Lec 01- Overview of Immune Responses Flashcards
1
Q
How can microbes survive in animals?
A
grow extracellular (immersed in nutrients)
2
Q
How can intracellular microbes survive?
A
replicate utilizing host-cell energy sources
3
Q
What is immunity?
A
defense mechanisms providing protection from infectious disease
self vs. non-self
4
Q
Noninfectious foreign substances
A
antigens (Ags)
5
Q
An immune response against microbes that causes tissue injury
A
Immunopathology
Collateral damage
6
Q
Antigens
A
substances which induce an immune response
7
Q
What do antigens include?
A
- proteins
- carbs
- lipids
- nucleic acids
8
Q
Smallest unit of an antigen
A
antigenic determinant
9
Q
How many amino acids/sugar residues are there in the smallest unit that an antibody can make?
A
3-6 amino acids
5-6 sugar residues
10
Q
Which molecules are multi determinant (multiple epitomes)?
A
All large structures of antigens
11
Q
What binds to conformational antigenic determinants?
A
Antibodies (dependent on folding of the molecule)
12
Q
What can recognize linear amino acid sequences?
A
T cell receptors
13
Q
What are antigens that can stimulate an immune response called?
A
Immunogens
14
Q
All _____ are antigens but not all antigens are ______.
A
All IMMUNOGENS are antigens but not all antigens are IMMUNOGENS
15
Q
Which molecules can bind to Ab’s or TCR’s, but not initiate an immune response?
A
Haptens
16
Q
Which type of immunity is the first line of defense against infection?
A
Innate immune system
17
Q
The innate immune system gives rise to ______.
A
acute inflammatory response
18
Q
What type of immunity has some specificity for microbes, but no memory?
A
innate immune system
19
Q
What type of immunity takes longer to develop?
A
adaptive immune system
20
Q
What type of immunity is highly specific and shows memory?
A
adaptive immune system
21
Q
2 other names for innate immunity
A
natural immunity
native immunity
22
Q
What type of immunity responds rapidly to infections and exists even before infection?
A
innate immunity
23
Q
What type of immunity doesn’t distinguish fine differences between microbes?
A
innate immunity
24
Q
3 principal components of innate immunity
A
1- physical and chemical barriers
2- phagocytic cells (macrophages/neutrophils), dendritic cells, natural killer cells, other innate lymphoid cells
3- blood proteins (complement system and other mediators of inflammation)
25
Timing differences of innate and adaptive immunity?
- Innate immunity = hours
| - Adaptive immunity = days, weeks
26
Innate immunity component examples:
Cellular and chemical barriers
- skin
- mucosal epithelia
- antimicrobial molecules
27
Innate immunity component examples:
Blood proteins
- complement
- acute phase proteins
- cytokines
- others
28
Innate immunity component examples:
Cells
- phagocytes (macrophages, neutrophils)
- dendritic cells
- natural killer cells
- innate lymphoid cells
29
Adaptive immunity component examples:
Cellular and chemical barriers
- lymphocytes in epithelia
| - antibodies secreted at epithelial surfaces
30
Adaptive immunity component examples:
Blood proteins
- antibodies
| - cytokines
31
Adaptive immunity component examples:
Cells
B and T lymphocytes
32
Specificity of innate immunity
- Molecules shared by groups of related microbes
| - Molecules produced by damaged cells
33
Specificity of adaptive immunity
microbial and nonmicrobial antigens
34
Diversity of innate immunity
limited
germline encoded
35
Diversity of adaptive immunity
- very large
| - receptors produced by somatic recombination of gene segments
36
Reactivity to self?
Innate = none
Adaptive = none
37
What type of immunity is also a "decision-making stage" of an immune response?
innate immune system
38
Innate immunity ________ the invader in the context of intracellular vs. extracellular microbes. It then sends the instructions to adaptive immunity.
evaluates
39
Cells communicate through what type of contact?
direct cell-to-cell contact
| cytokines and chemokines
40
What proteins regulate and coordinate many activities of the cells of innate and adaptive immunity?
cytokines
41
Each cell expresses a set of ___________________________ for several cytokines.
specific signaling receptors
42
What is the function of cytokines?
- growth and differentiation of all immune cells
| - activation of effector functions of lymphocytes and phagocytes
43
What large subset of cytokines regulate cell migration and movement?
chemokines
44
2 type of lymphocytes
B and T cells
45
Interactions between _____ and ____, and between ____ and ____ are critical to the development of specific immunity
T and B cells
T cells and Antigen-presenting cells (APCs)
46
Where do the T cells mature?
thymus
47
Where do the B cells mature?
bone marrow
48
T cell maturation is stimulated by what?
antigens
49
What type of immunity do T cells give rise to?
cellular immunity
50
What type of immunity do B cells give rise to?
humoral immunity
51
What type of pathogens for T cells and B cells?
T cells = Intracellular pathogens
B cells = Extracellular pathogens
52
Humoral immunity produces which soluble molecules?
immunoglobulins
53
What did Paul Ehrlich hypothesize?
- immune cells use receptors to recognize toxins
| - secrete receptors to combat microbes
54
What term did Paul Ehrlich coin?
antibodies = serum proteins that bind toxins
55
Ehrlich's concepts = what model?
Function of B cells in humoral immunity
56
Humoral adaptive immunity is mediated by what?
antibodies in:
- blood
- mucosal secretions
57
What do B lymphocytes (B cells) produce?
antibodies in blood and mucosal secretions
58
3 functions of antibodies (Abs)
- RECOGNIZE microbial antigens
- NEUTRALIZE the infectivity of microbes
- TARGET microbes for elimination by various effector mechanisms
59
What is the principal defense mechanism against extracellular microbes and their toxins?
Humoral adaptive immunity
-Abs bind and eliminate them
60
Elie Mechnikoff was considered the father of what?
Cell-mediated immunity
61
Cellular theory of immunity states____?
host cells are the principal mediators of immunity
62
What did Metchnikoff discover at Pasteur in 1883?
phagocytes
63
What was Metchnikoff unable to prove?
that specific immunity to microbes could be mediated by cells
64
Cellular theory of immunity became re-established when ______.
resistance to an intracellular bacterium could be transferred with cells but not serum
65
Specificity and mediation of cell-mediated immunity is due to _______.
T lymphocytes
66
T lymphocytes work in concert with _______ to eliminate microbes.
phagocytes
67
T lymphocytes mediate defense against _______.
intracellular microbes that are inaccessible to circulating Abs
- viruses
- some bacteria
68
Function of cell-mediated immunity
- destruction of microbes residing in phagocytes
| - killing of infected cells to eliminate reservoirs of infection
69
Function of T helper cells
eradication of extracellular microbes by helping B cells make effective Abs
70
Humoral immunity:
Microbe = Extracellular Microbes
1) Responding lymphocytes?
2) Effector mechanism?
3) Transferred by?
4) Functions?
1) B lymphocyte
2) Secreted antibody
3) Serum
4) Block infections and eliminate extracellular microbes
71
Cell-Mediated Immunity:
Microbe = Phagocytosed microbes in macrophage
1) Responding lymphocytes?
2) Transferred by?
3) Functions?
1) Helper T cells
2) Cells (T lymphocytes)
3) Activate macrophages to kill phagocytosed microbes
72
Cell-mediated Immunity:
Microbe = Intracellular microbes replicating within infected cell
1) Responding lymphocytes?
2) Transferred by?
3) Functions?
1) Cytotoxic T cells
2) Cells (T lymphocytes)
3) Kill infected cells and eliminate reservoirs of infection
73
What ensures that the immune response to a microbe (or non microbial antigen) is targeted to that microbe or antigen?
specificity
74
What enables the immune system to respond to a large variety of antigens?
diversity
75
What increases the ability to combat repeat infections by the same microbe?
memory
76
What increases the number of antigen-specific lymphocytes to keep pace with microbes?
clonal expansion
77
What generates responses that are optimal for defense against different types of microbes?
specialization
78
What allows the immune system to recover from one response so that it can effectively respond to newly encountered antigens?
contraction and homeostasis
79
What prevents injury to the host during responses to foreign antigens?
nonreactivity to self
80
When Ag is introduced and lymphocytes with receptors for Ag seek and bind it, they are triggered to _____.
proliferate and differentiate
gives rise to clones of cells that are specific for the Ag
81
Cells that seek and bind the Ag, react with the Ag to ______.
neurtralize or eliminate the Ag
82
Ag-specific cells late in the immune response are responsible for________.
memory in adaptive immunity
83
What did Dr. Jerne and Dr. Burnet suggest?
Clonal selection hypothesis
Ag-specific clones of lymphocytes develop before and independent of exposure to Ag
84
What is a clone?
A lymphocyte of one specificity and its progeny
85
4 steps of the Hypothesis of Clonal Selection
1) MATURE -- Lymphocyte clones mature in generative lymphoid organs (in absence of antigens)
2) ENTER -- Clones enter lymphoid tissue
3) ACTIVATED -- Clones activated (selected) by antigens
4) RESPONSE -- Antigen-specific immune responses occur
86
5 Phases of Adaptive Immune Responses
1) Antigen recognition
2) Lymphocyte activation (clonal expansion and differentiation)
3) Antigen elimination (antibodies and effector T cells)
4) Contraction/Homeostasis (apoptosis)
5) Memory
87
Primary vs. Secondary Adaptive Immune Response
Secondary response = more rapid and larger than primary response (memory)
88
In what phase do the expanded lymphocyte clones die?
contraction phase
homeostasis is then restored
89
Which English physician was the first to successfully vaccinate against smallpox?
Edward Jenner
Cowpox material >> 8 y.o. boy >> no disease developed when inoculated with smallpox later
90
Who is the father of immunology?
Dr. Pasteur
developed vaccines
91
What is active immunity?
- Conferred by a host response to a microbe or microbial Ags
- Provides resistance to infection
- Generates immunologic memory
92
What is passive immunity?
- Conferred by adoptive transfer of Abs or T cells specific for the microbe
- Provides resistance to infection
93
Which type of immunity generates immunologic memory (active or passive)?
Active immunity
94
B lymphocytes
1] Antigen recognition
2] Effector functions
1] Recognize soluble Ags and develop into Ab-secreting cells
2] Functions:
- Neurtalize microbe
- Phagocytize
- Complement activation
95
T helper lymphocytes
1] Antigen recognition
2] Effector functions
1] Recognize Ags on surface of Ag-presenting cells and secrete cytokines --> stimulate different immunity and inflammation
2] Functions:
- Activation of macrophages
- Inflammation
- Activation (proliferation and differentiation) of T and B cells
96
Cytotoxic T lymphocytes
1] Antigen recognition
2] Effector functions
1] Recognize Ags on infected cells
2] Function:
-Kill infected cells
97
Regulatory T cells
1] Antigen recognition
2] Effector functions
1] Self antigens
2] Functions:
-Suppress of other lymphocytes to prevent immune responses (to self antigens)
98
8 Cells of Innate Immunity
- neurtophil
- eosinophil
- basophil
- mast cell
- monocyte
- macrophage
- dendritic cell
- natural killer cell
99
WBC
- Normal range
- Mean
4,500-11,000
7,400
100
Neutrophils
- Normal range
- Mean
1,800-7,700
4,400
101
Eosinophils
- Normal range
- Mean
0-450
200
102
Basophils
- Normal range
- Mean
0-200
40
103
Monocytes
- Normal range
- Mean
0-800
300
104
Lymphocytes (T and B cells)
- Normal range
- Mean
1,000-4,800
2,500
105
Phagocyte function
Scavenger function
- ingest and destroy microbes
- get rid of damaged tissues
106
What cells are phagocytes?
- neutrophils
| - macrophages
107
4 Steps of Phagocyte Response
- RECRUITMENT of cells to infection site
- RECOGNITION of and activation by microbes
- INGESTION of microbes by phagocytosis
- DESTRUCTION of ingested microbes
108
Activated phagocytes also secrete _____ to promote or regulate immune responses
cytokines
109
What are polymorphonuclear leukocytes?
- Neutrophils in normal blood
- Nucleus = segmented into 3-5 connected lobules
- Most abundant population of circulating WBC
- Diameter = 12-15 um
110
Polymorphonuclear leukocyte (neutrophils) function
mediate the earliest phases of inflammatory reactions
111
Where are neutrophils produced?
bone marrow
| pleuripotent stem cells
112
Neutrophils arise from precursors that also give rise to _______.
Mononuclear phagocytes
113
What stimulates the production of neutrophils?
Granulocyte colony-stimulating factor (G-CSF)
| a cytokine
114
How many neutrophils does an adult human produce daily?
1 x 10^11
115
How long does a neutrophil circulate in the blood?
- hours or a few days
| - function in tissues for 1-2 days, then die
116
What stain is used for neutrophils?
neutral dyes
117
What stain is used for eosinophils?
eosin
118
What stain is used for basophils?
basic dyes
119
What are azurophilic granules?
- Lysosomes
| - Contain enzymes and other microbicidal substances
120
What happens after neutrophils bind and internalize yeast cells via phagocytosis?
- yeast is sequestered in phagosomes
| - fuse with azurophilic granules
121
What contributes to the killing of the phagosome?
- the production of ROS
| - the release of enzymes (neutrophil elastase) into the phagosome
122
What happens when neutrophils encounter hyphae?
- not able to internalize them
- azurophilic granules = free to deliver their contents into the nucleus
- triggers chromatin decondensation and NET release
123
What do NET contribute to?
immobilization and killing of extracellular organisms
COST = some tissue damage
124
NET formation characteristics
- rapid, active process (minutes)
- mediated by cell death-dependent process (NETosis)
- composed of DNA (from mitochondria) and histones
- decorated by proteins from 1' and 2' granules
125
NETosis
- chromatin decondensation
| - nuclear membrane disintegration
126
What is NET formation associated with?
- bacterial clearance
- thrombosis
- sepsis
- SLE
127
What protects against helminthes and reactions that cause allergic diseases?
- mast cells
- basophils
- eosinophils
128
Mast cells
- Filled with?
- Stained with?
- Histimines and other mediators
| - Giemsa >> PURPLE
129
Blood basophils
Stained with?
Giemsa >> BLUE
130
Eosinophil granules
- Filled with?
- Stained with?
- basic proteins
| - eosin (acidic dye) >> RED
131
8 Functions of Mast Cells
- Recruitment and activation of monocytes and macrophages
- Migration and activation of dendritic cells
- Recruitment and activation of T cells
- Recruitment and activation of neutrophils, basophils, and eosinophils
- Phagocytosis and/or antimicrobial activity
- Effects on epithelial cells, tight junction proteins, etc...
- Degradation of endogenous toxic mediators
- Degradation of snake venom components
132
Where are mast cells commonly found?
- sites that are exposed to the external environment (skin)
| - close to BV
133
Mast cells can regulate ____ and _____.
regulate vascular permeability and effector-cell recruitment
134
The mononuclear phagocyte system includes _____ and _____.
- Circulating monocytes
| - Resident tissue macrophages
135
What type of immunity do macrophages play a role in?
Innate & Adaptive immunity
136
Where do cells of macrophage lineage arise from?
Committed precursor cells in bone marrow
137
What stimulates macrophage formation?
Monocyte/Macrophage colony-stimulating factor (M-CSF)
138
Monocyte pathway
```
1- Bone marrow
2- Activated
3- Maturation
4- Enter blood circulation
5- Migrate to tissues
6- Mature into macrophages (especially during inflammation)
```
139
Fetus Mononuclear Phagocyte pathway
```
1- (Yolk sac) Hematopoietic stem cell
2- Embryonic tissue macrophage precursor
3- Blood
4- Differentiation in tissues
> Brain = Microglial cells
> Liver = Kuppfer cells
> Liver = Alveolar macrophage
> Spleen = Sinusoidal macrophages
```
140
Adult Mononuclear Phagocyte pathway
```
1- (Bone marrow) Hematopoetic stem cell
2- Monocyte/dendritic cell precursor
3- Monoblast
4- Blood
5- Monocyte
6- Macrophage activation in tissues
```
141
Mononuclear Phagocytes (Bone Marrow >> Peripheral Blood)
```
Bone Marrow:
> HSC
> GM-CFU
> M-CFU
> Monoblast
> Pro-monocyte
```
Peripheral Blood:
> Inflammatory monocyte
> Resident monocyte
142
Monocyte Differentiation Options
-Bone = osteoclast
-CNS = microglial cells
-Lung = Alveolar macrophage
-Liver = Kupffer cells
-Connective tissue = Histiocyte
-Spleen =
> White pulp macrophage
> Red pulp macrophage
> Marginal zone macrophage
> Metallophilic macrophage
143
6 Functions of Monocytes/Macrophages
```
1- Activation
2- Chemotaxis, tissue inflammation
3- Phagocytosis, scavenger function, tissue repair
4- Effector function
5- Antigen presentation
6- Immunomodulation
```
144
MO present Ags to helper T cells at the sites of infection that leads to ______.
- T cell activation
- Activation of cytokines >> Activation of MO
- Eradication of phagocytized microbes that are resistant to killing
145
Common dendritic cell precursors
ADULTS:
-Pre-classical DC >> Classical DC
- Plasmacytoid DC >> Plasmacytoid DC (pDCs)
- Monocyte >> Inflammatory DC
FETUS:
-Embryonic tissue precursor >> Langerhans cells
