Ch. 6 Disorders Of The Immune System Flashcards
Two forms of immune response?
Natural and acquired
Where is IgA found?
Mainly in mucosal secretions (tears, nasal, resp. tract), breast milk, intestinal tract
What does “immunity” mean?
From Latin term - exemption from duty
What is natural immunity?
Mechanical and cellular defense mechanism
Function of IgA?
Protective
What is acquired immunity?
Concept of self vs non self
Where is IgE found?
Trace amts in serum
3 protective proteins in natural immunity?
Complement, properdin, lysozyme
What secretes IgE?
sensitized plasma cells in tissue
What is properdin ?
Plasma protein that activates alternative complement pway
What are IgEs attached to?
Locally attached to mast cells
What are lysozymes?
Low molecular weight proteins
Function of IgE?
Mediates allergic rxns in tissues (hay fever, asthma) and protects against parasites
Where are lysozymes found?
Tears, nasal secretions, intestinal secretions
Where is IgD found?
Exclusively on B cells
What is immunocompetence?
Ability to mount a response
Function of IgD?
Participates in antigenic activation of B cells
What is the body’s first line of defense?
Skin - mechanical and chemical barriers
Is IgD released into serum of body fluids?
NO
What is the body’s second line I defense?
Skin - inflammatory response, phagocytosis
What is MHC?
Major histocompatibility complex
What is the body’s third line of defense?
Skin - specific immune responses
Why is MHC essential?
For presentation of antigens to T cells
What are the cells of the immune system?
Lymphocytes, plasma cells, macrophages
What is MHC aka?
human leukocyte antigen
Types of lymphocytes?
T and B
Two groups of MCH , and what are they receptors for?
Type 1 - R/Cs for CD8 Type 2 - r/cs for CD4
Types of t lymphocytes?
T helper (CD4+) T suppressor/cytotoxic (CD8+) Natural killer (NK) cells
Role of MHC in immune response?
antigen presenting cell (macrophage or B cell)
Major lymphoid organs?
Thymus, bone marrow, lymph nodes, tonsils, spleen, Peyer’s patches
Function of MHC?
presentation of antigen to T cells
What is Waldeyer’s ring?
Lymph nodes, tonsils, adenoids
Why are antigen presenting cells important?
T cells can only react to membrane bound antigens. W/O APCs there is NO T CELL RXN to antigens
What does a basophil become in tissue?
Mast cell
Where are MHC type 1 found?
On ALL NUCLEATED CELLS
What does a monocytes become in tissue?
Macrophage
What do MCH type 1 link APCs to?
suppressor and/or cytotoxic T lymphocytes
What does a b lymphocyte become in tissue?
Plasma cell
What do MCH type 2 mediate?
attachment of APC to helper T lymphocyte
Microscopic Difference between b lymphocyte and plasma cell?
Lymphocyte = scant cytoplasm, few organelles
Plasma cell = well developed cytoplasm and prominent rough ER
Function of MHC type 2?
presentation of EXOGENOUS ANTIGENS that are first internalized and processed
What is RER responsible for in plasma cells?
Production of immunoglobulins
What are HLA subtypes used for?
Used diagnostically to identify pathologies
Five classes of immunoglobulins?
IgG, IgM, IgA, IgE, IgD
What is HLA type B27 used to identify?
Psoriasis, ANKYLOSING SPONDYLITIS, Inflammatory bowel disease, Reiter’s syndrome (PAIR)
What are all immunoglobulins composed of?
Light and heavy chains
What is an epitope?
Antigenic site - can be many on an antigen
Which chains are the same in all immunoglobulins and which are specific to each?
Light chains the same
Heavy chains specific
What to antibodies to SOLUBLE antigens form?
Soluble complexes that can be found in circulation
What are the two regions on each chain of immunoglobulins?
Constant (Fc) and variable (Fab)
What to antibodies to NON-SOLUBLE antigens form?
Bind to fixed antigens on cells - coat the cell surface
What are the two light chains?
Kappa and lambda
What do antigen-antibody complexes do?
Bind and activate complement
What links immunoglobulin chains together?
Disulfide bonds between CYSTEINES
What is complement?
Effector system -> lysis of cells, agglutination, recruitment of inflammatory cells
What is the largest immunoglobulin?
IgM
What is hypersensitivity rxn Type I?
Anaphylactic
What is the function of IgM?
Neutralize microorganisms
What is hypersensitivity rxn Type II?
cytotoxic antibody mediated
How many complement binding sites does IgM have?
5
What is hypersensitivity rxn Type III?
immune complex mediated
What is the first immunoglobulin to appear on immunization or initial immune response?
IgM
What is hypersensitivity rxn Type IV?
cell mediated - DELAYED
What is a natural antibody against ABO blood group antigen?
IgM
Which hypersensitivity rxns are ANTIBODY mediated?
Types I, II, and III
What is the smallest immunoglobulin?
IgG
Which hypersensitivity rxns are CELL mediated?
Type IV
What is the most copious immunoglobulin?
IgG
Mnemonic to remember hypersensitivity rxns?
ACID
How much IgG is produced on initial immunization?
Small amounts- elevated with time
Which Ig is Type I hypersensitivity mediated by?
IgE
How are IgG amounts boosted?
Re-exposure to antigen
What cell type mediates hypersensitivity rxn type I?
Mast cells or basophils
Where can you find Fc receptors for IgG?
Macrophages, PMNs, lymphocytes, eosinophils, placenta
Which hypersensitivity rxn has a “late-phase” response?
Type I
What does IgG act as?
Opsonin
How long does type I hypersensitivity rxn take and why?
After 4-6 hrs. Slow reacting substances of anaphylaxis (SRS-As)
What is the only type of immunoglobulin to pass through placenta?
IgG
Diseases caused by type I hypersensitivity rxns?
Hay fever (allergic rhinitis), asthma, atopic dermatitis, anaphylactic shock
What is hay fever?
Allergic rhinitis. Typically seasonal allergy to pollen, can be due to other foreign substance
Signs/symptoms of hay fever?
nasal itching, sneezing, nasal/conjunctival inflammation
Tx for hay fever?
anti-histamines, vit. C, desensitization
What is asthma?
Rxn affecting bronchi. Hypersensitivity to inhaled antigens
Are all forms of asthma immunologically mediated?
NO
What is asthma mediated by?
SRS-As
Who is usually affected by asthma?
children
signs/symptoms of asthma?
coughing and wheezing
What mineral is indicated to relax airway muscles?
Magnesium
What is atopic dermatitis?
Eczema
When does atopic dermatitis usually occur?
childhood
What percentage of all children are affected by atopic dermatitis?
10%
What percentages of children affected w/ atopic dermatitis have family Hx?
50%
What is genetic predisposition to atopic dermatitis associated with?
hyperproduction of IgE in response to environmental allergens
What is the allergen that causes atopic dermatitis?
Can be anything. Inhaled, ingested in food, or direct skin contact
What does topical corticosteroid suppression of atopic dermatitis tend to lead to?
Asthma/hay fever developing later in childhood
What is anaphylactic shock?
Severe, systemic response to allergen
Common causes of anaphylactic shock?
Bee sting, anesthetics (hospital), radiographic contrast (hospital)
What is the mechanism of anaphylactic shock?
Massive release of histamine and other vasoactive substances
Signs/symptoms of anaphylactic shock?
Choking secondary to laryngeal edema, wheezing/SOB secondary to bronchial spasm, pulmonary edema, systemic circulatory collapse d/t hypotension
Tx for anaphylactic shock?
Epinephrine STAT, high flow O2 non-rebreather
What causes type II hypersensitivity?
Cytotoxic antibody that reacts to antigen in cells or tissue components
Which Ig mediates Type II hypersensitivity?
IgG or IgM
What does activation of complement in type II hypersensitivity lead to?
Cell lysis
Pathogenesis of type II hypersensitivity?
binding of antibody to antigen on cell surface -> complement activation -> cell lysis
Diseases caused by type II hypersensitivity rxn?
Hemolytic anemia, goodpasture syndrome, graves disease, myasthenia gravis, idiopathic thrombocytopenic purpura, erythroblastosis fetalis, rheumatic fever, bullous pemphigoid
What is hemolytic anemia?
Prototype type II rxn - several forms
Forms of hemolytic anemia?
systemic autoimmune disorder (eg. SLE), foreign chemicals (drugs rxn, attachment to RBCs as haptens)
What are the “two good pastures” affected in goodpasture syndrome?
Kidneys and lungs
Cause of goodpasture syndrome?
Autoimmunity to component of collagen TYPE IV that has become autoallergenic
signs/symptoms of goodpasture syndrome?
HEMOPTYSIS = most prominent. Dyspnea, cough, fatigue, fever, weight loss are common. 40% of pts have HEMATURIA
What is seen on x-ray of pt with goodpasture syndrome?
Bilateral alveolar opacities (d/t alveolar hemorrhage)
What causes Graves disease?
Autoantibody against thyroid r/c for TSH. Stimulatory => continuous synthesis of T3/T4 (hyperthyroid)
Signs/symptoms of Graves disease?
EXOPHTHALMOS, goiter, muscle wasting, fine hair, sweating, tachycardia, wt. loss, oligomenorrhea, tremor
What causes exophthalmos in Graves disease?
Igs directed to specific R/Cs in orbital fibroblasts and fat - results in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans
What is Myasthenia Gravis?
hypersensitivity type II disorder. Caused by autoantibody and Cell-mediated DESTRUCTION OF ACH RECEPTORS
Who is most commonly affected by myasthenia gravis?
young women
What makes symptoms of myasthenia gravis better/worse?
Worsen with muscle activity, improve with rest
How is myasthenia gravis diagnosed?
antibody testing to Ach r/c, electromyography, IV edrophonium challenge
Signs/symptoms of myasthenia gravis?
Most common = ptosis, diplopia, muscle weakness after using affected muscle, proximal limb weakness
What percentage of myasthenia gravis pts have affected ocular muscles?
Initially 40%, eventually 85%
What happens to hand grip in myasthenia gravis?
Alternates between weak and normal (milkmaid’s grip)
What happens to neck muscles in myasthenia gravis?
may become weak
When does generalized myasthenia develop in MG pts?
Usually w/in first 3 yrs
What happens to sensation and DTRs in MG pts?
NORMAL
What is a type III hypersensitivity rxn due to?
acute inflammation in response to circulating antigen-antibody immune complexes deposited in vessels or tissues
What do ag-ab complexes do in type III hypersensitivity rxns?
Can activate complement system OR bind to/activate certain immune cells => release of inflammatory mediators
What do the consequences of immune complex formation depend on in type III rxns?
Relative proportions of antigen and antibody in immune complex
Progression of type III hypersensitivity rxns?
Early - excess antigen, small ag-ab complexes which DO NOT activate complement. Later (antigen/antibody more balanced) - larger immune complexes, deposited in various tissues causing systemic rxns
Diseases cause by type III hypersensitivity rxns?
Serum sickness, poststreptococcal glomerulonephritis, arthus rxn, polyarteritis nodosa, systemic lupus erythematosus, rheumatoid arthritis, hypersensitivity pneumonitis
What is poststreptococcal glomerulonephritis?
Type III rxn, usually follows upper respiratory tract infection by nephritogenic streptococcal strain
Pathogenesis of poststreptococcal glomerulonephritis?
Antigen “planted” onto glomerular basement membrane during filtration -> complement inflammation evoked
What is the Arthus rxn?
immune-complex mediated rxn, involves deposition of ag-ab complexes mainly in the vascular walls, serosa, and glomeruli
According to CDC, how often are Arthus rxns reported after vaccinations?
RARELY
Which vaccines can cause Arthus rxns?
TETANUS toxoid-containing or DIPHTHERIA toxoid-containing
What is the antigen for polyarteritis nodosa in Arthus rxn?
UNKNOWN
Early stages of Arthus rxn?
focal fibrinoid necrosis, acute inflammation
Chronic stages of Arthus rxn?
wall destruction, microaneurysms, thrombosis, occlusion/infarct
Why is “nodosa” part of the name in Arthus rxn (polyarteritis nodosa)?
Because of fibrous nodules along medium size arteries that are affected (nodosa = knotty)
What is seen histologically in glomerulonephritis associated with SLE?
deposition of complement-activating immune complexes - IgG, and consequent infiltration by inflammatory cells
What are type IV hypersensitivity rxn?
DELAYED hypersensitivity - T cell mediated
Four subtypes of type IV hypersensitivity rxn, and cells involved?
Iva = Type 1 helper T cells, IVb = type 2 helper T cells, IVc = cytotoxic T cells, IVd = IL-8-secreting T cells
How are T cells activated (type IV hypersensitivity)?
sensitized after contact w/ a specific antigen, activated by REEXPOSURE to same antigen
How do T cells damage tissue (type IV hypersensitivity)?
by direct toxic effects OR through release of cytokines
Diseases caused by type IV hypersensitivity rxns?
Contact dermatitis (NO GRANULOMA), chronic transplant rejection, graft-vs-host dz, tuberculosis, leprosi, fungal infections, rxn to tumors, sarcoidosis, Type I DM, MS, Guillain-Barre syndrome, Hashimotos thyroiditis, PPD
What is type I DM theorized to be?
virally triggered autoimmune response (immune system attacks virus infected cells as well as Beta cells in pancreas)
What virus is implicated in type I DM?
Coxsackie virus family (German measles)
Types of transplantation? (4)
- autograft (self) 2. isograft/synergeneic graft (identical twin or clone) 3. homograft/allograft (w/in species) 4. xenograft
What should be tested for before allografting?
histocompatibility using HLA antigens
Types of transplant rejection? (3)
- hyperacute reaction 2. acute reaction 3. chronic rejection
What happens in chronic transplant rejection?
obliteration of arterial lumen
What determines the outcome of transfusion?
Major blood types (ABO system)
What agglutinin does Type A blood have?
B agglutinin
What agglutinin does type B blood have?
A agglutinin
What agglutinin does type AB blood have?
NONE
What agglutinin does type O blood have?
BOTH A and B agglutinin
Which blood types can type A GIVE to?
A, AB
Which blood types can type A RECEIVE from?
A, O
Which blood types can type B GIVE to?
B, AB
Which blood types can type B RECEIVE from?
B, O
Which blood types can type AB GIVE to?
AB
Which blood types can type AB RECEIVE from?
AB, A, B, O UNIVERSAL ACCEPTOR
Which blood types can type O GIVE to?
O, AB, A, B UNIVERSAL DONOR
Which blood types can type O RECEIVE from?
O
What happens if type A is given to a person who is type B?
HEMOLYSIS
What happens if type B is given to a person who is type A?
HEMOLYSIS
What happens if type A is given to a person who is type AB?
NO REACTION - Acid and water rxn rule
What happens if type AB is given to a person who is type A?
HEMOLYSIS
What happens if type A is given to a person who is type O?
HEMOLYSIS
What happens if type O is given to a person who is type A?
NO REACTION
What is Rh factor?
(+) or (-) charge on blood cells
What happens if Rh- mother has Rh+ fetus? (first pregnancy)
Nothing
What happens if Rh- mother has Rh+ fetus? (SECOND pregnancy)
Mother is sensitized to Rh+, => anti-Rh cells cause erythroblastosis fetalis in fetus
What should be given to an Rh- w/in 12 hrs postpartum?
RhoGAM - binds blood from fetus before immune system sensitized
Clinical features of Rh factor incompatibility?
- Hydrops fetalis 2. Erythoroblastosis fetalis 3. Icterus gravis neonatorum
If mother is Rh- and fetus is Rh+, what must father be?
Rh+
What is icterus gravis neonatorum?
jaundice of basal ganglia of brain
What is autoimmune disease?
abnormal response to self-antigens
How do you make diagnosis of autoimmune disease?
look for: 1. autoantibodies 2. immune mechanisms 3. indirect evidence (ex. If steroids help)
What causes autoimmune diseases?
Familial - genetic predisposition. Certain HLA-haplotypes more often linked to autoimmune diseases
Which sex is more commonly affected by autoimmune diseases?
Women
Types of autoimmune diseases? (2)
- systemic 2. single organ
Examples of systemic autoimmune diseases?
SLE, rheumatic fever, rheumatoid arthritis, systemic sclerosis, polyarteritis nodosa
Examples of single organ autoimmune diseases?
MS (CNS), Hashimotos thyroiditis/Graves disease (thyroid), autoimmune hemolytic anemia (blood), pemphigus vulgaris (skin), myasthenia gravis (muscle)
What percentage of SLE pts have ANA?
Virtually all
What percentage of SLE pts have kidney involvement?
75%
Characteristic sign of SLE?
Butterfly rash
When does first episode of acute rheumatic fever (ARF) most often occur?
Between 5 and 15 yrs - UNCOMMON before 3 or after 21
How do you test for rheumatic fever prevention?
test for group A streptococcal (GAS) infection in pt with pharyngitis
What is the incidence of rheumatic fever in the US?
<1/100,000
When do higher attack rates of ARF occur?
with certain streptococcal M protein serotypes and STRONGER HOST IMMUNE RESPONSE
Etiology of ARF?
GAS infection (host and environmental factors also important)
What do GAS M proteins share epitopes with?
Proteins in synovium, heart muscle, and heart valve
What is most often affected in rheumatic fever?
joints, heart, skin, CNS
What is rheumatoid arthritis (RA)?
SYMMETRICALLY inflamed peripheral joints
Which sex is more commonly affected by RA?
Women 2-3x more likely to be affected
Pathophysiology of RA?
immunologic abnormalities (type III hypersensitivity). Plasma cells produce RHEUMATOID FACTOR antibodies
Signs/symptoms of RA?
begins w/ systemic and joint systems - early morning stiffness, fatigue, malaise, anorexia, generalized weakness. Joints painful, swollen, stiff
How do you differentiate RA from osteoarthritis?
RA is characteristically SYMMETRIC
How long does morning stiffness typically last in RA pts?
> 60 min
Types of immunodeficiency diseases? (2)
Primary (congenital) and Secondary (acquired)
Primary immunodeficiency diseases? (3)
- Severe combined immunodeficiency 2. Isolated deficiency of IgA 3. DiGeorge’s syndrome
What is severe combined immunodeficiency?
defect of lymphoid stem cells - Pre-B, pre-T cells
What is the most common PRIMARY immunodeficiency disease?
Isolated deficiency of IgA (1:700)
Which primary immunodeficiency disease is often asymptomatic?
Isolated deficiency of IgA
What is DiGeorge’s syndrome?
T cell deficiency related to aplasia of thymus
What is AIDS?
Acquired Immunodeficiency Syndrome
What causes AIDS?
Human immunodeficiency virus (HIV) - RNA retrovirus
What does HIV do?
infects T HELPER CELLS (CD4)
Where is HIV stored in the body?
In macrophages and related phagocytic cells
Clinical presentation of HIV/AIDS?
Acute illness, asymptomatic infection, persistent generalized lympadenopathy
What is the terminal phase of HIV?
AIDS
Pathologic findings of CNS in AIDS?
meningitis, encephalitis, dementia
Pathologic findings of Mouth in AIDS?
Herpes labialis, THRUSH
Pathologic findings of lung in AIDS?
pneumonia
Pathologic findings of small intestine in AIDS?
malabsorption
Pathologic findings of large intestine in AIDS?
colitis, proctitis
Pathologic findings of skin in AIDS?
KAPOSI’S SARCOMA, dermatitis, folliculitis, impetigo
Pathologic findings of lymph nodes in AIDS?
lymphadenopathy
Pathologic findings of tumors in AIDS?
lymphoma
Opportunistic infections in lung in AIDS?
pneumocystitis carinii, aspergillus fumigatus, Candida albicans pneumonia
Opportunistic infections in GI in AIDS?
Candida albicans, herpes or CMV, stomatitis, esophagitis, mycobacterium avium-intracellulare, cryptosporidium enteritis, fungal or bacterial proctitis
Opportunistic infections in CNS in AIDS?
toxoplasma gondii encephalitis, cryptococcus neoformatns meningitis
Tumors that develop in AIDS? (3)
Lymphoma of lymph nodes or GI tract, lymphoma of CNS, Kaposi’s Sarcoma
4 types of immune deficiencies?
- decreased production 2. decreased activation 3. phagocytic cell deficiency 4. idiopathic dysfunction
3 types of decreased production that cause immune deficiency?
- B cells 2. T cells 3. B AND T cells
What does decreased production of B cells cause?
Brutons agammaglobulinemia
What is brutons agammaglobulinemia associated with?
Recurrent bacterial infections
Which sex is affected by Brutons agammaglobulinemia?
Boys (X LINKED)
What is caused by decreased production of T cells?
Thymic aplasia - DiGeorge syndrome
What does DiGeorge syndrome present with?
Tetany owing to hypocalcemia
What is caused by deficiency of B AND T cells?
severe combined immunodeficiency (SCID)
4 types of decreased activation that cause immune deficiencies?
- T Cells - IL12 r/c deficiency 2. B cells - hyper-IgM syndrome 3. B cells - Wiskott-Aldrich syndrome 4. Macrophages - Job’s syndrome
What is Wiskott-Aldrich syndrome?
X linked defect in ability to mount IgM response to bacteria
What is Wiskott-Aldrich syndrome associated with?
elevated IgA levels
Triad of symptoms of Wiskott-Aldrich syndrome?
recurrent pyogenic infections, thrombocytopenic purpura, eczema
What is Job’s syndrome?
failure of IFN-gamma production by helper T cells
3 types of phagocytic cell deficiencies that cause immune deficiencies?
- Leukocyte adhesion deficiency syndrome (type 1) 2. Chediak-Higashi disease 3. Chronic granulmoatous disease
4 idiopathic dysfunction that cause immune deficiencies?
- T cells - chronic mucocutaneous candidiasis 2. B cells - selective immunoglobulin deficiency 3. B cells - ataxia-telangiectasia 4. B cells - common variable immunodeficiency
What is amyloid?
Inert extracellular material defined in terms of its PHYSICAL properties (NOT biochemical)
Physical properties of amyloid?
Fibers 7.5 nm thick (electron microscopy), stains with Congo red (appears green under polarized light), Beta-pleated sheet (radiographic crstallography)
Biochemical types of amyloid?
AA amyloid, AL amyloid, many other forms
Clinical presentation of amyloid deposition? (2)
- systemic amyloidosis (deposition of amyloid in various organs) 2. localized organ-specific amyloid deposits (ex. Alzheimers dz in brain)
