1.

Innate
(natural)
Immunity
Nonadaptive immune response to microbial
pathogens as well as nonmicrobial antigens
(release via cell death/ injury)
2. Innate
Immunity
Effector
Cells
Phagocytic cells (netro,macro, mono), NK
cells, dendritic cells, microglial, Kuffer,
eosinophils, mast cells, mucosal/endothelial
cells
3. Toll-like
receptors
proteins expressed on activated effector cells;
recognize nonself antigens on pathogens and
damaged tissue antigens
4. Pathogen
associated
molecular
patterns
(PAMPs)
No present on all effector cells
(Endotoxin on GN bacteria and peptidoglycan
on GP bacteria)
5. NFkB "Master switch" to nucleus for induction of
inflammation
6. Interaction
with TLRs
on Effector
cells with
PAMPS
Genes are encoded for mediator production,
then mediators release into serum or spinal
fluid
7. Innate
Immunity
Mediator
NO, Cytokines, Adhesion molecules for
neutrophils, monocytes, ROS, antimicrobial
peptides, chemokines, complement proteins
and complement regulatory proteins
8. DAMPS Damage-associated molecular patterns: TLRs
react with these non self antigens on damaged
tissue, --> then releae proinflmmatory
cytokines and chemokines
Derived from: plasma membrane, nucleus, ER,
mitochondria, cytosol
9. NLR's Nucletotide-bind oligomerization domain
(NOD)- like receptors (NLRs) cytosolic
receptors expressed predominantly in dendritic
cells, monocytes and macrophages recognize
PAMPs/DAMPs
work with TLRs
10. Pathogens
that activate
NLRs
Salmonella typhimurium, Shigella flexneri,
pseudomonas aeruginosa, legionella
pneumophila, candida albicans, and certain
viruses (hepatitis c, adeonovirus, influenza
virus)
11. NLR
activated
actions
Inflammasomes activate Caspase-1--> increase
secretion of IL-1B and IL-18--> attract immune
cells to sites of infection
overwhelmed production cause pathogenesis of
Autoimmune disease
12. Noncellular
immunity
responses
to infections
1. Sequestration of Iron in liver and
macrophages by hepcidin
2. Syn/release of Acute phase reactants (APRs)
by liver
3. Protective bacterial flora in colon
4. Human B-defensins
5. Epithelial + Physiological + Chemical
barriers
13. Hepcidin Keeps iron away from bacteria (Iron: necessary
for bacterial growth and reproduction); IL-6
increase syn/release of Hepcidin from liver,
decreases iron reabsoptionin duodenum
14. APRs of
liver
IL-6 (most important cytokine to cause lier
syn/release of APRs), C-reactive protein (CRP),
C3b, C5a, ferritin
15. Protective
bacteria in
Colon
Limit dominance of pathogenic microbes,
compete for nutrients, activate host defenses
16. Defensins Antimicrobial peptides produced by mucosal
epithelial cells:
Attract neutrophils, prevent microbial
colonization of mucosa
17. Sebum Contains lactic acid and FA's, both reduce pH
of skin and inhibit bacterial growth
18. Physiologic
barriers of
protection
Fever: inhibit viral/bacterial reproduction;
IFN-y: activates macrophages, IFN- a/B:
inhibit viral growth, acid pH inhibits bacterial
growth
19. Adaptive
(acquired)
immunity
Antigens produced by microbial pathogens are
recognized by B/T lymphocytes which
eliminate microbial agents
20. B-
lymphocytes
Derive: Bone Marrow, stem cells
Differentiate into plasma cells that produce
Humoral response produce antibodies to kill
encapsulated extracellular bacteria, Also are
APC cells
21. Antibodies Destroy extracellular microbial pathogens
22. Naive B
Cells
Produce IgM and IgD
23. Class
(Isotype)
Switching
Produce other Igs involves changes in the
heavy chain locus in the constant region of the
gene
Induced by combo of CD40 ligand-mediated
signals and cytokines, which are modulated by
CD4 helper T cells
24. T cells involved in cell mediated immunity: destroy
intracellular microbial pathogens
25. T Cells CD4 (helper) and CD8 (cytotoxic) cells
Derived: Bone Marrow lymphocyte stem cells,
mature in thymus
Goljan: Chpt 4 Immunopathology
Study online at quizlet.com/_ov7te
26. CD4 cell types Naive (unstimulated) CD4 T cells
CD4 TH 1 Subset cells
CD4 TH 2 Subset cells
27. CD4 T cell function -Recognize antigens in association
with Class II MHC proteins
-Help macrophages kill intracellular
pathogens via release of IFN-y
-help produce clonal expansion of CD4
T cells in DTH via IL-2 release
-help activate CD8 cytotoxic T cells via
release of IL-2
28. CD4 TH 1 Subset
cells
memory T cells; produced via release of
IL-12 from Activated Macrophages in
DTH
29. CD4 TH 2 Subset
cells
Produced via release fo IL-4 from APCs;
causing naive CD4 T cells to
differentiate into this subset + B cells to
turn into IgE secreting plasma cells
Via IL-5: activate esosinophils (usefull
to kill kelminths)
Via IL-13: enhance IgE production and
mucus secretion by epithelial cells
(important in asthma)
30. CD8 cytotoxic T
cell types
Naive (unstimulated) CD8 cytotoxic T
cells,
CD8 cytotoxic subset memory cells
31. CD8 cytotoxic T
cell Function
Recognize antigens in association with
class I MHC proteins
Kill virus-infected, neoplastic, and
donor graft cells via release of perforins
and granzymes
32. Major
Histocompatibility
Complex (MHC)
On Chromosome 6, known as the
human leukocyte antigen (HLA)
system, Code for membrane-assoc.
glycoproteins: Located on all nucleated
cells/platelets except RBCs
HLA genes: transmitted to children
from parents
33. MHC class I Molecules: HLA-A, HLA-B, HLA-C
loci, are both codominatly expressed,
on all nucleated cells and platelets but
RBCs
Recognized by CD8 T cells and NK
cells: if altered=destroyed
34. MHC Class II Encoded by HLA-D region (Dp-DQ-DR
subregions)
Present on all APCs including: B cells
Macrophages and dendritic
cells
35. Rule of 8 CD8 T cells recognize MHC I (8x1=8)
CD4 T Cells recognize MHC II (4x2=8)
36. HLA Testing Many disease asociated with these genes
(pg 61)
Transplantation workup for graft
compatibility, disease risk for developing
it
37. Developing
Antibodies
against HLA
antigens
Pregnancy: caused by fetal-maternal
bleeds during preg/delivery
Blood Transfusion: from presence of HLA
antigen on platelet/leukocyte
Previous Transplantion: antibodies
develop against organ HLA antigens that
are foreign to the recipient
38. Type I
(immediate)
Hypersensitivity
IgE antibody-mediated activation of mast
cells or basophils, followed by AI reaction
Allergens first processed by APC function-
-> then release IL-4/5
39. IL-4 Plasma cells switch from IgM to IgE
synthesis
40. IL-5 Stimulates production/activation of
eosinophils
41. Mast Cell
activation
(reexposure)
allergens cross-link allergen-specific IgE
antibodies on mast cells, Release
Mediators: Early phase preformed and late
phase synthesized
42. Early phase: Release preformed histamine: increase
SM contraction, vasodila
Eosinophil chemotactic factor:
histaminase and aylsulfatase
Serotonin: vasodilation
CHemical produce swelling, constriction
of bronchi and terminal bronchioles
43. Late phase
reaction
Mast cells synthesize/release: PGs, LTs
and PAF
Basically Prolong AI
44. Type I Testing Scratch Test: postitive response to
histamin mediated wheal/flare
Radioallergosorbent test (RAST): detects
IgE antibodies in serum
45. Type II
(cytotoxic)
Hypersensitivity
antibody directed against antigens on cell
membrane/ECM
46. Cell lysis IgM-
mediated
IgM directed against antigen on cell
membrane activate complement system;
Cold IHA, ABO mismatch
47. Cell lysis IgG-
mediated
IgG attaches to BM/matrix--> activated
complement system--> C5a produced-->
neutrophil/monocytes recruited-->
enzymes/ROS release--> tissue damaged
Goodpasture syndrome, Acute Rheumatic
Fever
48. Phagocytosis fixed macrophages phagocytose
hematopoietic cells coated by IgG
anitbodies or complements(C3b)
Warm autoimmune hemolytic anemia,
ABO hemolytic disease of newborns
49. Antibody
dependent cell
Cytotoxicity
(ADCC) IgG
mediated
NK attaching to IgG in viraly infected
cell or cancer cell
50. ADCC IgE
mediated
eosinophil destruction of IgE-coated
helminth
51. AutoAntibody
aginst cell surface
receptor
IgG antibodies directed against cell
surface receptor impair function
Myathenia Gravis and Graves Disease
52. Type II
hypersensitivity
Tests
Direct Coombs test: detects IgG or C3b
or C3d attached to RBCs
Indirect Coombs Test: detects
antibodies in serum against antigens
on RBC surface
53. Type III
(immunocomplex)
Hypersensitivity
Circulating antigen-antibody
complexes that prduce AI with damage
to the tissue at site of deposition
Form Immunocomplexes activate
complement that attract neutrophils
(C5a), leading to tissue damage,
(usually vessel wall)
54. Arthus reaction localization of ICs
Farmers Lund--> pneumonitis
55. Type III testing Immunoflourescent staining of tissue
biopsies identifies IC depositions
(glomerulonephritis)
56. Type IV
Hypersensitivity
Antibody-independent, T cell-mediated
immunity(CMI) initiated by antigen
activated T cells of CD4/8;
Inflammatory response often delayed
(DTH: delayed-type hypersensitivity)
Functions: Infection control, graft
rejection, tumor surveillance
CMI diminished in elderly/people w/
AIDS
57. DTH Type of CMI primary involving
Macrophages (APCs) and CD4 T cells
How it works:
Macrophages interact with antigen as
APCs--> then interact with Class II
antigen sites on naive CD4 T cells-->
IL-12 from macrophages causing naive
CD4 cells to turn into CD4 TH1--> they
produce IFN-y: increases macrophage
phagocytosis/killing pathogen
Activated macrophages become
epethelioid cells
58. Granuloma Epithelioid cells, multinucleated giant
cells, rim CD4 T cells
59. PPD reaction of
DTH
Purified protein derivative containing
antigen: phagocytosed by Langerhans
cells in skin to process the PPD via Class
II receptors: initiate CD4 Th1 cells to be
activated produce inflammatory response,
peaks from 24-72 hrs
Dependent on CMI competency
60. DTH chronic
Asthma
Macrophages release IL-4/5 and eotaxin,
CD4 Th2 subset cells, eosinophils (IL-
5+eotaxin) they release MBP, cationic
protein and LTs
61. Allergic contact
Dermatitis
Pruritus, erythema, edema, vesicles
Poison ivy, topical drugs, rubber chemicals
Involves: Induction phase: CD4 Th1 subset
memory cells in lymph nodes presented by
Langerhan cells; effector cytotoxis CD8
memory T cells in circulation
Elicitation phase: cytokine release from
circulating effector T lymphocytes
62. CD8
cytotoxicity
cell interact with altered class I antigen
sites on neoplastic virus-infected, donor
graft cells which causes lysis
Lyse by: release perforins and granzymes
which are stored in granules w/in the cell
63. Test for Type IV
hypersensitivity
Patch Test: confirm allergic contact
dermatitis
suspected allergen on skin on patch and
looked for reaction
64. Tests to
evaluate CMI
intact
Quantitative count of T cells
Various mitogenic assays (function test of
T lymphocytes)
Eythematous skin reaction to Candida
65. Anergy no response to mitogenic assays and/or
skin response to Candida
66. Graft Viability absence preformed anti-HLA antibodies;
close matches for HLA-A, HLA-B, HLA-C
loci; ABO blood group compatibility(most
important for successful transplant)
67. Autograft Self to self, best survival rate
Ex: skin graft from one part of the body to
another
68. Syngeneic graft grafts between identical twins
69. Allograft Graft btw genetically different individuals
of same species
Ex: Cornea, Kidney, Bone Marrow
70. Xenograft Graft btw two different species
Ex: Pigs heart valve--> human
71. Hyperacute
Rejection
Irreversible reaction that occurs within
mins/hrs; Type II HSR
Small Vessel vasculitis, (neutrophilic
infiltrate w/ fibrinoid necrosis, and
thrombosis)
Causes: ABO mismatch, anti-HLA
antibodies
72. Acute Rejection Most Common rejection, Reversible
reaction w/in days/ weeks Type II/IV
HSR; Endothelialitis, interstitial tissue
inflammation
Reversible w/ immunosupressive therapy:
cyclosporine
73. Acute Rejection
Steps
Donor Organ with Dendritic cells w/
High levels of Both I/II MHC molecules:
Recipient CD4 T cells reacte against class
II and differ into Th1 memory cells--> this
makes them release cytoines for
macrophages leading to type IV DTH
Recipeint CD8 T cells react with MHC
class I molecules on donor and attach
parenchymal and endothelial cells
AR Type II: anti-HLA antibodies-->
against donor HLA antigens
74. Alloreactive
antiboides
Antibodies from one individual that will
recognize antigens on cells or tissues of
another, genetically nonidentical
individual
75. Chronic
Rejection
Irreversible reactiont hat occurs months-
years usually that have survived acute
rejection due to immunosuppression
therapy
Pathogenesis: chronic delayed
hypersensitivity involving CD4 T cells
76. CD4 T cell
released
Pathologic
Findings
-Atherosclerosis of vascular endothelium
(intimal smooth muscle cells)
-Smooth muscle proliferation leading to
obliteration of vascular lumen
-proliferation of fibroblasts leading to
interstitial fibrosis w/ atophy of epithelial
tissue
-interstitial infiltrate of plasma cells and
eosinophils
77. Transplant
Infections
Cytomegalovirus most common: CD8 T
cells control CMV infection
Sold organ transplant: Candida, followed
by Aspergillus
Bone Marrow transplant: Aspergillus
followed by Candida
78. Transplantation
Tests
-HLA matching Donor/recipient
-Compatibility donor/recipient
lymphocytes
-Lymphocyte Cross Match
79. HLA matching
Test
Identify class I/II proteins on
Recipient/donor lymphocytes (react
against battery of anti-HLA antibodies:
important for kidney/bone marrow
transplants prevents hyperacute reactions)
80. Compatibility
donor/recipient
Test
Mixed lymphocytes in culture
compatible: if lymphocytes do not undergo
mitosis
incompatible: if lymphocytes undergo
mitosis
81. Lymphocyte
Cross Match
Screen for presence of anti-HLA
antibodies in recipient
Recipient serum is reacted against donor
lymphocytes
Lysis of Donor Lymph: indicates recipient
has anti-HLA antibodies against certain
HLA antigens on donor lymphocytes
Absence of lysis of Donor Lymph:
indicates recipient doesnt have antiHLA
antibodies
Good for preventing hyperacute rejections
82. Graft-versus-
host (GVH)
reaction
Immunocompetent T cells in donor graft
recognize recipient antigens as foreign
and react against them
Recipeint must have MHC antigens that
are foreign to donor T lympho
83. Causes of GVH bone marrow(85% of cases)/liver
transplant, blood transfusion to T cell-
immunodeficient patient, newborn
84. Acute GVH Donor CD8 cytotoxic T cells recognize
host tissue as foreign (MHC antigens),
proliferate in host tissue and produce
severe organ damage
Type IV cytotoxic T cell HSR
85. Clinical finding
of GVH
Jaundice (bile duct necrosis), bloody
Diarrhea (GI mucosa ulceration),
Dermatitis, hepatosplenomegaly
86. Rx of GVH RX: antithymocyte globulin or monoclonal
antibodies before graft
Cyclosporing decrease severity of reaction
87. Autoimmune
Disease
Loss of self-tolerance, resulting in immune
reactions that are directed against host
tissue (self-antigens: MHC I/II,
nuclear/cytoplasmic antigens) Approx.
90% of all autoimmune diseases in women
88. HLA types of
Autoimmune
Disease
Class I related: Men> Women (ankylosing
spondylitis)
Class II related: Women> Men (RA)
Having HLA type associated w/
autoimmune Disease doent guarantee that
person will develop that disease
Environment Trigger required to initiate
the Autoimmune disease
89. Infection as
environmental
trigger
-Upregulation ofo co-stimulators on APCs
leading to formation of self-reactive CD4 T
cells and CD8 cytotoxic T cells
-Sharing antigens between host and
pathogen
-Polyclonal activation of B lymphocytes
90. Self reactive
Lymphocytes
release IL-2 causing clonal proliferation of
CD4 and CD8 T cells
91. Sharing
antigen btw
host/pathogens
Streptococcus pyogenes producing
pharyngitis have antigens in their M
proteins that are similar to antigen in
human heat, joints, and tissues-->
rheumatic fever
92. Polyclonal
activation of B
Lymphocytes
Formation of autoantibodies against host
tissue
Activators: Epstein-Barr Virus (EBV), HIV,
and CMV
93. Viruses of
Autoimmune
diseases
Coxsackievirus: myocardities (B3), type I
diabetes mellitus (B4)
Measles virus: allergic encephalitis
CMV: systemic sclerosis
EBV: hepatitis B, SLE, RA
Human Herpesvirus (HHV)-6, influenza A
virus: multiple sclerosis
94. Bacteria that
trigger
Autoimmune
Disease
S. Pyogenes: Rheumatic fever
Chlamydia tachomatis: Reiter syndrome
Enteric Klebsiella pneumoniae, Shigella
species: ankylosying spondylitis
Mycoplasma pneumoniae, Camplyobacter
jejuni: Guillain-Barre Syndr
95. Drugs that
trigger
Autoimmune
Disease
Procainamide and Hydralazine
Methyldopa
96. Procainamide
and
Hydralazine
bind to histones, cuasing them to become
immunogenic--> autoantibodies against
histones form
97. Methyldopa alters Rh antigens on surface RBCs--> IgG
against autoantibodies develop against the
Rh antigens--> splenic macrophages w/
receptors for IgG phagocytose/destroy the
RBCs-->Normaocytic anermia (Type II
HSR)
98. Sequestered
Antigens that
trigger
Autoimmune
Disease
Damage to the tissues may result in
autoimmune disease (azoospermia,
endophthalmitis, encephalitis)
99. Sequestered
Antigens
antigens that are not normally exposed to
immune system
Tissues with them: sperm, lens, uveal tract,
CNS
100. Intracellular
Sequestered
antigens that
trigger
Autoimmune
Disease
Antigens like DNA and Histones
SLE: genetic, immunologic, and
environmental factors damage cells
leading to the formation fo
autoantibodies against dsDNA
-Second exposure to the release fo DNA
produce immunocomplexes (type III
HSR) leading to various
manifestations of diease
101. UV light that
trigger
Autoimmune
Disease
UV radiation= malar rash in SLE
Induces apoptosis in keratinocytes,
releasing sequestered intracellular
nuclear antigens--> formation of ICs
(produce vasculitis)
102. Non-MHC genes
associated w/
Autoimmune
Disease
Group of genes that interfere with
normal immune regulation and self
tolerance
PTPN-22 and NOD-2, IRF5/STAT4
103. PTPN-22 gene encodes functionally defective prtein
tyrosine phosphatase tha tcont control
tyrosine kinase activity which is
important in lymphocyte response
Type 1 DM, Rheumatoid Arthritis
104. NOD-2 gene Implicated in Crohns Disease, allows
interstial bacteria to enter bowel and
produce chronic inflamation
105. IRF5, STAT4 MARKERS for Autoimmune diseases
IRF4: interferon regulatory Factor 5
increases interferon activity
STAT4: signaling molecule important
in lymphocyte activation
106. Classification of
Autoimmune
Diseases
Organ Specific disorders (Addison's
disease, pernicious anemia)
Systemic Disorders (SLE, RA, Systemic
sclerosis)
107. Lab evaluation of
Autoimmune
Disease
Serum antinuclear antibody test (ANA
test)
Specific antibody tests document organ
specific autoimmune disease
Autoantibodies involved in various
autoimmune diseases
108. Serum ANA test most useful screening for autoimmune
disease
ANAs are directed against various
nuclear antigens
Fluorescent antibody test: Patterns
(speckled, homogeneous,
nucleolar,rim) and titer (can be
followed at various time intervals for
disease activity)
109. Rim Pattern associated with anti- dsDNA
antibodies
110. Anti-dsDNA Antibodies against dsDNA are present in
patients with SLE who have renal disease
(glomerulonephritis)
111. Anti-histone Anti-histone antibodies present in drug-
induce Lupus
112. Anti-Smith
(Sm)
Acidic proteins, anti-smith antibodies
present in SLE
113. Anti-RNP Acidic Protein: Anti-ribonucleoprotein
antibodies present in systemic sclerosis
(most common) and SLE
114. SLE Chronic, multisystem, autoimmune disease
that primarily involves skin, joints, serosal
membranes, blood cells, nervous system
and kidneys
Primarly women of childbearing age;
colored folk
115. SLE: genetic
factors
Certain HLA associations: HLA-A1, HLA-
DR3
inherited deficiency of certain complement
components (C2 deficiency)
116. SLE:
Environmental
Triggers
Infectious agents (EBV)
UV light
Estrogen
Meds (procainamide, hydralazine)
117. SLE:
Mechanism
ICs (type III HSR: DNA-anti-DNA):
inflammation in skin, glomeruli/tubules,
joints and small vessels
Autoantibodies of various cytopenias with
RBCs, neutrophils, lymphocytes, and
platelets
118. SLE: Clinical
Constiutional
Findings
Constitutional: Fatigue, fever, arthralgia,
weight loss
119. SLE: Clinical
Hematologic
findings
anemia, neutropenia, lymphopenia,
thrombocytopenia
120. SLE: Clinical
Lymphatic
findings
Generalized painful lymphadenopathy and
splenomegaly
121. SLE: Clinical
MSK findings
Arthralgia most common (joint pain:
morning stiffness) and arthritis
symmetrical hands/wrist (PIP,MCP),
nonerosive, nondeforming unlike RA
122. SLE: Clinical
Skin Findings
Malar rash: butterly photosensitive;
cheeks/dridge of nose, sparing nasolabial
folds; IV light exposre initiates or
exacerbates rash
IC deposition along BM in both involved
and uninvolved areas of skin
123. SLE: Clinical
Renal Findings
Most common visceral organ involved,
Diffuse proliferative glomerulonephritis
and severe glomerular disease
Presents with nephritis (hematuria, RBCs
in urine, hypertension)
124. SLE: Clinical
Cardiovascular
Findings
Firbinous pericarditis (serositis): most
common
Libman-Sacks ednocarditis: sterile
vegetations over mitral valce surface
produce valve deformaty and mitral valve
regurgitation
125. SLE: Clinical
Respiratory
Findings
Pleuritis, pericarditis: example is serositis,
key finding in SLE
126. SLE: Clinical
CNS finding
Headache, psychosis, stroke, seizures
Vessel thrombosis causing strokes
associated with antiphospholipid
syndrome (APL)
127. SLE: Clinical
Pregnancy
related
Findings
Complete heart block in newborns may
occur: caused by IgG anti-Sjogren
syndrome (SS) -A (Ro) antibodies crossing
the placenta attacking newborns cardiac
conduction system
Recurrent spontaneous abortions
(placental vessel thrombosis: APL)
128. Drug Induced
Lupus
Erythematosus
Drugs: Procainamide (MC) and
hydralazine
Findings: Serositis (lungs, pericardium)
arthralgia, fever
129. Drug induced
lupus vs. SLE
distinguishing
features
-Antihistone antibodies
-no antibodies against native DNA
- no decrease in serum complement levels
- decrease incidence renal/cns disease
-symptoms disappear when drug
discontinued
130. SLE lab tests Serum ANA (100% sensitive) if False
positive test results: due to other
autoimmune diseases
Anti-dsDNA/Anti-Sm antibodies: high
specificity
APL antibodies: strokes, recurrent
abortions
LE cell: neutrophil containing
phagocytosed altered DNA
Immunofluorescence test: identify ICs in
band like distribution along dermal-
epidermal junction in involved/uninvolved
skin
131. SLE prognosis Improved survival in SLE due to advances
of diagnosis 90% 5 yr, 80% 10 year
survival rate
Cause of death: infection due to
immunosuppression and Chronic renal
failure
132. Systemic
Sclerosis
(scleroderma)
Multisystem disease characterized by
vascular dysfunction, excessive production
of collagen primarily in skin and visceral
organs, immune dysfunction
Female dominant: 3-4 decade, increase in
Black females
133. Types of
Scleroderma
Diffuse and limited
134. Scleroderma
pathogenesis
Increase in CD4Th2 cells: activate
inflammatory cells and fibroblasts
Increase autoantibody against DNA
topoiomerase I and centromeres
Endothelial dysfunction: earliest
manifestation
Progressive fibrosis: increase of PDGF,
TGF-B
135. Scleroderma
Endothelial
issue
Vascular injury, digital vessels; related to
cytokines release--> decrease vasodilators
(NO,PGI2) increase in vasoconstrictors
(endothelin)
damaged cells release PDGF and TGF-->
attracts fibroblasts and cause perivascular
fibrosis: narows lumen--> ischemia
136. Scleroderma
Clinical
Digital
findings
Raynaud phenomenon: MC initial finding
sequential color changes by
vasculitis/thrombosis and perivascular
fibrosis
Fingers tapered and claw-like, often digital
infarcts
137. Scleroderma
Cutaneous
findings
Skin MC organ, changes occur with edema
manifested as swollen fingers and hands-->
thickening of skin from fingers up extremity
-extensive dystrophic calcifications in
subcutaneous tissue
- radial furrowing around mouth
138. Scleroderma
GI findings
Esophagus: dysphagia w/ solids/liquids,
dysmotility, strictures/ulcerations, Barretts
esophagus
Stomach: dysmotility/ postprandial
bloating
SI: malabsoption, symotility, diverticula
LI: dysmotility, constipation
139. Scleroderma
Respiratory
Findings
Dyspnea, Pulmonary Hypertension:
interstitial fibrosis
Respiratory failure MCC of death
140. Scleroderma
Renal
Findings
hyperplastic arteriolosclerosis, malignant
hypertension
141. Clinical
findings in
limited
systemic
sclerosis
CREST:
Calcification, Raynaud phenomenon,
Esophageal dymotility, Sclerodactyly,
Telangiectasias
142. Scleroderma Lab
findings
Serum ANA positive 70-90% in both
diffuse and limited
Anti-topoisomerase.centromere
antibodies
143. Scleroderma Rx D-Pencillamine: slows skin fibrosis
Cyclophophamide: useful in interstitial
fibrosis
144. Noninfectious
inflammatory
myopathies
group of immune-mediated disorders
with symmetrical muscle involvement
and involvement of other organ systems
Polymoyositis (PM), dermatomyositis
(DM)
145. Polymyositis +
Dermatomyositis
Etiology
Female dominant and Black increase
incidence, 40-60 yrs old
increase risk of malignant neoplasms
(lung, bladder and lymphoma)
146. PM pathogenesis CD8 T cells/ CD4 Th1 subset cells
activate macrophages that damage
unidentified antigens in myocyte fibers
in skeletal muscle
Viruses trigger (HIV, HTLV-1)->
autoantibodies against t-RNA
synthetases and othe
rnuclear/cytoplasmic antigens of
skeletal muscle
147. PM clinical
Findings
Fever, morning stiffness, fatigue, weight
loss
Symmetrical, proximal muscle
weakness: upper/lower extremities,
trunk, shoulders, hips
Dysphagia for solids/liquids in
oropharynx/upper esophagus
Intersitial fibrosis
148. PM lab findings Increased Serum CK/aldolase
Positive ANA
Anti-Jo-1 antibodies
EMG: shows myopathic dysfuncion,
Biopsy: necrotic and regenerating
muscle, lymphocytic and macrophage
infiltrate, atrophy not prominent
149. PM and DM Rx Corticosteroids (first line)
150. Dermatomyositis
(DM)
Pathogenesis
Activated CD4 T cells target capillaries
in Skeletal muscle
Antibody/Compliment involved in
capillary damage,
Foci of myofiber injury accompanies
microvascular changes
151. DM clinical
findings
Muscle complaints similar to PM
Cutaneous findings: Reddish purple
papules called Gottron patches on
knuckles/PIP joints, Purple-red eyelid
discoloration: Heliotrope eyes
152. DM Lab Findings Muscle biopsy: inflammatory reaction,
Unlike PM atrophy of muscle
fibers=prominent feature
damage to capillaries in muscle leads
to ischemia and atrophy
153. Mixed Connective
Tissue Disease
(MCTD)
sign/symptoms similar to SLE, System
Sclerosis and PM
Female Dominant, 15-25 years old,
Renal disease uncommon
154. MCTD
Pathogenesis
Activation of T cells and B cells:
producing antibodies against U1-RNP
(ribonucleoprotein)
Vascular endothelial proliferation and
infiltrate of B/TCells
155. MCTD Findings Vascular: Raynaud phenomenon 95%
and sclerodactyly
MSK: Arthralgia and arthitis in hands
GI: esophageal dysmotility
Resp: pulmonary hypertension (APL),
pleuritis
Cadio: pericarditis, leukopenia,
CNS: trigeminal neuralgia
156. MCTD Lab
findings
Positive serum ANA
Ant-ribonucleoprotein (U1-
RNP=100%)
(ALP, Rheumatoid factor, anti-
dsDNA, anti-topoisomerase)
157. Immunodeficiency
Disorders (IDD)
Either primary (genetic) or secondary
disorders that involve defects in B
cells, T cells, compliment or
phagocytic cells
158. IDD risk factors Prematurity, Autimmune Diseases,
Lymphoproliferative disorders
(malignant lymphoma), Infections
(HIV), Immunosuppressive drugs
(corticosteroids)
159. Acquired
immunodeficiency
syndrome (AIDS)
MCC death due to infection worldwide
(sub-saharan africa most)
Caused by HIV retrovirus
160. HIV:
characterisitics
HIV retrovirus: reverse transcriptase
which converts viral RNA into proviral
dsDNA; but have ulcered skin or
mucosa for virus to enter CD4 T cells
or dendritic cells in tissue
HIV-1: US common, HIV-2: west
africa common
161. HIV retroviral
genes
-gag gene
-env gene
-pol gene
162. gag gene direct synthesis for inner structural
proteins (p24 core antigen)
163. env gene Direct synthesis for the viral envelop w/
outer structural protein give cell specificity
(glycoprotein [gp] 120 binds the virus to the
host CD4 T cell
164. pol gene directs synthesis for reverse transcriptase,
integrase and protease
165. Modes of
transmission
Sexual 80% of cases
1. Homo dudes taking it up the ass (50% in
US)
2. Heterosexual sex (30%) developing
countries
3. STD inc risk, Gonorrhea/Clamydia(3X),
syphilis(7X), herpes (25x)
Intravenous drug abuse: 20% of cases
Vertical Transmission: transplacental,
delivery, breast feeding
Accidental Needlestick: 0.3%
Blood Products with p24 antigen (1 in
>2million)
166. Body Fluids
with HIV
Blood, Semen, vaginal secretions, Breast
Milk
167. HIV-1 cell
types infected
Major cells infected: CD4 T cells,
macrophages, dendritic cells, astrocytes
HIV= cytotoxic to CD4 T cells: #s decrease
as disease progresses
Macrophages: have viral particles in
cytoplasmic vacuoles and they are resistant
to cytolytic effects of HIV; reservoirs for the
virus
Dendritic cells: reservoirs for virus
168. What
happens once
CD4 T cells/
Dendritic
cells
infected?
Cells are filled with viral particles, drain into
lymph nodes and spleen where virus is held
in check at patients immune system
Follicular dendritic cells in germinal centers
of lymph nodes are major reservoirs of virus
before latent stage of disease where it is
released blood and causes acute retroviral
syndrome
169. HIV-1 life
cycle
1. Gp 120 on viral envelop bind to CD4 +
chemokine co-receptors
2. Viral membrane fuses (Gp41) + Genome
gains entry into cytoplasm
3.Viral protease uncoats virus: releases viral
RNA
4. Reverse Transcriptase converts RNA--
>dsDNA
5. VIral integrase: inserts viral DNA into host
DNA: provirus (latent)
6. Activated host cel via extrinsic stimulus
(microbe infection)--> upregulation of
transcription factors(NK-kB), stimulate
cytokine genes
7. Cytokines: stim gene transcription of HIV
genome--> release of viral RNA into cytoplasm
8. Synthesis of HIV proteins produce HIV core
structure w/ RNA
9. HIV core structure migrate to cell membran,
acquire bilayer, form buds and detach
10. Able to infect others
170. HIV/Aids
test
ELISA, Western blot and nucleic acid assays,
p24 antigen, CD4 T cell count, HIV viral load
171. ELISA Screening test: detects anti-Gp 120, HIV-1,
HIV-2 antibodies (100% sensitive) + w/in 3
wks; all in 3 months
172. Western
blot and
nucleic
acid assays
Confirmation Test is ELISA is + or
indetermined
Positive test: presence of p24 antigen, pg41
antibodies or either gp120 or 160 antibodies
HIV-1 RNA in vitro nucleic acid assay replaces
Western Blot (100% s)
173. p24 antigen Indicator of active viral replication: present
before anti-gp 120 antibody
Test used by blood banks to screen HIV
174. CD4 T cell
count
Monitoring immune status: useful determining
progression of HIV and when to treat or when
to administer prophylaxis infection Rx
175. HIV viral
load
Detection of actively dividing virus, marker of
disease progression
Most sensitive test for diagnosis of acute HIV
before seroconversion
Recommended at least one time per year
176. HIV
infection:
Acute
phase
3-6 wks post-infection: fever, malaise,
generalized painful lymphadenopathy
(subsides after couple days) Highest risk of
coital contraction of HIV
177. HIV infection:
Asymptomatic
carrier phase
2-10 yrs post infection, CD4 T-cell count
>500 cells/mm3
virus replicates in follicular dendritic
cells/macrophages
Cytotoxic T cells control but do not clear
HIV reservoirs
178. HIV infection:
Early
symptomatic
phase
CD4 T-cell count 200-500 cells/mm3,
lymphadenopathy, fever, weight loss,
diarrhea
Non-AIDS defining infections: hairy
leukoplakia (EBV), oral candidiasis
179. AIDS criteria HIV-positie w/ CD4 T cell count <200
cells/mm3 and/or an AIDS-defining
condition
180. MC AIDS
defining
Conditions
Pneumocystis jiroveci pneumonia, systemic
candidiasis
181. AIDS defining
malignancies
Kaposi sarcoma, Burkitt Lymphoma (EBV),
primary CNS lymphoma (EBV), cervical
carcinoma
182. Death in AIDS Disseminated infections (CMV,
Mycobacterium avium-intracellulare
(MAI))
183. AIDS
infection:
Immunologic
Abnormalities
Lymphopenia, due to low CD4 T cell count
Cutaneous anergy, due to defect in CMI
from decrease CD4 T cells
Hypergammaglobulinemia due to
polyclonal B cell stim by EBV/CMV
CD4:CD8 ratio <1 (normally >2)
NK cell cytotoxicity function is decreased
184. CD4 count and
risks for
diseases
700-1500: normal
200-500: oral thrush, herpes zoster
(shingles), hairy leukoplakia
100-200: P. jiroveci pneumonia, AIDS
dimentia
<100: toxoplasmosis, crytpococcosis,
cryptosporidiosis
<50: CMV retinitis, MAI complex,
progressive multifocal
leukoencephalopathy, primary CNS
lymphoma (due to EBV)
185. Pregnant
women with
AIDS
RX w/ reverse transcriptase inhibitor
reduces transmission to newborns to <8%
186. RX of AIDS Earlier the better
Highly active antiretroviral
therapy(HAART): principal method of
preventing immune deterioration: use when
CD4 count 350-500
187. Rx Drug classes for
AIDS
- Nuceloside reverse transcriptase
inhibitors
-protease inhibitors
-nonucleoside reverse transciptase
inhibitors
-fusion inhibitors
-co-receptor antagonists (entry
inhibitors)
-HIV integrase strand transfer
inhibitors
188. Bruton
agammaglobulinemia
XR disorder, Failure of B-cells to
become mature B Cells (mutated
Tyrosine kinase)
All Ig's decreased, Increase in
autoimmune diseases
Rx: intravenous y-globulin
189. IgA deficiency Failureof IgA B cells to mature into
plasma cells, MC primary IDD
SP infections, Increase in
autoimmune diseases, atopic
disorders
Anaphylaxis if exposed to blodd
products that contain IgA
Decrease serum IgA and secretory
IgA
190. Common variable
immunodeficiency
(CVID)
Defect in B-cell maturation to
plasma cells, Adult IDD
SP infections, GI infections,
Pneumonia, increase autoimmune
diseases, Viral infections
Decrease Serum IGs
191. DiGeorge Syndrome
(thymic hypoplasia)
Chromosome 22 deletion, failure of
3/4th pharyngeal pouch to develop,
thymus/parathyroid gland dont
develop
CF: Bacterial sepsis, Viral
infections:(CMV,EBV,varicella)
Candida, Danger of GVH reaction,
hypoparathyroidism
Increase incidence of cleft lip and
Congenital heart defects
192. Hyper-IgM syndrome XR (70% of cases) mutation in
CD40 ligand on CD4 T cells(
normally reacts with B cells to
allow Ig class switching) now cant
have B cells go from IgM--> other
Igs
CF: Recurrent pyogenic infections
(dec IgG for proper opsonization)
Pneumonia due to P.jiroveci
193. Severe combined
immunodeficiency
(SCID)
XR type MCC: mutation in IL-2
receptor on Tcells (lack y-chain)
Defective CMI: lack T cells, Decrease
Igs, no thymic shadow
Rx: bone marrow transplant (patient
that don't reject allografts)
194. Adenosine
deaminase
deficiency
AR, lack of enzyme causes an increase
in deoxyadenosine which is toxic to B
and T cells
Rx: gene therapy
195. Wiskott-Aldrich
syndrome
XR: mutation in gene for protein that
assembles actin filaments in
cytoskeleton of all hematopoietic cells:
defect in actin causes problems for cell
migration, signal transdution
Inability to elicit IgM response to
capsular bacteria
Progressive deletion of B/T cells
Symptom triad: atopic eczema,
thrombocytopenia, SP infections
Increase risk of malignancy
Defective CMI
Decrease IgM, normal IgG, Increase
IgA/IgE
Rx: bone marrow transplant essential
for survival
196. Ataxia-
telangiectasia
AR disorder, Mutation in gene that
encodes for DNA repair enzymes,
thymic hypoplasia
Cerebellar ataxia,
telangiectasia(dilated vessels) in
eyes/skin
Inc malignancy risk
(lymphoma/leukemia,
adenocarcinoma)
Inc Serum a-fetoprotein (AFP)
Defective CMI: decrease total
lymphocyte count, defective t cell funct
Deficient antibody production to
viral/bacterial antigens
Dec IgA, IGE; normal to Inc IgM; dec
T cell function
197. Complement
System
Complements synthesized in the liver,
part of innate immunity and in acute
phase reactants of inflammation
circulate as inactive protein, activated
by: IgM, IgG-antigen complex,
endotoxin. only complement cleavage
are functional
198. C3a+C5a anaphylatoxins: stimulate mast cell
release of histamine
199. C3b opsonization
200. C5a Activation of neutrophil adhesion
molecules
Neutrophil chemotaxis
201. C5b-C9 membrane attack complex (MAC)
Cell lysis
202. Complement
pathway
3 pathways: Classical, alternative and
lectin
Final common pathway to make:
Membrane attack complex(C5b-C9)
203. Complement
pathways:
Classic
Pathway
C1, C4, C2: activated by ICs that contain
antibodies bound to an antigen: Require
antibody to activate pathway
204. Classic
Pathway: C1
esterase
inhibitor
Inactivate the protease activity of C1
C1 normally cleaves C2 and C4 to produce
C4b2a complex (C3 Convertase)
205. Complement
pathways:
Alternative
pathway
Activated by LPS (endotoxin), viruses,
fungi
C3-->(lps)-->c3b+Factor B+factor D--> C3
convertase
Factor B/D and properdin
206. Complement
pathways:
Lectin
pathway
Important for destruction of microbial
pathogens
Mannose-binding protein similar to C1
complex: protein complexes with mannose-
associated serine protease
the protein attaches to mannose and other
carbs molecules on wall of GN pathogens,
fungi, viruses, protozoa
207. Complement
pathways:
DAF
Decay accelerating Factor: on all cell
membranes of hematopoietic cells and
others in cell body
enhances degradation of C3+C5 convertase
in classical/alternative pathways
208. Hereditary
Angioedema
AD with deficiency of C1 esterase inhibitor
Continued C1 activation decreases C2+C4
and increases there cleavage products
which have anaphylatoxic activity, (normal
C3)
CF: Swelling of face, oropharynx, digits
209. C2 Deficiency MC complement deficiency
Association w/ Septicemia (usually S.
pneumoniae) and SLE
210. C6-C9
deficiency
Increased suseptibility to disseminated
Neisseria gonorrhoeae or Neisseria
meningitidis infection; MC in
children/neonates
211. Paroxysmal
nocturnal
hemoglobinuria
(PNH)
Acquired stem cell disease w/ mutation in
PIG(phosphatidyl inositol glycan)
complementation group A gene in myeloid
stem cell clone = defect of anchoring
inhibitors of complements on RBC,
platelets, neutrophils (inhibitors normally
degrade C3+C5 convertase on
hematopoietic cell membranes
Complement-mediated intravascular cell
lysis of those above
212. Complement
deficiencies
Uncommon, Predisposed to infection via:
ineffective opsonization, due to lack of
C3b
Defect in cell lysis, due to lack of MAC
components
213. Complement:
Opsonization
Defects
Due to recurrent pyogenic infections due
to encapsulated bacteria
Likely to occur at early age (few months to
few years of age)
214. Complement:
Deficiencies in
Classical
Pathway
C1, C4, C2: Not do to recurrent infections
but autoimmune diseases like: SLE most
common
215. Testing the
complement
system
Total hemolytic complement assay
(CH50)
Tests the functional ability of both
complement systems
216. Testing the
complement
system:
Classical
Pathway
Activation
Decreased C4, C3
Normal factor B
217. Testing the
complement
system:
Alternative
pathway
activation
Decreased factor B, C3
Normal C4
218. Amyloidosis Fibrillar protein deposited in interstitial
tissue, resulting in organ dysfunction by
pressure atrophy of adjacent cells
219. Amyloid Composed of linear nonbranching
filaments in B-pleated sheet
Stain: Eosinophilic staining with H&E
Congo red stain: turn amyloid red and
polarizing micrscopy shows an apple
green birefringence (due to B-pleated
sheet conformation)
220. Amyloidosis: 3
Major precursor
proteins
Ig light chains with (lambda) light
chains more frequent than K light
chains
Serum amyloid A (SAA) protein:
released from liver (inflammation)
Amyloid precursor protein (APP):
gene located on Chromosome 21
221. Amyloidosis: other
precursor proteins
Transthyretin(normal carrier of
thyroxine and reinoic acid)
B2-microgobulin: light chain
component of MHC
Prion proteins: normally maintain
neuronal membranes
222. Amyloidosis:
Pathogenesis
Misfolded proteins in most cases
(normally removed)
Monocyte enzyme defects may be
responsible for SAA in serum
223. Amyloidosis:
Clinical common
presentations
Fatigue, dyspnea, edema,
paresthesias, weight loss
224. Amyloidosis: in
Kidney
Proteinuria with nephrotic
syndrome
225. Amyloidosis: in GI diarrhea-->malabsorption of carbs,
proteins, fats
Macroglossia: issues w/ speech and
swallowing
226. Amyloidosis:
Cardiac
restrictive cardiopathy (amyloids in
between myocardial fibers)
Diastolic dysfunction: LHF;
Conduction defects
227. Amyloidosis: CNS Dementia, peripheral/autonomic
neuropathy
228. Amyloidosis: Liver Hepatomegaly: pressure atrophy but
functional impairment uncommon
229. Amyloidosis: Spleen Splenomegaly,
White pulp: impregnated with
grains of sand (sago spleen)
Red pulp: waxy apperance
(lardaceous spleen)
230. Amyloidosis:
Hemodialysis
MSK involved
Carpal tunnel syndrome, destructive
arthopathy, bone cysts/Fx's
231. Amyloidosis:
Hemostasis
abnormalities
Factor X deficiency (Factor X binds
to amyloid fibrils)
Pinch purpura: skin hemorrhages
around orbit and skin
232. Amyloidosis:
Diagnose
Techniques
Serum/urine Electrophoresis: monoclonal
spikes in serum/light chains
Tissue biopsy: detect amyloid
BM aspirate
Nuclear Imaging: technetium-labeled
aprotinin; SAP scintgraphy
Doppler Echo: ventricular filling
233. Amyloidosis:
Rx
Plasma cell dycrasias: Rx to control it
Anti-tumor necrosis factor drugs involved
in Kidney
Autologous bone marrow tranplants w/
preserved organ function
Hemodialysis or renal transplantation w/
renal failure
234. Amyloidosis:
Prognosis
Poor in systemic Amyloidosis
Better control of diseases that produce
inflammation-associated types of
amyloidosis has reduced incidence of these
types of systemic ones
235. Systemic
Amyloidosis:
Immunocyte
dycrasias
Primary
Amyloidosis
Plasma Cell disorders (Ex:multiple
myeloma)
Fibril Protein: AL
236. Systemic
Amyloidosis:
Reactive
systemic
amyloidosis
Secondary
Amyloidosis
Chronic Inflammation: RA (MC),
anylosing spondylitis, IBD
(Crohns,Ulcerative colitis), tuberculosis,
leprosy, osteomyelitis, renal cell
carcinoma, Hodgkin lymphoma, heroin
abusers
Fibril Protein: AA (from SAA)
237. Systemic
Amyloidosis:
Hemodialysis-
associated
amyloidosis
Chronic Renal Failure
Fibril Protein: AB2m (from B2-
microglobulin)
238. Hereditary
Amyloidosis:
Familial
Mediterranean
Fever
AR, Increased production of IL-1: Fever,
inflammation of serosal membranes
(pleura, peritoneum, synovium)
Fibril Protein: AA (from SAA)
239. Hereditary
Amyloidosis:
Familial
amyloidotic
neuropathies
AD; peripheral and Autonomic nerve
disorders
Fibril Protein: ATTR( from transthyretin)
240. Hereditary
Amyloidosis:
Systemic senile
amyloidosis
Amyloidosis of elderly patients (70+)
Predominantly involves heart
241. Localized
Amyloidosis:
Senile Cerebral
Alzheimer Disease
Fibril Protein: AB (amyloid precursor
protein of chromosome 21)
242. Endocrine Amyloid: Medullary carcinoma of thyroid Sporadic and familial (MEN IIa, IIb)
Fibril Protein: A Cal (amyloid from calcitonin)
243. Endocrine Amyloid: Islets of Langerhans Type II diabetes mellitus
Fibril Protein: AIAPP(amyloid from islet amyloid polypeptide)