Immunopathology Flashcards
(164 cards)
1
Q
Type I Hypersensitivity Rxn
A
Immediate hypersensitivity, injury caused by TH2 cells, IgE antibodies, mast cells, & other leukocytes in response to allergen
Ex: Anaphylaxis, bronchial asthma
2
Q
Type II Hypersensitivity Rxn
A
Antibody-mediated disorders/complement activation, secreted IgG & IgM antibodies injure cells by promoting phagocytosis or lysis & injure tissues by inducing inflammation
Antibody can stimulate receptor (like TSH - Graves) or inhibit (like ACh - Myastheria gravis))
3
Q
Type III Hypersensitivity Rxn
A
Immune complex-mediated disorders, IgG & IgM antibodies bind antigens usually in the circulation, & complex deposit in tissues and induce inflammation
4
Q
Type IV Hypersensitivity Rxn
A
Cell-mediated immune disorders, sensitized T lymphocytes (TH1 & TH17 cells and CTLs) cause tissue injury
5
Q
Type III Hypersensitivity Rxn
A
Immune complex-mediated disorders, IgG & IgM antibodies bind antigens usually in the circulation, & complex deposit in tissues and induce inflammation (ex: lupus)
6
Q
Type IV Hypersensitivity Rxn
A
Cell-mediated immune disorders, sensitized T lymphocytes (TH1 & TH17 cells and CTLs) cause tissue injury
(Ex: Rheumatoid arthritis)
7
Q
Th1 activates ____; Th17 activates ____; cytokines secreted by _____
A
IFN-gamma; IL 17, 22; CD4 T cell activated by class II MHC
8
Q
CD8 T cell activated by class I MHC causes tissue damage through
A
Direct cytotoxic T cell tissue damage
9
Q
Autograft
A
your own tissues
10
Q
Isograft
A
identical twin, same genetic background
11
Q
Allograft
A
same species, different genetic background
12
Q
Xenograft
A
different species
13
Q
Transplant rejection
A
Immune damage resulting from recipient response to allograft HLA antigens
Type IV hypersensitivity rxn
14
Q
Direct pathway of transplant rejection
A
Antigen presenting cells in graft (donor antigen presenting cell) present to CD8 & CD4 T-cells
15
Q
Indirect pathway of transplant rejection
A
Own self cells get a hold of one of allogenic peptides & present to immune system
16
Q
Humoral mechanism of transplant rejection
A
Ab bind to HLA (self) molecules in graft & activate complement
Causes acute inflammation & Type II hypersensitivity
Ag-Ab complexes form in circulation & cause Type III hypersensitivity - necrotizing, immune complex vasculitis
17
Q
Hyperacute rejection
A
Happens minutes to hours after transplantation Preformed Ab (from prior transplant, transfusion, etc.) react against Ag in allograft
18
Q
Hyperacute rejection causes
A
Type III hypersensitivity (immune complex formation)
Vasculitis w/ fibrinoid necrosis, thrombosis, ischemia
19
Q
Acute cellular rejection
A
Rapid progression after initiation
Occurs days to months after transplant
20
Q
Acute cellular rejection causes
A
Tubular damage & endothelitis
Extensive interstitial inflammation
Lymphocytic infiltrates & tubular necrosis
21
Q
Acute humoral rejection
A
Necrotizing vasculitis Intimal thickening (valve smaller) due to accumulation of fibroblasts, foamy macrophages, myocytes, smooth muscle proliferation
22
Q
Chronic rejection
A
Months to years after transplant
Humoral injury - proliferative vascular lesions
Cellular injury - cytokine induced proliferation of vascular smooth muscle & production of collagen in ECM
23
Q
Chronic rejection causes
A
Vascular changes, interstitial fibrosis, tubular atrophy, chronic inflammation
24
Q
Chronic rejection causes
A
Vascular changes, interstitial fibrosis, tubular atrophy (flat epithelium), chronic inflammation
25
Acute liver rejection
Mixed inflammatory cell infiltrates w/ eosinophils
26
Acute liver rejection triad of features
Portal tract inflammation
Bile duct epithelial damage
Endothelitis of portal vein & hepatic artery branches
27
Chronic liver rejection
Progressive disappearance of bile ducts due to direct immunologic destruction or loss of blood supply
Obliterative arteritis from proliferation of intimal layer
Results in portal & hepatic fibrosis
28
Graft arteriopathy
Intimal thickening occurs in long lengths of donor vessels
| Areas of vessels to narrow
29
Cyclosporine
Block nuclear factor of activated T cells (NFAT) necessary for IL-2 stimulation of T cells
30
Steroids
Suppress macrophage activity & inflammation
31
Azathioprine
Inhibits DNA synthesis of lymphocytes
32
Hematopoietic cell transplant
Stem cells harvested from donor bone marrow
33
Complications of hematopoietic cell transplant
Graft vs. host disease, infection, immunodeficiency
34
Graft vs Host Disease (GVHD)
Cell mediated rxn
Donor T cells recognize Host HLA antigens as foreign & mount Type IV reaction against graft elements and tissues
Destroy recipient cells (skin, GIT, liver, lungs)
35
Acute GVHD
days to weeks
Donor cytotoxic T cells or cytokines (from helper T cells) destroy epithelial cells
Skin: rash, exfoliation
GIT: ulcerative gastroenteritis
Hepatic: bile duct necrosis
Immunosuppression - more likely to get infection
36
Exfoliation
skin starts to peel off
37
Chronic GVHD
May follow acute or appear without acute phase
Autoreactive T cells derived from donor stem cells
Mimics systemic scerosis - generalized fibrosis of dermis & skin appendages, GI mucosa (strictures), bile ducts (jaundice)
38
Autoimmune disease criteria
Immunological reaction to a self-Ag or native tissue
Reaction primary to pathogenesis, not secondary to tissue damage
No other well-defined cause (exclude other diseases)
39
Autoimmune disease mechanism
Failure of tolerance/immune regulation (failure of T cell anergy, apoptosis of self-reactive cells, or regulatory CD4 T cell; molecular mimicry, polyclonal lymphocyte activation, exposure of cryptic antigenic determinants, emergence of sequestered Ag)
40
Hyper- or hypothyroidism self antigen
TSH receptor
41
Hyper or Hypoglycemia self antigen
Insulin receptor
42
Myasthenia gravis self antigen
Acetylcholine receptor
43
Blistering skin diseases self antigen
Epidermal cell adhesion molecules
44
Systemic lupus erythematosus (SLE) self antigen
Double-stranded DNA
| Histones
45
Diffuse scleroderma self antigen
Topoisomerase I
46
Limited scleroderma self antigen
Centromere proteins
47
Thyroiditis self antigen
Thyroid peroxidase
48
Systemic Lupus Erythematosus
Multisystem disorder
Clinically acute w/ flares & remissions, often febrile
Affects more females than males (9:1) & more black females
Usually starts between 20 & 40
49
SLE diagnostic criteria
Malar rash, Discoid rash, photosensitivity (UV light causes rash), painless oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, antinuclear antibodies
50
Malar rash
fixed erythema, butterfly rash, flat or raised
| Spares nasolabial folds usually
51
Discoid rash
erythematous raised patches with adherent keratotic scaling & follicular plugging; scarring may occur
52
SLE gene locus
HLA-DQ locus
| Creates B & T cells specific for self nuclear antigens
53
SLE environmental triggers
UV radiation, viruses, drugs, hormones
| Results in defective clearance of apoptotic bodies & increased burden of nuclear antigens
54
SLE pathogenesis
Antinuclear antibody complexes with self nuclear antigens
TLR stimulation of B cells & dendritic cells to complex - release IFN for further stimulation
High level of anti-nuclear IgG antibody production
55
SLE most common clinical manifestations
Hematologic (anemia or leukopenia, lymphopenia, thrombocytopenia; every pt), arthritis, skin rashes, fever, fatigue, weight loss, renal (proteinuria)
56
Hallmark of Lupus
Autoantibodies - antinuclear antibodies (ANAs)
| directed against nuclear Ag (DNA, histones, proteins bound to RNA, & nucleolar Ag)
57
ANA testing
Uses human tissue cell culture nuclei (Hep-2) as substrate
ANAs in serum bind substrate & fluorescent anti-IgG bind Ab
Can visualize amount & pattern of nuclei/Ab
58
Peripheral (rim) ANA staining pattern
Ab to ds-DNA
| Seen w/ lupus
59
Homogeneous (diffuse) ANA staining pattern
Ab to chromatin, ds-DNA, histones
| Seen w/ lupus & rheumatoid arthritis
60
Speckled ANA staining pattern
Ab to histones, ribonucleoproteins
| Seen w/ lupus, Sjogren syndrome, Systemic Scleroderma
61
Nucleolar ANA staining
Ab to nucleolar RNA
| Seen w/ lupus & scleroderma
62
SLE common antibody system
```
Native DNA (anti-ds-DNA), Histones (antihistone)
Less common - Anti-Sm, nuclear RNP, SS-A(Ro), SS-B(La)
```
63
Drug-Induced LE common antibody system
Antihistone
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Systemic Sclerosis - diffuse common antibody system
DNA topoisomerase I (Scl-70), Nuclear RNP
65
Limited Scleroderma - CREST common antibody system
Centromeric proteins (anticentromere)
66
Sjogren Syndrome common antibody system
RNP - ribonucleoprotein (SS-A(Ro) & SS-B(La))
67
Homogeneous (diffuse) ANA staining pattern
Ab to chromatin, ds-DNA, histones
| Seen w/ drug induced lupus & rheumatoid arthritis
68
Speckled ANA staining pattern
Ab to histones, ribonucleoproteins - least specific
| Seen w/ lupus, Sjogren syndrome, Systemic Scleroderma
69
Nucleolar ANA staining
Ab to nucleolar RNA
| Seen w/ lupus & systemic sclerosis - CREST
70
SLE common antibody system
```
Native DNA (anti-ds-DNA), Histones (antihistone)
Less common - Anti-Smith Ab, nuclear RNP
```
71
Drug-Induced SLE or RA common antibody system
Antihistone
72
Centromere ANA staining pattern
Ab to centromere
| Systemic sclerosis - CREST
73
SLE most common clinical manifestations
Hematologic (anemia or leukopenia, lymphopenia, thrombocytopenia; every pt), arthritis (hands, knees, ankles; painful inflammation w/o deformity), skin rashes, fever, fatigue, weight loss, renal (proteinuria)
74
SLE common antibody system
```
Native DNA (anti-ds-DNA), Histones (antihistone)
Less common - Anti-Smith Ab (ribonucleoprotein), nuclear RNP
```
75
Lupus vascular changes
Circulating immune complexes deposit in vascular beds, activate complement & cause inflammatory (Type III) rxn
Acute: vasculitis w/ fibrinoid necrosis of arteries/arterioles in any tissue
Chronic: layered fibrous thickening (collagen onion skin)
76
Lupus nephritis
Immune complex glomerulonephritis
Major cause of death in lupus pts
Immune complex deposition in glomeruli, basement membranes, larger blood vessels
Causes tubulointerstitial changes, thickening of capillary loops, proteinuria
77
Lupus serositis
Effusions usually involve pleura & pericardium
Acute: exudation of fibrin
Chronic: proliferation of fibrous tissue, thickened membranes, adhesions
78
Lupus effects on the heart
Frequent pericarditis, occasional myocarditis
Usually get nonbacterial endocarditis affecting any valve - appears on both sides of valve (typically AV valves)
Accelerated CAD d/t steroid therapy or immune damage
Common cause of death in lupus pts along with kidney damage
79
Lupus effects on the heart
Frequent pericarditis, occasional myocarditis
Usually get nonbacterial endocarditis affecting any valve - appears on both sides of valve (typically AV valves, called Libman-Sacks endocarditis)
Accelerated CAD d/t steroid therapy or immune damage
Common cause of death in lupus pts along with kidney damage
80
Lupus effects on lungs
Pleuritis
Acute: pneumonitis w/ alveolar damage, edema, hemorrhage
Chronic: interstitial & vascular fibrosis, pulmonary fibrosis & pulmonary hypertension
81
Lupus effects on the heart
Frequent pericarditis, occasional myocarditis
Usually get nonbacterial endocarditis affecting any valve - appears on both sides of valve (typically AV valves, called Libman-Sacks endocarditis)
Accelerated CAD d/t steroid therapy or immune damage
Common cause of death in lupus pts along with kidney damage
82
Lupus effects on CNS
involvement common
Focal neurologic defects, seizures, neuropsychiatric symptoms
Small vessel thickening, ischemia, microinfarcts
83
Cause of death with lupus (typically)
Renal failure, infection, CAD
84
Severity of lupus symptoms range from
mild dermatologic & joint symptoms to life threatening organ failure & cytopenias
Higher titers, more likely to have worse symptoms
85
Chronic discoid Lupus
Variety of skin lesions (plaques, erythema, scaling, atrophy) without systemic features
5-10% of cases develop into systemic lupus
86
Subacute cutaneous lupus
Diffuse, superficial, nonscarring, photosensitive lesions; mild systemic disease; some consider it an intermediate phase before full systemic lupus
87
Drug Induced Lupus
Lupus like syndrome with multiple organ involvement
Rash, fever, arthralgias, serositis; no renal or CNS pathology
Positive ANAs
Drug cessation can cause remission
88
Drug Induced Lupus
Lupus like syndrome with multiple organ involvement
Rash, fever, arthralgias, serositis; no renal or CNS pathology
Positive ANAs
Can be caused by drugs used to treat TB
Drug cessation can cause remission
89
Sjogren's Syndrome
Systemic disease, less severe than lupus
Autoimmune destruction of exocrine glands, primarily lacrimal & salivary glands
Mostly affects females in middle age
90
Sjogren's Syndrome pathogenesis
CD4 T cells against glandular epithelial self-Ag initiate disorder
Could be induced by viral infections
Systemic B cell hyperactivity
91
Sjogren's Syndrome pathogenesis
CD4 T cells against glandular epithelial self-Ag initiate disorder
Could be induced by viral infections
Systemic B cell hyperactivity lead to ANAs (auto-antibodies)
ANAs to ribonucleoproteins SS-A & SS-B
92
Sjogren's Syndrome morphology
T cell, B cell, plasma cells infiltrate ducts & vessels in glands
Follicle formation w/ germinal centers
Ductal epithelial hyperplasia causes obstruction
Acinar atrophy, fibrosis, fat replacement of parenchyma
93
Sjogren's Syndrome clinical course
Drying of mucous membranes leads to xerostomia, keratocunjunctivitis, nasal septal erosion, and perforation, dysphagia, dypareunia
Lymph nodes massively hyperplastic
Increased risk of B cell lymphoma
Systemic vasculitis w/ kidney (nephritis), lungs (pulmonary fibrosis), skin, CNS (peripheral neuropathy), & muscle occur 25% of time (associated SS-A Ab)
94
Systemic Sclerosis
```
Autoimmune disorder
Chronic inflammation, destruction of small vessels, & progressive tissue fibrosis
Rigidity, loss of specialized cells & function in skin & connective tissue
Mostly female (3:1) & 50-60 yr
```
95
Systemic Sclerosis most common cause of death
GIT, kidneys, heart, lungs, musculoskeletal system
96
Systemic Sclerosis pathology
Trigger/External stimuli causes endothelial cell injury & Immune response
Injury to blood vessel walls causes narrowing & thickening leading to ischemia/repair
Activation of immune response (T & B cells) causes release of autoantibodies & pro-fibrotic cytokines (TFG-B esp. & PDGF, IL-1, 13) - activate fibroblasts
Fibroblasts increase ECM protein synthesis & cause Fibrosis in skin & parenchymal organs
Result = Fibrosis & autoantibodies
97
What key cytokine leads to fibrosis in Systemic Sclerosis
TFG beta
98
Limited Sclerosis (CREST syndrome)
Limited skin involvement of face, forearms, & fingers
Late visceral involvement (relatively benign)
Anti-centromere Ab
99
CREST stands for:
C: calcinosis (calcium in skin)
R: Raynaud's phenomenon
E: esophageal dysfunction (acid reflux & decrease in motility)
S: sclerodactyly (thickening & tightening of skin on fingers/hands)
T: telangiectasias (dilation of capillaries - red marks on skin)
100
Raynaud's phenomenon
Spasm of blood vessels in response to cold or stress - tips of fingers pale
Can result in gangrenous necrosis (blackened fingertips, edema, dusky color)
CREST sclerosis symptom
101
Diffuse Sclerosis
Widespread skin involvement at onset
Early visceral involvement - multiple organ systems
Rapid progression - more severe
Ab to DNA topoisomerase I (anti-Scl-70)
102
Diffuse Sclerosis skin changes
Early: edema, lymphocyte infiltrates
Late: epidermal thinning, dermal/appendage fibrosis, subcutaneous calcifications, contractures (claw fingers, mask facies)
Vascular endothelial damage & fibrosis causes ischemia
103
Diffuse Sclerosis
Widespread skin involvement at onset
Early visceral involvement - multiple organ systems (GI, Renal, Lungs, heart, muscle - fibrosis & narrowing)
Rapid progression - more severe
Ab to DNA topoisomerase I (anti-Scl-70)
104
Systemic Sclerosis skin changes
Early: edema, lymphocyte infiltrates
Late: epidermal thinning, dermal/appendage fibrosis, subcutaneous calcifications, contractures (claw fingers, mask facies)
Vascular endothelial damage & fibrosis causes ischemia
105
Systemic Sclerosis GI changes
Esophagus - collagenization & fibrosis (dysmotility & reflux)
Small bowel - mucosal thinning, loss of villi/microvilli, fibrosis (malabsorption)
106
Systemic Sclerosis renal changes
2/3 of cases
Thickening of interlobular arteries, proliferation of intimal cells, collagen deposition, hyaline change
May cause hypertension
107
Systemic Sclerosis cause of death
Progressive, survival rate depends on severity (organs involved)
Renal, cardiac (restrictive cardiomyopathy), pulmonary (respiratory insufficiency & pulmonary hypertension), GI (reflux) dysfunction or failure
108
Rheumatoid arthritis
Systemic, autoimmune inflammatory disorder
Joints, skin, vessels, heart, lungs, soft tissue - very painful & deforming
More likely in women (3-5:1), any age (esp 40-70)
109
RA pathogenesis
unknown trigger
host susceptibility genes HLA-DRB1, PTPN22 (tyrosine phosphatase)
Enzymatic modification of self protein & failure of tolerance = T & B cell responses to self antigens
Production of rheumatoid factor (IgM auto-Ab to Fc portion of IgG) - complex deposition & joint injury
Cause Pannus formation; destruction of bone, cartilage; fibrosis; ankylosis
110
Citrullinated peptides (CCP)
Anti-CCP or T cell response to CCP contribute to chronic RA
111
RA morphology
Destructive joint inflammation
Edema, synovial cell hyperplasia, stromal & perivascular infiltrates
Fibrin deposition on synovial surface & exudation into joint space - loss of joint spaces
Pannus formation
Articular cartilage erosion, osteoclastic destruction of subchondral bone (causing ankylosis)
112
Pannus formation
granulation tissue, synovial & inflammatory cells, fibrous CT
Present in RA
113
Rheumatoid nodules
Skin at pressure points (elbow, occiput, lumbosacrum) & viscera (lungs, spleen, heart) develop nodules in 25% cases
Necrotic tissue, palisading macrophages, & fibrosis make up nodule
114
RA clinical course
Mild discomfort to progressive disability
| Malaise, fatigue, pain, swelling, stiffness, deformity in small & large joints
115
COD in RA
disease complications of amyloidosis & vasculitis
| Drug therapy complications of bleeding & infection
116
Juvenile Idiopathic Arthritis
117
Still's disease variant
Form of Juvenile idiopathic arthritis
| Febrile illness with hepatosplenomegaly, rash, & high WBC count
118
Mixed Connective Tissue Disease (MCTD)
Clinical syndrome w/ overlapping features of SLE & Systemic Sclerosis
Ab to ribonucleoprotein
Minimal renal disease & good response to steroid therapy
May evolve into classic SLE or SS
119
Immunodeficiency disorder clinically manifest as
infection (frequent, severe, resistant)
120
Primary Immunodeficiencies
Genetically determined defects of B & T lymphocytes
6 mo - 2 yrs
Repeated infection
Failure to thrive
121
X-Linked Agammaglobulinemia of Bruton
Mutation in tyrosine kinase gene (BTK gene) required to mature B cells from pre-B cell into immature B cell
Causes absence of mature B cells & no antibody production (agammaglobulinemia)
X-linked recessive (seen in males)
122
Infections usually seen w/ X-Linked Agammaglobulinemia of Bruton
Recurrent sinus, oropharyngeal, & respiratory inf.
D/t Staph, Strep, & H. influenza (all usually opsonized by Ab to be cleared by phagocytosis), enteric viruses & protozoa
123
Tx of X-Linked Agammaglobulinemia of Bruton
Parenteral immunoglobulin replacement for life
124
Common Variable Immunodeficiency
Hypogammaglobulinemia (usually all Ab classes, but sometimes only IgG)
Occurs 20-30 yr old
Intrinsic B cell defect (in differentiation) or Abnormal T cell signaling to B cells (increased suppressor of decreased helper)
Results in inability of B cells to become plasma cells
125
Infection caused by common variable immunodeficiency
Recurrent bacterial infections of sinuses & respiratory tract
Lack of IgA (increased enteroviral infections & protozoa)
126
Selective IgA deficiency
Most common, mild
Familial or acquired w/ measles
Serum IgA absent or low because IgA + B cells fail to mature
Other immunoglobulin types normal & cellular immunity intact
127
Infection caused by selective IgA deficiency
GI, respiratory, GU infections (secretion related)
| Increased risk to develop AI disorders & anti-IgA Ab
128
Hyper IgM syndrome
Failure of T cells (CD40 ligand) to induce B cell isotype switching from IgM to IgG, IgA, & IgE & to activate macrophages to remove intracellular microbes
IgM normal or up & all other isotypes absent
129
Infection by Hyper IgM syndrome
```
Recurrent pyogenic (lack of opsoniziation)
Intracellular organisms (lack of phagocytic activation)
Autoimmune lysis (IgM rxn against blood cells)
GIT lymphoid hyperplastic accumulations of IgM B cells
```
130
DiGeorge Syndrome
Interruption of 3rd & 4th pharyngeal pouch development causes aplasia or hypoplasia of thymus & parathyroids
T cell defect (as well as hypocalcemia, cardiac abnormalities, & defects of face (cleft palate) & aortic arch)
Chromosome 22q11 deletion common
Normal Ig levels
131
DiGeorge Syndrome
Interruption of 3rd & 4th pharyngeal pouch development causes aplasia or hypoplasia of thymus & parathyroids
T cell defect (as well as hypocalcemia, cardiac abnormalities (VSD) , & defects of face (cleft palate) & aortic arch)
Chromosome 22q11 deletion common
Normal Ig levels - infection of virus & fungi
132
Severe Combined Immunodeficiency (SCID)
Deficient cellular & humoral immune responses
| Combined T & B form rare, often just severe T cell defect
133
X-linked pattern of SCID
Mutation of common gamma-chain subunit of cytokine receptors
| Affects interleukins causing impaired lymphocyte development, proliferation, & function
134
Autosomal recessive pattern of SCID
```
Adenosine deaminase deficiency causes lympotoxic metabolites (deoxyadenosine, deoxy-ATP)
Failure of class II MHC expression leads to impaired T cell recognition of Ag
```
135
SCID symptoms
Early onset - thrush, diaper rash, failure to thrive
Recurrent infections from all microbes (bacteria, virus, fungi, protozoa)
Requires bone marrow transplantation
136
Wiskott-Aldrich Syndrome
Immunodeficiency, thrombocytopenia, & eczema (scaly red rash)
Genetic defect - progressive depletion of T & B cells
Ab levels normal or elevated, IgM is low
Poor or lack of Ab response to protein Ag, & polysaccharide Ag
X linked male
137
Wiskott-Aldrich syndrome symptoms
Hemorrhagic diathesis
Recurrent respiratory infections
Pyogenic bacteria, viruses, fungi
Early death (w/o bone marrow transplant)
138
Secondary Immunodeficiencies
Immune impairment in previously healthy person
Caused by diseases & physiologic states
Potentially reversible
139
AIDS occurs due to
HIV-1 retroviral infection
140
HIV enters cell by using
gp120 to bind to CD4 & gp41 to penetrate membrane
141
HIV destroys CD4 T cells through
1. Viral replication in infected T cell = death (cytopathic effect of virus)
2. Activation of uninfected T cells = activation-induced apoptosis
3. Expression of HIV peptides on infected T cell = killing of infected cells by virus-specific CTLs
142
HIV causes
CD4: Decreased response to antigens & decreased lymphokine secretion
CD8: decreased specific cytotoxicity
NK: decreased killing of tumor cells
B: depressed Ig production in response to new antigens (however have B cell activation with high Ig)
Macrophage: decreased cytotoxic ability, decreased chemotaxis, decreased IL-1 secretion & Ag presentation
143
Early acute phase of AIDS
Viral replication, viremia, viral seeding of lymphoid tissues
Fever, sore throat, myalgias
144
Middle, chronic phase of AIDS
Replication in lymphoid tissue persistant
| Lymphadenopathy, weight loss, night sweats, fatigue, fever, rash
145
Final, crisis phase of AIDS
Marked viral replication
Depletion of T cells = profound immune suppression
Fever, fatigue, weight loss, opportunistic diseases, neoplasms
146
AIDS defining neoplasms
Kaposi's sarcoma, B cell lymphomas, primary lymphoma of brain, invasive carcinoma of uterine cervix & anus
147
AIDS neoplasms can occur though
1. Increase in follicular T cell signal B cell hyperplasia (& thus hypermutation) - leads to B cell lymphomas
2. T cell depletion leads to unchecked infections (like EBV & KSHV) causing virus associated B cell lymphomas
148
Pneumocytis pneumonia
Complication of AIDS
Alveoli fill w/ foamy exudate, thickened interstitium
Bronchoalveolar lavage - coffee bean like w/ silver stain
149
Kaposi's Sarcoma
Associated w/ AIDS & immunosuppressed
Caused by KSHV (Kaposi sarcoma-associated herpes virus) due to herpes type 8 (HHV8)
Painful purple nodules on skin - often of hands or feet
Highly vascular
150
Fusion/entry inhibitors
Block co-receptors CXCR4 & CCR5 that bind to HIV to let it into cell
151
Reverse transcriptase inhibitors
```
First class of HIV drugs
Prevents reverse transcriptase of RNA into DNA
```
152
Integrase inhibitors
Prevents HIV DNA from being integrated into host DNA
153
Protease inhibitors
Blocks viral maturation by not allowing viral protease to activate viral proteins
154
Amyloidosis
Group of disorders - extracellular deposition & accumulation of abnormal, misfolded protein material (amyloids)
Cannot be degraded
Can occur systemically or in one organ/tissue
155
Amyloid stained w/
Starch-like staining rxn w/ iodine
| Seen with Congo red & green fluorescence under polarized light
156
Amyloid protein fibrils
95%
Fold into beta-pleated sheet
Binding sites for Congo red
157
Pentagonal component of amyloid
5%
| Glyco-protein related to normal serum protein from which it is derived
158
Amyloid derived from
conversion of soluble circulating protein precursors into insoluble fibrillar forms
159
Amyloid Light chain (AL)
Ig light chains derived from abnormal clones of B cells
Commonly primary (some secondarly to multiple myeloma)
Tends to involve heart, GIT, PNS, skin, & tongue
160
Amyloid associated (AA)
Secondary or reactive (after inflammatory or infectious states)
Fibrils related to non-immunoglobulin AA protein & serum precursor (SAA) - from hepatic cells stimulated by IL-1/6
Occurs w/ RA, IBD, drug abuse, renal cell CA, Hodgkin's lymphoma
Tend to involve kidneys, liver, spleen, lymph nodes, adrenals
161
ATTR amyloid
Mutant form of transthyretin (transports thyroxin & retinol) in PNS
Polyneuropathy
162
Beta amyloid protein
Deposited in cerebral blood vessels & plaques of pts w/ senile cerebral amyloidosis & Alzheimer's disease
Severe atrophy of cerebral cortex
163
Cardiac amyloid
Builds up between myofibers (subendocardial, interstitial)
| Causes stiffness of ventricles
164
Renal amyloid
In glomeruli, interstitial, vascular
| Kidneys pale & enlarged w/ smooth surface
