Advanced Patho Edapt Notes
Week 1: Immune System
Hypersensitivity Reactions
o The immune system functions to eliminate pathogens from the body using
various mechanisms
Pathogens are bacteria, viruses, and other microorganisms
o These mechanisms typically create a localized inflammatory response that
effectively eliminates the pathogen with minimal damage to the surrounding
tissues
o Individuals also come in contact with numerous foreign bodies (plant pollen,
food)
o Contact with these environmental antigens does not normally elicit an immune
response in a majority of individuals
o However, in predisposed individuals the immune system can mount a response
to environmental antigens, resulting in tissue damage that ranges from mild
irritation to life threatening anaphylactic shock
o These immune responses are referred to as allergic reactions or hypersensitivity
reactions
o Hypersensitivity reactions can be divided into 4 categories
Type I: Allergic Reaction
o On initial encounter with an allergen, the individual will produce IgE antibodies
o Once the allergen is cleared, the remaining IgE bind to mast cells, basophils, and
eosinophils that contain receptors for IgE
This process is referred to as sensitization
o When re-exposed to to the allergen the IgE located on the sensitized cells induce
immediate degranulation
o Degranulation causes the release of inflammatory mediators, such as histamine,
leukotrienes, and prostaglandins that result in vasodilation, bronchial smooth
muscle contraction, and mucus production
o Type I reactions can be local or systemic
Systemic reactions can result in anaphylaxis
Local reactions can produce rash, hives, itching
o Allergic asthma is an example of a type I reaction
Type II Hypersensitivity
o Tissue-specific and usually occurs as a result of haptens that cause an IgG or IgM
antibody mediated response
o The antibodies are specifically directed to the antigen located on the cell
membrane
o Haptens are small molecules that can cause an immune responses when it
attaches to a protein
o Macrophages are the primary effector cells of type II responses
, o The type II response begins with the antibody binding to the antigen and may
cause the following:
The cell to be destroyed by the antibody
Cell destruction through phagocytosis by macrophages
Damage to the cell by neutrophils triggering phagocytosis
Natural killer cells to release toxic substances that destroy the cell
Malfunction of the cell without destruction
o Examples of type II reactions
Drug allergies
Hemolytic anemia
Blood transfusion mismatch with resulting transfusion reaction and Rh
hemolytic disease
Type III Immune-Complex Reaction
o The type III hypersensitivity reaction is also an antigen-antibody response
o Major difference between type II and type III responses is that in a type II
response the antibody binds to the antigen on the cell surface, but in type III
responses the antibody binds to the antigen in the blood or body fluids and then
circulates to the tissue
o Type III reactions are not organ specific and use neutrophils as the primary
effector cell
o Immune-complex deposition (ICD) causes autoimmune diseases, which is often a
complication
o As disease progresses more accumulation of immune-complexes occurs and
when the body becomes overloaded the complexes are deposited in the tissues
and causes inflammation as the mononuclear phagocytes, erythrocytes, and
complement system fail to remove immune complexes from the blood
o Example of type III reactions: serum sickness
Type IV cell-mediated, delayed reaction
o Type IV hypersensitivity reactions are known as cell-mediated responses and use
lymphocytes and macrophages as primary mediators
o Unlike the first three type of responses, which are humoral immune functions,
type IV responses are mediated by t-lymphocytes and does not use antibodies
o A typical reaction from a type IV cell mediated response would be a localized
contact dermatitis
o When an individual comes in contact with the antigen, t-cells are activated and
move to the area of the antigen
o The antigen is processed and presented to macrophages, leading to epidermal
reactions characterized by erythema, cellular infiltration and vesicles
Immunodeficiency
o Primary vs secondary immunodeficiencies
Primary
Less common
Occur due to a defect of the development of the immune system
, Could involve antibody deficiencies, B and T-cell deficiencies,
defects in the phagocytic cells and deficiency of complement
Secondary
Conditions in which the immune systems become compromised
because of something else
Could be caused by cancer, effect from a drug (chemo that
suppresses the immune system), or infections that compromise
the immune system in a profound way
Common secondary immunodeficiency in the US is HIV
o HIV is a RNA virus that invades the body through an cell by
direct contact with an individual’s blood or body secretions
o HIV has a strong affinity for cells of the immune system,
especially CD4+ T cells
o Once the virus invades, it replicates to cause extensive
damage to the immune system
o Without a normally functioning immune system the
individual becomes susceptible to opportunistic infections,
cancer, neurological disease, wasting and death
o Biology of cancer
Cancer is another type of secondary immunodeficiency
Tumor is abnormal growth resulting from uncontrolled cellular
proliferation (neoplasm)
Any type of cell that is capable of cell division has potential for tumors
Benign or malignant
Benign
o Grow slowly, non invasive, well differentiated cells, grow in
a well contained capsule
Malignant
o Grow rapidly, invasive into other tissues, poorly
differentiated, not encapsulated, can spread distantly
(metastasis)
Carcinoma
90% of malignant tumors
Epithelial cells of organ surfaces and linings
Sarcomas
Connective tissues (bones and muscle)
Lymphomas
Involve blood or lymphatic systems
4 stages
Stage 1: no evidence of metastases
Stage 2: evidence of localized invasion
Stage 3: cancer cells have spread to regional structures
Stage 4: evidence of distant metastases
, TNM
T refers to primary tumor
N = the size of the tumor (the larger the number the bigger the
tumor)
M refers to the extent of metastases
o Formation of cancer
The formation of cancer begins with cell transformation and other factors
Transformation is the process whereby a normal cell becomes a cancer
cell
Controlled (normal) cellular proliferation involves stem cells and the cell
cycle
A stem cell is an immature undifferentiated cell that is capable of infinite
cellular division when stimulated
The cell cycle is the process whereby the stem cell undergoes the process
of cell division
Cell cycle has 2 parts: interphase (23 hours) and mitosis (1 hour cycle)
Interphase
o G0 quiescent phase – resting, nondividing, inactive stem
cell capable of growth and proper stimulus
o G1 prepatory phase – stimulated, stem cells are starting to
become metabolically active
o S phase – high rate of DNA replication in stimulated stem
cells
o G2 – preparation of cell structures for cell division
Mitosis
o M phase – active cell division to form 2 genetically
identical daughter cells
o Daughter cells can then undergo differentiation to become
a mature, end-stage specialized and functional cell with a
finite life span
o Once a cell has differentiated it can not normally regress
Apoptosis
o Aging, injured, or defective cells are eliminated from the
body by a natural cell death process all apoptosis
Cell division, proliferation, differentiation and death (apoptosis) are
strictly controlled by a number of regulatory genes to maintain and
balance between cell birth rate and cell death rate
Chromosomes of normal cells contain two types of regulatory genes
which have necessary function in normal cells
Proto-oncogenes: code for synthesis of growth factors or GF
receptors to promote cell growth = accelerator system
Tumor suppressor genes: stop further cell growth via triggering
cellular differentiation or apoptosis = braking system
Week 1: Immune System
Hypersensitivity Reactions
o The immune system functions to eliminate pathogens from the body using
various mechanisms
Pathogens are bacteria, viruses, and other microorganisms
o These mechanisms typically create a localized inflammatory response that
effectively eliminates the pathogen with minimal damage to the surrounding
tissues
o Individuals also come in contact with numerous foreign bodies (plant pollen,
food)
o Contact with these environmental antigens does not normally elicit an immune
response in a majority of individuals
o However, in predisposed individuals the immune system can mount a response
to environmental antigens, resulting in tissue damage that ranges from mild
irritation to life threatening anaphylactic shock
o These immune responses are referred to as allergic reactions or hypersensitivity
reactions
o Hypersensitivity reactions can be divided into 4 categories
Type I: Allergic Reaction
o On initial encounter with an allergen, the individual will produce IgE antibodies
o Once the allergen is cleared, the remaining IgE bind to mast cells, basophils, and
eosinophils that contain receptors for IgE
This process is referred to as sensitization
o When re-exposed to to the allergen the IgE located on the sensitized cells induce
immediate degranulation
o Degranulation causes the release of inflammatory mediators, such as histamine,
leukotrienes, and prostaglandins that result in vasodilation, bronchial smooth
muscle contraction, and mucus production
o Type I reactions can be local or systemic
Systemic reactions can result in anaphylaxis
Local reactions can produce rash, hives, itching
o Allergic asthma is an example of a type I reaction
Type II Hypersensitivity
o Tissue-specific and usually occurs as a result of haptens that cause an IgG or IgM
antibody mediated response
o The antibodies are specifically directed to the antigen located on the cell
membrane
o Haptens are small molecules that can cause an immune responses when it
attaches to a protein
o Macrophages are the primary effector cells of type II responses
, o The type II response begins with the antibody binding to the antigen and may
cause the following:
The cell to be destroyed by the antibody
Cell destruction through phagocytosis by macrophages
Damage to the cell by neutrophils triggering phagocytosis
Natural killer cells to release toxic substances that destroy the cell
Malfunction of the cell without destruction
o Examples of type II reactions
Drug allergies
Hemolytic anemia
Blood transfusion mismatch with resulting transfusion reaction and Rh
hemolytic disease
Type III Immune-Complex Reaction
o The type III hypersensitivity reaction is also an antigen-antibody response
o Major difference between type II and type III responses is that in a type II
response the antibody binds to the antigen on the cell surface, but in type III
responses the antibody binds to the antigen in the blood or body fluids and then
circulates to the tissue
o Type III reactions are not organ specific and use neutrophils as the primary
effector cell
o Immune-complex deposition (ICD) causes autoimmune diseases, which is often a
complication
o As disease progresses more accumulation of immune-complexes occurs and
when the body becomes overloaded the complexes are deposited in the tissues
and causes inflammation as the mononuclear phagocytes, erythrocytes, and
complement system fail to remove immune complexes from the blood
o Example of type III reactions: serum sickness
Type IV cell-mediated, delayed reaction
o Type IV hypersensitivity reactions are known as cell-mediated responses and use
lymphocytes and macrophages as primary mediators
o Unlike the first three type of responses, which are humoral immune functions,
type IV responses are mediated by t-lymphocytes and does not use antibodies
o A typical reaction from a type IV cell mediated response would be a localized
contact dermatitis
o When an individual comes in contact with the antigen, t-cells are activated and
move to the area of the antigen
o The antigen is processed and presented to macrophages, leading to epidermal
reactions characterized by erythema, cellular infiltration and vesicles
Immunodeficiency
o Primary vs secondary immunodeficiencies
Primary
Less common
Occur due to a defect of the development of the immune system
, Could involve antibody deficiencies, B and T-cell deficiencies,
defects in the phagocytic cells and deficiency of complement
Secondary
Conditions in which the immune systems become compromised
because of something else
Could be caused by cancer, effect from a drug (chemo that
suppresses the immune system), or infections that compromise
the immune system in a profound way
Common secondary immunodeficiency in the US is HIV
o HIV is a RNA virus that invades the body through an cell by
direct contact with an individual’s blood or body secretions
o HIV has a strong affinity for cells of the immune system,
especially CD4+ T cells
o Once the virus invades, it replicates to cause extensive
damage to the immune system
o Without a normally functioning immune system the
individual becomes susceptible to opportunistic infections,
cancer, neurological disease, wasting and death
o Biology of cancer
Cancer is another type of secondary immunodeficiency
Tumor is abnormal growth resulting from uncontrolled cellular
proliferation (neoplasm)
Any type of cell that is capable of cell division has potential for tumors
Benign or malignant
Benign
o Grow slowly, non invasive, well differentiated cells, grow in
a well contained capsule
Malignant
o Grow rapidly, invasive into other tissues, poorly
differentiated, not encapsulated, can spread distantly
(metastasis)
Carcinoma
90% of malignant tumors
Epithelial cells of organ surfaces and linings
Sarcomas
Connective tissues (bones and muscle)
Lymphomas
Involve blood or lymphatic systems
4 stages
Stage 1: no evidence of metastases
Stage 2: evidence of localized invasion
Stage 3: cancer cells have spread to regional structures
Stage 4: evidence of distant metastases
, TNM
T refers to primary tumor
N = the size of the tumor (the larger the number the bigger the
tumor)
M refers to the extent of metastases
o Formation of cancer
The formation of cancer begins with cell transformation and other factors
Transformation is the process whereby a normal cell becomes a cancer
cell
Controlled (normal) cellular proliferation involves stem cells and the cell
cycle
A stem cell is an immature undifferentiated cell that is capable of infinite
cellular division when stimulated
The cell cycle is the process whereby the stem cell undergoes the process
of cell division
Cell cycle has 2 parts: interphase (23 hours) and mitosis (1 hour cycle)
Interphase
o G0 quiescent phase – resting, nondividing, inactive stem
cell capable of growth and proper stimulus
o G1 prepatory phase – stimulated, stem cells are starting to
become metabolically active
o S phase – high rate of DNA replication in stimulated stem
cells
o G2 – preparation of cell structures for cell division
Mitosis
o M phase – active cell division to form 2 genetically
identical daughter cells
o Daughter cells can then undergo differentiation to become
a mature, end-stage specialized and functional cell with a
finite life span
o Once a cell has differentiated it can not normally regress
Apoptosis
o Aging, injured, or defective cells are eliminated from the
body by a natural cell death process all apoptosis
Cell division, proliferation, differentiation and death (apoptosis) are
strictly controlled by a number of regulatory genes to maintain and
balance between cell birth rate and cell death rate
Chromosomes of normal cells contain two types of regulatory genes
which have necessary function in normal cells
Proto-oncogenes: code for synthesis of growth factors or GF
receptors to promote cell growth = accelerator system
Tumor suppressor genes: stop further cell growth via triggering
cellular differentiation or apoptosis = braking system
