Immune System Flashcards
1
Q
Innate Immunity Receptor coding? Response to pathogens is Memory? Cells involved? Molecules involved?
A
Receptors that recognize pathogens are germline encoded
Response to pathogens is fast and nonspecific
No Memory
Neutrophils, Macs, Dendritic Cells, Natural Killer Cells (lymphoid origin)
Complement
2
Q
Adaptive Immunity Innate Immunity Receptor coding? Response to pathogens is Memory? Cells involved? Molecules involved?
A
Receptors that recognize pathogens undergo V(D)J recombination during lymphocyte development
Response is slow on first exposure. Memory response is faster and more robust.
T and B cells
Antibodies
3
Q
MHC Stands for Encoded by what gene? Function What does it bind?
A
Major Histocompatibility Complex
Human Leukocyte Antigen (HLA) gene
Presents antigen fragments to T cells and binds TCR
4
Q
MHC I Genes encoding it? Binds what receptors Which cells express it? Where is antigen loaded What kind of antigens? What kind of immunity does it mediate? What does it pair with and why? Where is peptide groove?
A
HLA A, B and C
Binds TCR and CD8
All nucleated cells (not RBCs)
Antigen loaded in RER with mostly intracellular peptides
Mediates viral immunity
Pairs with β2 microglobins (aids in transport to cell surface)
Peptide groove in α chain
5
Q
MHC II Genes encoding it? Binds what receptors Which cells express it? When is antigen loaded What does it look like?
A
HLA DR, DP and DQ
Binds TCR and CD4
Expressed only on APCs
Antigen is loaded following release of invariant chain in an acidified endosome
α and β chains pair with peptide groove in between
6
Q
Association with HLA A3
A
Hemochromatosis
7
Q
Association with HLA B27
A
“PAIR”
Psoriasis, Ankylosing Spondylitis, IBDm Reiter’s syndrome
8
Q
Association with HLA DQ2/DQ8
A
Celiac
9
Q
Association with HLA DR2
A
Multiple Sclerosis, Hay Fever, SLE, Goodpastures
10
Q
Association with HLA DR3
A
DM type 1, Graves’ Disease
11
Q
Association with HLA DR4
A
RA, DM type 1
12
Q
Association with HLA DR5
A
Pernicious anemia (B12 deficiency), Hashimoto’s thyroiditis
13
Q
Natural Killer Cells What do they do? What do they use to do it? How are they unique? What molecules enhance their activity? When are they induced to kill?
A
Induce apoptosis in virally infected cells or tumor cells
Use perforin and granzymes
Only lymphocyte member of innate immune system
“#2, get #12, tell him the boss needs to take out α and β”
Activity is enhanced by IL2, IL12, INFα, INFβ
Induced to kill when exposed to a nonspecific activation signal on target cell +/or to an absence of MHCI on target cell surface
14
Q
B cells functions
A
Make Abs: opsonize bacteria, neutralize viruses (IgG), Activate complement (IgM and IgG), Sensitize mast cells (IgE)
Allergy (Type I hypersensitivity): IgE
Cytotoxic (Type II hypersensitivity): IgG
Immune Complex (Type III hypersensitivity): IgG
Hyperacute and humorally mediated acute and chronic organ rejection
15
Q
T cell functions
Generally
CD4
CD8
A
Delayed cell mediated hypersensitivity reaction (IV)
Acute and chronic cellular organ rejection
CD4+ cells help B cells make Ab and produce cytokines to activate other cells of the immune system
CD8+ cells kill virus infected cells directly
16
Q
Differentiation of T cells
In Bone Marrow
In Thymus
In Lymph Node
A
In BM: T cell precursor In T: expresses TCR, CD4 and CD8 and then will switch to only expressing one of the CDs and a TCR In LN: CD8+ --> cytotoxic T cells CD4+: if exposed to IL12 --> Th1 if exposed to IL4 --> Th2
17
Q
Where is there Positive selection in T cell differentiation?
A
In the Thymic Cortex where T cells expressing TCR capable of binding self MHC survive
18
Q
Where is there Negative selection in T cell differentiation?
A
Medulla where T cells expressing TCR with high affinity for self antigens undergo apoptosis
19
Q
APCs # of signals needed for what?
A
Dendritic cell (Only APC that can activate naive T cell)
Macrophage
B cell
2 signals needed for T cell activation, B cell activation, and class switching
20
Q
Steps of naive T cell activation
A
- Foreign body is phagocytosed by dendritic cell
- Foreign antigen presented on MHCII
- MHCII + antigen recognized by TCR on Th cell or MHCI + antigen recognized by TCR on Tc cell
- Costimulatory signal given by interaction of B7 (DC) and CD28 (T cell)
- T cell activated: Th produced cytokines, Tc kills virus infected cells
21
Q
Steps of B cell activation and class switching
A
- Th cell activated
- B cell receptor mediated endocytosis
- Foreign antigen presented on MHCII
- MHCII + antigen recognized by TCR on Th cell
- CD40 receptor on B cell binds CD40 ligand on Th cell
- Th cell secretes cytokines that determine Ig class switching of B cell
- B cell activates and undergoes class switching, affinity maturation, and Ab production
22
Q
Th1
What do they secrete
What do they activate
What inhibits them
A
Secretes INFγ
Activates Macs
Inhibited by IL4 and IL10 from Th2
23
Q
Macrophage-Lymphocyte interaction
A
Activated lymphocyte –> INFγ –> Macs –> IL1 and TNFα –> lymphocytes
24
Q
Th2
What do they secrete
What do they activate
What inhibits them
A
Secrete IL4, IL5, IL10, IL13
Recruit eosinophils for parasite defense, promote IgE production by B cells
Inhibited by INFγ from Th1
25
```
Lymph Node
What is it?
Afferents?
Efferents?
Encapsulated?
Function
```
```
Secondary Lymphoid Organ
Many afferents
1 or more efferents
Encapsulated w/ trabeculae
Filtration by Macs, storage, activation of B and T cells, Ab production
```
26
Lymph Node Follicle
Location
Function
Primary vs Secondary
Outer cortex
B cell localization and proliferation
Primary: dense and dormant
Secondary: pale central germinal centers and are active
27
Lymph Node Medulla
| What does it consist of?
Medullary cords: closely packed lymphocytes and plasma cells
Medullary sinuses: Communicate with efferent lymphatics and contain reticular cells and Macs
28
```
Paracortex
Location
What does it house?
What does it contain?
What happens in an extreme cellular response?
Disease?
```
Between follicles and medulla
T cells
High endothelial venules through which T and B cells enter from blood
In extreme celular response, becomes enlarged
Not well developed in DiGeorge Syndrome
29
Lymph Drainage of Upper limb and lateral breast
Axillary
30
Lymph Drainage of Stomach
Celiac
31
Lymph Drainage of Duodenum and Jejunum
Superior Mesenteric
32
Lymph Drainage of Sigmoid Colon
Colic --> Inferior Mesenteric
33
Lymph Drainage of lower rectum and anal canal above pectinate line
Internal Iliac
34
Lymph Drainage of Anal Canal Below Pectinate Line
Superficial Inguinal
35
Lymph Drainage of Testes
Superficial and Deep Plexuses --> Para-Aortic
36
Lymph Drainage of Scrotum
Superficial Inguinal
37
Lymph Drainage of Thigh
Superficial Inguinal
38
Lymph Drainage of Lateral Side of Dorsum of the foot
Popliteal
39
What does Right Lymphatic Duct drain?
| What does Thoracic Duct drain?
Right arm, right chest, Right half of head
| Everything else
40
Sinusoids of the Spleen
What are they?
What are found nearby
Long Vascular Channels in red pulp with fenestrated "barrel hoop" basement membrane
Macrophages found nearby
41
Where are T cells in the spleen?
Periarterial lymphatic sheath (PALS) w/in white pulp
42
Where are B cells in the spleen?
Follicles w/in white pulp
43
What do macrophages do in the spleen?
Remove encapsulated bacteria
44
Splenic Dysfunction
Pathway
What are pts susceptible to?
↓ IgM --> ↓ Complement activation --> ↓ C3b opsonization --> ↑ susceptibility to encapsulated organisms
"SHiNE SKiS"
Strep pneumoniae, Haemophilis influenza type B, Neisseria meningitidis, Salmonella, Klebsiella pneumoniae, Group B Strep, E coli
45
Blood of pt post Splenectomy
Howell Jolly Bodies, Target Cells, Thrombocytosis
46
```
Thymus
Function
Encapsulated
Development
Origin of lymphocytes
```
Site of T cell differentiation and maturation
Encapsulated
From epithelium of 3rd Branchial pouches
Lymphocytes of mesenchymal origin
47
Thymus Cortex
Appearance
Kind of T cells there?
Kind of selection
Dense
Immature T cells
Positive selection (MHC restriction)
48
```
Thymus Medulla
Appearance
Kind of T cells there?
Histo
Kind of selection
```
Pale
Mature T cells
Epithelial Reticular cells containing Hassall's Corpuscles
Negative Selection (nonreactive to self)
49
Cytotoxic T cells
Function
What doe they release
Markers
Kill virus-infected cells, Neoplastic, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins (Perforin, Granzyme, Granulysin)
CD8
50
Perforin
Granzyme
Granulysin
Perforin: Helps deliver the content of granules to target cells
Granzyme: Serine Protease activates apoptosis inside target cells
Granulysin: Antimicrobial, induces apoptosis
51
Regulator T cells
Function
Markers
What doe they produce?
Help maintain specific immune tolerance by suppressing CD4 and CD8 T cells
CD3, CD4, CD25 (α-chain of IL2 receptor)
IL10 and TGFβ
52
What part of Ab recognizes Ag
Variable portion of L and H chains
53
Function of Fc portion of IgM and IgG
Fix complement
54
Composition of Fc and Fab fractions Re H and L chains
H contributes to both Fc and Fab
| L contributes only to Fab
55
Fab functions
Ag binding fragment
56
```
Fc portion
What is it?
Which end of the protein?
Function
Side chains
What does it determine?
```
```
Constant portion
Carboxy terminal
Complement binding @ CH2 (IgM and IgG only)
Carbohydrate side chains
Determine isotype (IgM, IgD...)
```
57
How is Ab diversity generated?
Light chain undergoes random VJ recombination
H undergoes random VDJ recombination
Random combination of H and L chains
Somatic Hypermutation following Ag stimulation (AID)
Addition of NTs to DNA during recombination by Terminal Deoxynucleotidyl Transferase
58
Mature B lymphocytes express what on their surface?
IgM and IgD
59
What mediates Isotype switching
Cytokines and CD40 ligand
60
IgG
Main Ab of what?
Abundance?
Function
Secondary Delayed Response
Most abundant type
Fixes complement, Crosses Placenta, Opsonizes bacteria, Neutralizes bacterial toxins and viruses
61
```
IgA
Function
Complement?
Single or group?
How does it cross epithelial cells
Where is it found?
```
Prevents attachement of bacteria and viruses to mucous membrane
Doesn't fix complement
Monomer in circulation, Dimer when secreted
Transcytosis where it picks up secretory component
Secretions (tears, saliva, mucus) and early breast milk (colostrum )
62
```
IgM
When is it produced?
Function
Placenta?
Single or group?
```
Primary immediate response to Ag
Fixes complement
Does not cross placenta
Monomer on B cells or Pentamer
63
IgD
Location
Function
Surface of B cells and in serum
| Unclear function
64
IgE
Mediates what kind of Immunity?
Function
Abundance
Mediates immediate (type I) hypersensitivity through release of inflammatory mediators (histamine). Mediates immunity to worms by activating eosinophils
Binds mast cells and basophils. Cross links when exposed to allergen
Lowest concentration
65
Thymus Independent Antigens
What is it?
What do they stimulate
Memory?
Ags lacking peptide component and thus cannot be presented on MHC to T cells
Stimulate release of Ab
Do not result in memory
66
Thymus Dependent Antigens
What is it?
What do they stimulate
Memory?
```
Ags containing protein component
Stimulate class switching
Memory results of direct contact of B cells w/ Th cells (CD40-CD40 Ligand interaction)
```
67
C3b
Opsonization
68
C3a and C5a
Anaphylaxis
69
C5a
Neutrophil Chemotaxis
70
C5b-9
Cytolysis by MAC
71
Complement Pathways
Classic: IgG and IgM
Alternative: Microbe Surface Molecule
Lectin: Mannose or other sugars on microbe surface
72
Opsonins
IgG and C3b
73
Inhibitors of Complement pathway
Decay-Accelerating Factor (DAF) and C1 esterase inhibitor
74
Alternative Complement Pathway
Spontaneous and Microbal Surfaces turn C3 into C3b
B --> [D] --> Bb
C3 --> [C3bBb (C3 Convertase)] --> C3a + C3b
75
Classic Complement Pathway
Ab --> C1
C2 --> [C1] --> C2a and C2b
C4 --> [C1] --> C4a and C4b
C3 --> [C4bC2a (C3 convertase)] --> C3a + C3b
76
Lectin Complement Pathway
Mannose Binding Lectin --> [MASP] --> C1-like Complex
C4 --> [C1LC] --> C4a + C4b
C3 --> [C4b2a] --> C3a + C3b
77
Common Complement Pathway
C3bBb3b (C5 convertase)
C4b2a3b (C5 convertase)
C5 --> [C5 convertase] --> C5a + C5b
C5b + C6 through C9) = MAC
78
C1 Esterase Inhibitor Deficiency
Presentation
Contraindications
Hereditary Angioedema
| ACE inhibitors Contraindicated
79
C3 Deficiency Presentation
Severe, recurrent pyogenic sinus and respiratory tract infections
Susceptibility to Type III hypersensitivity reactions
80
C5-C9 Deficiency
Recurrent Neisseria Bacteremia
81
DAF (GPI anchored enzyme) deficiency
Complement mediated lysis of RBCs and Paroxysmal Nocturnal Hemoglobinuria
82
IL1
Secreted by what cell?
Function
Macrophages
Endogenous pyrogen. Causes fever, acute inflammation, activates endothelium to express adhesion molecules, Induces chemokine secretion to recruit leukocytes
83
IL6
Secreted by what cell?
Function
Macrophages and TH2
| Endogenous pyrogen. Fever and Production of acute phase proteins
84
IL8
Secreted by what cell?
Function
Macrophages
| Neutrophil chemotactic
85
IL12
Secreted by what cell?
Function
Macrophages and B cells
Induces differentiation of Th1 cells
Activate NK cells
86
TNFα
Secreted by what cell?
What does it mediate?
Function
Macrophages
Mediates septic shock
Activates endothelium, Leukocyte recruitment, Vascular leak
87
Interleukin Mnemonic
```
"Hot T-Bone stEAk"
IL1: Hot (fever)
2: stimulate T cells
3: Stimulates Bone marrow
4: IgE
5: IgA
```
88
Cytokines secreted by all T cells w/ function
IL2: Stimulates growth of Th, Tc, and Treg cells
IL3: Supports growth and differentiation of bone marrow stem cells (like GM CSF)
89
Interferon-γ
What kind of cells secrete it?
Function
Th1 cells
Activate Macrophages and Th1 cells
Suppresses Th2 cells
Antiviral and antitumor properties (upregulates MHCI and MHCII and Ag presentation in all cells)
90
Cytokines secreted by Macrophages
1, 6, 8, 12, TNFα
91
Cytokines secreted by Th2 cells
4, 5, 6, 10
92
IL4
What kind of cells secrete it?
Function
Th2
Induces differentiation into Th2 cells
Promotes growth of B cells
Enhances class switching to IgE and IgG
93
IL5
What kind of cells secrete it?
Function
Th2
Promotes differentiation of B cells
Enhances class switching to IgA
Stimulates Eosinophils
94
IL10
What kind of cells secrete it?
Function
Like what other molecule
Th2 and Treg
Modulates immune response
Inhibits actions of activated T cells and Th1
Similar to TGFβ in that it inhibits inflammation
95
Interferon
Kinds
Function
α, β, γ
Place uninfected cells in an antiviral state
Induce production of ribonuclease that inhibits viral protein synthesis by degrading viral mRNA
Activate NK cells
96
IFNα and IFNβ function
Inhibit viral protein synthesis
97
T cell surface markers
Th
Tc
T: TCR, CD3 (associated with TCR), CD28 (binds B7 on APC)
Th: CD4, CD40 lingand
Tc: CD8
98
B cell surface markers
"Drink Beer at the Bar when you're 21"
| Ig, CD19, CD20, CD21 (EBV receptor), CD40, MHCII, B7
99
Macrophage surface markers
CD14, CD40, MHCII, B7, Fc receptor, C3b receptor
100
NK cell surface markers
CD16 (binds Fc of IgG), CD56
101
Anergy
What is it?
B vs T
Self-reactive T cells become non reactive without costimulatory molecule
B cells also become anergic but tolerance is less complete than in T cells
102
Superantigen
Produced by what?
Mechanism
S Pyogenes and S aureus
| Cross link β region of T cell receptor to MHCII on APC activating T cell and producing massive release of cytokines
103
```
Endotoxin
AKA
Made by what?
Receptor?
Other cells involved?
```
Lipopolysaccharide
Gram neg
Directly stimulate Macrophages by binding to CD14
Th not involved
104
Classic Antigen Variation in Bacteria
Salmonella (2 flagellar variants), Borrelia (relapsing fever), Neisseria gonorrhoeae (pilus protein)
105
Classic Antigen Variation in Viruses
Influenza
Major = Shift
Minor = Drift
106
Classic Antigen Variation in Parasites
Trypanosomes (programmed rearrangement)
107
```
Passive Immunity
Means of acquisition
Onset
Duration
Examples
```
Receiving preformed Abs
Rapid
Short (Ab half life is 3 weeks)
IgA in breast milk, Antitoxin, Humanized monoclonal Abs
108
Diseases in which patients are given preformed Abs as treatment?
"To Be Healed Rapidly"
| Tetanus toxin, Botulinum toxin, HBV, Rabies virus
109
```
Active Immunity
Means of acquisition
Onset
Duration
Examples
```
Exposure to foreign Ag
Slow
Long lasting
Natural infection, vaccines, toxoid
110
Combined passive and active immunization can be given in the case of...
HBV or Rabies
111
Live Attenuated Vaccine
What kind of response does it generate?
Examples
Cellular response
| Measles, Mumps, Rubella, Varicella, Yellow Fever, Polio (Sabin)
112
Inactivated or Killed Vaccine
What kind of response does it generate?
Examples
Humoral Immunity
| Cholera, HAV, Rabies, Polio (Salk)
113
Hypersensitivity Reactions that are Ab mediated?
I, II, and III
114
```
Type I Hypersensitivity Reaction
Description
Process
Onset
Test
```
Anaphylactic and Atopic
Free Ag cross-links IgE on presensitized mast cells and basophils triggering release of vasoactive amines that act at post-capillary venules (histamine)
Rapid because of preformed Ab
Skin test for specific IgE
115
```
Type II Hypersensitivity Reaction
Description
Process
Mechanisms
Test
```
Cytotoxic. Ab mediated
IgM, IgG bind to fixed Ag on "enemy" cell leading to cellular destruction
Opsonization, Complement activation, Ab-Dependent Cell-Mediated cytotoxicity (ADCC) due to NK cells
Direct and Indirect Coombs' Test
116
Type III Hypersensitivity Reaction
Description
Process
Immune Complex
| Ag-Ab (IgG) complex activates complement which attracts Neutrophils which release lysosomal enzymes
117
```
Serum Sickness
What is it?
PathoPhys
Timeframe
Frequency
What causes it?
Presentation
```
Immune Complex Disease
ICs are deposited in membranes where they fix complement leading to tissue damage
5-10 days after exposure
More common than Arthus
Drugs acting as haptens
Fever, Urticaria, Arthralgias, Proteinuria, Lymphadenopathy
118
```
Arthus Reaction
What is it?
PathoPhys
Presentation
Test
Frequency
```
Local Subacute Ab mediated hypersensitivity type III reaction
Intradermal injection of Ag induces Abs which form Ag-Ab complexes in the skin which activate complement
Edema, Necrosis
Immunofluorescent staining
Less common than serum sickness
119
```
Type IV Hypersensitivity Reaction
Description
Process
Transferable?
Mnemonic
Test
```
Delayed T cell mediated reaction
Sensitized T lymphocytes encounter Ag and release lymphokines leading to macrophage activation. No Ab involvement
Not transferable in serum
"4Ts: Tcells, Transplant rejection, TB skin test, Touching (contact dermatitis)"
Patch test, PPD
120
Hypersensitivity Reactions
```
"ACID"
I: Anaphylactic and Atopic
II: Cytotoxic
III: Immune Complex
IV: Delayed (cell mediated)
```
121
Examples of Type I Hypersensitivity Reactions
Anaphylaxis (allergy)
| Allergic and Atopic disorders (Rhinitis, Hay Fever, Eczema, Hives, Asthma)
122
Examples of Type II Hypersensitivity Reactions
```
"Go PIE TRAP"
Goodpasture's Syndrome
Pernicious Anemia
Idiopathic Thrombocytopenic Purpura
Erythroblastosis Fetalis
Acute Hemolytic Transfusion Reaction
Rheumatic Fever
Autoimmune Hemolytic Anemia
Bullous Pemphigoid, Pemphigus Vulgaris
```
123
Examples of Type III Hypersensitivity Reactions
```
"LAPPS"
SLE
Arthus
Polyarteritis nodosa
PSGN
Serum Sickness
```
124
Examples of Type IV Hypersensitivity Reactions
```
"Ms PuGG's CD"
MS
PPD test for TB
Gullian Barre
Graft vs Host
Contact Dermatitis (Poison Ivy, Nickel allergy)
```
125
Allergic Reaction to blood transfusion
Type
Presentation
Treatment
Type I
Urticaria, Pruritus, Wheezing, Fever
Antihistamines
126
Anaphylactic Reaction to blood transfusion
Severity
Precaution
Presentation
Severe
IgA deficient individuals must receive blood that lacks IgA
Dyspnea, Bronchoconstriction, Hypotension, Respiratory Arrest, Shock
127
Febrile NonHemolytic Transfusion Reaction (FNHTR)
Type
Mechanism
Presentation
II
Host Ab against donor HLA Ags and leukocytes
Fever, Headaches, Chills, Flushing
128
Acute Hemolytic Transfusion Reaction (AHTR)
Type
Mechanism
Presentation
```
II
Intravascular hemolysis (ABO blood group incompatibility) or Extravascular hemolysis (host Ab reaction against foreign Ag or donor RBC)
Fever, Hypotension, Tachycardia, Flank Pain, Hemoglobinemia (intravascular), Jaundice (extravascular)
```
129
```
ANA
Anti dsDNA, Anti Smith
Anti-Histone
RF, CCP
Anti centromere
Anti Scl70 (topoisomerase)
```
```
SLE, nonspecific
SLE
Drug induced SLE
RA
CREST
Scleroderma (diffuse)
```
130
Anti-Mitochondiral
IgA anti endomysial, IgA anti Tissue Transglutaminase
Anti BM
Anit Desmoglein
Primary Biliary Cirrhosis
Celiac Disease
Goodpasture's Syndrome
Pemphigus vulgaris
131
Anti-Microsomal, Anti-Thyroglobulin
Anti Jo1, Anti SRP, Anti Mi2
Anti SSA, Anti SSB
Anti U1 RNP
Hashimoto's Thyroiditis
Polymyositis, Dermatomyositis
Sjogren's
Mixed connective tissue disease
132
Anti Smooth Muscle
Anti Glutamate Decarboxylase
cANCA
pANCA
Autoimmune hepatitis
DM1
Wegeners
Microscopic polyangiitis, Churg Strauss syndrome
133
No T cells
Bacteria
Virus
Fungi/Parasites
Sepsis
CMV, EBV, VZV, Chronic Respiratory and GI viruses
Candida, PCP
134
No B cells
Bacteria
Virus
Fungi/Parasites
Encapsulated bacteria "SHiN SKiS"
Enteroviral Encephalitis, Poliovirus
GI Giardiasis (no IgA)
135
No Granulocytes
Bacteria
Virus
Fungi/Parasites
Staph, Burkholderia cepacia, Serratia, Nocardia
N/A
Candida, Aspergillus
136
No Complement
Bacteria
Virus
Fungi/Parasites
Neisseria
N/A
N/A
137
```
X linked (Burton's) Agammaglobinemia
PathoPhys
Inheritance
Presentation
Findings
```
Defect in BTK (a tyrosine kinase gene) --> no B cell maturation
Recurrent bacterial infections (bacteria, enterovirus, Giardia- get these 3 whenever defect in immunoglobulins) after 6 months of age
Norma pro-B cells, ↓ # of B cells, ↓ Immunoglobulins of all classes
138
Selective IgA Deficiency
Frequency
Presentation
Labs
Most common primary immunodeficiency
Majority Asymptomatic. Sino-Pulmonary Infections, GI infections, Autoimmune disease, Anaphylaxis to IgA containing blood products
Low IgA with normal IgM and IgG. False positive βhCG test due to heterophile Ab
139
```
Common Variable Immunodeficiency (CVID)
PathoPhys
Epidemiology
Risks
Labs
```
Defect in B cell maturation by many causes
Acquired in 20s-30s
Infections with bacteria, enterovirus, Giardia- get these 3 whenever defect in immunoglobulins
Autoimmune disease**, Lymphoma**, Sinopulmonary infections
Normal # of B cells with ↓ Plasma cells and Immunoglobulin
140
```
Thymic Aplasia
Name
PathoPhys
Genetics
Presentation
Labs
XR
```
DiGeorge Syndrome
Failure to develop 3rd and 4th Pharyngeal Pouches
22q11 deletion
Tetany (hypocalcemia), Recurrent viral/fungal infections (T cell deficiency), Congenital Heart and Great Vessel Defect
↓ T cells, ↓ PTH, ↓ Ca
Absent Thymic Shadow on CXR
141
IL12 Receptor Deficiency
PathoPhys
Presentation
Labs
↓ Th1 response
Disseminated Mycobacterial Infections
↓ IFNγ
142
```
Hyper IgE Syndrome
Name
PathoPhys
Presentation
Labs
```
Job's Syndrome
Th1 cells fail to produce IFNγ leading to inability to attract neutrophils
"FATED"
course Facies, cold (non inflamed) staphylococcal, Abscesses, retained primary Teeth, ↑IgE, Dermatologic problems (eczema)
↑IgE
143
Chronic Mucocutaneous Candidiasis
PathoPhys
Presentation
T cell dysfunction --> Candida albicans infection of skin and mucous membrane
144
```
Severe Combined Immunodeficiency
Kind of disorder
PathoPhys
Presentation
XR
Histo
Blood
Treatment
```
Combined B and T cell disorder
Defective IL2 receptor (most common, X linked) or Adenosine Deaminase deficiency
Failure to thrive, Chronic Diarrhea, Thrush. Recurrent viral, bacterial, fungal, and protozoal infections
No Thymic shadow
No Germinal centers on lymph node biopsy, ↓ T cell recombinant Excision Circles (TREC)
No B or T cells in peripheral blood
Bone Marrow Transplant
145
Ataxia Telangiectasia
PathoPhys
Presentation
Labs
Defect in ATM gene coding for DNA repair enzyme
Cerebellar defects (ataxia), Spider angiomas (Telangiectasia), IgA deficiency
↑AFP
146
Hyper IgM Syndrome
PathoPhys
Presentation
Antibodies
Defective CD40L on Th cells = inability to class switch
Severe pyogenic infections in early life
↑IgM, ↓ IgG, IgA, and IgE
147
```
Wiskott-Aldrich Syndrom
Inheritance
PathoPhys
Presentation
Labs
```
XL
WASP gene mutation = T cells unable to reorganize actin cytoskeleton
"TIE"
Thrombocytopenic Purpura, Infections, Eczema
↑IgE, ↑IgA, ↓IgM, Thrombocytopenia
148
```
Leukocyte Adhesion Deficiency Type 1
Dysfunction of what?
PathoPhys
Presentation
Findings
```
Phagocyte Dysfunction
Defect in LFA1 integrin (CD18) protein on phagocytes
Recurrent bacterial infections, absent pus formation, Delayed separation of umbilical cord
Neutrophilia
149
```
Chediak Higashi Syndrome
Dysfunction of what?
Inheritance
PathoPhys
Presentations
Histo
```
Phagocyte dysfunction
AR
Defect in lysosomal trafficking regulator gene --> MT dysfunction in phagosome-lysosome fusion
Recurrent pyogenic infections by Staph and Strep, Partial Albinism, Peripheral Neuropathy
Giant Granules in Neutrophils
150
```
Chronic Granulomatous Disease
Dysfunction of what?
PathoPhys
Presentation
Diagnostic test
```
Phagocyte dysfunction
Lack of NADPH oxidase --> ↓ ROS and absent respiratory burst in neutrophils
Susceptibility to catalase + organisms (S aureus, E coli, Aspergillus)
Abnormal dihydrorhodamine (DHR) flow cytometry test
Nitroblue Tetrazolium due reduction test no longer preferred
151
Synteneic Graft
Graft from Identical Twin or Clone
152
Hyperacute Transplant rejection
Onset after transplantation
PathoPhys
Presentation
Minutes
Type II: Preformed antidonor Ab
Occludes graft vessels causing ischemia and necrosis
153
```
Acute Transplant rejection
Onset after transplantation
PathoPhys
Reversible?
Histo
```
Weeks
Cell mediated reaction: CTLs react against foreign MHC
Reversible with immunosuppression
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
154
```
Chronic Transplant rejection
Onset after transplantation
PathoPhys
Reversible?
Histo
```
Months to years
Non-self MHCI recognized as self and presents non-self Ag
Irreversible
T cell and Ab mediated vascular damage (obliterative vascular fibrosis), Fibrosis of graft tissue and blood vessels
155
```
Graft Vs Host Disease
Onset after transplantation
PathoPhys
Presentation
What kind of transplants
When can it be potentially beneficial?
```
Varies
Grafted T cells attack host
Maculopapular rash, Jaundice, HSM, Diarrhea
Usually in Bone Marrow and Liver Transplants
Potentialy beneficial in Bone Marrow Transplant
156
Cyclosporine
MoA
Use
Tox
Binds Cyclophilins. Complex blocks differentiation and activatino of T cells by inhibiting Calcineurin thereby preventing production of IL2 and its receptor
Suppress organ rejection. Autoimmune disorders
Nephrotoxicity, HTN, Hyperlipidemia, Hyperglycemia, Tremor, Gingival Hyperplasia, Hirsutism
157
```
Tacrolimus
AKA
MoA
Use
Tox
```
FK506
Binds FK binding protein thereby inhibiting calcineurin and secretion of IL2 and other cytokines
Organ transplant
Nephrotoxicity, HTN, Hyperlipidemia, Hyperglycemia, Tremor
158
```
Sirolimus
AKA
MoA
Use
Tox
```
Rapamycin
Inhibits mTOR thereby inhibiting T cell proliferation in response to IL2
Kidney transplant w/ cyclosporine and corticosteroids. Drug Eluting Stents
Hyperlipidemia, Thrombocytopenia, Leukopenia
159
Azathioprine
MoA
Use
Tox
Antimetabolite precursor to 6MP that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes
Kidney transplantation, Autoimmune disorders (including glomerulonephritis and hemolytic anemia)
Bone Marrow Suppression
160
```
Muromonab CD3
AKA
MoA
Use
Tox
```
OKT3
Ab that binds CD3 on T cell surface. Blocks cellular interaction with CD3 protein responsible for T cell signal transduction
Kidney Transplant
Cytokine release syndrome, Hypersensitivity Reaction
161
Recombinant IL2
Name
Use
Aldesleukin
| Renal Cell Carcinoma, Metastatic Melanoma
162
Recombinant EPO
Name
Use
Epoetic Alfa
| Anemias (especially renal failure)
163
Recombinant Granulocyte CSF
Name
Use
Filgrastim
| Recovery of bone marrow
164
Recombinant Granulocyte Macrophage CSF
Name
Use
Sargramostim
| Recovery of Bone Marrow
165
Recombinant IFNα Use
HBV, HCV, Kaposi Sarcoma, Leukemias, Malignant Melanoma
166
Recombinant IFNβ Use
MS
167
Recombinant IFNγ Use
Chronic Granulomatous Disease
168
Recombinant IL11
Name
Use
Oprelvekin
| Thrombocytopenia
169
Recombinant Thrombopoietin Use
Thrombocytopenia
170
Omalizumab
anti IgE Ab used in asthma
171
Rituximab
Anti CD20 Ab used in B cell Non-Hodgkin's Lymphoma
172
Abciximab
Anti GP IIb/IIIa Ab used to prevent cardiac ischemia in unstable angina and in pts treated with percutaneous coronary intervention
