Immune System Pathology, Introduction to Immunopathologies, Organ Transplant Rejection: Class I MHC and Class II MHC Proteins

Immune System Pathology, Introduction to Immunopathologies, Organ Transplant Rejection: How the Immune System Distinguishes between “Self” and “Non-Self”

Immune System Pathology, Introduction to Immunopathologies, Organ Transplant Rejection: HLA Typing for Transplant

Immune System Pathology, Introduction to Immunopathologies, Organ Transplant Rejection: Introduction

Immune System Pathology, Introduction to Immunopathologies, Organ Transplant Rejection: Host-Versus-Graft Disease (HVGD) and Graft-Versus-Host Disease (GVHD) 

Immune System Pathology, Introduction to Immunopathologies, Immunopathologies: Clinical Consequences

Immune System Pathology, Introduction to Immunopathologies, Immunopathologies: Categories

Immune System Pathology, Introduction to Immunopathologies, Hypersensitivity Disorders

Immune System Pathology, Introduction to Immunopathologies, Hypersensitivity Disorders: Type I Immediate Hypersensitivity

Immune System Pathology, Introduction to Immunopathologies, Hypersensitivity Disorders: Type II Antibody-Mediated

Immune System Pathology, Introduction to Immunopathologies, Hypersensitivity Disorders: Type III Immune Complex-Mediated

Immune System Pathology, Introduction to Immunopathologies, Hypersensitivity Disorders: Type IV T-Cell-Mediated (Delayed)

Immune System Pathology, Introduction to Immunopathologies, Autoimmune Diseases: Epidemiology and Impact

Immune System Pathology, Introduction to Immunopathologies, Autoimmune Diseases: General Mechanism Underlying Autoimmune Disease

Immune System Pathology, Introduction to Immunopathologies, Autoimmune Diseases

Immune System Pathology, Introduction to Immunopathologies, Autoimmune Diseases: The Spectrum of Attack

Immune System Pathology, Introduction to Immunopathologies, Immunodeficiency Syndromes

Immune System Pathology, Introduction to Immunopathologies, Immunopathologies (Knowledge Check)

MHC proteins:

• Are self antigens
• Display other antigens
• Were first identified on leukocytes
• Are also known as Human Leukocyte Antigens (HLA)
• There are two main classes that play a role in transplantation—MHC I and MHC II

Class I MHC:

• Expressed on virtually all nucleated cells
• Present antigens originating from inside of cells to CD8+ T cells
• HLA-A
• HLA-B
• HLA-C

Class II MHC:

• Expressed on Antigen Presenting Cells (APCs):
  • Dendritic cells
  • Macrophages
  • B cells
• Present antigens originating from outside of cells to CD4+ T cells
• HLA-DR
• HLA-DP
• HLA-DQ

MHC proteins:

• ALL cells display MHC molecules
• MHC are highly variable proteins
• MHC from one individual unlikely to be similar to those in another person

Immune system distinguishes between:

• “Self” versus “Non-Self”
• Type of MHC proteins on the cell surface

HLA typing for transplant:

• The closer the HLA match, the lower the risk of rejection
• Three categories of HLA similarity:
  • Autologous: The donor and the recipient are the same person
  • Syngeneic: The donor and the recipient are identical twins
  • Allogeneic: The donor and the recipient have similar HLA types, whether or not they are related

Organ transplant rejection:

• Immune system goal of eliminating “non-self”
• Advances in transplantation may come from new methods of immune system suppression
• Transplant rejection can be humoral or cell-mediated
• The immune reaction can be from the host or donor tissues

Organ transplant rejection:

• Process of transplant rejection:
  • Cell-mediated immune responses
  • Humoral immune responses
• HLA plays a key role in both immune responses
• Major categories of transplant rejection
  • Host-Versus-Graft Disease (HVGD)
  • Graft-Versus-Host Disease (GVHD)

Immunopathologies:

• Dysregulation of multiple components
• Wide range of clinical consequences
  • Allergies
  • Chronic pain
  • Tissue injury
  • Death

Over 100 immunopathologies have been identified. These include:

• Over 100 primary immunodeficiencies 
• Around 80 autoimmune disorders

Immunopathologies can be grouped into four main categories:

• Hypersensitivity disorders
• Autoimmune diseases
• Transplant rejection 
• Immunodeficiency syndromes

Hypersensitivity disorders:

• Excessive immune system activation
• In response to harmless antigens
• Can produce tissue injury or disease
• Autoimmune diseases and transplant rejections are classified as hypersensitivity reactions.

Type I hypersensitivity reactions:

• IgE-mediated
• Includes allergy and asthma
• Rapid development

Inflammatory effects:

• Blood vessel dilation
• Airway constriction
• White blood cell recruitment

Type II hypersensitivity reactions:

• IgG- or IgM-mediated
• Against cell surface antigen

Type III hypersensitivity reactions:

• IgG- or IgM-mediated
• Insoluble antigen-antibody complexes
• Indirect inflammation

Type IV hypersensitivity reactions:

• Do not involve antibodies
• T-cell-mediated
• Direct or indirect effects
  • CD8+ direct cell cytotoxicity
  • CD4+ delayed-type hypersensitivity reactions

Autoimmune diseases - epidemiology and impact:

• Third most common disease in the US
• Affecting 5-8% of the population (14-22 million people)
• Occur more often in women (78%)
• Occur in all ages
• Incidence varies with ethnicity

Immune response differences between men and women:

• Women:
  • Increased antibody production
  • Increased risk of autoimmune disease
• Men:
  • More severe inflammation
  • More severe disease

General mechanism underlying autoimmune disease:

• Loss of tolerance
• Inability to distinguish “self” and “non-self”

Tolerance:

• Is an active process
• Requires contact between self antigens and the immune system

Factors thought to play a role:

• Genetics
• Gender
• Environment

Autoimmune diseases:

• Breakdown in “self” vs. “non-self” discrimination
• ≥ 15 autoimmune disease
• Autoimmunity may be involved in > 80 conditions
• Wide range of diseases and variety of symptoms
• Can affect almost any part of the body

Autoimmune diseases - spectrum of attack:

• Single Organ: Antibody or cell-mediated response against antigens of a specific organ
• Systemic: Antibody-mediated, immune-complex-based pathology

Immunodeficiency syndromes:

• Abnormalities in the immune system that cause susceptibility to diseases that are normally prevented
• Classification of Immunodeficiencies:
  • Immune system branch (dysfunction)
  • Primary (inherited) vs. secondary (acquired)

Type 1 hypersensitivity:

• Excessive activation of the immune system following exposure
• Allergy, eczema, asthma

Autoimmune disease:

• Breakdown of self versus no-self recognition
• Rheumatoid arthritis and multiple sclerosis

Transplant rejection:

• Host versus Graft disease
• Cells from donor bone marrow attack cells of the host’s body

Immunodeficiency syndrome:

• HIV/AIDS
• An abnormality in one or more branches of the immune system that causes a person to be susceptible to infection

Cotran et al. 1999

Porth 2005

Johnson et al. 1999

Janeway et al. 2005

NIH-ADCC 2002

Albert, 1999

Parham 2005

Yates et al. 2004

Introduction: Allergic and Other Hypersensitivity Disorders: Merck Manual Professional

Fairweather et al, The American Journal of Pathology. 2004, 2005, 2008, 2010

Tse et al. 2004

Davidson et al. 2001

Marieb 2004

MHC = Major Histocompatibility Complex

HLA = Human Leukocyte Antigen

IgE = Immunoglobulin E

IgG/IgM = Immunoglobulin G/M