Immuno Flashcards

1
Q

What is the distribution of immune cell composition in healthy humans?

A
Neutrophil (40-75%)
Lymphocyte (20-50%)
Monocyte (2-10%)
Eosinophil (1-6%)
Basophil (
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2
Q

What is a form of B cell hyperplasia?

A

Multiple Myeloma

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3
Q

What is a form of T cell hyperplasia?

A

Leukemia, lymphoma

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4
Q

What are the functions of the immune system?

A

protection

surveillance

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5
Q

What is the difference between an immunogen and an antigen?

A

immunogen leads to a productive immune response

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6
Q

What are the characteristics of innate immune system?

A

not specific
includes barriers, complement, cytokines
phagocytic
fast-minutes to hours

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7
Q

What are the characteristics of adaptive immune system?

A

variable
days
B and T lymphocytes

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8
Q

Why are infants and the elderly more susceptible to infections?

A

infants-incomplete immune system

elderly-weaker response, no new T cells

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9
Q

How does nutrition impact the immune system?

A

less zinc and iron available

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10
Q

What are some properties of cytokines?

A
secretion is limited
most paracrine (can be autocrine or juxtacrine)
more than one affect-pleiotropic
overlapping-redundant
antagonistic or synergistic
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11
Q

What are chemokine functions?

A

stimulate directional migration of leukocytes
activate integrins
leukocyte activation
chemotaxis

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12
Q

What are inflammatory chemokines?

A

turned on by infection and stimulate inflammation

examples-IL8, MCP-1, MIP3a, MIP1alpha, IP-10

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13
Q

What are lymphoid chemokines?

A

expressed in lymphoid organs, mediate recirculation, constitutively expressed
examples-SLC, BLC, MIP3alpha, SDF-1

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14
Q

How do cytokine receptors signal?

A

signal mostly through JAK/STAT

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15
Q

What does stem cell factor do?

A

released from bone marrow stroma

renewal and induce differentiation into pluripotent stem cell

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16
Q

What does IL7 do?

A

stimulates lymphoid progenitor

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17
Q

What does IL3 do?

A

induces maturation early in myeloid lineage

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18
Q

What cytokines act on neutrophils to mature?

A

IL3, GM-CSF, G-CSF

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19
Q

What cytokines act on monocytes to mature?

A

IL3, GM-CSF, M-CSF

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20
Q

What activates the classical pathway?

A

antibodies (IgM and IgG)

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21
Q

What are anaphylatoxins and how do they work?

A
stimulate cellular degradation by acting as a chemotactic for neutrophils
increase vascular permeability
smooth muscle contraction
histamine release from mast cells
C5a phagocytosis via CR1 on macrophages
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22
Q

What is the C3 convertase in the classical pathway?

A

C4b2a

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23
Q

What is the C5 convertase in the classical pathway?

A

C4b2a3b

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24
Q

What activates the alternate pathway?

A

random deposition of C3b

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25
What is the C3 convertase in the alternate pathway?
C3bBb
26
What is the C5 convertase in the alternate pathway?
C3bBb3b
27
What are the cofactors in the alternate pathway?
B, D, properdin
28
What activates the lecithin pathway?
Mannose binding lectin or ficolins binding to carbohydrates
29
What cleaves C2 and C4 in the lecithin pathway?
MASP (MBL associated serine protease)
30
What is opsonization?
C3b which is recognized by phagocytes | enhances phagocytosis of microbes
31
What are the complement receptors on phagocytic cells?
1, 3, 4 (kiss of death)
32
What complement receptor functions as a costimulator of B cells?
CR2
33
What does DAF do?
membrane inhibitor | dissociates C4b, C3b
34
What does MCP do?
membrane inhibitor | dissociates C4b, C3b, promotes cleavage by Factor 1
35
What does C1 inhibitor do?
prevents proteolytic activity of C1 complex
36
What do CD59 and S protein do?
prevent assembly of MAC
37
What is the antigenic determinant?
exact area of recognition on antigen
38
What is the immune system capable of seeing?
``` chemicals nucleic acids carbohydrates lipids peptides ```
39
How do B and T cells differ in what they can recognize?
B-anything T-peptide increasing size increases immunogenicity
40
What is the immunodominant epitope?
dominate over others in the elicitation of immune responses
41
What is cross reactivity?
recognizing ligand will see antigen but may also see an unrelated antigen example-M cells after strep infection
42
What is a hapten and how does it cause anemia?
hapten-non immunogenic but can interact with a carrier protein to become immunogenic example-penicillin binding to RBC-->causes anemia
43
What is the purpose of a booster vaccine?
memory response to maintain level of antibody
44
What is passive immunization?
immunoglobulin | maternal to fetal transmission
45
What is active immunization?
live attenuated inactivated or killed nucleic acid
46
What is antigenic sin?
immunodominant epitope dominate the response and mask the new epitopes that on their own might elicit a response
47
What are the two forms of antibodies?
B cell receptor | secreted antibodies
48
What are the functions of antibodies?
neutralize toxins prevent entry and spread of pathogens eliminate microbes
49
What is the constant region?
little genetic variation imparts function of antibody defines isotype
50
What is the variable region?
determines binding of antigen | ratio of kappa to lambda is 2:1
51
What is the hypervariable region?
forms the antigenic determinant | also called the complimentary determining regions
52
What is the importance of the hinge region?
flexibility | important in B cell activation-crosslinking
53
What is the difference between affinity and avidity?
affinity-single Ab-Ag complex | avidity-overall strength of attachment
54
What is significant about IgG?
activates complement crosses placenta osponization sensitize NK cells
55
What is significant about IgM?
heaviest-pentamer can neutralize activates complement
56
What is significant about IgA?
dimeric-cross via an accessory Poly Ig receptor | can cross epithelium
57
What is significant about IgE?
short half life | coat mast cells, allow release of granules upon allergic binding
58
What is the difference between the primary and secondary response?
antibodies initially IgM switch to IgG second response-higher concentration, shorter time, increased affinity
59
How are monoclonal antibodies formed?
collect B cells and place in myeloma and then look for antibodies
60
What is isotype?
epitopes on constant region and show no variation within a species
61
What is allotype?
epitopes in constant region that show variation within a species
62
What is idiotype?
epitopes in variable region that show variation within the same individual (IgM for different pathogens)
63
How is MHC I organized in humans genetically?
set of 3 genes (A, B, C) | located on chromosomes 6
64
How is MHC II organized in humans genetically?
set of 3 genes (DP, DQ, DR) | located on chromosome 6
65
What factors contribute to variation in MHC?
``` co-dominance-both parental alleles equally represented polymorphism-different alleles polygenic-can express all 3 class I and up to 4 class II ```
66
What is the structure of MHC I?
peptide bonding at alpha 1 and alpha 2 alpha 3 recognizes CD8 beta 2 microglobulin is conserved portion
67
What is the structure of MHC II?
peptide bonding at alpha 1 and beta 1
68
Where is MHC I expressed?
all nucleated cells
69
Where is MHC II expressed?
only professional APCs (dendritic cells, macrophages, B cells)
70
What polymorphism is associated with New Guinea?
HLA-A11 | impacts EBV
71
What polymorphism is associated with West Africa?
HLA-B53 | associated with recovery from malaria
72
What happens in Bare Lymphocyte syndrome I?
missing MHC I | leads to bacterial infections but no problem with viral infections
73
What happens in Bare Lymphocyte syndrome II?
missing MHC II leads to impaired CD4 development fatal unless bone marrow transplant
74
What innate immune cells are located in the tissue?
macrophage dendritic mast cell
75
What innate immune cells are located in the blood?
eosinophils basophils neutrophils
76
What do pattern recognition receptors do? What are some specific examples of what they recognize?
``` recognize patterns in PAMPs or DAMPs viral-dsRNA, ssRNA bacteria-LPS, flagellin fungal-mannoproteins parasite-glycosylinositol ```
77
How do toll like receptors work?
signal through MyD88 | activate NFKB
78
What are NOD receptors?
cytoplasmic
79
What are RIG like receptors?
cytoplasmic, recognize virus
80
What are scavenger receptors?
recognize phosphatidylserine | sign of cell damage for apoptosis
81
What is the local effect of TNF alpha?
inflammation
82
What are the systemic effects of TNF alpha?
brain-fever liver-acute phase protein synthesis low output for heart thrombosis and coagulation
83
What can lead to septic shock?
IL 1,6, TNF alpha
84
What is the timeline of reaction to a viral infection and how does this happen?
secretion of IL12, TNF alpha/beta, IFN beta NK responds to 12/alpha in return they upregulate MHC I expression NK starts the killing and cytotoxic T cells mediate the final killing
85
What do neutrophils do?
short half life migrate to sites due to recruitment by macrophages killing through ROS, NO, defensins, enzymes end in formation of NETS (neutrophil extracellular traps) to immobilize pathogen
86
What do eosinophils do?
fight parasitic infection active in allergic responses recognized via FcR, trigger IgE response
87
How is MHC I processed?
``` cytosolic broken by proteases calnexin binds MHC in ER next complex calreticulin/ERp57/Tapsin peptide enters by TAP and bind in ER ```
88
How is MHC II processed?
``` extracellular degraded by cathepsin MHC I in ER binds invariant CLIP remains, CLIP degraded by HLA-DM endosomes meet and binding can occur ```
89
What is expressed to change an immature DC into a mature DC?
expression of CCR7 | now it goes to the lymph node
90
What are characteristics of a plasmocytoid dendritic cell?
B220 antiviral secrete INF-1
91
What are characteristics of a conventional dendritic cell?
CD11 good for tissue immunity secrete IL6, IL12, TNF
92
What is cross presentation?
extracellular that is presented via CD8/MHCI | helpful with viruses so that they do not infect the dendritic cells
93
What are the components of the TCR?
alpha/beta chains with CD3 co-receptor of CD4 or CD8 contain ITAMS for downstream signaling
94
What is MHC restriction? What is allorecognition?
MHC-bias to self MHC set in thymus normally won't see foreign MHC can if there is allorecognition
95
What are the costimulatory signals for TCR?
CD28 and B7
96
What adhesion molecules are necessary for TCR?
LFA-1 and ICAM (on APC)
97
What two events does DAG participate in during the signal transduction?
PKC-->NKFbeta | Activate Ras-->AP-1
98
What does IP3 cause in signal transduction?
Increase in Ca | Calcinerin activation-->NFAT
99
What does B7 on the APC bind to and what is the result?
CD28 on T cell, signal leads to IL2R on T cell DC produces IL2 to have T cell divide clonally divide
100
What changes occur as a cell goes from a naive T cell to an effector T cell?
Loss of L selectin Gain VLA4 Increase LFA1
101
What signal and transcription factor for Treg cells? What do they produce?
TGFbeta via FOXP3 | produce TGFbeta and IL10
102
What signal and transcription factor for Th17 cells? What do they produce?
TGFbeta and IL6 via RORyT (Irish man with liver issues-acute phase also) produce IL6 and IL17
103
What signal and transcription factor for Th1 cells? What do they produce?
IL12 and IFN gamma via Tbet | produce IL2 and IFN gamma
104
What signal and transcription factor for Th2 cells? What do they produce?
IL4 via GATA3 | produce IL4 and IL5
105
How does Th1 cell function?
macrophage activation requiring IFN gamma and IL 12 induces expression of CD40L converts macrophage into better phagocyte by secreting IL1, IL12
106
What do Th17 cells do?
secrete inflammatory chemokines that recruit and activate neutrophils important in IBS, psoriasis, multiple sclerosis, arthritis
107
What is perforin?
aids in delivering granzymes
108
What are granzymes?
serine proteases which activate apoptosis
109
What is Fas?
FasL expression leads to Fas/FasL interaction leading to activation of apoptosis
110
How are memory cells formed?
Rely on IL7, 15 for survival and MHC peptide
111
How is the T cell response terminated?
expression of CTLA4 to compete with binding for B7
112
Where does antigen independent B cell maturation occur?
bone marrow
113
What is characteristic of Pro B cells?
CD19 expression growth by IL7 heavy chain VDJ recombination
114
What is characteristic of Pre B cells?
surrogate light chain | VJ recombination
115
What is VDJ recombinaton?
mediated by VDJ recombinase activating RAG1/RAG2
116
What Immunoglobulin is formed first?
IgM
117
Which light chain is formed first?
kappa
118
What is characteristic of immature B cells?
has IgM | undergoes negative selection-exposed to self antigens-->die if they recognize
119
Where does the antigen dependent phase occur?
lymph node
120
What is characteristic of a mature B cell?
IgM and IgD | naive until they see an antigen and undergo clonal selection
121
What is characteristic of a pro T cell?
no CD8, CD4 or TCR proliferate with IL7 beta chain recombination
122
What is characteristic of a pre T cell
beta chain present and CD3 | VJ recombination
123
What is characteristic of a double positive T cell?
complete T cell receptor | positive and negative selection will occur
124
What is positive selection for a T cell?
must be able to recognize MHC
125
What is negative selection for a T cell?
exposed to macrophages (if bind with high affinity they die)
126
What happens to a single positive T cell?
leave thymus and enter circulation | clonal selection when they encounter an antigen
127
What is the order of maturation in the thymus?
cortex to medulla
128
What is combinatorial diversity?
different combinations of VDJ
129
What is junctional diversity?
different nucleotides added by TdT
130
What causes X linked agammaglobulinemia?
BTK defect
131
What is missing in Di George syndrome?
thymus so no T cells
132
What is missing in X linked SCID?
no gamma gene so IL7 is defective | T cells do not develop
133
What does the BCR require?
Ig alpha beta coreceptors
134
What is part of the coreceptor complex?
CD19, CD21, CD81
135
What is important about T independent B cell antigens?
little B cell memory
136
Where does the B cell pick up its antigen?
follicular dendritic cell
137
What happens in the interaction between B cell and Th2 cell?
meet at para-cortical junction T cell makes CD40L produce IL4,5,6 B cell moves into follicle-->germinal center for proliferation and differentiation
138
How does IgG form?
IFN gamma
139
How does IgA form?
TGF beta
140
How does IgE form?
IL-4
141
How does IgM form?
IL 2
142
What is somatic hypermutation?
mutations in CDR3 to incrase affinity
143
What are memory B cells?
leave germinal center
144
What keeps a germinal center from dying?
CD40L from follicular Th cells
145
What is neutralization?
block toxin blocks virus against adhesins to block colonization
146
What is ADCC?
Fc receptors on NK cells recognize antibody and crosslink | IgG helps with apoptosis
147
What is necessary for eosinophil activation?
IgE for IL5
148
What is important about a polysaccharide vaccination?
activating Th and B when a protein is added to a polysaccharide
149
What does a paneth cell do?
secrete antimicrobial defensins
150
What does the epithelial cell do?
secrete defensins, mobilize pathogens with cilia
151
What do goblet cells do?
secrete mucus
152
What takes up antigens and where are they presented?
M cells take up antigen and present them to Peyers Patches to activate lymphocytes
153
How doe a lymphocyte home to blood vessel?
alpha4beta7 binding to MADCAM1
154
How does a lymphocyte home to gut epithelium (lamina propria)?
CCR9 binding to CCL25
155
How does a lymphocyte home to gut epithelium?
alphaEbeta7 binding to E-cadherin
156
How does mucosal tolerance occur?
Treg cells secrete IL10 to make sure T cells do not over react to commensal bacteria
157
What is an oral vaccine?
rotavirus to increase IgA in GI
158
What is an intranasal vaccine?
influenza to secrete IgA in upper airway