Inflammation - Mechanisms of Disease - Cytokines; Hypersensitivity Reactions; Lab Diagnosis; Intro to Immune Disease Flashcards
(203 cards)
1
Q
Are most inflammatory cytokines long- or short-lived mediators?
Can they often _______ other mediators.
A
Short-lived;
activate
2
Q
What are the two preliminary molecules to be released during inflammation?
A
Histamine, serotonin
(vasoactive amines)
3
Q
What cell is the main mediator of histamine/serotonin release?
A
Mast cells
4
Q
What endothelial receptor does histamine bind?
What are the effects?
A
H1;
arteriolar dilation,
increased venule permeability,
some smooth muscle contraction
5
Q
Serotonin (5-HT) functions mainly as a _______________.
It is a neurotransmitter in the _______ _______ (in contrast to its role in the brain).
A
Vasoconstrictor;
GI tract
6
Q
Which arachidonic metabolites mediate vasodilation?
A
PGI2, PGE1, PGE2, and PGD2
7
Q
Which arachidonic metabolites mediate vasoconstriction?
A
Thromboxane A2, leukotrienes C4, D4, and E4
8
Q
Which arachidonic metabolites mediate vascular permeability?
A
Leukotrienes C4, D4, and E4
9
Q
Which arachidonic metabolites mediate leukocyte chemotaxis and adhesion?
A
Leukotriene B4;
HETE
10
Q
Arachidonic acid is derived from ________ acid.
A
Linoleic
11
Q
What type of receptor do arachidonic acid metabolites bind?
A
GPCRs
12
Q
What is the role of COX-1?
What is the role of COX-2?
A
Expressed in most tissues — homeostatic function;
inflammation
13
Q
What two arachidonic acid metabolites act to balance one another out?
A
PGI2 — TXA2
(vasodilation, anti-platelet agreggation — vasoconstriction, pro-platelet aggregation)
14
Q
PGD2 is produced by _____ cells and causes vaso________ and ________ vessel permeability.
It is a ___________ chemoattractant.
A
Mast,
-dilation,
increased;
neutrophil
15
Q
PGE2 causes vaso________ and is _______algesic.
It can cause cytokine-induced ______.
A
-Dilation, hyper;
fever
16
Q
5-HETE is a ___________ chemoattractant.
A
Neutrophil
17
Q
What are the main products derived from prostaglandin H2?
A
Prostaglandins (PGI2, PGD2, PGE2);
TXA2
18
Q
What are the main products derived from the action of 5-lipoxygenase?
A
5-HETE;
leukotrienes (B4, C4, D4, E4);
lipoxins (A4, B4)
19
Q
What lipoxygenase products inhibit neutrophil adhesion and chemotaxis?
A
Lipoxin A4,
lipoxin B4
20
Q
What cytokines promote neutrophil chemotaxis?
A
Leukotriene B4;
5-HETE;
IL-8;
C3a;
C5a
21
Q
What effects do leukotrienes C4, D4, and E4 have?
A
Vasoconstriction;
bronchoconstriction;
venule permeability
22
Q
What arachidonic acid metabolites are anti-inflammatory?
A
Lipoxins
23
Q
What drug blocks lipoxygenase?
What drugs block leukotriene receptors?
A
Zileuton;
montelukast, zafirlukast
24
Q
What cell types produce TNF and IL-1?
A
Macrophages;
dendritic cells
25
What effect(s) does TNF have on metabolism?
And appetite?
Increased lipid and protein mobilization;
suppressed
26
\_\_\_\_\_\_\_\_\_\_ chemokines maintain tissue architecture.
Homeostatic
27
C5a activates the __________ pathway of arachidonic acid metabolism.
Lipoxygenase
28
Which arachidonic acid metabolites counteract the inflammatory effects of leukotrienes?
Lipoxins
29
Which arachidonic acid metabolite counteracts the inflammatory effects of thromboxane A2?
PGI2
30
Anti-leukotriene medications (zileuton, montelukast, zafirlukast) are able to relieve the effects of asthma by reducing what leukotriene-mediated process?
Bronchospasm
31
Name the produced local inflammatory effect of TNF and IL-1 action on each of the following:
**Endothelium**
**Leukocytes**
Endothelium - increased **permeability** and **leukocyte** **adhesion**
Leukocytes - **activation**
32
Name the produced systemic protective effects of TNF, IL-1, and IL-6 action on each of the following:
**Brain**
**Liver**
**Bone marrow**
Brain - **fever**
Liver - increased **acute phase proteins**
Bone marrow - **leukocyte production**
33
What pathological effect does TNF have on the heart?
What pathological effect does TNF have on endothelial cells?
What pathological effect does IL-1 have on skeletal muscle and adipose?
**Low cardiac output**;
**hypercoagulability** and increased **permeability**;
**insulin resistance**
34
TNF blockers increase patient susceptibility to \_\_\_\_\_bacterial infections.
TNF blockers increase patient susceptibility to **myco**bacterial infections.
35
What is the main inhibitory factor of the complement cascade?
**C1 inhibitor**
| (C1 INH)
36
Hereditary angioedema is an inherited deficiency of what?
C1 inhibitor
37
Delay accelerating factor prevents the formation of what complement structure?
CD59 prevents the formation of what complement structure?
**C3 convertase** (C4b/C2b);
the **MAC**
38
What disorder is here described:
## Footnote
*a deficiency in delay accelerating factor and/or CD59 leads to increased complement-mediated hemolysis, particularly at night.*
Paroxysmal nocturnal hematuria
39
Why does the hemolysis of paroxysmal nocturnal hematuria occur at night?
Hypoxic stress
| (increased while sleeping)
40
Which are the clotting factors dependent on vitamin K?
II, VII, IX, and X;
proteins C and S
41
**True/False**.
Calcium binds the γ-carboxylated aspartic acid residues on clotting factors II, VII, IX, and X.
**False**.
Calcium binds the γ-carboxylated ***glutamic*** acid residues on clotting factors II, VII, IX, and X.
42
Which clotting factors are specific to the intrinsic pathway?
Which clotting factors are specific to the extrinsic pathway?
Which clotting factors are specific to the common pathway?
XII, XI, IX, V;
VII, TF;
X, V, prothrombin, fibrinogen
43
Which clotting test assesses the functioning of the intrinsic pathway?
Which clotting test assesses the functioning of the extrinsic pathway?
**PTT** *(**XII**, **XI**, **IX** --\> X, V, II, fibrinogen)*;
**PT** *(**VII** --\> X, V, II, fibrinogen)*
44
**True/False**.
Factor XII (Hageman factor) can be activated by collagen, basement membranes, and activated platelets.
**True**.
Factor XII (Hageman factor) can be activated by collagen, basement membranes, and activated platelets.
45
Describe the common pathway of the coagulation cascade.
X+ V --\>
cleave prothrombin to **thrombin** --\>
cleaves fibrinogen to **fibrin**
46
What protein activates plasminogen to plasmin?
What serum protein is released by the liver to bind (and reduce the activity of) activated plasmin?
Tissue plasminogen activator (TPA);
α2-antiplasmin
47
Clotting factor ____ activates kallikrein (thus activating the bradykinin cascade).
Clotting factor **VIIa** activates kallikrein (thus activating the bradykinin cascade).
48
**True/False**.
Different infectious agents can cause different types of inflammation (e.g. acute vs. reactive; purulent vs. granulomatous vs. necrosis vs. scarring; etc.).
**True**.
Different infectious agents can cause different types of inflammation (e.g. acute vs. reactive; purulent vs. granulomatous vs. necrosis; etc.).
49
Many purulent (suppurative) infections are caused by gram-\_\_\_\_\_\_\_\_ cocci and gram-\_\_\_\_\_\_\_\_ bacilli (rods).
Many purulent (suppurative) infections are caused by gram-**positive** cocci and gram-**negative** bacilli (rods).
50
**True/False**.
Purulent (suppurative) inflammation due to infectious causes typically rises due to chronic bacterial infections.
**False**.
Purulent (suppurative) inflammation due to infectious causes typically rises due to ***acute*** bacterial infections.
51
Staphylococcal and streptococcal infections are causes of ____________ inflammation (acute).
TB and syphilis infections are causes of ____________ inflammation (chronic).
Staphylococcal and streptococcal infections are causes of **suppurative** (**purulent**) inflammation.
TB and syphilis infections are causes of **granulomatous** (**mononuclear**) inflammation.
52
*Mycobacterium tuberculosis* stain with acid-fast due to the presence of _______ \_\_\_\_\_\_ in their cell walls (as opposed to LPS).
*Mycobacterium tuberculosis* stain with acid-fast due to the presence of **mycolic acids** in their cell walls (as opposed to LPS).
53
Most cytopathic/cytoproliferative inflammatory reactions are caused by _______ infections.
Most cytopathic/cytoproliferative inflammatory reactions are caused by **viral** infections (e.g. HHSV, HPV, CMV).
54
Which of the four hypersensitivity reactions are antibody-mediated?
**I, II, III**
(IV is mediated by T cells)
55
Which antibody class mediates type I hypersensitivity reactions?
IgE
56
Which antibody classes mediate type II hypersensitivity reactions?
IgG, IgM
57
Which antibody classes mediate type III hypersensitivity reactions?
IgG, IgM, IgA
58
What cell type mediates type IV hypersensitivity reactions?
T cells
59
Type I hypersensitivity reactions are basically just errant _____ \_\_\_\_\_ degranulations due to ____ receptor cross-linking.
This is the cause of **anaphylactic** reactions.
Type I hypersensitivity reactions are basically just errant **mast cell** degranulations due to **IgE** receptor cross-linking.
This is the cause of **anaphylactic** reactions.
60
Type __ hypersensitivity reactions are basically just errant **mast** **cell** degranulations due to IgE receptor cross-linking.
This is the cause of ___________ reactions.
Type **I** hypersensitivity reactions are basically just errant **mast** **cell** degranulations due to IgE receptor cross-linking.
This is the cause of **anaphylactic** reactions.
61
Type ___ hypersensitivity reactions are basically just errant antibody-self interactions (can be cytotoxic or altering to normal cell physiology).
Type **II** hypersensitivity reactions are basically just errant antibody-self interactions (can be cytotoxic or altering to normal cell physiology).
62
Type **III** hypersensitivity reactions are mediated by \_\_\_\_\_\_\_\_-\_\_\_\_\_\_\_ immune complexes.
Type **III** hypersensitivity reactions are mediated by **antibody**-**antigen** immune complexes.
63
Which two hypersensitivity reactions can be mediated via complement?
HSR **II** and HSR **III**
64
Which cell type mediates the ***first*** phase (immediate) of type I hypersensitivity (allergies)?
Which cell type mediates the ***second*** phase (after four hours) of type I hypersensitivity (allergies)?
Mast cells;
neutrophils, eosinophils, monocytes, basophils, CD4+ lymphocytes
65
What is the primary chemical mediator of type I hypersensitivity (allergies)?
Histamine
66
What are the three subtypes of type II hypersensitivity?
**1**. Antibody-mediated \_\_\_\_\_\_\_\_\_\_\_
**2**. Antibody-mediated ___________ or \_\_\_\_\_\_\_\_\_\_\_
**3**. \_\_\_\_\_\_\_\_\_-mediated
What are the three subtypes of type II hypersensitivity?
**1**. Antibody-mediated **cytotoxicity**
**2**. Antibody-mediated **cellular dysfunction** or **anti-receptor**
**3**. **C****omplement**-mediated
67
In type III hypersensitivity reactions, antigen-antibody complexes deposit where?
In tissues
68
Name a few tissues that are favorable deposit spot for type III hypersensitivity reaction antigen-antibody complexes.
## Footnote
**Kidneys**
**\_\_\_\_\_\_**
**\_\_\_\_\_\_**
**\_\_\_\_\_\_**
**Serosal membranes**
**Heart**
Kidneys
**Skin**
**Joints**
**Vessels**
Serosal membranes
Heart
69
Name a few tissues that are favorable deposit spot for type III hypersensitivity reaction antigen-antibody complexes.
## Footnote
**\_\_\_\_\_\_**
**Skin**
**Joints**
**Vessels**
**\_\_\_\_\_\_ \_\_\_\_\_\_**
**\_\_\_\_\_\_**
**Kidneys**
Skin
Joints
Vessels
**Serosal membranes**
**Heart**
70
Name the hypersensitivity reaction associated with each of the following disorders, respectively:
**Hashimoto's** thyroiditis
**Arthus** reaction
**Transfusion** reaction
**Anaphylaxis**
II
III
II
I
71
Name the hypersensitivity reaction associated with each of the following disorders, respectively:
**Grave's** hyperthyroidism
**SLE**
**Chronic transplant** rejection
**Hay fever**
II
III
IV
I
72
Name the hypersensitivity reaction associated with each of the following disorders, respectively:
**Pemphigus vulgaris**
**Myasthenia gravis**
**Goodpasture's** syndrome
**T1DM**
II
II
II
IV
73
What are the two main types of type IV hypersensitivity reaction?
A. **Delayed** (cellular mediation by TH cells and macrophages)
B. **Cytotoxic** (cellular mediation by TC cells)
74
Which type of type IV hypersensitivity reaction is involved in the macrophage recruitment and granuloma formation seen in diseases such as sarcoidosis or TB?
**Delayed** type IV HSR
75
Which type of type IV hypersensitivity reaction involves very large, complex antigens?
**Delayed** type IV HSR
76
Name the type IV hypersensitivity reaction subtype associated with each of the following disorders, respectively:
**Graft rejection**
**Tuberculosis** granulomas
**Fungal** granulomas
**Cytotoxic** (TC cells)
**Delayed** (TH cells and macrophages)
**Delayed** (TH cells and macrophages)
77
Name the type IV hypersensitivity reaction subtype associated with each of the following disorders, respectively:
**Sarcoidosis**
**Tumor cell surveillance**
**Viral** infection response
**Delayed** (TH cells and macrophages)
**Cytotoxic** (TC cells)
**Cytotoxic** (TC cells)
78
The necrotizing ________ is the hallmark of a delayed type IV hypersensitivity reaction.
It is characterized by macrophage (e.g. histiocytes, giant cells) accumulation and potential caseation.
The necrotizing **granuloma** is the hallmark of a delayed type IV hypersensitivity reaction.
It is characterized by macrophage (e.g. histiocytes, giant cells) accumulation and potential caseation.
79
What are the three main categories of transplant rejection (host-vs.-graft)?
1. **Hyperacute**
2. **Acute**
3. **Chronic**
80
Most cases of transplant rejection are mediated via type ____ hypersensitivity reactions.
Most cases of transplant rejection are mediated via type **IV** hypersensitivity reactions.
## Footnote
*(Note: hyperacute rejection is a type II HSR.)*
81
\_\_\_\_\_\_\_\_\_ transplant rejection is caused by preformed recipient _________ and can lead to fever and rapid failure of the organ shortly after the recipient blood flow is anastomosed to the donor organ.
**Hyperacute** transplant rejection is caused by preformed recipient **antibodies** and can lead to fever and rapid failure of the organ shortly after the recipient blood flow is anastomosed to the donor organ.
82
There are two overlapping subcategories of acute transplant rejection, _________ and _________ transplant rejection.
These processes are mediated by _______ cells.
There are two overlapping subcategories of acute transplant rejection, **cellular** and **vascular** transplant rejection.
These processes are mediated by **TC** cells.
83
**True/False**.
All of the following are potential characteristics of acute transplant rejection:
***Endotheliitis***
***Vasculitis***
***Renal tubulitis***
***Irreversible damage***
***Thrombosis***
**False**.
All of the following are potential characteristics of acute transplant rejection:
***Endotheliitis***
***Vasculitis***
***Renal tubulitis***
***_Reversible_ damage***
***Thrombosis***
84
How long after transplantation will hyperacute transplant rejection first manifest?
How long after transplantation will acute transplant rejection first manifest?
How long after transplantation will chronic transplant rejection first manifest?
**Nearly instantaneous**;
**weeks-to-months**;
**months-to-years**
85
Hyperacute rejection is especially likely in recipient females that have a history of \_\_\_\_\_\_\_\_\_\_\_.
This is due to extra humoral antibodies developed against any of the thousands of fetal antigens found on fetal \_\_\_\_\_\_.
Hyperacute rejection is especially likely in recipient females that have a history of **childbirth**.
This is due to extra humoral antibodies developed against any of the thousands of fetal antigens found on fetal **RBCs**.
86
Which transplant rejection category is basically an immune-mediated atherosclerosis?
This process is mediated via what cell type?
Chronic transplant rejection;
TC lymphocytes
87
Chronic transplant rejection category is basically an immune-mediated ___________ characterized by interstitial fibrosis and vessel stenosis in the allograft that is unresponsive to treatment.
This process generally occurs over ______ or ______ (timeframe) post-transplantation.
Chronic transplant rejection category is basically an immune-mediated **atherosclerosis** characterized by interstitial fibrosis and vessel stenosis in the allograft that is unresponsive to treatment.
This process generally occurs over **months** or **years** (timeframe) post-transplantation.
88
Which transplant rejections are treatable?
(Hyperacute, acute, chronic)
Hyperacute, acute
89
\_\_\_\_\_-vs.-\_\_\_\_\_ disease is most commonly seen in bone marrow / stem cell transplants and results from donor lymphocytes attacking the recipient.
This condition is treated with \_\_\_\_\_\_\_\_\_\_\_\_.
**Graft**-vs.-**host** disease is most commonly seen in bone marrow / stem cell transplants and results from donor lymphocytes attacking the recipient.
This condition is treated with **corticosteroids (high-dose)**.
90
Preservation injury is a ________ (type of necrosis) organ necrosis most commonly caused by lengthy transport of the organ from the donor to the recipient.
Preservation injury is a **coagulative** organ necrosis most commonly caused by lengthy transport of the organ from the donor to the recipient *(ischemic conditions)*.
91
What post-transplant disorder results in leukocyte hyperplasia and potential B cell malignancy?
Note: it is associated with the following factors:
**Allograft antigen stimulation**
**EBV infection**
**Carcinogens**
**Immunosupressants**
Post-transplant lymphoproliferative disorder
92
D. Delayed type
93
B. Complement-mediated cytotoxic reaction
94
E. CD-8 T Lymphocytes
95
A. Granulomatous lymphadenitis
96
D. Immune complex deposition with inflammatory tissue damage
97
F. T-lymphocyte cell-mediated cytotoxicity
98
What does an elevated sedimentation rate (ESR) indicate?
Inflammation
99
Chronic/active inflammatory conditions result in elevated sedimentation rate (ESR) because of increased \_\_\_\_\_\_\_\_\_\_.
Chronic/active inflammatory conditions result in elevated sedimentation rate (ESR) because of increased **fibrinogen**.
(leads to increased clumping --\> faster sed. rate)
100
**True/False**.
An elevated sedimentation rate is a non-specific marker of inflammation.
**True**.
An elevated sedimentation rate is a non-specific marker of inflammation.
101
What rule of thumb allows for calculation of a patient's expected sedimentation rate?
**Women**: \< 20 mm/hr
**Men**: \< 15 mm/hr
**Rule of thumb:**
Men: age / 2 mm/hr
Women: age / 2 + 5 mm/hr
102
**True/False**.
ESR is extremely variable from person to person.
True.
103
An increase in what plasma factors lead to an elevated sedimentation rate?
An decrease in what plasma factors lead to an elevated sedimentation rate?
Fibrinogen, immunoglobulins;
albumin
104
What changes in RBCs lead to an elevated sedimentation rate?
Anemia, macrocytosis
105
A patient presents with an ESR over 100 mm/hr. What conditions must be in your differential?
Neoplastic disease;
infection;
temporal arteritis
106
What purpose does serum protein electrophoresis allow in laboratory diagnosis?
Comparison of relative protein levels
(can be useful in diagnosing nephrotic syndrome, monoclonal gammopathies, agammaglobulinemias, cirrhosis, protein-loss, etc.)
107
What is the order of substances shown in a serum protein electrophoresis?
**Albumin --- α1 --- α2 --- β --- γ**
108
What are the main components of the **α1** and **α2** sections in a serum protein electrophoresis?
**α1-antitrypsin**;
**α2-macroglobulin**, **haptoglobulin**
109
What are the main components of the **β** section in a serum protein electrophoresis?
**Complement;**
**transferrin**
110
What are the main components of the **γ** section in a serum protein electrophoresis?
**Immunoglobulins** (IgM, IgG, IgA)
111
What condition does this serum protein electrophoresis show?
Hypogammaglobulinemia
112
What condition does this serum protein electrophoresis show?
Monoclonal gammopathy
(e.g. multiple myeloma; Waldenstom's syndrome)
113
What condition does this serum protein electrophoresis show?
Hepatic cirrhosis
114
What condition does this serum protein electrophoresis show?
Nephrotic syndrome
115
What is a leukocyte left shift?
A leukocytosis characterized by immature WBCs
116
\_\_\_\_\_\_\_\_\_ infections usually result in neutrophilia.
\_\_\_\_\_\_\_\_\_ infections and _________ usually result in eosinophilia.
\_\_\_\_\_\_\_\_\_ infections usually result in lymphocytosis.
**Bacterial** infections usually result in neutrophilia.
**Parasitic** infections and **allergies** usually result in eosinophilia.
**Viral** infections usually result in lymphocytosis.
117
**True/False**.
Elevated CRP is a marker of inflammation while elevated fibrinogen is a marker of a lack of inflammation.
**False**.
***Both*** elevated CRP and elevated fibrinogen are markers of inflammation.
118
Immunodeficiency disorders may be classified as \_\_\_-cell (antibody) or \_\_\_-cell (cellular) or combined ___ and ___ cell deficiencies.
The defects may be **primary** (congenital) or **secondary** (acquired).
Immunodeficiency disorders may be classified as **B**-cell (antibody) or **T**-cell (cellular) or combined **B** and **T** cell deficiencies.
The defects may be **primary** (congenital) or **secondary** (acquired).
119
What disorder is described below?
## Footnote
*'A block in differentiation of pre-B cells into B cells due to mutation of tyrosine kinase called Bruton’s tyrosine kinase (btk) gene on the x-chromosome.'*
Bruton's X-linked agammaglobulinemia
120
What cell type is deficient in X-linked agammaglobulinema (Bruton's disease)?
B cells
121
**True/False**.
Patients with X-linked agammaglobulinema are at increased risk of most pyogenic viral infections.
**False**.
Patients with X-linked agammaglobulinema are at increased risk of most pyogenic ***bacterial*** infections.
122
Which immunoglobulin classes are decreased in X-linked agammaglobulinemia (Bruton's disease)?
**All classes**
| (IgG, IgA, IgM, IgE, IgD)
123
The patient described below is most likely to be what gender?
## Footnote
*A 9 month year old ______ presents with recurrent pneumonia due to S. aureus infection. Further examination reveals decreased serum levels of all immunoglobulin classes, absent peripheral B cells, and rudimentary tonsils.*
**Male**
(Bruton's X-linked agammaglobulinemia)
124
Why can patients with Bruton's X-linked agammaglobulinema handle most viral, fungal and parasitic infections?
Intact T cell activity
125
What is the most common primary immunodeficiency syndrome?
What is the most common presentation?
**Selective** **IgA** **deficiency**;
most patients are **asymptomatic**
126
Selective IgA deficiencies lead to an increased risk of what infection types?
**Sinopulmonary** and **gastrointestinal**
127
What disease type is similar to Bruton's X-linked agammaglobulinema but presents equally in both men and women?
Common variable immunodeficiency
128
Which primary immunodeficiency type is characterized by hypotonia, T cell absence, and underdeveloped lymph node paracortex and absent thymus?
Afflicted patients are at an increased risk of what infection types?
DiGeorge syndrome;
viral, fungal and protozoal infections
129
What constellation of immunodeficiency disorders is characterized by decreased levels of T cells, B cells, and all immunoglobulin types?
SCID
130
Name the disorder described below:
* X-linked immunodeficiency characterized by 1) _recurrent_ _infections_, 2) hemorrhage 2° to _thrombocytopenia_ and _eczema_.
* Presents in babies in the first few months of life with petechia and infections – otitis media.
Wiscott-Aldrich Syndrome
131
The three characteristic components of Wiscott-Aldrich syndrome are:
(1) Recurrent \_\_\_\_\_\_\_\_\_\_\_
(2) \_\_\_\_\_cyto\_\_\_\_\_
(3) \_\_\_\_\_\_\_\_\_
The three characteristic components of Wiscott-Aldrich syndrome are:
(1) Recurrent **infections**
(2) **Thrombo**cyto**penia**
(3) **Eczema**
132
In particular, congential defects in T-cell function cause increased susceptibility to _________ infections.
In particular, congential defects in T-cell function cause increased susceptibility to ***Candida*** infections.
(E.g. chronic mucocutaneous candidiasis)
133
Hyper-IgM syndrome is mainly caused by defective _____ on ___ cells.
Hyper-IgM syndrome is mainly caused by defective **CD40L** on **TH** cells.
(CD40L is necessary for Ig class-switching)
134
**True/False**.
Bruton's X-linked agammaglobulinemia leads to increased risk of Giardiasis.
True.
135
The risk of graft-vs.-host disease (GVHD) is __________ in patients with SCID due to _________ T cells.
The risk of graft-vs.-host disease (GVHD) is ***increased*** in patients with SCID due to ***maternal*** *T cells*.
136
**True/False**.
Selective IgG deficiencies are the most common primary immunodeficiency. Afflicted patients may present with anaphylaxis if given blood transfusions (due to IgG in transfusion).
**False**.
Selective Ig***_A_*** deficiencies are the most common primary immunodeficiency. Afflicted patients may present with anaphylaxis if given blood transfusions (due to Ig***A*** in transfusion).
137
Selective IgA deficiencies often present with combined Ig\_\_ deficiency.
Selective IgA deficiencies often present with combined Ig**G** deficiency.
138
**True/False**.
The following immunodeficiencies all predispose patients to rheumatoid conditions:
**Bruton's X-linked agammaglobulinema**
**IgA deficiency**
**Common variable immunodeficiency**
True.
139
What is the metabolic basis of gout?
Hyperuricemia
140
\_\_\_\_% of cases of acute gout affect the hallux.
**50**% of cases of acute gout affect the hallux.
141
Many cases of acute gout are preciptated by some form of \_\_\_\_\_\_\_.
Many cases of acute gout are preciptated by some form of **stress** *(e.g. dietary overindulgencence, excessive alcohol intake, physical / emotional fatigue, etc.)*.
142
Chronic gouty arthritis occurs in __ - \_\_% of gout patients.
Chronic gouty arthritis occurs in **10** - **15**% of gout patients.
143
**True/False**.
The soft tissue tophi seen in chronic gout are painless and nontender.
True.
144
90% of chronic gout patients develop some form of ______ impairment.
Patients are also prone to develop **arteriosclerosis** and **diabetes** **mellitus**.
90% of chronic gout patients develop some form of **renal** impairment.
Patients are also prone to develop **arteriosclerosis** and **diabetes** **mellitus**.
145
Gouty joint fluid contains long needle sodium urate crystals that show strong __________ \_\_\_\_\_\_\_\_\_\_ under polarizing microscopy.
Gouty joint fluid contains long needle sodium urate crystals that show strong **negative** **birefringence** under polarizing microscopy.
146
Why does gout preferentially affect peripheral joints?
Decreased temperature
| (lower urate solubility)
147
Net urate clearance is only \_\_\_% of the filtered load (due to reabsorption).
Net urate clearance is only **10**% of the filtered load (due to reabsorption).
148
Name a few risk factors for gout.
Males;
older age;
high SES;
obesity;
high alcohol intake
149
A patient with no history of trauma or osteopenia presents with a tender and swollen right hallux.
Name a few joint pathologies that might be in your differential.
Gout;
septic arthritis;
pseudogout
150
Gout is caused by ____________ crystals that are _________ (birefringence-status).
Pseudogout is caused by ____________ crystals that are _________ (birefringence-status).
Gout is caused by **monosodium urate** crystals that are **negatively birefringent**.
Pseudogout is caused by **calcium pyrophosphate** crystals that are **positively birefringent**.
151
Each different clinical type of amyloidosis differs in the composition of the deposited \_\_\_\_\_\_\_\_\_. In any given patient the _________ molecule deposited in each organ is the same.
Each different clinical type of amyloidosis differs in the composition of the deposited **protein**. In any given patient, the **amyloid** molecule deposited in each organ is the same.
152
All amyloids stain red with the _______ \_\_\_\_\_ stain. But when these section are viewed with polarized light they exhibit a _______ birefrigency. This feature of amyloid can be used to identify it in tissue sections.
All amyloids stain red with the **Congo red** stain. But when these section are viewed with polarized light they exhibit a **green** birefrigency. This feature of amyloid can be used to identify it in tissue sections.
153
Each form of amyloidosis is characterized by deposits made of three main components:
1. Fibrillary protein (95%)
2. Amyloid P component (5%)
3. Glycosoamynoglycan
**Which part differs between amyloid disorders?**
**The fibrillary protein**
154
You suspect a patient has amyloidosis. How do you confirm the diagnosis?
Skin or rectal biospy
155
**True/False**.
In all forms of systemic amyloidosis, the disease is ultimately fatal.
True.
156
**True/False**.
Isolated amyloidopathies only affect single organs and are not necessarily fatal.
True.
157
**True/False**.
The following chronic inflammatory diseases have all been shown to cause a decrease in patient risk of amyloidosis.
**Tuberculosis.**
**Lung abcesses.**
**Osteomyelitis.**
**Reumatoid arthritis.**
**Systemic Lupus erythematous.**
**Drug addiction.**
**Hodgkin's disease.**
**Renal Cell carcinoma.**
**False**.
The following chronic inflammatory diseases have all been shown to cause a *_increase_* in patient risk of amyloidosis.
**Tuberculosis.**
**Lung abcesses.**
**Osteomyelitis.**
**Reumatoid arthritis.**
**Systemic Lupus erythematous.**
**Drug addiction.**
**Hodgkin's disease.**
**Renal Cell carcinoma.**
158
What chemical stains amyloid in tissue?
Iodine
159
Progressive systemic sclerosis (scleroderma) is a systemic disease characterized by the presence of excessive _________ throughout the body.
Progressive systemic sclerosis (scleroderma) is a systemic disease characterized by the presence of excessive **fibrosis** throughout the body.
160
Systemic sclerosis is associated with CREST syndrome.
For what does CREST stand?
**C** \_\_\_\_\_\_\_\_\_\_
**R** __________ phenomenon
**E** __________ dysmotility
**S** Sclerodactyly
**T** Telangiectasia
**C** **Calcinosis**
**R** **Raynaud's** phenomenon
**E** **Esophageal** dysmotility
**S** Sclerodactyly
**T** Telangiectasia
161
Systemic sclerosis is associated with CREST syndrome.
For what does CREST stand?
**C** Calcinosis
**R** Raynaud's phenomenon
**E** Esophageal dysmotility
**S** \_\_\_\_\_\_\_\_\_\_
**T** \_\_\_\_\_\_\_\_\_\_
**C** Calcinosis
**R** Raynaud's phenomenon
**E** Esophageal dysmotility
**S** **Sclerodactyly**
**T** **Telangiectasia**
162
Scleroderma patients are ANA-\_\_\_\_\_\_\_ (positive/negative).
Scleroderma patients are ANA-**positive** (95% of cases).
163
**True/False**.
Scleroderma likely arises from a combination of immunological and ischemic causes.
**True**.
Scleroderma likely arises from a combination of immunological and ischemic causes.
164
Scleroderma patients typically show what laboratory results?
* ANA-positive
* Elevated ESR
* Anemia
165
A 63-year-old man complains of chronic back pain has multiple lytic lesions in his vertebral bodies, with anemia, rouleaux formation, a monoclonal gammapathy with free IgG light chains in his urine and a bone marrow aspiration revealing sheets of plasma cells. Two years previously, he was told he had a “plasmacytoma”. Urinalysis reveals 4+ proteinuria A renal biopsy reveals focal and segmental glomerular and interstitial vascular deposits of amorphous eosinophilic material that is Congo-red positive and PAS negative.
What is the most likely diagnosis of this patient's renal presentation?
Amyloid nephropathy secondary to multiple myeloma
166
Fracture healing follows the following steps:
1. Fracture
2. _________ formation
3. Organized \_\_\_\_\_\_\_\_\_
4. Fibrous \_\_\_\_\_\_\_\_\_
5. Ossification
6. Remodeling
Fracture healing follows the following steps:
1. Fracture
2. **Hematoma** formation
3. Organized **hematoma**
4. Fibrous **callus**
5. Ossification
6. Remodeling
167
Fracture healing follows the following steps:
1. Fracture
2. Hematoma formation
3. Organized hematoma
4. Fibrous callus
5. \_\_\_\_\_\_\_\_\_\_
6. \_\_\_\_\_\_\_\_\_\_
Fracture healing follows the following steps:
1. Fracture
2. Hematoma formation
3. Organized hematoma
4. Fibrous callus
5. **Ossification**
6. **Remodeling**
168
\_\_\_\_\_\_\_\_ ________ (or ________ \_\_\_\_\_\_\_\_) is a non-infectious infarction of bone and bone marrow that can arise from a number of antecedent conditions.
**Avascular necrosis** (or **aseptic necrosis**) is a non-infectious infarction of bone and bone marrow that can arise from a number of antecedent conditions.
169
Many cases of **avascular (aseptic) necrosis** result due to changes in the __________ of the bone.
The list of related conditions other than post-traumatic includes idiopathic, \_\_\_\_\_\_\_-induced, and \_\_\_\_\_\_\_-induced necrosis.
Many cases of **avascular (aseptic) necrosis** result due to changes in the **_microcirculation_** of the bone.
The list of related conditions other than post-traumatic includes idiopathic, **_alcohol_**-induced, and **_corticosteroid_**-induced necrosis.
170
What is the most common cause of osteomyelitis?
Staphylococcus aureus
171
\_\_\_\_\_\_\_\_\_\_ is a general term meaning reduced bone mass.
**Osteopenia** is a general term meaning reduced bone mass (can encompass the terms osteoporosis or osteomalacia or both).
172
In osteomalacia, the bones are \_\_\_\_\_.
In osteoporosis, the bones are \_\_\_\_\_.
In osteomalacia, the bones are **soft**.
In osteoporosis, the bones are **brittle**.
173
What are two pathological conditions seen in the bone as a result of hyperparathyroidism?
**Renal osteodystrophy** (results from chronic renal disease);
## Footnote
**osteitis fibrosa cystica**
174
What disease is characterized by structurally weakened bones that have an abundance of cement lines (sometimes referred to as a mosaic pattern)?
Paget's disease
175
A patient presents with increased hat size, gait changes, and deafness.
What diagnosis is at the top of your differential?
Paget's disease
176
**True/False**.
Eczema mainly involves the dermis.
**False**.
Eczema mainly involves the ***epi***dermis.
177
What three forms of dermatitis mainly affect the epidermis?
Eczema;
erythema multiforme;
psoriasis
178
What disorder is described by the following?
## Footnote
*"Characterized by widened intercellular space or with vesicles formation, scale crust, eosinophil infiltrate, and presented as papules, plaques or vesicles."*
Eczema
179
Erythema multiforme is an acute _________ eruption of _________ necrolytic dermatitis.
Erythema multiforme is an acute **targetoid** eruption of **epidermal** necrolytic dermatitis.
180
Erythema multiforme is usually secondary to what?
Infection;
drug use;
malignancy
181
Identify the disorder:
## Footnote
*"**Chronic** **scaly**/pustular dermatitis with idiopathic **neutrophil** aggregates in the scaly upper epidermis and elongation of the rete ridges of the epidermis."*
Psoriasis
182
Name two forms of dermatitis that mainly affect the dermis.
Urticaria (hives);
scleroderma
183
Erythema __________ (a self-limited form of \_\_\_\_\_\_\_\_itis) exhibits ill-defined reddish, tender nodules on legs, often associated with infection, drug use, sarcoidosis, inflammatory bowel disease, and malignancy.
Erythema **nodosum** (a self-limited form of **pannicul**itis) exhibits ill-defined reddish, tender nodules on legs, often associated with infection, drug use, sarcoidosis, inflammatory bowel disease, and malignancy.
184
\_\_\_\_\_\_\_\_\_\_\_ describes a pathological process of losing intercellular connections of the keratinocytes and therefore presenting as bulla clinically.
**Acantholysis** describes a pathological process of losing intercellular connections of the keratinocytes and therefore presenting as bulla clinically.
185
Pemphigus vulgaris involves antibodies against:
Bullous pemphgoid involves antibodies against:
**Desmogleins** (desmosomes);
**BP1**, **BP2** (hemidesmosomes)
186
Dermatitis \_\_\_\_\_\_\_\_\_\_\_\_: an autoimmune dermatitis with granular deposit of Ig\_\_ against gliadin and reticulin at the tips of dermal papillae.
Associated with ___________ insensitivity.
Dermatitis **herpetiformis**: an autoimmune dermatitis with granular deposit of Ig**A** against gliadin and reticulin at the tips of dermal papillae.
Associated with **gluten** insensitivity.
187
\_\_\_\_\_\_\_ _______ (common wart): Discrete benign squamous papilloma (benign growth of the keratinocytes) caused by ______ infection.
**Verruca vulgaris** (common wart): Discrete benign squamous papilloma (benign growth of the keratinocytes) caused by **HPV** infection.
188
What is the most common bacterial infection presentation among children?
**Impetigo**: reddish macules / pustules on face and hands + shallow erosion / honey-colored crusts in later stage
189
Impetigo is characterized by reddish macules / pustules on the _______ and _______ + shallow erosion / honey-colored ______ in later stage
Impetigo is characterized by reddish macules / pustules on the **face** and **hands** + shallow erosion / honey-colored **crusts** in later stage
190
What are the two main infectious agents that cause impetigo?
*Staphylococcus aureus*;
Group A streptococcus (*Streptococcus pyogenes*)
191
What is here defined:
## Footnote
*"superficial fungal infection confined to stratum corneum of the epidermis, hair/hair follicles, or nail --- caused by dermatophytes"*
Tinea (dermatophytosis)
192
Auto-reactive lymphocytes that are not removed in the process of clonal ________ will then be inactivated in the process of clonal \_\_\_\_\_\_\_\_.
Auto-reactive lymphocytes that are not removed in the process of clonal **deletion** will then be inactivated in the process of clonal **anergy**.
193
Which serum autoantibodies are highly diagnostic for SLE?
Anti-Smith
+
anti-dsDNA
194
\_\_\_\_ out of the following 11 are necessary for clinical diangosis of SLE.
A. Malar rash – “Butterfly rash”
B. Discoid rash – Erythematous, Keratotic, scaling, follicular plugging and/or atrophic dermatitis.
C. Photosensitivity
D. Oral/Nasophayngeal ulcers, usually painless
E. Arthritis – non-erosive arthritis involving at least 2 joints
F. Serositis – pleuritic, pericarditis – effusions, friction ribs
G. Renal – significant proteinuria and/or cellular casts
H. Neuropsychiatric - seizures, psychosis
I. Hematologic – Hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
J. Immunologic disorder – Anti-DS-DNA, Anti-Sm antibodies, antiphospholipid antibodies, anti-cardiolipin antibodies, false positive serologic test for syphilis (VDRL)
K. ANA
**4** out of the following 11 are necessary for clinical diangosis of SLE.
A. Malar rash – “Butterfly rash”
B. Discoid rash – Erythematous, Keratotic, scaling, follicular plugging and/or atrophic dermatitis.
C. Photosensitivity
D. Oral/Nasophayngeal ulcers, usually painless
E. Arthritis – non-erosive arthritis involving at least 2 joints
F. Serositis – pleuritic, pericarditis – effusions, friction ribs
G. Renal – significant proteinuria and/or cellular casts
H. Neuropsychiatric - seizures, psychosis
I. Hematologic – Hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
J. Immunologic disorder – Anti-DS-DNA, Anti-Sm antibodies, antiphospholipid antibodies, anti-cardiolipin antibodies, false positive serologic test for syphilis (VDRL)
K. ANA
195
Both SLE and rheumatoid arthritis are associated with R\_\_\_\_\_\_\_\_\_'s phenomenon.
Both SLE and rheumatoid arthritis are associated with R**aynaud**'s phenomenon.
196
Both SLE and rheumatoid arthritis are type _____ hypersensitivity reactions.
Both SLE and rheumatoid arthritis are type **III** hypersensitivity reactions.
197
What is the main causal mechanism of the damage caused by autoantibodies in SLE and rheumatoid arthritis?
Antibody complexes activate complement in tissues
198
Rheumatoid factor found in synovium forms immune complexes with Ig\_\_\_ antibodies that fix \_\_\_\_\_\_\_\_\_, leading to a type III hypersensitivity reaction causing joint tissue damage.
Rheumatoid factor found in synovium forms immune complexes with Ig**G** antibodies that fix **complement**, leading to a type III hypersensitivity reaction causing joint tissue damage.
199
Name the main cell type(s) or immune substrates involved in each of the following:
## Footnote
**Hyperacute transplant rejection**
**Acute transplant rejection**
**Chronic transplant rejection**
Immunoglobulins
CD8+ T cells
CD4+ T cells, macrophages
200
What are the three cytopathic 'M's of human herpes simplex virus infection seen in infected cells?
**Multi**\_\_\_\_\_\_\_\_\_\_
**M**\_\_\_\_\_\_\_\_\_\_
Nuclear **M**\_\_\_\_\_\_\_\_\_\_
**Multinucleation**
**Molding**
Nuclear **Margination**
(NOTE: above changes result in ground glass nuclei)
201
Describe the pathologic nuclei seen in CMV infection.
"Owl's eye" nuclear inclusions with characteristic halo
202
**Human herpes simplex virus**
Multinucleation
Molding
Nuclear Margination
(ground glass nuclei)
203
# Infection with what organism is apparent in these cells?
"Owl's eye" nuclear inclusions with characteristic halo
**Cytomegalovirus**
("Owl's eye" nuclear inclusions with characteristic halo)
