privileged 
 
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Thank you 
 


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