export_immunology test 1 Flashcards
1
Q
Variolation
A
Inoculation of a small amount of pus or scaberous material from an infected individual
Goal= induce a milder form of the disease
2
Q
Herd immunity
A
When the majority of a population is immune it significantly reduces pathogen reservoir and lowers probability of an uninfected person contracting the disease
3
Q
Innate immunity
A
In place prior to infection
Rapid
Early defense
Responds same way to repeated exposures
Recognizes general structures of microbes
Limited diversity
Barriers: skin, mucosal epithelia, antimicrobial chemicals
Blood protein: complement
4
Q
Adaptive immunity
A
Provided by T and B lymphocytes
Response improves w/ subsequent exposure
Highly specific recognition system
Results in immunological memory
Large diversity
Barrier: lymphocytes in epithelia, Ab secreted at epithelial surfaces
Blood proteins: Ab
Cells: lymphocytes
5
Q
Phagocytes, NK cells
A
Examples of cells of innate immunity
6
Q
B lymphocytes, t lymphocytes, antibodies, effector t cells
A
Examples of cells of adaptive immunity
7
Q
Antigen
A
Any foreign substance that induces a specific immune response or is a target of such a response
8
Q
Humoral immunity
A
Mediated by B cells and results in antibody production and is most effective against extracellular microbes and their toxins
9
Q
Cell mediated immunity
A
Mediated by T cells and results in activation of phagocytes or killer cells and is most effective against intracellular microbes
10
Q
Humoral immunity
A
Extracellular microbes
B lymphocytes respond
Effector mechanism: secreted Ab
Transferred by serum
Functions: Block infections and eliminate extracellular microbes
11
Q
Cell-mediated immunity
A
Microbes: Phagocytosed microbes in macrophage
Responding lymphocyte: Helper T lymphocyte
Effector mechanism: T lymphocytes
Function: Activate macrophages to kill phagocytosed microbes
12
Q
Cell-mediated immunity
A
Microbe: intracellular microbes replicating w/ in infected cell
Responding lymphocyte: Cytotoxic T lymphocyte
Effector mechanism: T lymphocytes
Function: Kill infected cells and eliminate reservoirs of infection
13
Q
Active immunity
A
Induced by exposure to a foreign antigen
Has memory
14
Q
Passive immunity
A
Induced by the transfer of serum or lymphocytes from a specifically immunized individualt to a naive individual eg maternal Ab or antiserum
No memory
15
Q
Specificity, diversity, memory, clonal expansion, specialization, contraction and homeostasis, nonreactivity to self
A
Cardinal features of adaptive immune response (7)
16
Q
lymphocyte repertoire
A
Total number of antigenic specificities of the lymphocyte of an individual is called?
17
Q
Immunologically naive
A
Individuals and lymphocytes that have not encountered a particular antigen are?
18
Q
B lymphocytes
A
Only cells capable of producing Ab
Recognize extracellular antigens
Differentiate into plasma cells
Mediate humoral immunity
19
Q
T lymphocytes
A
Only recognize protein antigens presented to them by antigen presenting cells in the context of major histocompatability complex molecules
Provide help to other cells in the form of cytokines, or become killer cells which kill infected cells
Mediate cell mediated immunity
20
Q
Regulatory T cells
A
Mainly function to inhibit or limit immune responses
21
Q
Natural Killer cells
A
Involved in innate immunity to viruses
22
Q
Antigen presenting cells
A
Dendritic cells, macrophages, B cells
23
Q
B lymphocyte
A
Responds to microbes
Effector function: Neutralization of microbe, phagocytosis, complement activation
24
Q
Helper T lymphocyte
A
Effector functions: activation of macrophages, inflammation, activation of T and B lymphocytes
25
Cytotoxic T lymphocytes
Recognizes infected cell expressing microbial antigen
Kills infected cell
26
Regulatory T lymphocyte
Suppresses immune response
27
Natural killer cell
Kills infected cell
28
Cytokines
Large and heterogenous group of secreted proteins produced by many cell types that mediate and regulate many aspects of innate and adaptive immunity
29
Cytokines
May be inactive/active
Can be pleiotrophic,redundant, antagonize or synergize
Autocrine, paracrine, or endocrine
30
Innate immune response
Barriers: Skin and mucosa - continuous epithelia
Inflammation: Recruitment and activation of cells and plasma proteins from the blood to kill microbes
Antiviral defense: Cytokine- mediated response in which cells aquire resistance to viral infection, and killing of virus-infected cells by NK cells
31
Adaptive immune response
Ab- bind to extracellular microbes, block their ability to infect host cells, promote their ingestion and destruction by phagocytes
Phagocytes: Ingest microbes and kill them, helper T cells enhance microbicidal abilities of phagocytes
Cytotoxic T cells: Kill cells infected by microbes that are inaccessible to Ab and phagocytic destruction
32
Dendritic cells
Located in epithelia
Capture microbes and antigens
Travel thru lymphatic system to draining lymph nodes
Present antigen to naive T cells
33
naive B cells
WHole antigens or microbes in lymph are captured by ? in the lymph nodes
34
Helper T cells
Help other cells by secreting cytokines
Some remain in secondary lymphoid organs and provide cytokines to aid in activation of B cells while others exit organs and travel to site of infection and help to activate phagocytic cells
35
Cytotoxic T cells
Develop into effector cells
Go looking for infected cells and kill them
36
B cells
Make antibodies of the IgM calss, then depending on the type of T cell help they receive undergo a class switch to other ab types like IgA, IgG, or IgE with the same original antigen specifity but different functions
37
Affinity maturation
Some cells will undergo modification and produce antibodies w/ increased affinity for the antigen which is called?
38
Plasma cells
B cells differentiate into these which reside in the bone marrow and secrete antibodies for the life of the individual
39
Neutralizing antibodies
Bind to the surface of microbes and prevent them from infecting cells
40
Opsonizing antibodies
Target microbes for uptake and destruction by phagocytic cells
41
Production of memory cells
Ultimate goal of vaccination
42
Leukocytes
Most numerous blood cell
43
Basophils
Least numerous blood cell
44
Neutrophils
Mediate early inflammatory responses
Segmented nucleus, cytoplasm contains granules which don't stain well w/ dyes
Of the monocytic lineage
Short lived but act fast
45
Specific granules
Contain enzymes such as lysozyme, collagenase, and elastase
46
Azurophilic granules
Lysosomes containing other enzyme and microbicidal substances such as defensins and cathelicidins
47
Monocytes
Immature heterogenous circulating cells w/ little function
In blood
48
Macrophages
In tissue
Kill microbes, promote wound healing, resolve inflammatory responses
Guided by cytokines
Important for clearing apoptic cells
49
Apoptosis
Good death
Normal way cells turn over
Nuclear cleavage and breakdown of the cells into membrane encapsulated vesicles
These are recognized by macrophages and engulfed and destroyed w/ no leakage of cellular componenets
50
Necrosis
Bad death
Leads to disruption of the cell membrane and leakage of cellular contents (inflammatory)
51
Mast cells
Not normally in circulation
Reside beneath epithelial layers
Contain abundant granules filled w/ histamine and other vasoactive mediators
Coated w/ IgE Ab and are important in defense against helminths
Mediate allergic response
52
Basophils
Circulating blood granulocyte similar to mast cells
Coated w/ IgE, function in defense not certain
53
Eosinophils
Worm responses
Circulating blood granulocyte found lining mucosal sites
Granule enzymes are effective against parasitic infection but can also cause collateral damage to host cells
54
DC, B cells, and macrophages
What are the professional APCs?
55
Antigen presenting cells
Present antigen to T cells
56
Dendritic cells
Important for activating naive T cells
57
Macrophages
Important for antigen presentation to effector CD4 T cells at sites of infection
Causes the T cell to provide cytokine activation of the ? for enhanced microbial killing
58
B cells
Present antigen CD4 T cells in the lymph nodes and spleen and thereby receive help for antibody class switching
59
B and T lymphocytes
Cells of adaptive immunity
Express clonally distributed antigen receptors
60
T cells
Mature in thymus
61
CD3
Which marker is for all T cells?
62
ab Heterodimers except for gd T lymphocytes which use gd heterodimers
What do T cells use for antigen receptors?
63
CD4= II
CD8 = I
Which MHC complex do CD4+ use vs CD8+ T lymphocytes?
64
B cell differentiation
and
Macrophage activation
F ( CD4+ helper T lymphocytes)
65
Killing of infected cells and tumor cells
What is the function of CD8+ cytoxic T lymphocytes?
66
Suppresses other T cells so it regulates immune response
What is the function of Regulatory T cells?
67
Helper and cytotoxic functions
F ( gd T lymphocytes)
68
Ab production
F (B lymphocytes)
69
Killing of virus infected cells
F (NK cells)
70
Suppress/activate innate and adaptive immune response
F ( NKT cells)
71
NKT cells
What non T cell uses ab heterodimer as well?
72
Nk and NKT cells
Which cells use CD16 as markers?
73
Common lymphoid precursor > Bone marrow> blood lymph> lymph nodes and spleen> Mature
How do B lymphocytes mature?
74
Common lymphoid precursor> Thymus> Blood lymph> Mucosal and cutaneous lympoid tissues> Mature
How do T lymphocytes mature?
75
Nucleus: Naive
Activated: Cytoplasm
When does a lymphocyte have a lot of nucleus vs cytoplasm
76
Primary/central lymphoid organs
Where lymphocytes first express antigen receptors and attain their phenotypic and functional maturity
Thymus and bone marrow
77
Secondary/peripheral lymphoid organs
Where naive lymphocytes are activated and develop into effector cells
Spleen/lymph nodes
78
B lymphocytes, T lymphocytes, and NK cells
What does the common lymphoid progenitor give off?
79
Blood cells
What does the common myeloid progenitor give off?
80
Thymic dendritic cells
Present antigen to immature T cells and aid in their development
81
Thymocytes
Name for immature T cells
82
Lymph node
Location of initiation of adaptive immune responses to lymph borne antigens
83
Blood stream
How do naive lymphocytes enter the lymph node?
84
Dendritic cells thru afferent lymphatic vessels
How does antigen enter lymph nodese?
85
```
T= CCR7
B= CXCR5
```
What receptors do naive T and B cells use?
86
Spleen
Location where aging and damaged blood cells and opsonized microbes are removed and destroyed
87
Homing
Process of directing cells to their functional sites
88
Recruitment
Movement of cells from the circulation into sites of infection or injury.
Inflammation
89
Adhesion of the leukocytes to the enodthelial lining
What does leukocyte recruitment depend on?
90
Selectins
Mediates the initial step of Low affinity binding of leukocytes to endothelium
91
L selectin
Expressed on lymphocyte
| Helps naive T and B cells get out of vasculature at site of lymph node.
92
E and P selectins
On endothelial surface/side
| Expression is increased by TNF and IL-1
93
Integrins
Mediate increased binding of cells to endothelium
Can be on leukocyte or endothelium
Expression increased by cytokine
Leukocyte ones start as low affinity and become high affinity upon activation
94
Partially activated when encounters receptor
How are integrins activated?
95
Chemokines
Tell cells where to go
| Structurally homologous cytokines that stimulate leukocyte movement bot in homing and recruitment
96
CXC, CC, C, CXXXC
What are the classes of chemokines?
97
CXCL8 is a chemokine
| CXCR1 is a receptor
What is CXCL8 vs. CXCR1
98
Chemokines and cytokines flag down neutrophils causing a rolling movement. The flags are most concentrated at the center of the infection. Neutrophils slow down. At some point high affinity integrin is expressed which causes it to stop and flatten and crawl until it finds a spot where it can get b/t 2 endothelial cells and get to vasculature
How are leukocytes recruited into tissues?
99
L-selectin, CCR7, LFA-1
What are the naive T cell homing receptors?
100
E and P selectin ligand, CXCR3, CCR5, LFA 1, and VLA 4
What are the activated T cell receptors?
101
L selectin: L selectin ligand
CCR7: CCL19 or CCL21
LFA-1: ICAM-1
What are the ligands for the receptors of the naive T cells?
L selectin:
CCR7:
LFA-1:
102
E and P selection ligand: E of P selectin
CXCR3: CXCL10
CCR5: CCL4
LFA-1:ICAM or VCAM
What are the Activated T cell ligands?
E and P selectin ligand:
CXCR3
CCR5
LFA-1:
103
L selectin
Responsible for initial weak adhesion of naive T cell to high endothelial venule in lymph node
104
LFA w/ ICAM
Stable arrest on high endothelial venule in lymph node
105
E and P selectin ligand
Responsible for initial weak adhesion of effector and memory T cells to cytokine activated endothelium at site of infection
106
Activate integrins and chemokines
What do CCXR and CCXL's do?
107
Innate immunity
First line of defense against infection
Exists prior to encounter w/ microbe
Rapid response
Effective defense against most microbes, but pathogenic microbes can evade some defenses
Directs development of adaptive immunity
108
Not known consciously> Inflammation> Naive B and T cells (adaptive immune response)>Clonal expansion
Phases of initial immune response
109
Pathogens
Microbes that can cause disease
110
Virulence
Degree to which a pathogen can cause disease
111
Host sees it is being invaded
First step in innate immunity
112
Sentinel cells
Have surface receptors for molecules that are normally expressed by microbes, but never in higher animals
Recognize the presence of microbes
Live in tissues, not circulation
113
PAMPS (Pathogen-associated molecular patterns)
Microbial substances that stimulate innate immunity
| Recognized by pattern recognition receptors
114
Germline, limited diversity
Where are receptors of innate immunity made?
115
Somatic recombination of gene segments, greater diversity
Where are receptors of adaptive immunity made?
116
Innate: Nonclonal
Adaptive: Clonal
Is innate/adaptive clonal/nonclonal
117
Clonal
Copies of all lymphocytes w/ distinct specificities express different receptors
118
Adaptive
Does innate/adaptive have autoimmunity?
119
DAMPs or Damage associated molecular patterns
Endogenous molecules that are produced or released from damaged and dying cells
Recognized by immune system
Not typically released by apoptotic cells
120
LPS
What is the main thing that gets recognized on gram negative bacteria?
121
PRR recognizees teichoic acid, surface protein, and lipoteichoic acid
What recognizes what on gram positive bacteria?
122
TLR4 with LPS
What is the big TLR for gram negative bacteria?
123
1. TLR1 and 2
2. TLR2
3. TLR5
4. TLR 2 and 6
What are the TLRs for
1. Bacterial lipopeptides
2. Bacterial peptidoglycan
3. Bacterial flagellan
4. Bacterial lipopeptides
124
TLR 7 and 8
Which TLRs recognize ssDNA in the endosome?
125
MyD88 except TLR3 (thru TRP)
All TLRs go through _______ except ________ which signals thru _____
126
TLR3 w/ TRP
What signals interferon response genes to be activated and starts an antiviral response and signals to make type I interferons?
127
Macrophage mannose receptor
Binds terminal mannose and fucose residues of glycoproteins and glycolipids
128
Scavenger receptors
Bind to acetylated low density lipoproteins. Sialated in mammals but not microbes
129
N-formylmethionyl receptors
All bacterial proteins and few mammalian proteins are initiated w/ N-formylmethionine
130
Defensins
Small cationic peptides produced by epithelial cells, neutrophils, NK cells and CTL. Directly toxic to microbesand activate inflammatory cells
Have antibiotic effects
131
Cathelicidins
Produced by neutrophils and epithelial cells
| Produced as a precursor, cleavage stimulated by cutokines. Can bind and neutralize LPS
132
CD14
What is part of TLR4 binding to LPS?
133
Cytoskeletal changes > Migration into tissues
What does activation of the seven a-helical transmembrance receptors cause?
134
Killing of microbes
What does activation of TLRs or mannose receptors lead to?
135
NK cells
Cells of the lymphocyte lineage that recognize stressed or infected cells and directly kill them
136
Secreting IL-12 to NK cells and NK cells activating macrophage by secreting IF-y
What gives macrophages the extra added capability of killing microbes?
137
1. Kill things
| 2. Activate macrophages
2 functions of NK cells
138
2 receptors: activating and inhibitory (dominant)
If the inhibitory receptor is engaged, or the Class I MHC complex is present, the cell will not be killed
If the inhibitory complex is not engaged or if the MHC is inhibited, the cell will be killed.
How do NK cells kill things?
139
1. B-1 cells
2. Epithelial y:S cells
3. NKT cells
What are the innate like lymphocytes?
140
Make natural Ab
F (B-1 cells)
141
Produce cytokines rapidly
F( Epithelial y:S and NKT cells)
142
MHC class IB
What are the ligands of the Epithelial y:S cells?
143
Lipids bond to CD1
What is the ligand and what is it bound to of the NKT cells?
144
No
Can innate like lymphocytes be boosted?
145
B-1 cells
Present in peritoneal cavity and spleen
Limited receptor diversity
Specific for polysaccharide and lipid antigens
Produced w/o evidence of infection
Mainly IgM
146
T-independent antigen
What makes IgM?
147
Binds to microbes and activates complement
What does IgM do?
148
Opsonins
Soluble molecules that bind to the surface of microbes and induce their uptake by phagocytic cells thru specific receptors on the cell for the opsonin molecule
149
Complement pathway
Series of plasma proteins work together to opsonize microbes, promote recruitment of phagocytes to the site of infection and in some cases directly kill microbes. Can activate inflammatory response
150
1. Classical- Ab bound to antigen
2. MB-Lectin
3. Alternative-Complement can bind directly to microbe
3 ways to start complement pathway
151
1. Recruitment of inflammatory cells
2. Opsonizations of pathogens
3. Killing of pathogens
3 outcomes of complement pathway
152
Inflammation
What do C3A and C5A cause?
153
1. C3 is cleaved into C3A and C3B
2. C3A(inflammatory) is released, C3B stays w/ the microbe (becomes C5)
3. C5 is cleaved into C5A (inflammatory) and C5B (which stays w/ microbe)
4. If this keeps going, causes MAC pore which causes osmotic lysis
What happens after complement is activated?
154
1. Opsonization and phagocytosis
2. Stim of inflammatory rxns
3. Complement mediated cytolysis
3 functions of complement
155
Inflammatory response
Major outcome of innate immune activation is the induction of acute inflammation which is the accumulation of leukocytes, plasma proteins, and fluid from the blood at an extravascular site of tissue injury or infection
156
1. IL-1
2. TNF
3. IL-6
4. CXCL8
5. IL-12
First cytokines made in innate immunity (5)
157
Fever, shock, mobilization
What are the systemic effects of cytokines?
158
TNF
What cytokine is known to cause shock?
159
IL-1 and TNF
Which cytokines activate vascular endothelium?
160
IL-12
Which cytokine activates NK cells
161
Radicals
How do INOS and oxidase kill?
162
Killing microbes
Inflammation enhanced adaptive immunity
Tissue remodeling
What are the effector functions of activated macrophages?
163
ROS and Nitric Oxide
Which molecules produced in activated macrophages kill microbes?
164
TNF
Responsible for negative sytemic effects
Shock
Can't be stopped once it starts
Causes low output in the heart, thrombus, increased permeability in blood vessels, and Insulin resistance
165
Cause fever and leukocyte production
| IL 6 and IL 1 also cause acute phase proteins which are opsonins
What do TNF, IL-1, and IL-6 do systemically that is positive?
166
Antiviral response
Protection agains viruses is primarily an adaptive immunity concern, but innate plays a role too
167
1. Inhibition of viral protein synthesis
2. Degradation of viral RNA
3. Inhibition of viral gene expression and virion assembly
What are the 3 parts of the antiviral state? The three actions of type I IFNs?
168
Type I: a and B
| Type II: gamma
What are Type I vs Type II IFNs?
169
Ab
Circulating substance w/ in the serum of animals immunized w/ an attenuated form of diphtheria toxin that could provide protection against challenge w/ the virulent organism
AKA antitoxin/Ig
170
Antigen
Substance Ab recognize
171
Membrane bound and soluble
2 forms of Ab
172
Membrane bound Ab
Function as B cell receptor
173
Soluble Ab
From antigen stimulated B cells (plasma cells)
174
Serology
[] of Ab for an antigen determined via serial dilutions
| Last binding observed = titer
175
Neutralization
Activation of complement system
Opsonization of pathogens
Ab-dependent cell-mediated cytotoxicity
Ab-mediated mast cell activation
(5)Effector functions
176
Fc Region
Part of Ab
Has effector function
Non-antigen binding portion
Few variations b/t Ab classes
177
Fab region
Part of Ab
Antigen binding site
Highly variable
Distinguish Abs made by one clone of B cell vs another clone
178
Gamma > Ig
Which globulin makes up the biggest chunk of globulins?
179
Monoclonal
Single clone
Steep peak
Indicates cancer
180
CDRs (Complementarity-determining Regions) 1, 2, and 3
Most of the Ab variability is contained w/ in 3 short regions called the hypervariable region
181
CDR3
Which CDR has most contact w/ antigen?
182
K and gamma
2 types of light chains that are functionally the same?
183
IgA: Mucosal immunity
IgE: Defense agains Parasites and hypersensitive
IgG1: Opsonization complement activation
IgM: 1st responder
Function of
IgA
IgE
IgG1
IgM
184
```
IgM+ = Early infection
IgG+ = Later stage infection
```
When you test cats for toxo, what do the results mean?
185
Secreted Ab
Short tail Ab
| Hydrophilic
186
Membrane bound
Transmembrane region
| Hydrophobic
187
Monoclonal Ab
Specific for specified single epitrope on antigen
Fuse B cells from immunized animal w/ myeloma cell line
Purpose: Diagnosis of infectious and systemic diseases
Targeting cells and molecules
Detection of tumors
188
Rearrangement and expression of H and L chains
What accompanies maturation of B cells from bone marrow progenitors?
189
Antigen
Any substance that can by sepcifically bound by an ab or T cell receptor
190
Epitope
Portion of antigen bound by Ab or TCR
191
Hapten
Small chemical too small to be immunogenic (to induce an Ab response)
Won't stim immune system
192
Carrier
Protein or polysaccharide that is conjugated to hapten to act as an immunogen (induce Ab response)
193
Hapten carrier complex
Induces Ab response to hapten
| Ex: vaccines
194
Determinant
Epitrope
| Portion of macromolecule Ab binds to
195
Linear determinant
On external surface or inaccessible unless denatured
Adjacent AA recognized
AA are together
196
Conformational determinant
AA residues not in sequence but become spatially positioned next to each other in the folded protein
197
Neoantigenic determinants
Modification of proteins by glycolsylation, phosphorylation, ubiquitination, acetylation, and proteolysis
Production of new epitopes not present before modification
198
Affinity
Strength of binding b/t single epitope and ab binding site
199
Avidity
Cumulative strenght of attachment of all Ab binding sites to epitopes
200
Change in heavy chain of constant region
How do isotypes switch?
