Immunity and Diseases of Immune Origin Flashcards
The Body’s Defenses – Three Lines of Defense
Barriers
Inflammatory Response
Immune Response
- Barriers –
skin, mucous membranes, secretions
- Inflammatory Response –
cells (leukocytes),
molecules (mediators)
- Immune Response –
Antibodies (humoral),
Cytotoxic T cells (cellular)
Antigen (Ag) -
A substance that can induce an
immune response when introduced into an
animal.
Antibody (Ab) -
A protein that is produced in
response an antigen. The antibody binds the
antigen that stimulated its production. All
antibodies are immunoglobulins.
Immunoglobulin (Ig) -
A glycoprotein composed
of heavy and light chains that functions as an
antibody.
Schematic Structure of a Typical Immunoglobulin (Antibody) Molecule
(5)
• Heavy chains (2)
• Light chains (2)
• Variable regions form
antigen-binding site (Fab)
• Constant end (Fc) receptor
for attachment of phagocytic
cells)
• Complement binding
• IgM -
first immunoglobulin to
appear in an immune response
• IgG -
principal immunoglobulin of
the secondary immune response.
Only immunoglobulin capable of
crossing the placental barrier
• IgA -
principal immunoglobulin in
external secretions of mucosal
surfaces, tears, saliva, and
colostrum
• IgE -
plays an important role in
immediate hypersensitivity
reactions and parasitic infections
• IgD -
thought to activate the B-
lymphocyte
Primary and Secondary Lymphoid Organs
• All lymphocytes arise in the
bone marrow
Primary lymphoid organs
(2)
– Bone marrow
– Thymus
• Secondary lymphoid organs
(4)
– Lymph nodes
– Tonsils
– Spleen
– Mucosal-associated lymphoid tissue (MALT)
There are two
types of
lymphocytes,
B
cells and T cells
• They look alike in
their H&E
phenotype, but
they are
completely
different
B lymphocytes
become
plasma cells and secrete
antibodies when
challenged by antigen
• Antibodies are essential
for humoral immunity
X-linked Agammaglobulinemia (Bruton Agammaglobulinemia) XLA
• X-linked genetic disease – more common in males
• X-linked agammaglobulinemia (XLA)
• A primary immunodeficiency disease
• B lymphocytes unable to mature to plasma cells
• Can’t make antibody and are deficient in opsonization
• Recurrent bacterial infections
X-linked Agammaglobulinemia (Bruton Agammaglobulinemia) XLA
tx
Treatment: intravenous infusions of immunoglobulin every 3-
4 weeks for life (passive immunity)
Natural Killer Cell – NK Cell
(3)
• A component of the innate immune system
• A type of cytotoxic lymphocyte
• Do not have markers for B or T cells
T Lymphocytes
(3)
• CD4+ (T Helper Cell) - quarterback
• CD8+( Cytotoxic T Cell) - effector
• Cell-mediated defense against intracellular pathogens
– Viruses, fungi and one important bacterial disease (tuberculosis)
Function of the Thymus
(3)
• T cells become educated
• Learn self from non-self
• Self-reacting T cells are
deleted
B lymphocytes leave the — and populate lymph nodes
bone
marrow
T lymphocytes leave the
and populate lymph nodes
thymus
Immune System
(7)
• Self / non-self recognition
• General / specific
• Natural / adaptive
• Innate / acquired
• Humoral / cell-mediated
• Active / passive
• Primary / secondary
Extracellular pathogens
(2)
– Most bacteria
– Humoral immunity
Intracellular pathogens
(2)
– Viruses, fungi, some bacteria
– Cellular immunity
Innate immunity (born with)
(4)
– Physical and chemical barriers
(epithelia and antimicrobial
substances)
– All phagocytic cells (neutrophils,
macrophages, NK cells)
– Complement proteins
– Cytokines (TNF, IL-1, interferon)
Adaptive immunity (not born with,
requires exposure)
(3)
– Antibodies
– Lymphocytes
– Cytokines (IL-2, IL-12)
Antibody-Dependent Immunity: First Exposure (no antibody available)
• Innate immunity – phagocytosis and killing by macrophages and neutrophils with the help of
complement proteins
– C3b – opsonization
– C3a – histamine release from mast cells enhancing inflammation
– C5a - histamine release and chemotaxis of neutrophils
– C5b, 6, 7, 8, 9 – membrane attack complex (MAC)
• Formation of antibodies
– Too late for first exposure
– Memory B cells formed
Antibody-Dependent Immunity: Second Exposure (antibody available)
• Memory B cells quickly make specific antibody
(4)
– Neutralize toxins
– Bind pathogens
– Serve as opsonins
– Activate complement cascade via classic pathway
Humoral immunity is the
first line of defense against
— pathogens
extracellular
Antibody-dependent immunity
Cellular immunity is the
first line of defense against
— pathogens
intracellular
Antibody-independent immunity
Major Histocompatibility Complex (MHC) Molecules
(3)
• MHC molecules were originally discovered on leukocytes and called
Human Leukocyte Antigens (HLA)
• All cells of the body have MHC molecules
• MHC molecules are recognition molecules that allow the immune system
to distinguish self from non-self
• MHC Class 1 molecules are located
on the surface of most cells
• MHC Class 2 molecules are found on
Antigen-Presenting Cells (APCs)
– APCs:
(3)
dendritic cells, macrophages, Langerhans cells
If the invading organism is a virus, fungus or Mycobacterium, the first
line of defense is
cellular immunity, not humoral immunity
organism
APC
CD4
CD8
Phagocytosis by antigen presenting cell
Coupling of antigen to MHC-II molecule and presentation to CD-4 T lymphocyte
Secretion of cytokines to generate CD8 cytotoxic T lymphocyte
Elimination of cells that harbor the pathogen
CD4+ T Helper Lymphocyte
(2)
- The recognition arm of cellular
immunity – the bloodhounds - Role is to look at all the MHC-2
molecules in the body (on APCs) to
determine if they’re clean or dirty
CD4 Helper T- Lymphocytes are — Restricted
MHC-2
CD4+ T Helper cell
secretes
IL-2
IL-2
• IL-2 signals naïve
lymphocytes to
differentiate into CD8+
cytotoxic lymphocytes
CD8 Killer T-Lymphocytes
(3)
• The effector arm of cellular immunity –
the Marines
• Role is to scout the body for dirty
MHC-1 molecules on somatic cells and
kill them
• AKA: Cytolytic T-cells, Killer T cells,
Cytotoxic lymphocytes, CTLs
CD8 Killer T-Lymphocytes are — Restricted
MHC-1
exposing virus to humoral
immune system
hepatocyte (perforins),
MMUNE INJURY
DISEASE:
TYPE I
HYPERSENSITIVITY
Immediate hypersensitivity
Recipe
• Antigen
• IgE antibodies
• Mast cells
TYPE I REACTION: IMMEDIATE HYPERSENSITIVITY –
CLINICAL RESPONSE PATTERNS
(5)
• “Hay fever”
• Asthma
• Hives
• Angioedema
• Anaphylactic shock
TYPE I REACTION: IMMEDIATE HYPERSENSITIVITY –
ANAPHYLAXIS
(3)
• Anaphylaxis (Greek) – ana (excessive) + phylaxis (protection)
• Systemic anaphylaxis
• Local anaphylaxis
IMMUNE INJURY DISEASE:
TYPE II HYPERSENSITIVITY
• Antibody mediated
hypersensitivity
• Antibody mediated
hypersensitivity
• Cells – (2)
• Cell surface receptors –
(1)
• Extracellular matrix
material – (1)
• Cells – erythrocytes,
platelets
• Cell surface receptors –
acetylcholine receptor
• Extracellular matrix
material – laminin,
desmoglein
Outcome of Antibody-Dependent Cytotoxic Reactions Against Cells
(2)
• Lysis – complement mediated (MAC)
• Phagocytosis - opsonization
Blood Transfusion Reaction - ABO Blood Incompatibility (2)
• ABO mismatch leads to
intravascular hemolysis
• Antibody-coated
erythrocytes destroyed
by both complement-
mediated lysis and by
phagocytosis in spleen
Myasthenia Gravis (1)
Antibody blocks
acetylcholine receptor
Grave’s disease (2)
- Antibody-mediated
stimulation of cell function - Antibody stimulates TSH
receptor
IMMUNE INJURY DISEASE:
TYPE III HYPERSENSITIVITY
• Immune Complex Disease
Target Antigens in Type III Disease
• Exogenous antigen –
• Endogenous antigen –
post-streptococcal glomerulonephritis
lupus erythematosus
Post-Streptococcal Glomerulonephritis
(7)
• Pharyngitis caused by certain strains of
Streptococci (“Strep throat”) – exogenous antigen
• Immune complexes formed in antigen excess
(small)
• Failure of the immune system to quickly clear
complexes from the circulation
• Immune complexes filter out in renal glomeruli
• Complexes fix complement and generate pro-
inflammatory molecules
• Glomerulonephritis – proteinuria, hematuria,
hypertension, fever, lower back pain
• No infection – only sterile inflammation
Lupus Erythematosus
(8)
• A multisustem autoimmune disease
most common in adult women in
child-bearing years
• Type III Hypersensitivity -
Immune Complex Disease
• Immune complexes are deposited
throughout the body, especially
kidney and blood vessels
• Renal failure due to immune-
mediated glomerulonephritis
• The patient’s own tissues are the
antigen
• Autoantibodies - anti-nuclear
antibodies (ANA)
• Involves many tissues and organs
• Butterfly rash
Type III Reaction – Immune Complex Disease
(2)
• Glomerulonephritis
• Vasculitis
Organs Involved in SLE
(7)
• Skin
• Joints
• Kidney
• Heart – Libman-Sachs
endocarditis
• Serosal Surfaces
(pericardidits, pleuritis)
• Central nervous system
• Arthritis, arthralgia,
heart and lung
involvement, anemia,
bone marrow depression,
vasculitis, skin rashes
Examples of Type IV Reactions – Cell-Mediated Hypersensitivity (3)
• Tuberculin reaction
• Contact mucositis (nickel, cinnamon)
• Contact dermatitis (nickel, poison
ivy)
Mantoux Tuberculin Skin Test – PPD Test (4)
• Type IV delayed hypersensitivity reaction to
protein from M. tuberculosis
• Intracutaneous tuberculin injection
• T-cells sensitized by prior infection
recruited to area
• Produces an area of induration
Poison Ivy Contact Dermatitis (2)
• CD8 cytotoxic lymphocytes
• Type IV immune injury
Development of Autoimmunity
• Loss of
• Arises from a combination of
(2)
self-tolerance
– Susceptibility genes
– Environmental triggers (infections and tissue damage)
Central tolerance
– Developing T cells –
– Developing B cells –
deletion of self-reacting T cells in the thymus
receptor editing or deletion of self-reacting B cells in
the bone marrow
Peripheral tolerance
(3)
– Anergy – functional inactivation
– Supression by regulatory T cells
– Deletion by activation-induced cell death
Rheumatoid Arthritis (4)
• Chronic, systemic inflammatory
disease that may affect many
tissues and organs – joints, skin,
blood vessels, lungs, muscles
• Genetic susceptibility
• Environmental arthritogen
• Tumor necrosis factor (TNF) –
therapeutic target
Hyperplastic synovium with dense chronic inflammatory infiltrate –
pannus
Pannus errodes articular cartillage, leading to
joint destruction and
ankylosis
Rheumatoid Factor
Rheumatoid factor is an antibody against an
antibody
Rheumatoid Factor
IgM autoantibody to the
Fc portion of IgG
Skin Involvement in RA - Rheumatoid Nodules (2)
• Pressure points
• Granulomas
Systemic Sclerosis
(3)
• An autoimmune disease of adults, predominately females,characterized by excessive fibrosis
• May be limited to the skin or be widespread affecting various organ systems
• May be associated with otherautoimmune diseases
Localized Form
• Skin involvement only
• No organ involvement
Morphea – mild localized disease
Limited Form
C R E S T Syndrome
Diffuse Form (2)
• Generalized involvement
• Skin and viscera
• Slow continuous replacement
of
loose fibrovascular
connective tissue with dense
collagen
• Fibrosis causes
loss of
mobility and altered function
of organs - skin, esophagus,
salivary glands, kidneys, lungs,
heart, muscle
Scleroderma
(4)
• Acute myelogenous leukemia
• Bone marrow transplant
• Graft versus host disease
• Scleroderma
Systemic Sclerosis – Oral Findings
(4)
• Microstomia
• Xerostomia
• Generalized widening of PDL
space
• Mandibular resorption
Systemic Sclerosis
(3)
• Mask-like face
• Telangiectasia
• Raynaud phenomenon
Raynaud Phenomenon
(3)
• Arterial spasm in
response to cold or
emotional stress
• Pallor, cyanosis and
then erythema
• Numbness, tingling or
pain on recovery.
Hands and Fingers
(2)
• Fibrosis, stiffness, deformity
• Ischemia, atrophy and ulceration
CREST Syndrome: A Limited Form of Scleroderma
• Calcinosis
• Raynaud Phenomenon
• Esophageal dysfunction
• Sclerodactly
• Telangiectasia
• Calcinosis
– Calcium deposits in the skin
• Raynaud Phenomenon
(2)
– Spasm of vessels
– Response to cold or stress
• Esophageal dysfunction
(2)
– Decrease in motility
– Acid reflux
• Sclerodactly
(2)
– Thickening and tightening of the skin
– Fingers and hands
• Telangiectasia
(2)
– Dilation of capillaries
– Red lesions on skin
Sjogren Syndrome
(5)
• Chronic, systemic autoimmune
disease that may be associated
with other autoimmune diseases
• Middle-aged females (9:1)
• Benign lymphoepithelial lesion
(BLEL) with variable salivary gland
enlargement
• Dry eyes and dry mouth (sicca
syndrome
• Increased risk of lymphoma
Laboratory Findings in Sjogren Syndrome
• Autoantibodies to ribonucleoproteins
– Anti-SS-A (anti-Ro)
– Anti-SS-B (anti-La)
• Rheumatoid factor (RF) – IgM
autoantibody to the Fc portion of IgG
• Anti-nuclear antibodies (ANA)
• Anti-salivary duct antibodies
Sicca Complex
(2)
• Xerostomia
• Xerophthalmia -
keratoconjunctivitis sicca
immune reaction against
external “antigens”:
ALLERGY or HYPERSENSITIVITY
Immune reaction against
your own tissues:
AUTOIMMUNITY
Too little immunity:
Immune deficiency
• IgA deficiency –
little morbidity
• Severe combined immunodeficiency (SCID) –
mortality
Defects in humoral immunity
(4)
• Bruton X-linked agammaglobulinemia
• IgA deficiency
• Hyper IgM syndrome
• Common variable immune deficiency (CVID)
Defects in cellular immunity
(4)
• DiGeorge syndrome
• Bare lymphocyte syndrome
• Severe combined immunodeficiency (SCID)
• Acquired immumodeficiency syndrome (AIDS)
Bruton X-Linked Agammaglobulinemia
(7)
• Failure of B cell maturation to plasma cells
• No plasma cells
• No antibodies
• No germinal centers in lymphoid tissue
• Recurrent bacterial infections
• X-linked inheritance – affects only males
• Lyonization protects females who are carriers
IgA Deficiency
(5)
• Common immune deficiency (1:700)
• Defect in differentiation of IgA secreting plasma cells
• Low levels of circulating and secretory IgA
• Low morbidity
• Recurring infections of respiratory and gastrointestinal tracts
Hyper IgM Syndrome
(5)
• Defect in class switching from IgM to IgG and IgA antibody production
• High levels of IgM
• No IgG or IgA
• Recurring bacterial infections
• X-linked inheritance
Common Variable Immune Deficiency (CVID)
(5)
• Common primary immunodeficiency
• A heterogenous group of 20–30
immunodeficiencies
• Symptoms: all exhibit hypogammaglobulinemia
due to different causes
• Recurring bacterial infections
• Treatment: intravenous infusion of
immunoglobulins
DiGeorge Syndrome
(5)
• Congenital absence of structures
derived from the 3rd and 4th branchial
pouches
• Thymic and parathyroid aplasia
• No cellular immunity - no T Cells
(neither CD4 nor CD8)
• Hypoparathyroidism
• Defects in humoral immunity
Bare Lymphocyte Syndrome
(6)
• Antigen presenting cells don’t express MHC Class II molecules
• Mutations in the genes encoding transcription factors
• No MHC Class II molecules on APCs
• No antigen presentation to CD4 T cells
• No cellular immune response
• Misnomer – “bare APC syndrome” would be more accurate
Severe Combine Immune Deficiency (SCID)
(4)
• A heterogenous group of diseases caused by defective development of both T and B cells
• No T cells
• No B cells
• No humoral and cellular immunity - lethal
Human Immunodeficiency Virus - AIDS
(7)
• HIV gp 120 is a perfect fit for the
CD4 receptor on T cells
• HIV gp 41 promotes fusion
• HIV kills CD4 cells
• As CD4 cells are killed, cellular
immunity fails, followed by humoral
immunity
• Infections by intracellular pathogens
as cellular immunity fails
• Infections by extracellular pathogens
as humoral immunity fails
• Neoplasms
Oral Lesions in AIDS
(9)
• Aphthous-like ulcers
• Candidiasis
• Kaposi sarcoma (HHV-8)
• Human papilloma virus lesions - papillomas
• Herpes simplex virus lesions
• Hairy leukoplakia (Epstein Barr virus)
• Accellerated periodontitis
• Necrotizing ulcerative gingivitis, periodontitis, stomatitis
• Neoplasms (squamous cell carcinoma, lymphoma)
Lesions in Immunocompromised Patients
The clinical appearance of a lesion depends on:
(2)
• Effect of the immune system
• Effect of the agent
