immunity Flashcards
bodys lines of defense, which are specific?
- Barriers – skin, mucous membranes, secretions
- Inflammatory Response – cells (leukocytes),
molecules (mediators) - Immune Response – only one that is specific
Antibodies (humoral),
Cytotoxic T cells (cellular)
Antigen (Ag) -
Antigen (Ag) - A substance that can induce an
immune response when introduced into an
animal.
Antibody (Ab)
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) -
Immunoglobulin (Ig) - A glycoprotein composed
of heavy and light chains that functions as an
antibody.
Schematic Structure of a Typical Immunoglobulin (Antibody) Molecule
• IgM -
• IgM - first immunoglobulin to
appear in an immune response
IgG -
IgG - principal immunoglobulin of the secondary immune response.
Only immunoglobulin capable of crossing the placental barrier
IgA -
IgA - principal immunoglobulin in
external secretions of mucosal
surfaces, tears, saliva, and
colostrum
IgE -
IgE - plays an important role in
immediate hypersensitivity
reactions and parasitic infections
IgD
gD - thought to activate the B-
lymphocyte
lymphocyte
Primary and Secondary Lymphoid Organs
• All lymphocytes arise in the bone marrow
• Primary lymphoid organs
– Bone marrow
– Thymus
• Secondary lymphoid organs
– Lymph nodes
– Tonsils
– Spleen
– Mucosal-associated lymphoid tissue (MALT)
Subsets of
Lymphocytes
B and T
distinguishing b and t cells
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? role?
plasma cells
secrete antibodies when
challenged by antigen
• Antibodies are essential
for humoral immunity
Agammaglobulinemia (Bruton Agammaglobulinemia)
inheritence?
more common in?
type of dx?
result?
deficeint in what immune function?
susceptiable to?
tx?
- 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
- Treatment: intravenous infusions of immunoglobulin every 3-4 weeks for life (passive immunity)
QB of IS?
Tcells (CD4)
types of t cells
T Lymphocytes
• CD4+ (T Helper Cell) - quarterback
• CD8+( Cytotoxic T Cell) - effector
role of t cells
• Cell-mediated defense against intracellular pathogens
– Viruses, fungi and one important bacterial disease (tuberculosis)
Natural Killer Cell
• A component of the innate immune system
• A type of cytotoxic lymphocyte
• Do not have markers for B or T cells
Function of the Thymus
• T cells become educated
• Learn self from non-self
• Self-reacting T cells are
deleted
Lymph Nodes and lymphocytes
• B lymphocytes leave the bone
marrow and populate lymph nodes
• T lymphocytes leave the thymus and populate lymph nodes
IS balance
• Self / non-self recognition
• General / specific
• Natural / adaptive
• Innate / acquired
• Humoral / cell-mediated
• Active / passive
• Primary / secondary
classifications of pathogens, examples and immunity responsible for defense
• Extracellular pathogens
– Most bacteria
– Humoral immunity
• Intracellular pathogens
– Viruses, fungi, some bacteria
– Cellular immunity
innate immunity
components?
(born with)
– Physical and chemical barriers (epithelia and antimicrobial substances)
– All phagocytic cells (neutrophils,
macrophages, NK cells)
– Complement proteins
– Cytokines (TNF, IL-1, interferon)
Adaptive immunity
components?
(not born with, requires exposure)
– Antibodies
– Lymphocytes
– Cytokines (IL-2, IL-12)
Antibody-Dependent Immunity: First Exposure (no antibody available) what happens?
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
– Neutralize toxins
– Bind pathogens
– Serve as opsonins
– Activate complement cascade via classic pathway
arms of adaptive immunity, depend on?
humoral and cellular, both Ab dependent
• Humoral immunity is the
first line of defense against?
extracellular pathogens
• Cellular immunity is the
first line of defense against?
intracellular pathogens
MHC
• 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
• MHC Class 1 molecules are located on the surface of most cells
• MHC Class 2
• MHC Class 2 molecules are found on Antigen-Presenting Cells (APCs)
– APCs: dendritic cells, macrophages, Langerhans cells
activation path of CD8 cells thru CD4 cells
• If the invading organism is a virus, fungus or Mycobacterium, the first line of defense is cellular immunity, not humoral immunity
CD4+ T Helper Lymphocyte
Role?
• The recognition arm of cellular
immunity – the bloodhounds
• Role is to look at all the MHC-2molecules in the body (on APCs) to determine if they’re clean or dirty
CD4 Helper T- Lymphocytes are MHC-2 Restricted
CD4 releases what cytokine with activation, results in?
CD4+ T Helper cell
secretes IL-2
• IL-2 signals naïve
lymphocytes to
differentiate into CD8+
cytotoxic lymphocytes
CD8 Killer T-Lymphocytes
role? names?
• 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 MHC-1 Restricted
how CD8 cells kill
• CD8 Killer T-Lymphocytes kills
hepatocyte (perforins),
exposing virus to humoral
immune system
OR perforin+granuzymes/ FAS
Immune Injury Disease
Hypersensitivity Reactions
types?
Types I, II, III, IV
type 1 hypersensitivity
recipe?
Immediate hypersensitivity
Recipe
• Antigen
• IgE antibodies
• Mast cells
clinical responses seen in type 1 hypersensitivity
• “Hay fever”
• Asthma
• Hives
• Angioedema
• Anaphylactic shock
most common clinical manifestation of type 1 hyper
hay fever
hives of types 1 hyper
can form but also be more profound with bronchoconstriction
anaphylaxis of type 1 hyper
local?
mass release of immune chemicals that can lead to shock
can be localized or systemic
localized type 1 hyper rxn
angioedema (lips)
systemic type 1 hyper rxn
can be due to exaggerated response such as bee stings
type 2 hyper sensitivity
can target what?
• Antibody mediated
hypersensitivity
• Cells – erythrocytes,
platelets
• Cell surface receptors –
acetylcholine receptor
• Extracellular matrix
material – laminin,
desmoglein
examples of type 2 hypersensitivity
Outcome of Antibody-Dependent Cytotoxic Reactions Against Cells
type 2 rxn
• Lysis – complement mediated (MAC)
• Phagocytosis - opsonization
Blood Transfusion Reaction - ABO Blood Incompatibility
what kind of hypersensitivity is this?
what happens?
type 2 rxn
* ABO mismatch leads to
intravascular hemolysis
* Antibody-coated
erythrocytes destroyed
by both complement-
mediated lysis and by
phagocytosis in spleen
Autoimmune Thrombocytopenic Purpura
presentation?
type 2
Ab produced in spleen against plattlet Ag (GPIb)= macrophage destruction of plattlet in spleen
type 2 hyper against cell receptors
myasthenia gravis
graves dx
Myasthenia Gravis
Myasthenia Gravis
• Antibody blocks
acetylcholine receptor
graves dx
• Antibody-mediated
stimulation of cell function
• Antibody stimulates TSH
receptor
hyperthyroidism
type 2 rxns against ECM
examples
laminin and desmoglein
mucus membrane pemphigoid
pemphigus vaulgaris
type 3 rxns due to?
immune complexes
type 3 rxn mechanism
PMN role in type 3 rxn
act as pahgo but have regurrgitatiojn of lysozomal enzymes leading to fibrinoid necrosis of endothelial wall
Target Antigens in Type III Disease
example dx?
• Exogenous antigen – post-streptococcal glomerulonephritis
• Endogenous antigen – lupus erythematosus
Post-Streptococcal Glomerulonephritis
results from?
signs?
does infection occur?
- 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
what kind of hypersensitivity?
involves what systems? especially which ones?
renal failure possible?
demographic?
renal?
what is the Ag?
lab finding?
common superficial manifestation?
- 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 3 diseases of vessels
vasculitis and glomerulonephritis
organs involved in
SLE
- 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
type 4 hypersensitivity due to?
cell mediated hypersensitivty
examples of type 4 hypersensitivity
• Tuberculin reaction
• Contact mucositis (nickel, cinnamon)
• Contact dermatitis (nickel, poison
ivy)
contact dermititis
usually seen on the skin with exposure to allergenic agent
allergic contact stomatitis mechanism
Ag bind langerhans cells
present Ag to LN in conn tissue for T cell sensitization
secondary expsoure to the Ag results in activation of sensitzed T cells causing cytokine release and hypersensititvty
PPD test
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
how could contact mucositis occur in the mouth
buccal mucosa, to cinnamon chewing gum or nickel
type of hyper? cell involved?
poison ivy contact dermatitis
- CD8 cytotoxic lymphocytes
- Type IV immune injury
development of autoimmunity, arises from?
• Loss of self-tolerance
• Arises from a combination of
– Susceptibility genes
– Environmental triggers (infections and tissue damage)
Mechanisms of Immunological Tolerance
central and peripheral
- Central tolerance
– Developing T cells – deletion of self-reacting T cells in the thymus
– Developing B cells – receptor editing or deletion of self-reacting B cells in the bone marrow
• Peripheral tolerance
– Anergy – functional inactivation
– Supression by regulatory T cells
– Deletion by activation-induced cell death
Rheumatoid Arthritis
what tissues are effected?
genetic/environment?
TNF role?
• 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, plays a role in tissue damage by preventing osteoblast maturation
RA histology
Hyperplastic synovium with dense chronic inflammatory infiltrate = pannus
• Pannus errodes articular cartillage, leading to joint destruction and ankylosis
RA due to
• Rheumatoid factor is an antibody against an antibody
• IgM autoantibody to the Fc portion of IgG
Skin Involvement in RA
Rheumatoid Nodules= presssure points/ granulomas
key cytokine of RA pathogenesis
TNF
RA pathogenesis/ flow chart
CD4 activated w unknown Ag and stimulate autoab production
CD4 will also activate macrophages and other cells of the joint synovium to cause pannus formation
systemic sclerosis
type of dx?
demographic?
characterized by?
what systems can be affected?
can be associated with?
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 other autoimmune diseases
spectrum of systemic sclerosis
tissue involvement?
what accumulates in systemic sclerosis/what happens?
what does this cause?
- 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
systemic sclerosis oral findings
• Microstomia
• Xerostomia
• Generalized widening of PDL space
• Mandibular resorption: Condyle, Corinoid Process and Angle
systemic Sclerosis
face?
blood vessels?
hands?
• Mask-like face
• Telangiectasia-pinpoint areas
• Raynaud phenomenon
Raynaud Phenomenon
• Arterial spasm in
response to cold or
emotional stress
• Pallor, cyanosis and
then erythema
• Numbness, tingling or
pain on recovery.
Hands and Fingers of systemic scleroderma
Fibrosis, stiffness, deformity
• Ischemia= atrophy and ulceration
CREST syndrome
limited form of scleroderma
Calcinosis
– Calcium deposits in the skin
• Raynaud Phenomenon
– Spasm of vessels
– Response to cold or stress
• Esophageal dysfunction
– Decrease in motility
– Acid reflux
• Sclerodactly
– Thickening and tightening of the skin
– Fingers and hands
• Telangiectasia
– Dilation of capillaries
– Red lesions on skin
Sjogren Syndrome
type of dx?
can be associated with?
presents as what histo?
signs?
demogrpahics?
increased risk of? classified as?
- 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
classified as an Autoimmune Exocrineopathy
lab findings of SS
• Autoantibodies to ribonucleoproteins
– Anti-SS-A (anti-Ro)
– Anti-SS-B (anti-La)
• Rheumatoid factor (RF) – IgM
autoantibody to the Fc portion of IgG (non-specific)
• Anti-nuclear antibodies (ANA), non-specific
• Anti-salivary duct antibodies, non-specific
sicca complex of SS
• Xerostomia
• Xerophthalmia -keratoconjunctivitis sicca
oral patholgy associated with xerostomia
caries
Improper Immune reaction against external “antigens”: result in
ALLERGY or HYPERSENSITIVITY
Immune reaction against
your own tissues: results in?
AUTOIMMUNITY
Too little immunity: results in?
Immune deficiency
Spectrum of Immunodeficiency Diseases
Primary and Secondary Immune Deficiencies
Defects in humoral immunity examples
• Bruton X-linked agammaglobulinemia
• IgA deficiency
• Hyper IgM syndrome
• Common variable immune deficiency (CVID)
Defects in cellular immunity examples
• DiGeorge syndrome
• Bare lymphocyte syndrome
• Severe combined immunodeficiency (SCID)
• Acquired immumodeficiency syndrome (AIDS)
Bruton Agammaglobulinemia
what is wrong?
result?
recurrent infection?
demographics? why is one sex protected?
- 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
commnality?
mortality?
recurring infections where?
• 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
due to?
susceptiable to?
inheritance?
- 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)
primary or secondary?
group of dx?
symptom?
susceptiable to?
tx ?
- Common primary immunodeficiency
- A heterogenous group of 20–30 immunodeficiencies
- Symptoms: all exhibit hypogammaglobulinemia (decreased Ig) due to different causes
- Recurring bacterial infections
- Treatment: intravenous infusion of immunoglobulins
DiGeorge Syndrome
• 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
what is wrong?
mutation? result?
• 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)
• 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 mechanism
what fails?
what can occur as a result?
• 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 can arise
Possible Oral Lesions in AIDS
• 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)
candidasis in AIDS
can appear in a variety of forms; pseudomembraneous, erthymatous
karposi sarcoma with AIDS
appear as lesions on the face or gingiva; red in appearence
HSV oral presentation in AIDS
similarly ulcerative but can vary due to the immune compromised state
in immunocompromised pts the clinical appearance of a lesion depends on
• Effect of the immune system
• Effect of the agent
AIDS – Oral Hairy Leukoplakis
can occur on lateral aspect of the tongue and have similar appearence to EBV
bilateral lesion
AIDS – Human Papilloma Virus
can form papillomas on lip
AIDS – Necrotizing Ulcerative Periodontitis
gingiva can undergo necrosis
